Andrew F Colhoun MD

1. Kidney stones for primary careDietary and medical evaluation and preventionA summary of AUA guidelines Andrew F Colhoun MD

2. Disclosures • None • Material adapted from AUA guidelines (www.auanet.org)

3. Etiology • Common - affects nearly 1 in 11 individuals in the United States and rising.1 • At least 50% experience another stone within 10 years of the first occurrence.2 • Overweight/obesity,1,12 hypertension13 and diabetes14 associated with an increased risk of stone disease. • Calcium oxalate is most common stone in industrialized world • Dehydration is the most common cause of stone formation

4. Importance of fluids • Cohort study (n=108) by Hoskingset al in 1983 16 • Increased fluids and avoid “dietary excess” • Mean follow-up 63 months • 58% of patients showed no new stone formation • RCT of recurrent calcium oxalate stone formers20 • Randomized to a high fluid intake compared to no change in fluid • Recurrence rate of 12% versus 27%, respectively, at 5 years • Is beverage type important? • Only soft drinks evaluated in an RCT (n=1,000)21 • Baseline soft drink consumption > 160 ml daily (~1/2 can) • Randomized to avoid soft drinks or continue their typical beverage consumption • 3 year follow-up • Avoidance group with lower rate of stone recurrence (58.2% vs 64.6%, p=0.023) • Effects limited - phosphoric acid-based (e.g. colas) rather than citric acid-based soft drinks

5. Multicomponent diet • Consists of normal calcium (RDA), low sodium, low animal protein intake17 • Superior to a low calcium diet in preventing stone recurrence in hypercalciuric, recurrent calcium oxalate stone-forming men • Independent effects of calcium, sodium and animal protein could not be assessed • Another multicomponent diet: high fluid, high fiber, low animal protein intake19 • Not shown to be superior to a high fluid diet in preventing stone recurrence in a group of 102 first-time calcium oxalate stone formers • Confounder: control group had higher urine volumes than the study group • Another RCT - no benefit of low animal protein diet in reducing stone recurrence22 • three groups: low animal protein diet, high fiber diet or a control group with no recommendations • Therefore, only combined effect of low sodium, low animal protein, normal calcium intake has been shown to reduce the likelihood of stone recurrence

6. New diagnosis – guideline statements 1 & 2 • Elucidate medical conditions, dietary habits or medications that predispose to stone disease • Check chemistries: BMP, UA • Abnormally high serum calcium should cause PTH draw • Primary hyperparathyroidism should be suspected when serum calcium is high or high normal • Low vitamin D may mask primary hyperparathyroidism, or contribute to secondary hyperparathyroidism • Consider endocrine evaluation, imaging or referral for consideration of parathyroidectomy

7. Further workup – guideline statements 3-7 • 24 hr urine collection and stone analysis

8. Urine volume – guideline statement 8 • Stones form when there is a high concentration of stone forming salts • Therefore, fluid intake is the main determinant of urine volume and the critical component of stone prevention • No definitive threshold for urine volume • Accepted goal is at least 2.5 liters of urine daily • No data to support the use of urine color as a guide • Sugar-sweetened beverages demonstrated an increased risk of stone formation33

9. Calcium – guideline statement 9 • Lower calcium diet in the absence of other dietary measures is associated with an increased risk of stone formation - paradox • lower calcium intake -> insufficient chelation of dietary oxalate in the gut -> increasing oxalate absorption and urinary oxalate excretion • RDA defined as 1,000-1,200 mg/day for most individuals • Sodium intake is linked to urinary calcium excretion • Target of ≤ 2,300 mg sodium intake daily • Supplemental calcium may be associated with an increased risk of stone formation • Observational study of older women24 • Supplement users were 20% more likely to form a stone • Most patients obtain adequate daily calcium from foods and beverages and supplementation not needed

10. Oxalate – guideline statement 10 • Restricting oxalate-rich foods generally recommended for calcium stone formers • List of the oxalate content of foods - Harvard School of Public Health (https://regepi.bwh.harvard.edu/health/Oxalate/files/Oxalate%20Content%20of%20Foods.xls) • Urinary oxalate influenced by calcium intake (mentioned previously) • Should consume calcium from foods and beverages primarily at meals to enhance gastrointestinal binding of oxalate • Should still adhere to RDA of calcium • Patients with malabsorptive conditions (IBS, gastric bypass) • May benefit from calcium supplements at meals • Calcium serves as oxalate binder • 24 hr urine monitoring can be used to ensure that hypercalciuria does not result

11. Citrate and uric acid – guideline statements 11 & 12 • Urinary citrate is a potent inhibitor of calcium stone formation.80 • Hypocitraturia is a common risk factor for stone disease with an estimated prevalence of 20-60%.81,82 • Urinary citrate excretion is determined by acid-base status • Metabolic acidosis or dietary acid loads enhance renal citrate reabsorption, reducing urinary excretion • RTA, chronic diarrhea, carbonic anhydrase inhibitors • Foods with acid load: meats, fish, poultry, cheese, eggs • Foods with alkali load: fruits and vegetables • Dietary citrate increases urinary citrate excretion by conversion to bicarbonate in vivo • Insufficient data on which foods may contain enough to make specific dietary recommendations • Diet-derived purines account for an estimated 30% of urinary uric acid.94 • “High purine" foods: specific fish and seafood (anchovies, sardines, herring, mackerel, scallops and mussels), water fowl, organ meats, glandular tissue, gravies and meat extracts • "Moderately-high" sources of purines: shellfish, game meats, mutton, beef, pork, poultry and meat-based soups and broths.96,97 • Uric acid crystal formation and growth occur in more acidic urine.94 • H/o uric acid stones - increase the alkali load and decrease the acid load

12. Medications • Vitamin C converted to oxalate • Dose of 1000mg daily increases urinary oxalate by 20-60% • Turmeric and cranberry tablets has also been linked to higher urine oxalate73,74 • Vitamin D (high doses) – increased calcium absorption • Triamterene & protease inhibitors – can precipitate and form radiolucent calculi • Acetazolamide & topiramate – carbonic anhydrase inhibition causes changes similar to distal RTA

13. Gout and stones – guideline statement 19 • Low urine pH is most common risk factor for uric acid calculi, not hyperuricosuria115 • “Reduction of urinary uric acid excretion with the use of allopurinol in patients with uric acid stones will not prevent stones in those with unduly acidic urine” • First-line therapy is alkalinization with potassium citrate • Allopurinol may be considered when alkalinization fails • IBD, chronic diarrhea and ileostomies • Patients with gout may form calcium stones from uric acid nidus

14. References • http://www.auanet.org/guidelines/medical-management-of-kidney-stones-(2014)