Kidney Stones: Medical and Surgical Management Fredric L Coe, Elaine M Worcester, Andrew P Evan, James E Lingeman
Page numbers followed by b refer to box, f refer to figure, and t refer to table
Acetazolamide 235, 236, 502, 506, 590
inhibits carbonic anhydrase activity 506
Acid 172
base 374
balance 259
homeostasis 443
parameters 234, 234f
buffering 443
excretion, renal mechanisms of 444
homeostasis 228
load 236, 298
retention, chronic 452
stone, nonuric 621f
Acidic urine 386, 517
Acidification 465
test 451
Acidogenic diet 165
Acidosis 232f, 236, 263f, 264, 265, 267, 268f, 473
acute effects of 261
chronic effects of 263
normobicarbonatemic 237
overproduction 443
Acquired immune deficiency syndrome 608
Acylcarnitine 232
Addison's disease 357
metabolism 491f
phosphoribosyltransferase deficiency 482, 491, 492, 493f, 494f, 524, 549
Adenoma 233, 364f
double 361, 365, 366
diphosphate 251
monophosphate 232, 491f
triphosphate 188, 226, 232f, 444, 446f
hydrolysis 445
African green monkey renal epithelial cells 144
Air 595
Alanine-glyoxylate aminotransferase 169, 413, 417f
Albumin 65
Alfuzosin 611
Alkali 383
citrate 473
therapy 314, 382, 459
treatment, clinical basis of 524
Alkaline urine 447
Alkalinuria 447, 455
Allopurinol 344, 506, 537, 590
Alpha-intercalated cell 445f
Alpha-ketoglutarate 227
Aluminum 397
containing drugs 590
magnesium potassium urate 590
American Urological Association 562, 566, 601, 608, 609t, 626, 641, 693, 698, 699
Amino acid 233f, 483
cystine 482
transporter 482
Aminoglycoside 609, 610
plus metronidazole 610
Aminopenicillins 505, 654
Ammonia 246
Ammonium acid urate 91, 93, 163, 581, 590, 705
stones 403, 523
Amorphous silica 590
Amoxicillin 505, 608, 609
Ampicillin 505, 607, 609
Androgen 194
deficiency 194
receptor 192
Anemia, hemolytic 458
Anesthesia 640, 654, 657
Angiomyolipoma 589
Angiotensin converting enzyme inhibitors 237, 490, 592
Animal protein 7, 9, 11
Anion exchanger 444, 445, 473
Anion gap, normal 443, 447
Anodontia 464
Antegrade techniques 627
Antibacterials 505, 590
Antibiotic 507, 610
prophylaxis 653
therapy, periprocedural intravenous 683
Antidiuretic hormone 489
Antiglomerular basement, development of 645
Antimicrobials 610t
Antiproteases 94
Antiretropulsion devices 663
Aonyx cinerea 163
Aortic dissection 589
Apatite 8385, 126, 547
stone formers 135
Apoptosis 195
Appendicitis 588, 589
Aqueous crystallizing solution 25
Arachnocampa luminosa 162
Armamentarium 678
Aromatase 193
Arthralgia 356
Aryl hydrocarbon receptor 170
Ascorbic acid 10
Atazanavir 94, 503
calculi 94f
Atomic bomb survivors 620
Atomic force microscopy 22
studies 41
Avulsion 633
Azapeptide inhibitor 503
Azoospermia, obstructive 464
Bacteria 436
Bacteriuria 610
asymptomatic 609, 610t
Balloon dilator, small 687
Bariatric procedures, surgical anatomy of 387f
Bariatric surgery 325, 384, 386, 388t
malabsorptive 393t
modern 388
Bartter's syndrome 169, 217, 473, 476, 477
Baseline tests 457
Basement membrane 156f
Beckwith-Wiedemann syndrome 464
Benzbromarone 506
Benziodarone 508
Beta lactamase inhibitor 654
Betadine 655
Bicarbonate 534
concentration 260
luminal concentration of 249
sensitive adenylate cyclase gene 218
Bicarbonaturia 228, 229, 447
Bile acid 385, 401
malabsorption 385
sequestrants 397, 400
Biliopancreatic diversion 384, 389f
Biopsies, cortical 128, 135, 137
Biplanar fluoroscopy 639
Bisphosphonate 175, 314
Bladder 595, 653
calcium oxalate stones 169
diverticulum 607
neurogenic 546
stone 169
endemic 404
Bleeding 642
Blood 188, 595
count, complete 612
levels 188, 189
pressure 286
urea nitrogen 534, 591
Boari flap reconstruction 633
Body mass index 514, 514f, 515f, 517f, 642
Body surface area 416
Bone 196, 198, 207, 259, 456, 595
alkaline phosphatase 304
calcium balance 279, 293f
cell 308
cellular functions 194
cortical thickness of 169
disease 281, 454, 456
metabolic 473
severe 355f
treatment of 313
formation rate 306
fracture 6
histomorphometric findings 307t
histomorphometry 304
histopathology 303
biopsy 413f
stromal cells 195
content 303, 305
density 170, 171, 259, 281, 303305, 305t
resorption 171
structure 195
surface extension 306
turnover, biochemical markers of 304
disease 326, 374, 384
small 386t, 396, 398f, 402
obstruction 589
resection, small 117, 120, 133
surgery 386
Brush border membrane 199
Brushite stone 91f
formers 130
section of 91f
surface of 91f
Bypass kidney stone 118
Cakut’ syndrome 464
Calcitonin 235
Calcitriol 287, 288f, 289f
serum values of 288f
Calcium 2, 165, 171, 187, 204, 226, 235, 246, 282, 283, 289f, 290, 299, 330, 331, 357, 386, 390, 393, 397, 417f, 508, 534, 535, 590
absorption 248, 278, 279f
adaptation 196
balance 280, 280f
carbonate 22, 163
chelator 227
citrate imbalance 343
daily excretions of 335f
diet, low 280, 344
homeostasis 196, 213f
influx, cumulative 264f
intake 310
integrative physiology of 246
kidney stones 278f
mineral distribution of 187
nephrocalcinosis 447, 467
nephrolithiasis 12f, 447, 467
osteogenic source of 456
oxalate 28, 32, 33f, 40f, 55, 77, 80, 84f, 94, 100, 126, 143, 163, 173, 204, 321f, 322, 330, 334f, 337f, 341f, 343f, 351f, 417f, 455f, 502, 525, 547, 590, 593f
oxalate crystal 38f, 413f
inhibitor 166f, 434
oxalate dihydrate 29, 79, 80f82f, 84f, 89f, 418, 431
oxalate kidney stones 7t
oxalate monohydrate 29, 78f, 79, 79f, 81f, 84f, 105, 418, 431, 434, 582f, 642
stone, large 582f
oxalate renal stone 34f
oxalate stone 7, 77, 82, 82f, 84, 85f, 102f, 166, 239, 240, 381, 416, 652
idiopathic 104f
recurring 416
oxalate tissue deposits 416
oxalate trihydrate phase 29
oxalate uroliths 169
phosphate 22, 33f, 40f, 55, 83, 87, 89, 93, 100, 117, 162, 163, 204, 246, 321f, 330, 334f, 337f, 340f, 341f, 350f, 351f, 445, 455f, 459f, 502, 590, 707
amorphous 22
crystal interactions 143
interstitial 98f
precipitation, prevention of 246
spherulites 105f
stones 11, 136f, 240, 256f, 692
plaque 99f
proximal tubule delivery of 293
reabsorption 294f
renal stones 278f
sensing receptor 170, 327, 472, 474f
serum 328f
stones 11, 324, 335
formers 321, 340, 344t
hyperuricosuric 523
prevention of 525
supplementation 399f
urate 91
wasting 473
Calciuria 471
Calgranulins 65
Calpodes ethlius 162
Calvariae, incubation of 262, 268f
Calvarial cells 264f
Calyceal diverticulum 570, 604, 643, 674, 685, 686f
incidence of 686
Calyceal stones
smaller 701
untreated 559, 560
Calyces 127
Cancer 522
Canine silica stones 164
Carbohydrates 7
dioxide 255
skeleton 227f
Carbonate apatite 84
Carbonic anhydrase 444, 446, 448, 456, 506
inhibitors 506, 525
Carnitine 232
Caroli's disease 464
Cationic amino acids 455
Caveolin-1 scaffolding protein 169
C-cell hyperplasia 368
Ceftriaxone 505
Celecoxib 611
Celiac disease 384, 394, 395, 395f
injury 120
types 195
Central maltese cross pattern 524
Cephalexin 607
Cephalosporin 505, 610
first-generation 609
second-generation 609
Cerebrospinal fluid 213
Charge-coupled device 660
Chemotherapy 523
Chlorhexidine 655
Chloride 473, 534
anions 249
channel 473
proton exchanger 169
Chlorine 204
Chlorothiazide 537
Chlorthalidone 176, 294f, 295f, 299, 344
Cholestyramine 397, 401, 401f
effects of 401f
Cinacalcet 175
Ciprofloxacin 505, 607, 609
Cirrhosis 451
Citrate 55, 226228, 239, 251, 314, 330, 331, 335f, 343, 386, 390, 393, 405, 434, 435, 535, 692
concentration and excretion rates 229
metabolism 230f, 232f, 233
oxidation, regulation of 234f
preparations 238t
renal handling of 231f
special role of 342
structure of 227f
supplementation 538
therapy 238
transport 230
Citric acid 226, 227f, 228f, 230f, 238
Classical nucleation theory 18
Clavulanate 609
Clavulanic acid 608
Clindamycin 610
Clinical Research Office of Endourological Society 572
Cobra angiographic catheter 690, 691
Colectomy 379t, 381
disease of 378
Colesevelam 397
Colestipol 397
Colitis, ischemic 589
Collagen mineralization 45
Collateral injury 668
Collecting duct cells 550
Colloidal surface texture 33
Colon 681
disease of 378
Colonic disease 381
Colony-forming units 591
Complementary metal oxide semiconductor 649, 660
Complex stone disease 601
Computed tomography 322, 358, 470, 502, 578f, 594, 598, 600f, 612, 693
imaging 137, 569
scans 532
Confusion 608
Constipation 356, 358
Controversies regarding radiation safety 619
Coumadin therapy 608t
Creatinine 330, 535
Crohn's colitis 378
Crohn's disease 83, 377, 378, 382, 384, 400, 401, 403, 516
Crohn's symptoms 377
adhesion 146, 147
aggregates 48
epithelia 143
molecule 144
location of 155, 156f
morphology of 157f
nucleation of 146
passage 322
retention 143
Crystallization inhibitors 342
Crystalluria 149, 493, 496, 501, 516
Cumulative end-stage renal disease 545f
Cystic fibrosis 484
Cystic kidney disease 546
Cystine 92, 93, 120, 163, 482, 486, 487, 535
binding thiol drugs 488, 490
dimethylester 488
nephrolithiasis 93
stone 11, 92, 135, 240, 583, 652
bilateral 707f
formers 133
typical 94f
pathophysiology of 482
physiology of 482
Cystinuria 5, 93, 98, 117, 127, 133, 134f, 435, 482, 484488, 490f, 491, 549, 591
treatment of 491
Cystitis 589
Cystoscopy 656f
Cysts 465, 467, 470, 471
cortical 465
Cytokines 68
Cytoplasmic acetyl-CoA 234f
da Vinci robot 669
Dalmatianization 163
D-amino-oxidase 436
Darunavir 503
Darwinian natural selection 226
Dead spots 148
Deafness 169
Dehydration 20, 489
Dehydroepiandrosterone 192
Dent's disease 5, 169, 217, 325, 473475, 482
Deoxyribonucleic acid 418, 608
Depression 356
Diabetes 6, 327, 545, 551f, 634
mellitus 6, 65, 447, 514, 518, 519f, 546, 645
Diarrhea 235, 401
Dicalcium phosphate 567
Diclofenac 611
Diet 383, 396
and stone disease 7
role of 310
Dietary alkali intake, estimation of 254f
Digital flexible ureteroscopy 661f
Dihydrate mineral phase 29
Dihydrotestosterone 192
Dihydroxyadenine 482, 524
Dihydroxyglutarate 418
Dimercapto-succinic acid 559
Distal calcium delivery 295f
Distal convoluted tubule 120f, 207
Distal nephron
calcium 285
reabsorption 282
Distal obstructive ureteral stone 600f
Distal renal tubular acidosis 87f, 98, 117, 131, 132f, 169, 325, 327, 448, 449t, 453, 454f, 459f, 467, 473, 455f
etiology of 448t
primary 217
Distal ureteric stones, management of 625t
Diverticulitis 588, 589
Dorsal lithotomy 656f
Doxazosin 611
Drosophila melanogaster 166, 231
Drug-induced stones, treatment of 509
Dual-energy X-ray absorptiometry 304, 538
Ductal stones 127
Ducts of Bellini 98, 120f, 125f, 126, 126t, 322, 348, 430f, 455
Duodenal switch 389f
Duodenum 248, 681
Dysfunctional elimination syndrome 532
Efavirenz 504
Egyptian Urological Association 699
Ehlers-Danlos syndrome 464
Elastosis perforans serpiginosa 490f
Electrohydraulic technology 639, 640
Endocrine 357
Endoskeletons 162
Endourologic technique 668
End-stage kidney
disease 492
failure 413f
End-stage renal disease 7, 117, 120, 412, 413, 431, 468, 473, 492, 544, 546, 546f, 551, 588, 704
Enteric hyperoxaluria 375, 384, 397t
causes of 384t
Enteritis 589
Enterococcus faecalis 610
aldehyde oxidase 496
replacement 436
Enzyme-linked immunosorbent assay 59, 191
Ephedrine 505
calculi 506
Epithelial calcium channel 169
Epithelial cell 147, 150f
layers 204
Epithelial membrane antigen 146f
Epithelial phenotypical changes 147
Epithelial sodium channel 502
Epithelium, papillary surface 103f
Escherichia coli 606, 608
Estimated glomerular filtration rate 551
Estrogen 194, 235
synthesis 192
Ethylene glycol 149151, 151f
European Association of Urology 562, 565, 566, 626, 650, 698
Extracellular fluid 171f, 188
Extracorporeal shock wave lithotripsy 5, 349, 351f, 485, 488, 503, 565, 589, 609, 612, 629, 630, 674, 707, 709f
Fanconi syndrome 169
Fanconi-Bickel syndrome 476
Fat 595
accumulation 517
low 397
malabsorption 385
soluble vitamins 392
Fatigue 356
Fatty acids 385
Febrile complications 664
Fiberoptic technology 660
Fibroblast growth factor 192, 213f, 287, 288f, 289f, 309
regulation of 267
Fibromyalgia 589
dose-dependent 645
interstitial 122, 548
Fistula, nephrocutaneous 691
Flavin adenine dinucleotide 228f, 232, 495
Flexible ureteroscopes 567, 649, 657f, 659, 660, 674, 676, 685, 687, 691, 698
Flies 165
Fluid 297, 346, 383
extravasation of 681
Fluorescein 35
Fluoroquinolone 609, 610, 654
Fluoroscopic guided puncture 675, 676
Fluoroscopy 594
Folate 232
Foraminal stenosis 589
Fosfomycin 610
Four-dimensional computed tomography 364
Fourier-transform infrared spectroscopy 87
Framingham offspring study 261
Furosemide 507, 590
chronic 533
Gallbladder 374
Gallstones 6
Gastric banding 393
adjustable 389f
Gastric bypass 588
absorption 56
alkali losses 326
anatomy and physiology 374
bleeding 591
calcium secretion versus absorption 279
disease 415f
tract 196, 246, 374, 412
Gene therapy 437
General endotracheal anesthesia 640
Genetic hypercalciuric stone 170, 170f, 171, 171f, 176, 303
Genitourinary system 589
Gentamycin 149
Gibbs-Thomson effect 20, 21
Glafenine 504
Glands, hyperplastic 370
Glenn-Anderson ureteral advancement 689
Glenn-Anderson ureteroneocystostomy 689
Glial cell line derived neurotrophic factor 465
Glomerular filtration rate 239, 292, 326, 416, 443, 453, 485, 544, 592, 593, 608
Glomerulonephritis 546
Glomerulosclerosis 548
Glucose 255, 289
6-phosphate deficiency, autosomal recessive 516
transport 251
Glyceraldehyde 3-phosphate dehydrogenase 265
Glycogen 255
Glycolate oxidase 436
Glycoproteins 692
Glycosaminoglycans 57, 145
Glycosylation 62
Glyoxylate reductase 169, 417f, 418
mutations of 414
Gnathostoma vietnamicum 163
Gonadal steroids 192
Gout 6, 327
Gower's in vitro model system 31
G-protein-coupled receptor 190
Granulomatous disease 357
Granulomatous structures 157f
hormone 193
plate 193
Guaifenesin 505, 590
calculi 505
Guanosine triphosphate 228f
Gynecologic pelvic surgery 653
Hearing loss 458
disease, coronary 6
failure, congestive 588
valves 607
Helicobacter pylori 507
incidence of 633, 634, 644
retroperitoneal 567
subcapsular 644
symptomatic 633
Hematuria 482, 516, 644, 666, 567, 686, 705, 706, 708f
gross 634
macroscopic 705
Hemihypertrophy, congenital 464
Hemodialysis 435
Hemolysis 608
Hemolytic syndrome 608
Hemorrhage 589, 633
ranges, incidence of 633
Hepatic fibrosis, congenital 464
Hereditary hypomagnesemia-hypercalciuria syndrome 473
Herpes zoster 588, 589
High magnification scanning electron microscopy 46f
High-resolution micro-computed tomography 113f, 125f
High-resolution scanning electron microscopy 34f
Holmium laser fiber 662
Holmium:yttrium aluminum garnet laser 711
Hormone 189, 287
regulation 190
role of 308
Horse-shoe kidney 464, 573f, 687, 687f, 688
Hounsfield units 582, 598, 612
Human calcium oxalate 114f, 173
Human chorionic gonadotropin 612
Human idiopathic hypercalciuria 171t
Human immunodeficiency virus 502
Human kidney
biopsies 155f
stones 77
Human serum albumin 65
Human xanthinuria 168
Hyaluronic acid 147f
Hydrochlorothiazide 344, 473, 537
Hydrogen ion buffering 262
Hydronephrosis 169, 422f, 546, 692f
obstructive 421f
persistent 600f, 603
proximal 600f
Hydroxy-2-oxoglutarate aldolase 418
Hydroxyapatite 23, 62, 84, 325
interstitial 61
Hydroxyproline 173
dehydrogenase 436
feeding 166f
Hydroxypyruvate 417f
reductase 169, 418
mutations of 414
Hypercalcemia 327, 357t, 472
Hypercalciuria 13, 80f, 89f, 100, 164, 169, 175, 176, 187, 204, 209, 217, 218, 259, 277f, 284, 287, 289, 303, 308, 336, 356, 451, 455, 456, 467, 469, 471473, 474f, 475, 477, 506, 531, 532, 537, 538, 690, 705
absorptive 290, 305, 473, 477
acid-induced 297f
etiologic categories of 236
fasting 305, 473
human monogenic 278, 464, 471
hyperprolactinemic 175
idiopathic 100, 259, 276, 277, 277f, 278, 279f, 280, 280f284f, 285, 286f, 288f290f, 292, 295f, 303, 305, 307t, 435, 476
protein induced 172
Hyperkalemia 251f, 256, 447, 473, 489
Hypermagnesemia 169, 219
Hyperoxalemia 169
Hyperoxaluria 13, 84f, 149, 151, 169, 325, 387, 392, 393, 401, 412, 415f, 416, 507, 532, 538, 550, 705
moderate-to-severe 416
primary 84f, 98, 117, 138f, 143, 154, 155f, 169, 327, 412, 413, 413f, 414, 414f, 415f, 416t, 417f, 418, 418t, 432f, 433, 434, 482, 549, 591
types 117, 122, 137, 325, 412, 413, 706
secondary 416, 418
severe 390
Hyperparathyroidism 357, 371, 464, 468, 469, 472, 588, 591
inherited 472
persistent 368
primary 6, 89f, 98, 117, 129f, 209, 325, 326, 328f, 330, 355, 357, 361, 371, 472
recurrent 368
Hyperphosphaturia 169, 214, 217
Hyperplasia 361, 365
Hypersensitivity reaction 608
Hypertension 6, 10, 357, 358, 546, 551f, 631, 634, 704
arterial 473
familial hyperkalemic 473, 477
Hyperthyroidism 357
Hypertrophic disorders 464
Hyperuricemia 170, 508, 551f
Hyperuricosuria 163, 170, 516, 523, 537, 690
acquired causes of 516
Hypobicarbonatemia 444
Hypocalcemia 190, 256, 473
autosomal dominant 472
familial 473, 477
Hypocalcemic hypercalciuria, autosomal dominant 325
Hypocalciuria 219
familial hypercalcemic 325
hypercalcemia, benign familial 357
Hypocitraturia 13, 14, 226, 230, 232f, 236, 237, 246, 381, 386, 402, 447, 452, 455, 456, 471, 473, 477, 506, 531, 532, 537
clinical pathophysiology of 236
idiopathic 237
mechanisms of 232f
Hypokalemia 235, 326, 447, 457, 458, 476, 477
Hypokalemic paralysis, episodes of 473
familial 218, 477
low serum 326
Hypomagnesuria 219, 400
Hypoparathyroidism 370, 472
Hypophosphatemia 190, 217, 447, 473, 475, 690
Hypophosphatemic rickets, hereditary 169, 217, 473, 475
Hypothesis 268, 382
Hypothyroidism 357
Hypotonia-cystinuria syndrome 485
Hypouricemia 496, 523
Hypouricosuria 496
Ibuprofen 611
Idiopathic calcium
oxalate stone 99f, 101f, 116f
former 98, 100f, 106f, 111f, 112f, 117, 120, 126, 129f, 336
phosphate stone formers 347
Ileocolitis 377
Ileostomy 117, 131, 325
Indapamide 344
Indinavir 94, 502
Indomethacin 473
Infantile hypercalcemia, idiopathic 169, 472
Infection 642, 681
recurrent 686
signs of 693
Inflammatory bowel disease 6, 376, 377, 377t, 516, 538, 588, 589
Inflammatory response syndrome 609
Infundibular stenosis 570
Injury 349
Inner medullary collecting duct 106, 144, 119f, 249, 454f
Inositol hexaphosphate 57
Insulin 289
role of 522
Intact stone-plaque complex, examination of 110
Inter-alpha-trypsin inhibitor 68
Interfacial energy, reduction of 21
International Cystinuria Consortium 484
Interstitial fibrosis, medullary 120
Intestinal calcium absorption 169
Intestinal disease 376
small 384
Intestinal lipase inhibitors 384
Intestine 209, 455
small 374
Intracellular calcium
buffer 169
transport 209
Intracellular carbonic anhydrase 255
Intracorporeal lithotripsy devices, development of 649
Intrarenal collecting system 685, 687f, 691, 695
Intrarenal surgery, retrograde 629, 652
Intratubular crystalline deposits 117
Ionized plus complexed forms 188
Ions 116, 232
Irrigation pressure 669
mesenteric 384, 589
reperfusion injury 62, 66
Jejunoileal bypass 384386, 387f
induced enteric hyperoxaluria 143
Jejunum 199, 681
Juxtamedullary nephrons 249
Kaplan-Meier analysis 559
Ketorolac 611
Kidney 196, 207, 246, 456, 595, 653
damage 433
disease 416
chronic 6, 7, 237, 247, 260, 327, 387, 412, 473, 476, 482, 544, 551, 551f
failure 433
monitored 434
preservation of 414f
reduced 416
injury, acute 492, 547, 549
loss of 642
stone 3, 5, 98, 176, 238, 355, 475, 530, 544, 545, 547, 588, 645
consortium 413f
disease 565
formation 98f, 164, 332f, 531
formers, evaluation of 330t
history of 3f
incidence 3, 4
natural history of 559
pathology of 215
prevalence of 3, 559
prevention 8f
recurrence 3, 4
silica-induced 504
types of 44f
Kidney, ureter and bladder 618, 707f709f, 713f
Krebs cycle 226
Kyphoscoliosis 356f
Lanthanum carbonate 397
Laparoscopic surgery, role of 698
Laser 661
fiber 662
papillotomy 471
Laxative abuse 404
Lesch-Nyhan syndrome 506, 516, 549, 706
Leukemias 357
Levofloxacin 607
Lich-Gregoir procedure 689
Linear growth 193
Lipotoxicity 520
role of 520
Lithium 357
Lithogenicity 508
Lithotomy 654, 678
electrohydraulic 569, 661
intracorporeal 650
pneumatic 569
ultrasonic 661
ureteroscopic 652
Lithotripters 638, 640
aperture 640
electrohydraulic 631, 639, 652
electrokinetic 661
electromagnetic 566
intracorporeal 660
piezoelectric 566
pneumatic 661
technology 638
trigger shock waves 639
ultrasonic 678, 693
Liver 246, 595, 681
disease 451
Loin-pain hematuria syndrome 468
Loops of Henle 42f, 58, 101f, 102, 111, 116, 116f, 120, 120f, 128, 135, 476
Lowe's syndrome 475
Lower pole stone 629, 666
Lower ribs, costochondritis of 589
Lymphomas 357
Macrocallista nimbosa 162
Macrolides 610
Macromolecules 57
Madin-Darby canine kidney cells 144
Magnesium 7, 10, 56, 189, 204, 235, 246, 330, 344, 375, 386, 397, 400, 435, 474, 508, 534, 535, 692
absorption of 248
ammonium 707
phosphate 89, 163, 705
deficiency 375
mineral distribution of 187
oxalate 56
transport 200
urate 91
crystallopathy 168
tubules 166, 167, 167f, 168
Mammalian nephron 445f
Mammary gland 246, 249
Marfan's syndrome 464
Matrix stones 581
Maximally acidic urine 447
Meckel's diverticulum 589
Medical expulsive therapy, trial of 589
Medium chain triglyceride supplements 397
Medium fibroblast growth factor 268
Medullary sponge kidney 117, 120, 464, 465f, 466, 467, 468f, 469, 469f
disease 137, 139f
partial 471f
severe case of 470f
stone, computed tomography image of 139f
unilateral 470f
Menopause 469
Metabolic acid 260, 261
Metabolic acidosis 169, 235, 266f268f, 443, 447, 458, 476
hyperchloremic 217, 252, 256f, 473
medium simulating 262
Metabolic disorders 705
Metabolic syndrome 327, 514
Metanephric blastema 466f
Metasilicic acid 505
Metastability, upper limit of 323, 338, 340
Methionine 58, 405
Micro-computed tomography 102, 104f, 115f, 168f, 454f
Microhematuria 475
Midureteral stone 708f
Milk alkali syndrome 357
Minerals 374
balance, hereditary disorders of 215
homeostasis 189
metabolism, regulation of 187
Minimally invasive parathyroidectomy, success of 367
Mitochondria 414
citrate metabolism 232f
enzyme 4-hydroxy-2-oxoglutarate, deficiency of 415
transporters 232
Mobile hydrogen nuclei 619
Molecular weight, low 64, 469, 473
Monitoring urine potassium excretion 383
Monogenic mutations 448
Mood disorder 608
Multigland disease 361
Multi-institutional cohort study 650
Multiorgan abnormalities 171f
Multiorgan dysfunction syndrome 591
Multiple echogenic foci 708f
Multiple endocrine neoplasia 466
type 1 358, 367, 472
type 2 368, 472
Multiple medullary tip stones 426f
Muscle 595
Myeloma, multiple 357
Myeloproliferative disease 588
Myeloproliferative disorders 522
N-acetyl-sulfamethoxazole 590
Narrow-caliber ureteroscopes 625
National Health and Nutrition Examination Survey 259, 545, 551
Nausea 706
Nelfinavir 503
Neobladder 683, 684
Nephrectomy 488, 674, 698
Nephric ducts 467
Nephrocalcinosis 155f, 169, 218, 323, 412, 414, 416, 420f, 423f, 428f, 431, 432f, 434, 447, 451, 452, 465, 470f, 471f, 472475, 477, 533, 590, 604
frequency of 432f
intratubular 143f
medullary 452, 469
progression of 468f
severe papillary 468f
Nephrogenesis 467
Nephrolithiasis 5, 6, 6t, 13f, 143, 173, 204, 215, 236, 238, 467, 468, 472, 473, 477, 514, 525t, 531533, 536t, 537t, 551t, 590, 604, 606, 607, 618, 621
adult 204
drug-induced 501, 509
hypocitraturic 236
hypophosphatemic 473
presentation of 588
radiological imaging of 618
symptomatic 653
Nephrolitholapaxy, bilateral percutaneous 632
anatrophic 570, 579
bleeding, post-percutaneous 682
laparoscopic 630
anatrophic 630, 700
and robotic anatrophic 700
percutaneous 100, 109, 548, 559, 565, 568, 569, 571, 604, 608, 624, 629631, 643, 674, 651, 674, 680, 683, 698, 699, 707, 711
Nephron, upper 465
contrast-induced 597
crystalline 549
Nephrostolithotomy, percutaneous 485
drainage, percutaneous 667
tube 644
percutaneous 694
Net acid
excretion 517, 522f
load 299
Neutral phosphate 434
Nicotinamide adenine dinucleotide 228f, 495
Nitrofurantoin 607, 608, 610
Nonadsorbing polymers 27f
Non-bicarbonate buffer 444
Nonclassical crystallization processes 18, 22
Noncontrast computed tomography 425f428f
Nonprotease inhibitor antiretroviral-based treatment 504
Nonstaghorn calculus 650
Nonsteroidal anti-inflammatory drug 597, 612
Nonvolatile acid 44
Normal glands, location of 359
Normocalciuria 169, 170, 305
Novel interstitial plaque structures 135
factor kappa-b ligand, receptor activator of 309
magnetic resonance imaging 471
medicine scans 600
scintigraphy 600
Obesity 6, 117, 547, 588, 652
intestinal bypass surgery for 128
severe 389f
Octacalcium phosphate 89
Oral antimicrobials, mechanism of action of 608t
Oral citrate therapy 238
Oral fluid intake 488
Organs 195
Orthopedic hardware 607
Orthotopic liver transplantation 436
Osteoblastic collagen synthesis 267f
Osteoblasts 194, 195, 208, 208f, 264f, 268f
Osteoclast 194, 195, 208, 208f, 264f, 268f
Osteocyte 194, 195
apoptosis 194
Osteoid 195
Osteomalacia 473
Osteopenia 314
Osteopontin 5759, 68, 145, 153
expression 59
Osteoporosis 6, 473, 588
Osteoprotegerin 194, 309
Ostwald-Lussac law of stages 19
Ovarian torsion 589
Oxalate 7, 9, 173, 330, 331, 335f, 345, 375, 386, 390, 393, 535
anion exchanger 169
binders 397
binding agents 398
content 9
degradation 436
degrading bacteria 391, 397, 401
enteric hyperabsorption of 416
injury 434
low 397
nephropathy, acute 549
precursors 173
Oxalobacter formigenes 9, 391, 436, 507
Oxalosis 412
systemic 413f, 434
Oxiadipate 232
Oxolinic acid 505
Oxypurinol 590
Paget's disease 357
Pain 642, 686
kinds of 322
musculoskeletal 588
Pancreas 374
Pancreatic insufficiency 384
Pancreatitis 358, 396
Papillary biopsy 129f, 132f, 134f, 136f, 138f, 139f
light micrographs of 124f
Papillary calcification 170
Papillary interstitial tissue 128
Papillary interstitium 85f
Papillary plaque, urine correlates of 109f
Para-aminohippuric acid 232
Paracellular transport 206
Parafollicular tissues, location of 359f
Parathyroid adenoma 360, 362f, 369f
ectopic 368
intrathymic 364f
right lower 363f
undescended right lower 364f
Parathyroid cancer 365f
surgery for 370
Parathyroid carcinoma 370
large 370f
Parathyroid gland 196, 211f, 213f, 362f, 363f, 367f, 370
abnormal 360
hyperplastic 360f
large 363f
location of 358
number of 358
undescended lower 359
Parathyroid hormone 165, 171, 189, 190, 209, 210, 213f, 259, 267f, 268f, 291, 308, 356, 472, 473, 534
fasting 287
intraoperative 366f, 367f
serum 287, 288f, 289f, 327
Parathyroid surgery 358t
Parathyroid tissues, location of 359f
Parathyroidectomy 328f, 355f, 366, 371
indications for 357
minimally invasive 361, 365, 366f
cystoscopes 649
kidney stone disease 530
nephrolithiasis 537t
stone disease 704
urolithiasis, incidence of 705
urologic population 652
inflammatory disease 589
pain syndrome 589
stones, larger 701
structures 600f
Pelvicalyceal system 675
Pelvis 127
Peptic ulcer 358
Periodic acid-Schiff 150, 156f
Periplaneta americana 162
Phenazopyridine 505
Pheochromocytoma 357
Phosphate 246, 288f
absorption of 248
crystals 322
inorganic 246
low serum 473
nephropathy, acute 154
triple 593f
Phosphaturia 169
Phosphocreatine 250
Phosphorus 165, 172, 188, 204, 330, 375, 534, 535
mineral distribution of 187
transport 198
Photosensitivity 608
Phytate 7, 10, 57
Piezoceramic elements 639
Piperacillin 610
chemistry 447
free fatty acid 521f
Plug formation, mechanisms of 126
Pneumohydrothorax 569
Politano-Leadbetter procedure 689
Polyacrylamide gel electrophoresis 62f
Polyaspartic acid 102
Polycystic kidney disease
autosomal dominant 464
autosomal recessive 467
Polydipsia 356, 477
Polyelectrolytes 24
Polyethylene glycol 196
Polymer-induced liquid precursor 33f, 36f, 40f
Polyuria 169, 356, 473, 477
Posner's clusters 23, 30, 39
aggregation of 30
Post-transplantation biopsy 143f
Potassium 10, 204, 330, 344, 386, 405, 508, 534, 536
alkali 459f, 524, 525
treatment 525t
bicarbonate 489
channel, medullary 64
chloride 311
citrate 168, 174, 238, 240, 293, 296f, 297, 299, 311, 343, 524f, 537
administration 5
effects of 295f, 296f
induces complex 174
deficiency 235, 237
magnesium citrate 239
rich foods 7
urate 91
Pregnancy 235, 610, 691
antibiotic use in 610
ectopic 589
Prenucleation clusters, existence of 22
Proliferating cell nuclear antigen 149, 156f
Propidium iodide 147f
Prostate 595
Protease inhibitors 502, 504, 581, 590
Protein 116, 172, 299, 344, 345
aggregates 19
catabolic rate 299
intake 296, 299, 310
Proteinuria 169
Proteoglycans 145
Prothrombin fragment 58, 68
Provocative acid-loading tests 458
Proximal convoluted tubule 248, 251
Proximal renal
stones 651
tubular acidosis 236, 448
Proximal tubular
cells 550
proteinuria 169
Proximal tubule 249, 282, 284f
cytoplasmic citrate metabolism 234f
reabsorption 282
Proximal ureter 566, 569
Proximal ureteral stones 624, 651, 711
large 627
Pseudoephedrine 505, 506
Pseudohypoaldosteronism 477
Pyelocalicotomy 579
intravenous 594, 598, 599f, 653, 686
retrograde 657, 686f, 691, 713f
Pyelography, intravenous 323
Pyelolithotomy 570
laparoscopic 572, 573f, 575, 630
and robotic 699, 707, 712
Pyelonephritis 467, 468, 588, 589
acute 608
xanthogranulomatous 604, 698
Pyeloplasty 713f
laparoscopic 701
Pyeloureteral abnormalities 464
Pyloric stenosis, congenital 464
Pyridinoline 304
Pyridoxal phosphate 391
Pyridoxine 10, 434, 435, 437
Pyrimidine nucleotide 232
Pyrophosphate 56, 435
Quantitative computerized tomography 304
Questionable ureteral duplication 603
Quick parathyroid hormone 367
Quinolones 608
Rabson-Mendenhall syndrome 464
enteritis 384
injury 83
Radiolucent stones 323
Rana pipiens 162
Randall's plaque 29, 46, 60, 61, 63, 77, 79, 79b, 83, 85f, 99, 100, 101f, 102, 104, 105, 109, 111f, 112, 113f115f, 116, 116f, 121, 121f, 123f, 128, 130, 135, 140, 396, 430f, 452
earliest stages of 42f
scanning electron microscopy of 103f
Randomized controlled trial 3, 309, 576, 643
Rash 608
Reactive oxygen species 65, 66, 68
Regional enteritis 377
Reimplanted ureter 690
Renal access, endoscopic-guided 676
Renal acid excretion 444
Renal acidification
abnormal 453t
mechanisms of 444f
principles of 444f
Renal anomalies 674
Renal artery
aneurysm 566
fibromuscular dysplasia 464
Renal blood flow 592, 593
Renal calcifications 169
Renal calculi 162, 358, 650
Renal calyces 707f
Renal calyx stones 575
Renal cells 143
Renal citrate
handling 230
metabolism 226, 233
transport 230
Renal colic 321
recurrent episodes of 539
Renal damage 639
Renal deterioration, development of 604
Renal dysfunction 690
Renal failure 169, 472, 475
Renal hematomas 634
Renal inner medullary collecting duct 322
Renal magnesium excretion 381
Renal neoplasms 589
Renal obstruction, unilateral 593
Renal outer medullary potassium 473
Renal pathology 382, 396
Renal pelvic stone 709f, 710
Renal pelvis 569, 576, 596f
Renal phosphate wasting 169
Renal physiology 593t
Renal replacement therapy 435
Renal salt wasting 476
Renal stone 114f, 473, 650
asymptomatic 601
composition of 581, 652
density 581
disease 355
fragility 581
infection related 583
intraparenchymal 426f
location and conformation 575
management of 627
number 579
Renal subcapsular hematoma 567
Renal surgery, percutaneous 609
Renal tissue injury 117
Renal transplantation 690
Renal trauma 634
Renal tubular acidosis 120, 132f, 253f, 260, 330, 443, 447, 453, 547, 590
classification of 447t
incomplete 246, 256f
Renal tubule, calcium infarction of 443
Renal ultrasound 533, 653
Renal unit loss 668
Residual stones, incidence of 664
Resorptive hypercalciuria 591
Restrictive index 597
Retroperitoneal ultrasound image 692f
Retroperitoneum 595t
Rhodnius prolixus 162
Rickets 169, 473
Ritonavir 503
Robotic assisted anatrophic nephrolithotomy 700
Robotic pyeloplasty 701, 713f
Robotic surgery, role of 698
Rodent bone 176
Rodent phenotype 169, 170
Routine ureteral stenting 711
Roux-en-Y gastric bypass 384, 387f, 390
Ruptured ovarian cyst 589
Sacroiliitis 589
S-adenosylmethionine 232
Salivary glands 374
Sandwich therapy 578
Sarcoidosis 325, 326, 357, 588
Scanning electron microscopy 47f, 157f
Sclerostin 309
Sepsis 591
severe 591
Septic shock 591
Sestamibi scanning 362, 363, 363f, 368
Sestamibi tests 365f
Shock wave lithotripsy 122, 429, 549, 559, 565567, 571, 572, 582, 624, 625, 628, 629, 638, 641, 643, 650, 683, 698, 699, 709
complications 643
monotherapy 642
revolutionized 638
Sialic acid
modifications 64
residues 62
Silica 163, 504, 505
Single nucleotide polymorphism 60, 218
nonsynonymous 233f
absorptiometry 304
emission computerized tomography 362
Sinopulmonary infections, chronic 464
Sjögren's syndrome 451, 455, 458
malformations, severe 641
maturity 187
muscle 250, 252
cells 251
Skin-to-stone distance 642
Sleeve gastrectomy 389f
Smooth cystine stones 583
Sodium 7, 9, 11, 120, 165, 173, 204, 286, 299, 330, 345, 386, 405, 508, 534, 536
acid urate 126
alkali 525
treatment 525t
citrate 238
dodecyl sulfate 62f
hydrogen exchanger 520
hypochlorite 36f
intake 294, 310
interaction of 296
proximal tubule delivery of 293
urate 91, 524
Soluble adenylyl cyclase gene 312
Southeast Asian ovalocytosis 253
Spherites 162
Spinal bone density, low 477
Spinal deformities 169
Spleen 595, 681
Spondylolisthesis 589
Spontaneous ureteral stone passage 562
acid phase of 252
alkaline phase of 251
Staghorn calculi 577, 601, 604t, 642, 710
classification of 605t
complete 700
Staghorn monotherapy 642
Staghorn morphometry 681
classification 681
Staghorn renal calculi 577, 579
Staghorn stone 91f, 560
Stagnant urine 127
Staphylococcus aureus 607, 608
Steatosis 520
Steinstrasse 634, 642, 667
Stent symptoms, management of 669
Stereomicroscopy 87f
Stevens Johnson's syndrome 608
Stimulants 506
Stomach 248
Stone 83, 416, 419, 434, 627
activity of 323
analysis 90b, 323t
burden 323
classification 681
complications 681
clearance 624
composition 126t, 581, 652, 674
conformation 577
containing diverticulum, ureteroscopic management of 686
containing kidney 690
density 582
disease 544, 705
management of 622
treatment of 473
drug-induced 501, 509
factors 565, 571, 651
formation 171, 692
clinical evaluation of 321
drug-induced 501
general considerations of 28
incidence of 590
mechanism of 590
metabolic aspects of 430
model of 116
fragments, nonstruvite 624
free rate 624, 625, 630, 650
growth 79b, 83b, 87b, 651
imaging of 420
inorganic composition of 163
location 649, 674
major component of 85, 87
management of 638, 649, 674
medical management of 434
passage 321
plaque complex 110
producing kidney 690
production, mechanism for 336
range, treatment of 704
removal procedures, long-term effects of 549
retrieval devices 662
retropulsion 663
risk factors, urinary concentrations of 337f
size 572, 573, 575, 651, 674
small 618
surgery 588
treatment of 382
types of 590
Streptomyces hyaluronidase 146
Stromal cells 194, 195
Struvite 69, 163
stone formers 547
Succinyl coenzyme 227
Sugars 10, 297, 345
Sulbactam 609
Sulfadiazine 94
Sulfamethoxazole 94, 504, 607609, 654
Sulfasalazine 504
Sulfonamides 504, 590, 610
Sulfur 204
Superstiff wire 685
Swiss lithoclast 660, 661
Systemic diseases, screening for 325t
Systemic inflammatory response syndrome 591
Systemic lupus erythematosus, glomerular complications of 451
Tamm-Horsfall protein 57, 61, 62, 62f, 63f, 64, 68, 238, 249, 336
Tamsulosin 611
Tazobactam 610
Technetium 99m mercaptoacetyl triglycine 601
Terazosin 611t
Testicular torsion 589
Testosterone 192
Tetracycline 607, 610
double-label protocol 307
Thiazide 297, 299, 313, 344, 357, 471, 473
diuretics 174, 235, 237, 293
segmental nephron effects of 294f
sensitive sodium chloride cotransporter 314
Thiazolidinedione 521f
Thiosulfate 175
gland 364f
tissue 363f
location of 359f
Thyrothymic ligament 359
Tienilic acid 508
Tissue 595
damage, acute 644
mineralization, patterns of 98
repair 68
triglyceride 517f
type 595
Titrated non-bicarbonate buffer 444
Topiramate 506, 590
Total body sestamibi scan 370f
Tractip laser fiber 669
Transcellular transport 205
Transient receptor potential proteins, structure of 206f
Transmission electron microscopy 34, 111
Transplant urolithiasis, treatment of 691
Trans-stomal ureteroscopy 683
Transureteroureterostomy ureters 712
Trauma 384
Triamterene 502, 590
salts 590
stones 502
Tricarboxylic acid 226, 228f
cycle 226
Triglycerides 255
Trimethoprim 607610, 654
Tuberculosis 357
Tubo-ovarian abscess 589
abnormalities 469
atrophy 548
apical membrane of 150f
apical surface of 147f
epithelial cells 155, 156f
epithelium 155f
function, monogenic disorders of 473t
injury, attenuation of 149
morphology, general evaluation of 152f
nephrocalcinosis 118
segment 447
necrosis factor alpha 309, 592
solid 357
Tursiops truncatus 163
Typical urine chemistry abnormalities 532t
Ulcerative colitis 376, 377
Ultrasonography 362, 594, 595t
mechanism of 594f
Ultrasound 362, 420
sonography test 675
Ultraviolet light microscopy 306
United Nations Scientific Committee 620
United States Renal Data System 547
Upper tract dilation, setting of 603
Upper tract urothelial
cancer, development of 683
disease 695
Upper urinary tract 683, 689
stones, removal of 638
Urates 91
Urea splitting bacteria 683
Ureaplasma 607
Urease, bacterial source of 253
Ureter 653
navigate narrow aspects of 658f
Ureteral access sheaths 649, 658, 658f
Ureteral avulsion 667
Ureteral calculi 624
Ureteral dilation 610, 657
Ureteral inflammation 610
Ureteral injury 667
Ureteral kinks 665
Ureteral orifice 665, 689
setting of 665
Ureteral perforation 631
Ureteral reimplantation technique 689
Ureteral stent 583, 650
placement 667
removal of 664
Ureteral stone 568, 649, 653
based on randomized controlled trials 625
blind extraction of 649
episode, acute 588
management of 624, 711
treatment of 650t
Ureteral stricture 566, 568, 653, 659, 668
disease 607
Ureteral wall 665
Ureterolithotomy 570, 575
first retroperitoneoscopic 701
laparoscopic 627, 699
and robotic 701
open 627, 699
Ureteropelvic junction 422f, 424f, 569, 603, 627
obstruction 607
Ureterorenoscopy 567
Ureteroscope 633, 649, 657
advanced 686
flexibility, loss of 669
Ureteroscopic portion 655
Ureteroscopic stone 661
extraction 688, 691
removal 561
surgery 654
Ureteroscopic task 684
Ureteroscopy 110, 429, 548, 565, 566, 566t, 567, 571, 609, 624, 625, 649, 657, 660f, 683, 684, 686, 688, 690, 695, 707, 711
future of 669
indications for 649
room setup scheme 655f
semirigid 659, 660
Ureterovesical junction 425f
Urethral outlet obstruction 607
Uric acid 55, 91, 93, 100, 120, 126, 162, 163, 168, 321f, 322, 330, 333, 334f, 386, 405, 502, 518f, 523, 524f, 525, 536, 547, 581, 593f
bladder stones 170
nephrolithiasis 240
epidemiology of 514
etiologic causes of 515f
idiopathic 515f, 518, 518f, 519f
solubility 379f, 515f
stones 11, 91, 240, 327, 379, 533, 618, 621f, 705
epidemiology 514
formers 518f
morphologies of 92f
pathophysiology 514
prevalence of 514
proportion of 514f
risk of 379t
treatment 514
supersaturation 380
index of 519f
Uricosuric drugs 508
Urinary acid excretion 298
Urinary acidification defects 520f
Urinary alkalinization 489
Urinary ammonium 447, 520f, 521f
Urinary anion gap 447, 457
Urinary buffer 444
Urinary calcium 13f, 235, 525
Urinary catheters, chronic 583
Urinary citrate 457, 525
evolutionary origins of 226
excretion 226, 235t
physiologic regulation of 233
impact of 237
levels of 692
Urinary diversion 609, 683, 685, 690
Urinary factors 13
Urinary glycoproteins 692
Urinary lithogenic chemistry 458
Urinary magnesium 235
Urinary obstruction 482, 593
bilateral 593
effects of 593t
Urinary osmolar gap 458
Urinary oxalate 418f
Urinary pellet calcium analysis 151f
Urinary phosphate 229
Urinary stasis 83b
Urinary stones 77, 94, 95, 619, 622
disease 13f, 704
Urinary sulfate 523
Urinary tract 709
immunity 170
infection 64, 86f, 468, 477, 566, 591, 604, 606, 607, 633, 650, 705, 706
complicated 606t
epidemiology of 604
recurrent 546
treatment of 531, 608t
obstruction, pathophysiology of 591
Urine 380, 692
calcium 13, 259, 280f, 295, 328, 342
and volume 333
concentration 298f
distribution of 276f
excretion 289, 292f, 296f, 297f, 334f
losses 282f
phosphate 283
chemistry 447
citrate 14, 56f
concentration 342
excretion 342
contamination of 253
creatine 417f
crystallization inhibitors, biology and clinical relevance of 55
excretions, molarities 336
flow, low 386
interpretation 326
leakage rate 700
magnesium 331
matrix molecules play special role 336
organic acids 418t
osmolal gap 458
oxalate 13, 416, 417f, 436
excretion 394f, 395f, 398f, 415f
phytate 7
proteins 58
sodium 348f
excretion 292f, 295f
supersaturation 347f
uric acid 14
volume 298, 331, 516, 532
Urography 471f
intravenous 618, 707
Urolithiasis 374, 386t, 402, 443, 452, 504, 546, 687, 692, 698, 701, 702, 704, 705
animal models of 162
idiopathic 386t
management of 690, 698, 699, 712
open surgical management of 712
pathophysiology of 455
polygenic rat model of 168
prevalence of 377t
risk of 392f
treatment of 711, 712
ureteroscopic management of 695
Urologic disease 546
Urologic stone
size 571
surgery 570
laparoscopic 570
Urologic surgery 609
Uromodulin 170
Urosepsis 681
Urothelium damage 662
Uroxatral 611
Vacuolar adenosine triphosphatase 446f, 451
Vas washdown hypothesis 116
Vas washdown theory 104
Vesicoureteral reflux 689
Vipomas 357
Viscera injury 676
A intoxication 357
B6 10, 435, 437
C 7, 10, 507, 590
overdose of 549
deficiency 375
hormone system 281
metabolic pathway 190
metabolism 197, 474f
metabolites, overview of 212f
receptor 169, 192, 281
receptor, number of 170, 303
resistant rickets, hereditary 169
supplements 508
D2 191
D3 191, 472
synthesis 190
Volatile acid 444
Volvulus 589
Vomiting 706
von Kossa method 153f, 157f
von Kossa positive tubules 153f
von Kossa stained sections 151f
Wave technology 641
White blood cell 591
Widespread tissue uricosis 170
Wilms’ tumor 464
Wolff's duct 465
Worsening renal function 690, 693
Xanthine 163
dehydrogenase 491, 491f
oxidase 495
inhibitors 383
oxidoreductase, deficiency of 495
stones 524, 581
Xanthinuria 168, 482, 495
type I 495
type II 496
X-linked hypoxanthine guanine phosphoribosyltransferase deficiency 516
Yasue method 135
Young's syndrome 464, 467
Zonisamide 507
Chapter Notes

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1Characteristics and Formation of Kidney Stones
Andrew P Evan

Epidemiology of Kidney StonesCHAPTER 1

Eric N Taylor,
Gary C Curhan
Kidney stones are highly prevalent, are a major cause of morbidity, and inflict a large cost on the healthcare system. Epidemiologic studies have quantified the increasing incidence and prevalence of nephrolithiasis and have delineated a wide variety of dietary, nondietary, and urinary risk factors for kidney stone formation.
At least four considerations should be kept in mind in any review of kidney stones. First, it is necessary to prioritize studies that focus on actual kidney stones as an outcome, rather than urine composition. The difficulties of using urine composition as a proxy for kidney stone risk are manifest by the wide array of well-established nonurinary kidney stone risk factors and data implicating the renal interstitium as the site of initial stone formation.13 Second, the importance of many kidney stone risk factors vary by individual characteristics such as age, sex, and BMI. Third, there is a relative scarcity of randomized controlled trials (RCTs) in the field of kidney stone prevention. Thus, data from well-performed observational studies can be considered in the clinical setting when devising treatment plans to reduce kidney stone recurrence. Finally, RCTs and large observational studies that help inform current understanding of kidney stone risk factors consist of participants with known calcium oxalate nephrolithiasis or populations who likely have a predominance of calcium oxalate stone disease. Thus, some conclusions from studies of calcium kidney stone disease (e.g. RCT data for water intake and stone prevention) are by necessity applied, albeit carefully and with attention to renal physiology, to less common stone types.
The prevalence of nephrolithiasis, defined as a history of stone disease, varies by age, sex, race, and geography. The prevalence in the United States increases with age and is approximately 11% for men and 7% for women: kidney stones occur in about 1 in 11 people in the United States.4 Kidney stone prevalence has increased steadily over the last 35 years for men and women, whether black, Hispanic, or white (Fig. 1.1).4,5 Although the prevalence is consistently lower in blacks and Hispanics than in whites, increases in prevalence over time have been higher for blacks and Hispanics.4 Increased detection of asymptomatic stones resulting from the increasing use and sensitivity of radiologic studies may explain in part the rise in prevalence.
zoom view
Fig. 1.1: Prevalence of history of kidney stones by age and race.4,5
Relatively few population-based studies of the prevalence of nephrolithiasis have been conducted outside of the United States. Prevalence of stone disease has increased in Japan6 and Germany.7
A study of over 1 million individuals in the United States found geographic variability with a north–south and west–east gradient; the highest prevalence of self-reported nephrolithiasis was in the southeastern United States.8
Although the prevalence of nephrolithiasis has been consistently found to be higher in men than women, a decrease in the male-to-female ratio was suggested by a study of hospital discharges.9 Data from the Nationwide Inpatient Survey between 1997 and 2002 found a 4male-to-female ratio 1.3:1. Similarly, the male-to-female prevalence ratio in the most recent NHANES data was ∼1.5, substantially lower than the commonly reported ratio of 2–3:1.
The incidence of nephrolithiasis, defined as the first stone event, also varies by age, sex, and race. White males have the highest incidence rates. In men, the incidence begins to rise after age 20, peaks between 40 and 60 years at ∼3/1,000/y and then declines.1012 In women, the incidence is higher in the late 20s at 2.5/1,000/y and then decreases to 1/1,000/y by age 50, remaining at this rate for the next several decades.1114
As with prevalence, attempts to compare kidney stone incidence rates over time are complicated by trends toward more frequent imaging and concomitant diagnosis of asymptomatic kidney stones. Over a 24-year period in Iceland, the total incidence of kidney stones increased by nearly 28%.15 However, this increase was due solely to the diagnosis of asymptomatic stones; the annual incidence of symptomatic kidney stones did not increase significantly in either men or women.
A study in Rochester, Minnesota raised the possibility that incidence rates may be decreasing. Using the same methodology as a study performed 30 years earlier, the recent study reported incidence rates since 1990 may be falling in men and have leveled off in women.16 Because there were only 157 cases in men and 91 in women, additional larger studies are needed.
zoom view
Fig. 1.2: Proportion of types of kidney stones in first-time stone formers (N = 11,666).Courtesy: Professor Michel Daudon is from Paris, France.
zoom view
Fig. 1.3: Proportion of types of kidney stones in recurrent stone formers (N = 8,671).Courtesy: Professor Michel Daudon is from Paris, France.
Recurrence Rates
Case series suggest 30–40% of untreated individuals will form another stone within 5 years after the initial episode.12 The recurrence rates in the control arms of RCTs and an observational study from Olmstead County17 are lower. The risk of recurrence is influenced by stone type and urinary composition. Features associated with higher rates of recurrence include younger age, male sex, a family history of kidney stones, and uric acid stones.17 Fortunately, randomized trials demonstrated that interventions can reduce the likelihood of recurrence by >50%.1821
Calcium containing kidney stones are the most common, accounting for >80% of incident and recurrent kidney stones (Figs. 1.2 and 1.3).2225 The majority (>80%) of calcium stones have calcium oxalate as their major constituent; predominantly calcium phosphate stones are less common.26 Uric acid stones represent between 5% and 10% of stones, followed by cystine, struvite, and other less common stone types.2225 Analysis of stone composition in developing countries27,28 confirms the preponderance of calcium oxalate nephrolithiasis worldwide.
Stone composition can vary by country. Although the majority of kidney stones in one Japanese series were 5calcium oxalate, the proportion of uric acid stones was 16%,29 higher than reported in many other countries. A high prevalence of struvite stones still occurs in some nonindustrialized countries: women in Sub-Saharan Africa had struvite present in 43% of kidney stones.30
Kidney stone composition also may have changed over time. For example, the proportion of struvite stones in Australia decreased from 14% in the 1970s to <7% 40 years later,31 presumably reflecting improvement in management of urinary tract infections in the Australian population. Some26 but not all32 series suggest that the proportion of calcium phosphate in calcium stones may have increased over time. The reason for a potential increase in calcium phosphate temporally is unknown; there has been speculation that preventive or therapeutic maneuvers (such as potassium citrate administration or extracorporeal shock wave lithotripsy [ESWL]) may contribute.26
Finally, kidney stone composition varies by sex, body size, and a variety of comorbidities. Women with calcium stones tend to have a greater proportion of calcium phosphate in kidney stones compared to men,22,26,32 and uric acid stones are more common in men than women.33 Independent of age and gender, higher BMI and diabetes mellitus are both associated with uric acid as compared with calcium kidney stones,33,34 a phenomena presumably due to the lower urine pH associated with insulin resistance.35
The financial burden of nephrolithiasis in the United States is difficult to quantify but is in the billions of dollars. In the year 2000, estimates for the annual healthcare expenditure associated directly with kidney stones ranged between $2.1 billion36 and $4.5 billion37 (or about $5.75 billion in year 2010 dollars). Indirect annual costs of stones in 2000 (due to lost days of work) were estimated to be $775 million37 (about $995 million in 2010 dollars).
Relatively few studies outside the United States have examined the costs of kidney stone disease. In 2010, the annual budget impact for stone disease in France was estimated to be about 590 million Euros38 (about $775 million dollars using average 2010 exchange rates). If France had the same population as the United States in 2010, the cost would have been about $3.7 billion.
Costs due to stone disease in the United States appear to have increased substantially over time. In 2000, the cost of treating and diagnosing stones in the emergency department in the United States was estimated at just under $500 million.36 In a recent study, hospital emergency department charges (which are often higher than actual costs) for stone disease increased annually by 10% over a 4-year period and by 2009 totaled $5 billion39 (about $4 billon in year 2000). Reasons for these increased hospital charges are unclear, but may be due in part to higher utilization of computed tomography.
Family History
Studies of twins and populations have demonstrated that the common forms of stone disease are heritable.40 A family history of stone disease more than doubles the risk of incident kidney stone formation41 and increases the risk of stone recurrence by 60%.17 The increased risk is likely due to both genetic predisposition and similar environmental exposures. Numerous genetic causes of rare forms of nephrolithiasis (e.g. cystinuria and dent disease) have been identified, but information is still limited on genes that contribute to risk of the common forms of stone disease.
In a cross-sectional Canadian study, individuals of Arabic, west Indian, west Asian, and Latin American descent were more likely to be stone formers than those of European descent.42 Overall, African Americans have a lower frequency of stones.4,5
Systemic Disorders
There is substantial evidence that nephrolithiasis is a systemic disorder. Well-known conditions that lead to calcium kidney stone formation include primary hyperparathyroidism, renal tubular acidosis, and Crohn's disease. A wide variety of other common conditions including obesity, diabetes mellitus, gout, and gallstones have been linked to the development of kidney stones, and a history of kidney stones is a potential risk factor for the development of systemic diseases such as osteoporosis, chronic kidney disease, coronary heart disease, and hypertension (Table 1.1).
Increasing body size, assessed by weight, body mass index or waist circumference, increases the risk of stone formation independent of other risk factors including diet;43 for unexplained reasons, the impact is greater in women than in men.6
Table 1.1   Common conditions associated with nephrolithiasis.
Systemic conditions that are risk factors for nephrolithiasis
Systemic conditions for which nephrolithiasis may be a risk factor
Primary hyperparathyroidism
Inflammatory bowel disease
Osteoporosis/bone fracture
Coronary heart disease
Chronic kidney disease
For example, the risk of stone formation for individuals with a BMI ≥ 30 kg/m2 compared with those with a BMI 21–23 was 30% higher among men but nearly twofold higher among women. Although individuals with higher BMI have markedly different 24-hour urine composition than those with lower BMI, including higher urine oxalate and uric acid and lower urine pH,44,45 the calculated relative supersaturation was significantly higher only for uric acid. Additional research is needed to explore further why obesity, independent of diet, may increase the risk of calcium kidney stone formation.
Diabetes mellitus has also been associated with an increased risk of stone formation, independent of diet and body size.46 Cross-sectionally, individuals with a history of diabetes were >30% more likely also to have a history of nephrolithiasis. Prospectively, a history of DM increased the risk of stone formation by 30–50% in women but not in men. In support of these findings, a study based on NHANES III data found that the risk of being a stone former increased with an increasing number of metabolic syndrome traits.47
The association between hypertension and nephrolithiasis is complex. Some prospective studies reported that individuals with hypertension were more likely to develop kidney stones,48,49 but large-scale prospective cohort studies to date have not identified hypertension as an independent risk factor for kidney stone formation.50,51 However, a history of kidney stones is clearly associated with an increased risk of developing hypertension.5052 In large-scale prospective studies that accounted for differences in age, diet, body size, and other comorbidities, individuals with kidney stones were about 25% more likely to develop hypertension than their nonstone forming counterparts.50,51
Other common diseases such as gout and cholelithiasis are associated with higher risk of kidney stones. In a cross-sectional study, individuals with gout were 50% more likely to have a history of stones.53 When examined prospectively, individuals with a history of gout had a twofold higher risk of incident nephrolithiasis, independent of diet, weight, and medications.54 Large-scale prospective cohort studies report that participants with a history of gallstones are about 30% more likely to develop incident symptomatic kidney stones after adjusting for differences in diet, body size, and other comorbidities.55
The identification of kidney stone disease as a risk factor for other conditions provides additional evidence that nephrolithiasis is a systemic disorder. For example, a number of studies report lower bone mineral density in individuals with a history of nephrolithiasis compared with those who do not.56 The potential mechanism(s) of bone loss in stone formers is unknown, but it is possible that higher urine calcium may result in a negative calcium balance. In a study of 46 stone formers and their first-degree relatives followed for 3 years, the correlation between higher baseline 24-hour calcium excretion and subsequent decrease in femoral neck z-score was −0.37.57 This relation was independent of calcium intake and 24-hour urine markers of dietary acid load such as ammonium and sulfate. Previous reports suggest that individuals with nephrolithiasis may have higher risk of bone fracture.58,59 In a longitudinal study of 624 individuals with history of kidney stones living in Rochester, Minnesota, the risk of an incident vertebral fracture was > 4 times that expected for Rochester individuals of comparable age.59 A recent study utilizing electronic medical record data from the United Kingdom compared > 50,000 individuals with diagnostic codes for urolithiasis to over 500,000 participants without such codes matched on age and sex. The risk of incident bone fracture in individuals with a history of kidney stones was 10% higher in men and also was higher in women between the ages of 30 and 79 (the highest hazards ratio in women was 1.52 for those aged 30–39 years).60
Recent data also implicate kidney stone disease as an independent risk factor for the development of coronary heart disease. In a case-control study including over 15,000 participants with a mean follow-up of 9 years, participants with a history of kidney stones were 31% more likely to have an incident myocardial infarction after adjustment for a wide variety of comorbidities.61 In large prospective cohort studies, a history of kidney stones was associated with an increased risk of incident coronary heart disease in women (but not men) that was independent of age, body size, dietary intakes, and comorbid conditions.62 A prospective study of over 3 million individuals in Alberta, Canada, found a history of nephrolithiasis was associated with an increased risk of coronary heart disease and 7stroke; the risks were higher in women than in men and in younger than older individuals.63
Table 1.2   Dietary factors that may increase or decrease the risk of calcium oxalate kidney stones.
Dietary factor
Proposed mechanism(s)
Increase risk
Increased urinary calcium excretion
Increased urinary oxalate excretion
Animal protein
Increased urinary calcium excretion; reduced urinary citrate excretion
Vitamin C
Increased oxalate generation and excretion
Increased urinary calcium
Decrease risk
Dietary calcium
Binding of dietary oxalate in gut
Potassium-rich foods
Increased urinary citrate excretion; reduced urinary calcium excretion
Inhibition of calcium oxalate crystal formation
Reduced dietary oxalate absorption; inhibition of calcium oxalate crystal formation
Cross-sectional data from NHANES III64 as well as case-control studies65,66 and a cohort study67 suggest that kidney stones may represent an independent risk factor for chronic kidney disease. Using the same database mentioned above, investigators performed a prospective study of nearly 2 million individuals in Alberta, Canada, and found a history of nephrolithiasis was associated with an increased risk of developing chronic kidney disease (CKD) or end-stage renal disease (ESRD); however, the absolute risks were small.
Environmental Factors
Occupations or settings with higher insensible fluid losses, such as a hot environment, increase risk of stone formation by reducing urine volume.68 The risk will also be higher when individuals have restricted access to water or bathroom facilities, leading to lower fluid intake and lower urine volume. It is possible that global warming and continued urbanization may increase the world wide burden of nephrolithiasis in the future.69
Because most data on the relation between diet and stone disease come from observational and physiologic studies, care must be taken when interpreting studies of diet and risk. Retrospective assessments of diet may be biased because individuals who develop stones may subsequently change their diet. Results from studies that use change in urine composition as a surrogate for actual stone formation should viewed with caution because the composition of the urine does not completely predict risk and not all the components that modify risk are included in the calculation of supersaturation (e.g. urine phytate). Thus, prospective studies that assess a variety of nutrients are best suited for examining the associations between dietary factors and risk of actual stone formation. Finally, associations between specific dietary factors and risk may vary by age, sex, and body size.
Dietary Risk Factors: Calcium Oxalate Stones
More than 80% of kidney stones contain calcium, and the majority of calcium stones consist primarily of calcium oxalate70 (see Fig. 1.2). Because calcium oxalate is most common, the majority of studies have focused on risk factors for this stone type. Dietary factors associated with increased or decreased risk are listed in Table 1.2.
In the past, higher calcium intake was believed to increase the risk of stone formation. However, there is now substantial evidence demonstrating that a higher calcium diet is associated with a reduced risk of stone formation. One potential mechanism to explain this apparent paradox is that the higher calcium intake will bind dietary oxalate in the gut, thereby reducing oxalate absorption and urinary excretion.718
Several large prospective observational studies in men and women consistently support a reduced risk of stone formation with increasing dietary calcium intake. Compared to individuals in the lowest quintile of dietary calcium intake, those in the highest quintile had more than a 30% lower risk of forming a stone.10,13,14 These results were adjusted for multiple factors, including age, body mass index, total fluid intake, the use of thiazide diuretics, and the intake of nutrients such as animal protein, magnesium, phosphorous, sodium, and potassium. In the Women's Health Initiative Observational Study, higher dietary calcium also was associated with a lower risk of incident kidney stones.72 Calcium intake is an example of how the impact of a risk factor may vary by age: there was an inverse association between dietary calcium and stone formation in men younger than 60 years of age, but no significant association was found for men 60 years or older.73
These observational findings have been confirmed by a 5-year randomized controlled clinical trial that compared stone recurrence in 120 men with a history of calcium oxalate nephrolithiasis and idiopathic hypercalciuria assigned to a diet low in calcium (400 mg/d) or to a diet with “normal” calcium content (1,200 mg/d) and lower amounts of animal protein and sodium.18 Of note, 1,200 mg/d would represent a “high” calcium diet for many free-living individuals (in one prospective cohort study, men who subsequently developed an incident symptomatic kidney stone had mean dietary calcium of about 800 mg/d10). In addition, participants in both arms of the RCT were advised to avoid consuming a variety of specific foods high in oxalate. The risk of developing a recurrent stone on the higher calcium diet was 51% lower than for the low-calcium diet (Fig. 1.4).18
Unlike their counterparts consuming the low-calcium diet, the men in the “normal” calcium diet arm of the trial had significant decreases in 24-hour urine oxalate compared with baseline, suggesting that intestinal oxalate binding by calcium may have played a role in the study results. The “normal” calcium diet also resulted in a 49% decrease in urine calcium excretion compared to baseline, likely due to the concomitant restriction of sodium and animal protein intakes. Because dietary sodium and animal protein may influence calcium stone formation, this trial, although suggestive, did not directly address the independent role of dietary calcium in the pathogenesis of kidney stones.
It is possible that dairy products (the major source of dietary calcium) may contain as yet unidentified factors that inhibit calcium kidney stones. The men in the low-calcium diet arm in the RCT displayed in Figure 1.2 decreased calcium intake by limiting intake of milk, yogurt, and cheese. However, large-scale prospective cohort studies have reported that dietary calcium from nondairy sources (in addition to dietary calcium from dairy) also is independently associated with a reduced risk of kidney stones.74
zoom view
Fig. 1.4: Comparison of low versus normal calcium diets for kidney stone prevention.18
The impact of supplemental calcium on stone risk may be different from dietary calcium. In an observational study of older women, calcium supplement users were 20% more likely to form a stone than women who did not take supplements.13 The Women's Health Initiative randomized trial also found an increased risk with calcium supplementation (1,000 mg/d), though the supplements also contained 400 IU/d of vitamin D3.75 In younger women and men, there was no association between calcium supplement use and risk of stone formation.10,14 The discrepancy between the risks from dietary calcium and calcium supplements, at least in the observational study, may be due to the timing of calcium intake. Calcium supplements are not typically taken with meals, which would diminish binding of dietary oxalate.
Because the absolute risk of forming the first kidney stone by a supplement user is only slightly increased (1.2 cases/1,000 women per year compared to 1.0/1,000 per year), supplement use is not a major contributor to stone risk. However, individuals with a history of calcium nephrolithiasis should be encouraged to obtain calcium from dietary rather than supplemental sources.9
Although urine oxalate is a well-established and important risk factor for calcium oxalate stone formation, the role of dietary oxalate in the pathogenesis of calcium oxalate nephrolithiasis remains unclear.76 First, the proportion of urinary oxalate derived from dietary oxalate is controversial; estimates range from 10% to 50%.76 Thus, a substantial proportion of urinary oxalate is derived from the endogenous production such as the metabolism of glycine, glycolate, and hydroxyproline. Second, other dietary factors influence urine oxalate. For example, vitamin C supplementation may be an important contributor7779 because it can be metabolized to oxalate. Third, much of the oxalate in food may not be readily absorbed due to low bioavailability. Finally, there is variation between individuals with respect to the GI absorption of dietary oxalate. For instance, up to one-third of patients with calcium oxalate nephrolithiasis may have higher absorption of dietary oxalate.80 The reasons for the higher absorption are unclear but likely candidates include genetic predisposition and the intestinal microbiota. One study found individuals with a history of calcium oxalate nephrolithiasis were less likely to be colonized with Oxalobacter formigenes, an intestinal bacterium that degrades oxalate.81
Older reports of the oxalate content in food may be unreliable due to measurement issues, related to the quality of the assay procedure as well as the variability in oxalate content of the same food items. More recently, however, reliable assays for the direct determination of the oxalate content of food, including ion chromatography and capillary electrophoresis, have been developed. One study used these new methods to measure the oxalate content of >200 food items, measuring several different samples for each food and also performing each measure in triplicate (the values can be found at Some representative foods from this list are shown in Table 1.3. Although they are sometimes grouped into “very high” or “high” oxalate categories, this distinction is arbitrary. An individual can consume large amounts of oxalate by eating individual foods that are very high in oxalate or by eating larger quantities of foods that are more moderate in oxalate content.
Large-scale prospective studies of the relation between dietary oxalate and kidney stone formation have been completed. Surprisingly, the impact of dietary oxalate, even when comparing substantial differences in intake, was modest in men and older women and not associated with stone formation in younger women.82 These population-based data should not be interpreted to mean that dietary oxalate restriction is ineffective at preventing kidney stone recurrence in selected individuals, particularly those with higher urine oxalate excretion. There is likely a subgroup of patients who have increased oxalate absorption, which would result in an increased risk of calcium oxalate stone formation.
Table 1.3   Oxalate content of some foods.
Serving size
Oxalate content (mg) per serving
Corn meal/grits
Milk chocolate
½ cup cooked
½ cup
1 cup
1 oz
1 medium
1 cup
½ cup
1 oz
1 oz
½ cup
1 cup
1 oz
1 cup
½ cup
1 cup
A comprehensive list of the oxalate content of individual food items (expressed as mg/serving) can be found at
Higher sodium intake results in decreased renal tubule sodium reabsorption with a subsequent reduction in calcium reabsorption. Restriction of sodium intake is a highly effective means of lowering urine calcium and therefore represents a mainstay in the dietary treatment of calcium nephrolithiasis. A RCT of dietary salt restriction in calcium oxalate stone formers with idiopathic hypercalciuria demonstrated that for every 100 mmol decrease in urine sodium, urine calcium decreased by about 100 mg/d.83
Previous prospective cohort studies found a positive, independent association between sodium consumption and new kidney stone formation in women but not men.10,13 In the Women's Health Initiative Observational Study, women in the highest compared with lowest quintile of sodium intake had a 61% increased risk of incident nephrolithiasis.72
Animal Protein
Higher animal protein intake may increase urinary calcium and decrease urinary citrate,84 thereby increasing the risk of stone formation. However, when studied prospectively, 10animal protein was associated with an increased risk in men but not women.10,13,14,72 Further, the increased risk in men was only found among men with BMI < 25 kg/m2.73
Higher dietary potassium intake was associated with a lower risk of incident stone formation in men and older women10,13,73 possibly by reducing urine calcium excretion85 or increasing urine citrate. Recent data also shows that higher dietary potassium was associated with lower risk of incident stones in younger women.115
Higher intake of sucrose increases urinary calcium excretion independent of calcium intake.86 In prospective studies, sucrose was associated with an increased risk in women and fructose was associated with an increased risk in men and women.13,14,87
Although higher magnesium intake may reduce dietary oxalate absorption, randomized trials of magnesium supplements did not find a protective effect on stone recurrence, though the dropout rates in these studies were high. In prospective observational studies, higher dietary magnesium was associated with a lower risk of stone formation in men73 but not women.13,14
Vitamin C
Vitamin C (ascorbic acid) can be metabolized to oxalate and may increase the risk of calcium kidney stone formation. Consumption of 1,000 mg of supplemental vitamin C twice daily increased mean urinary oxalate excretion by 22%, but there was notable between-person variability.78 In a prospective observational study, men who consumed 1,000 mg or more per day of vitamin C had a 40% higher risk of stone formation compared to men who consumed <90 mg/d (the recommended dietary allowance).73 In a prospective cohort study of Swedish men, supplemental vitamin C use was associated with a near doubling of the risk of incident kidney stones.88 While these data do not support the restriction of dietary vitamin C (because many foods high in vitamin C contain alkali, which could raise urine citrate and thereby inhibit calcium oxalate crystal formation), calcium oxalate stone formers should avoid high-dose vitamin C supplements.
More research is needed to elucidate the relation between vitamin C intake, oxalate metabolism, and kidney stone risk. First, it is uncertain whether vitamin C intake is associated with risk in women. Second, feeding studies of vitamin C and urine composition may be substantially complicated by ex vivo nonenzymatic conversion of urinary vitamin C to oxalate in the collection vessel during storage and/or analysis.89
Vitamin B6
Although high-dose vitamin B6 (pyridoxine) reduces oxalate production in selected patients with type 1 primary hyperoxaluria,90,91 it is unclear if there would be benefit from the use of vitamin B6 supplements to prevent common stone disease. In an observational study, higher intake of vitamin B6 was not associated with a reduced risk of kidney stone formation in men.92,93
Phytate, found in whole grains and beans, was observed to reduce risk of stone formation in younger women,14 possibly by directly inhibiting calcium oxalate crystal formation.
Dietary Patterns
Although the examination of individual nutrients provides valuable insights, it may be easier for patients to follow certain types of dietary patterns than modifying individual nutrients. Relatively few studies have examined the impact of overall diet or dietary patterns on risk of stone formation. The Dietary Approaches to Stop Hypertension (DASH) diet, which is high in fruits and vegetables, moderate in low-fat dairy products, and low in red and processed meats, represents a novel potential means of kidney stone prevention. In a large, prospective observational study of three distinct cohorts, a higher dietary DASH score (meaning a diet more similar to the DASH diet) was associated with a 40–45% reduction in the risk of incident kidney stone formation.94 Although participants in the highest compared with lowest quintile of dietary DASH score in this study had a marked reduction in risk of kidney stones, their dietary oxalate intake was about 60% higher. The association between higher DASH score and lower stone risk was independent of age, body size, hypertension, diabetes, thiazide use, and intakes of total calories, fluid, caffeine, and alcohol.11
The potential mechanism(s) underlying the impact of a DASH diet on kidney stone risk require elucidation. Intakes of fruit and vegetables have a major effect on urine composition. In a metabolic study of 12 adults, the complete elimination of fruits and vegetables from the diet lowered urine oxalate by 31% but also decreased urine citrate and increased urine calcium.95 The net effect was an increase in urinary supersaturation with respect to calcium oxalate. In a cross-sectional study of nearly 3,500 individuals with and without nephrolithiasis, higher dietary DASH scores were associated with slightly higher 24-hour urine oxalate excretions but lower 24-hour urine citrate and higher 24-hour urine volume.96 Recently, a randomized trial compared the effects of a DASH-style diet versus a low-oxalate diet on urine composition in 57 individuals with recurrent nephrolithiasis and urine oxalate > 40 mg/d.97 Although limited by small size and a high drop-out rate, the results were provocative. The DASH diet resulted in urine citrate that was > 220 mg/d higher compared with the low-oxalate diet. Although other differences were not statistically significant compared with the low-oxalate diet, the DASH diet resulted in higher urine oxalate, higher urine volume, and lower urine supersaturation with respect to calcium oxalate.
Dietary Risk Factors for Other Stone Types
For the less common stone types, little data exist to support the role of specific dietary factors in kidney stone formation. It is possible to speculate about the impact of diet based on urine composition and our current understanding of pathophysiology, but it should be remembered that the many of the older recommendations for calcium oxalate stone prevention based on urine composition or pathophysiologic considerations were later found not to be supported by prospective studies of actual stone formation.
Uric Acid Stones
Although higher urine uric acid also contributes, the major determinant of uric acid crystal formation is low urine pH (the solubility of uric acid increases markedly as the urine pH increases from 5.0 to 6.5). Decreasing consumption of meat, chicken, and seafood will decrease purine intake and, therefore, reduce uric acid production; this may also increase urinary pH by reducing acid production. Higher intakes of fruits and vegetables raise the urine pH and should reduce the risk of uric acid crystal formation.
Given the well-documented association between greater weight and higher uric acid production and excretion and lower urine pH,44,45 it would be reasonable to encourage dietary intakes designed to maintain a healthy weight in individuals with recurrent uric acid stones.
Cystine Stones
Restricting sodium intake may reduce the urinary excretion of cystine.98 The solubility of cystine increases as urinary pH rises,99 thus higher fruit and vegetable consumption may be beneficial. There is little evidence to support the dietary restriction of proteins high in cystine, though reducing animal protein intake may be beneficial by increasing urine pH.
Calcium Phosphate Stones
Because patients with type 1 (distal) renal tubular acidosis and stone disease may benefit from alkali supplementation, they may also benefit from a diet high in fruits and vegetables. It should be noted, however, that an increase in urinary pH can increase the risk of calcium phosphate crystal formation. Dietary maneuvers directed at decreasing urinary calcium excretion (such as sodium and animal protein restriction) would also be expected to decrease calcium phosphate stone recurrence. It is unknown whether dietary phosphorus restriction would decrease calcium phosphate stone risk.
Total Fluid
Nephrolithiasis is a disease driven by the urinary concentration of lithogenic factors. Thus, fluid intake, the main determinant of urine volume plays a critical role in kidney stone formation. Prospective observational data consistently demonstrate that higher fluid intake is associated with lower risk of incident kidney stones.10,13,14 In a 5-year RCT of first time calcium stone formers, higher water intake resulted in a marked reduction in kidney stone recurrence.100 In this trial, 99 participants were assigned higher water intake with a 24-hour urine volume goal of 2 L, whereas no specific intervention was employed for the 100 participants in the control arm. At baseline, 24-hour urine volume was about 1 L in both groups. Individuals in the high water intake group were instructed to measure their 12urine volume at home every 2–3 months. Participants in the high water intake group (Group 1 in Fig. 1.5) had a mean 24-hour urine volume just over 2.5 L/d at years 3, 4, and 5 of the trial and had more than a 50% reduction in stone recurrence compared to the control group (Group 2).
zoom view
Fig. 1.5: Water intake and recurrent stone events in individuals with calcium nephrolithiasis. Group 1 randomized to high water intake and Group 2 without intervention.Source: Reproduced with permission from Borghi L, Meschi T, Amato F, et al. Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study. J Urol. 1996;155:839-43.
Individual Beverages
While total fluid intake is most commonly discussed, the type of beverage consumed may influence risk beyond just the volume of the beverage consumed.101 The associations between specific beverages, accounting for fluid intake, with kidney stone formation are presented in Table 1.4.
Despite previous beliefs to the contrary, alcoholic beverages, coffee, and tea are not associated with an increased risk of kidney stone formation. In fact, observational studies have consistently found that coffee, tea, beer, and wine are associated with a reduced risk of stone formation.101103 The mechanisms for these protective associations may be related to inhibition of antidiuretic hormone action in the kidney by caffeine and inhibition of antidiuretic hormone secretion by alcohol. In large-scale prospective studies, caffeine intake is independently associated with a lower risk of incident stones.104 The role of tea deserves special mention. There is a widespread belief that tea is high in oxalate and should be avoided. A cup of tea contains 14 mg of oxalate. Although this is not insignificant, the bioavailability does not appear to be high. A feeding study of tea demonstrated a negligible impact on urinary oxalate.105
Table 1.4   Select beverages and risk of incident stone formation101 with possible mechanism.
Proposed mechanisms
Types associated with lower risk
Caffeine induced diuresis, leading to decreased urinary concentration
Alcohol induced diuresis, leading to decreased urinary concentration
Orange juice
Increased urine citrate excretion
Types associated with higher risk
Sugar-sweetened soda
High-fructose content possibly leading to increased urinary excretion of calcium, oxalate, and uric acid
Citrus juices, such as orange and grapefruit juice, theoretically could reduce the risk of calcium stone formation by increasing urine citrate. The prospective studies found that compared with participants who consumed less than one serving per week of orange juice, participants who consumed one serving per day or more had a 12% lower risk of incident kidney stone formation.101 This association was independent of differences in age, race, body size, comorbidities, dietary intakes, and consumption of other beverages. Grapefruit juice intake was not associated with risk. One feeding study found that grapefruit consumption increased not only urine citrate but also urine oxalate.106
The relation between citrate-containing beverages and urine citrate is complex. A major determinant of urine citrate excretion is acid-base status: alkalosis decreases renal tubule reabsorption of filtered citrate and increases urinary citrate excretion.107 Thus, the effect of an orally administered citrate-containing fluid on urine citrate depends in part on fluid pH. Beverages with lower pH will have a predominance of hydrogen ion as the accompanying citrate cation, whereas beverages with higher pH have potassium as the accompanying cation. Unlike potassium citrate, intestinally absorbed citrate in the protonated form is neutral from an acid-base standpoint and would be expected (in the absence of very large quantities that overwhelm the liver's capacity to metabolize citrate to bicarbonate) to have minimal impact on urinary citrate. This principle was illustrated in a crossover metabolic study of 13 volunteers on standardized diets who consumed the same 13volume of water, lemonade, or orange juice with meals.108 Although participants consumed identical quantities of citrate in lemonade and orange juice, only orange juice resulted in higher urine citrate excretion.
An early report about the increase in urine citrate by homemade lemonade109 generated substantial enthusiasm about this beverage for preventing stone recurrence. However, subsequent studies did not consistently replicate the findings. The citrate and malate content of lemonade and several diet sodas were measured,110 with most beverages containing <8 meq of alkali per liter. Thus, it would take consumption of at least several liters per day to have an expected increase in urine citrate.
The consumption of sugar-sweetened sodas (“soft drinks”) is clearly associated with a higher risk of incident kidney stones,101103 but the exact mechanism is uncertain. Sugar-sweetened sodas contain fructose, which has been associated with an increased the risk of kidney stones.87 Dietary patterns associated with sweetened soda consumption were found to increase the risk of stone formation.94 Intakes of other sugar-sweetened beverages, such as punch, also are associated with higher risk of kidney stones.101
The 24-hour urine collection provides important prognostic information and guides preventive recommendations. Like many laboratory tests, urine results have traditionally been categorized into “normal” and “abnormal.” However, this grouping is unsatisfactory. Substantial differences in kidney stone risk associated with higher or lower 24-hour urine values occur within ranges considered “normal.”77 Urine values are continuous so the dichotomization into “normal” and “abnormal” is arbitrary and potentially misleading. Thus, while terms of abnormal excretion such as “hypercalciuria,” “hyperoxaluria,” or “hypocitraturia” are often used clinically and in the scientific literature, the limitations of these terms should be acknowledged.
Urine Calcium
Hypercalciuria had traditionally been defined as urine calcium excretion > 300 mg/d in men and > 250 mg/d in women111 on a 1,000-mg/d calcium diet, but more commonly used definitions have lower thresholds and no dietary requirement. Using the traditional definitions, ~0–40% of patients with calcium stone disease will be classified as having hypercalciuria. Although possibly reasonable from a calcium balance perspective, there is insufficient justification with respect to stone formation to use different thresholds for males and females.
zoom view
Fig. 1.6: Percentage of individuals without a history of nephrolithiasis who subsequently developed incident urinary stone disease (USD) by quartile of baseline urinary calcium (Ca) excretion.112 Blue bars are men; Orange bars are women.
Higher urine calcium is an established, major risk factor for calcium kidney stone formation. In a large cross-sectional study of over 2,200 stone formers and 1,100 nonstone formers, participants with 24-hour urine calcium >350 mg were between 5 and 6 times as likely to have a history of kidney stones compared with participants with 24-hour urine calcium <100 mg.77 The higher kidney stone risk associated with higher 24-hour urine calcium started well below usual cutoffs for “hypercalciuria” and was independent of age, 24-hour urine creatinine, and other urinary factors. In a 9 year prospective cohort study that included over 3,000 men and women without a history of nephrolithiasis at baseline, higher urine calcium was strongly associated with an increased risk of developing an incident kidney stone (Fig. 1.6).112 For each ~100 mg/d higher urine calcium at baseline, the risk was 20% higher for incident kidney stone formation.
Urine Oxalate
Hyperoxaluria is often defined as urinary oxalate excretion >45 mg/d, though here too a variety of thresholds are in use. Elevated urinary oxalate excretion is 3–4 times more common among men (~40%) than in women (~10%).77 Mean urinary oxalate levels are only slightly higher in kidney stone cases than in controls, but in multivariate 14models urine oxalate is clearly an important independent risk factor for stone formation.77 Depending on their age, women with 24-hour urine oxalate >40 mg were between 2.5 and 3.5 times as likely to have a history of kidney stones compared with women with 24-hour urine oxalate <20 mg.77 Men with 24-hour urine oxalate >50 mg were over 3 times as likely to have a history of kidney stones compared with men with 24-hour urine oxalate <25 mg.77 Of note, in men and women the risk begins to rise well below the 45 mg/d level.
Urine Uric Acid
The relation between uric acid excretion and calcium stone disease is unsettled. Some early cross-sectional studies reported that hyperuricosuria (typically defined as >800 mg/d in men or 750 mg/d in women) was more frequent in patients who form calcium stones than controls.113 However, in the cross-sectional study of over 2,200 stone formers and 1,100 nonstone formers, a higher urine uric acid was associated with a lower likelihood of being a stone former in men, and there was no higher risk in women.77 A double-blind trial of allopurinol successfully decreased recurrence rates of calcium stones in patients with hyperuricosuria suggesting that uric acid is important,19 but it is possible that the beneficial effect of allopurinol was through a mechanism unrelated to lowering of urine uric acid.
Urine Citrate
Hypocitraturia, often defined as 24-hour excretion < 320 mg/d, increases risk of calcium stone formation114 and is found in 5–11% of first time stone formers.77 There is suggestive evidence that increasing urinary citrate into the high-normal range could provide additional protection.77 Individuals with 24-hour urine citrate <300 mg were between 3 and 4 times as likely to have a history of kidney stones compared with those with 24-hour urine citrate >800 mg.77 As with other urinary factors, the risk varied by urine citrate level even within the “normal” range.
Epidemiologic studies have greatly expanded our understanding of risk factors for stone disease. A variety of dietary, nondietary, and urinary risk factors contribute to the risk of kidney stone formation and the importance of these varies by age, sex, and BMI. There is a paucity of randomized trials in the field, and more interventional studies are needed to further our understanding of risk factors for the “hard” outcome of kidney stone formation.
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