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.

sepsis

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

stones)

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• www.auanet.org

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

used

Guidelines/Reviews

• American Urologic Association www.auanet.org

• European Urological Associationhttp://uroweb.org

• 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