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Renal Calculi: Preventing Kidney Stones and their Recurrence Michel Pontari M.D

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  • Renal Calculi: Preventing Kidney Stones and their

    RecurrenceMichel Pontari M.D

  • Epidemiology

    • Lifetime prevalence of kidney stone disease is estimated at 1-15% 1

    • Overall prevalence –NHANES 2

    • 10.6% in men• 7.1% in women• Male female 1.49:1- was 1.7:1 in 1997 3 -

    Rising in women1. Romero V et al. Rev Urol 12: e86, 20102. Stamatelou KK et al. Kidney Int 63: 1817, 20033. Scales CD et al. J Urol 177:397, 2007

  • Stone Analysis

    • Calcium oxalate: mono or dihydrate• Calcium phosphate: • pure suspicious for RTA• Medullary sponge kidney• Primary HPTH

    • Struvite: urea splitting bacteria, elevated pH• Uric acid• Cysteine

  • Who to screen

    • Not everyone who gets a kidney stone will get another

    • Screen those at greater risk of recurrence• By medical and dietary history• Already had recurrence• Had life threatening problem with first stone, i.e.


  • Medical risk factors for stone disease

    • Obesity• Type 2 diabetes• Gout• Hyperparathyroidism• Distal renal tubule acidosis (RTA)• Malabsorptive GI disorders: bariatric surgery,

    Chrohn’s, UC, pancreatic dz, celiac sprue• Sarcoid• Genetic: 1o Hyperoxaluria, cystinuria, Lech-Nyhan, CF

  • Meds associated with stones

    • Calcium supplements 1

    • Vit C 2

    • Carbonic anhydrase inhibitors• Protease inhibitors

    1. Curhan GC et al Ann Int Med 126:497, 19972. Traxer O et al J Urol 170: 397, 2003

  • Dietary factors that contribute to stones

    • High or low calcium intake• Excessive animal protein• Excessive salt use• Low fluid intake• Limited intake of fruits and vegetables

  • Other factors contributing to stones

    • Family history• Occupation• Dehydration

    • Environmental

  • Clinical evaluation

    • Imaging • Blood tests• Urine tests• Stone analysis

  • Imaging for Anatomic abnormalities

    • Medullary sponge kidney• UPJ obstruction• Hydronephrosis• Horseshoe kidney• Multiple stones

  • Ureteral stone

  • Medullary calcinosis

    Case contributed byDr. Mohammad Taghi

    Niknejad, Radiopaedia .org

  • Horseshoe kidney

    Courtesy of Medbullets

  • Blood tests

    • Creatinine • Sodium• Low K+/ low CO2/ elevated chloride = Distal

    renal tubular acidosis• Calcium: high normal or above• Uric acid: Gout, can contribute to uric acid or

    calcium stones• (PTH)

  • Urine tests

    • Crystals• pH• Low: uric acid• High: calcium phosphate and struvite stones

    • Bacteria• 24 hour urine on random diet, no more

    calcium load. Check urine creatinine for complete sample

  • Treatment to prevent stones (or dissolve them)

    • Dietary management• Pharmacological management• (surgery- to completely remove residual


  • Fluids

    • 500 ml water load shown to significantly reduce urinary saturation of CaOx 1

    • 5 year RCT of high fluid diet to produce urine volume of > 2L versus controls with no recs 2• High fluid group urine volume 2.5x higher• Stone recurrence rate less than half (12% vs. 27%,

    p=0.008)• Time to recurrence 39 vs. 25 months (p=0.016)

    1. Borghi L et al. Nephron 81 (suppl 1): 31, 19992. Borghi L et al J Urol 155: 839, 1996

  • Type of fluids 1?

    • Decreased risk: water, coffee, tea, beer, wine, orange juice

    • Increased risk: sugar sweetened drinks and punch

    • Citrus fruit and juices: mixed results

    1. Ferraro PM et al Clin J AM Soc Neph 8:1389, 2013

  • Calcium• Cause of most calcium stones is unknown• 30-60% of stone formers have hypercalciuria• Stone risk is affected by factors other than

    hypercalciuria• Inverse association of calcium intake and stone

    formation (in men < 60) 1

    • Calcium binds oxalate in gut and excreted as insoluble complex in the stool; oxalate absorption higher from gut with lower Ca++ 2

    1. Curhan GC et al Ann Int Med 164: 885: 20042. Hess B et al Nephr Dial Transplnt 13:2241, 1998

  • Timing of calcium supplements• Calcium supplement 1 g tid with meals versus

    one dose at bedtime 1• 24 hour calcium levels increased in both phases• Urinary oxalate declined when calcium given with

    meals• Ca ox saturation increased when calcium not given

    at meals• AUA and EAU guidelines recommend that

    recurrent calcium stone formers take 1000-1200 mg dietary calcium as food (suppl with meals)

    • 1. Domrongkitchalporn et al Kidney Int 65: 1835, 2004

  • Citrate• Inhibits stones by complexing with calcium• Acid /base sensitive• Lower with acid • Higher with alkali

    • DASH diet leads to lower stone rates (Diet approaches to stop hypertension)• Higher alkali load with fruits and vegetables• 16% higher citrate on DASH like diets 1

    • Citrus not shown in RCT (try orange juice)1, Taylor EN et al Clin J AM Soc Nephrol 5:2315, 2010

  • Interaction of Sodium and Calcium

    Cardiovascular and other effects of salt consumptionFrancesco P. Cappuccio. Kidney International Supplements (2013) 3, 312–315

  • Animal Protein

  • Animal Protein• Acid load -high content of sulfur containing

    amino acids-• low urine pH and low citrate• Bone reabsorption of calcium• Decreased proximal tubule reabsorption of

    calcium• Uric acid from breakdown of purines• EAU and AUA: restriction of non dairy animal

    protein in calcium oxalate and uric acid stone formers with high urinary uric acid•

  • Medical Therapy: Calcium stones

    Hypercalciuria Thiazides + K Citrate or KCL

    Hypocitraturia Potassium Citrate

    Hyperuricosuria Allopurinol

  • Calcium stones

    • Thiazide diuretics• Enhance Ca reabsorption directly in DRT and

    indirectly in PRT• Low sodium diet• 47% reduction risk in stone recurrence 1

    • Potassium Citrate: RR 0.35 stone recurrence 2

    • Allopurinol-xanthine oxidase inhibitor

    1. Fink HA et al Ann Int Med158: 535, 20132. Barcelo P et al J Urol 150: 1761, 1993

  • Oxalate

    • Urinary oxalate• Dietary oxalate 50% contribution • Increased intestinal absorption in stone formers 1

    • Diarrhea leads to poor absorption• Intestinal resection• Malabsorptive conditions

    • 3 forms of inherited primary hyperoxaluria• Increased with Vitamin C• Decreased with Pyridoxine (Vit B6)

    1. Krishnamurthy MS et al J Urol 169: 2030, 2003.

  • Medical therapy: HyperoxaluriaPrimary Pyridoxine (type I)

    Enteric Potassium CitrateCitric acid

    RTA Potassium Citrate

  • Uric Acid

    Becomes more soluble at pH 6 or greater

    Benn, C et al Physiology Physiology of Hyperuricemia and Urate-Lowering TreatmentofFRontiers in Medicine Ciara. (2018).. 5. 10.3389/fmed.2018.00160.

  • Uric acid stones

    • 6-10% of all stones• Risk factors• Low urine pH• Low urine volume• hyperuricosuria

    • Treatment 1• Potassium Citrate 15-30 meq bid, to pH 6 or above• Refractory to alkalinization, add Allopurinol

    1. Pearle MS et al. J Urol 192:316, 2014

  • Cystine Stones

    • Rare inherited autosomal recessive mutation with defect in renal and intestinal transport of dibasic AA’s resulting in excessive urinary excretion of cystine (and ornithine, lysine and arginine)

    • First line therapy• High fluid in take urine output of > 3L/day• Restrict sodium (100 meq/d)and animal protein• Potassium citrate to raise pH to 7-7.5

  • Medical Therapy for Severe Cystinuria

    Cystine binding thiol drug to increase solubility by a thiol-disulfide exchange that results in a complex with cysteine that is more soluble-Tiopronin-D-penicillamine

  • Struvite stones (infection stones)

    • Alkaline urine (pH >7.2)• Urease producing organisms• Proteus• Klebsiella

    • Urine supersaturated with • Magnesium• Ammonium• Phosphate Meng, M. Struvite and Staghorn Calculi

    Medscape 2019

  • Treatment of struvite stones

    • Surgical removal of all stone• Culture specific antibiotic therapy• Acetohydroxamic acid• In RCT reduces stone growth and prolong interval

    to stone growth 1

    • 22-62% minor side effects• 15% DVT• Reserved for patients at high risk of struvite

    recurrence of not surgical candidate1. Hiatt RA et al . Am J Epidemiol 144:25, 1996

  • Follow-up

    • Imaging• 24 hour urine collections• Na2+ for dietary intake• K+ for compliance with K Citrate• Sulfate and BUN for measure of animal protein

    intake• BMP, uric acid, LFT depending on the drug


  • Guidelines/Reviews

    • American Urologic Association

    • European Urological Association

    • Systematic review on RCT’s• Fink HA et al Ann Int Med 158:535, 2013

    • Review article• Morgan MSC and Pearle MS BMJ 352: i52, 2016