Faculty Bibliography

OBJECTIVE:To assess the effectiveness of an empiric approach to metabolic stone prevention. METHODS:Using medical claims from a cohort of working age adults with kidney stone diagnoses (2008-2017), we identified the subset who were prescribed thiazides, alkali therapy, or allopurinol-collectively known as preventive pharmacologic therapy (PPT). We distinguished between those who had 24-hour urine testing prior to initiating PPT (selective therapy) from those without it (empiric therapy). We conducted a survival analysis for time to first recurrence for stone-related events, including ED visits, hospitalizations, and surgery, up to 2 years after initiating PPT. RESULTS:Of 10,125 patients identified, 2744 (27%) and 7381 (73%) received selective and empiric therapy, respectively. The overall frequency of any stone-related event was 11%, and this did not differ between the 2 groups on bivariate analysis (P = .29). After adjusting for sociodemographic factors, comorbidities, medication class, and adherence, there was no difference in the hazard of a stone-related event between the selective and empiric therapy groups (hazard ratio, 0.97; 95% confidence interval, 0.84-1.12). When considered individually, the frequency of ED visits, hospitalizations, and surgeries did not differ between groups. Greater adherence to PPT and older age were associated with a lower hazard of a stone-related event (both P < .05). CONCLUSION/CONCLUSIONS:Compared to empiric therapy, PPT guided by 24-hour urine testing, on average, is not associated with a lower hazard of a stone-related event. These results suggest a need to identify kidney stone patients who benefit from 24-hour urine testing.

The Consensus Group deliberated on a number of questions concerning urine and stone analysis over a period of months, and then met to develop consensus. The Group concluded that analyses of urine and stones should be routine in the diagnosis and treatment of urinary stone diseases. At present, the 24-h urine is the most useful type of urine collection, and accepted methods for analysis are described. Patient education is also important for obtaining a proper urine sample. Graphical methods for reporting urine analysis results can be helpful both for the physician and for educating the patient as to proper dietary changes that could be beneficial. Proper analysis of stones is also essential for diagnosis and management of patients. The Consensus Group also agreed that research has shown that evaluation of urinary crystals could be very valuable, but the Group also recognizes that existing methods for assessment of crystalluria do not allow this to be part of stone treatment in many places.

Background: Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) is a rare monogenic disorder caused by SLC34A3 pathogenic variants, characterized by renal phosphate wasting, hypophosphatemia, hypercalciuria (HC), elevated 1,25-dihydroxyvitamin D, nephrocalcinosis (NC), and urinary stone disease (USD). Previously we reported a high prevalence of kidney cysts in CYP24A1 deficiency. Thus, in the current study, we characterized cyst presence in HHRH, another monogenic cause of HC, NC, and USD.
Method(s): Medical records from Mayo Clinic and Rare Kidney Stone Consortium research results were queried for all patients with genetically confirmed HHRH diagnosis. Clinical characteristics and imaging data are summarized in table 1.
Result(s): Among 12 patients with SLC34A3 pathogenic variants (7 monoallelic, 5 biallelic), 42% (5/12) were males. Median age at clinical presentation was 17 yrs (range 8-46) and at genetic confirmation 42 yrs (range 9-66). None had a family history of cystic kidney disease. Kidney cysts (Figure 1) were present in 75% (9/12), among whom median age at first kidney imaging and first cyst detection was 41 yrs (range 9-64). Median number of cysts per patient was 3 (range 1-23). The number of cysts >=5 mm in size was above the 97.5th percentile of an age-and sex-matched control population in 6/9 (67%). At least 2 cysts >=5 mm in size were found in 100% of children.
Conclusion(s): We found a strong association between HHRH and kidney cysts. Similarities in the biochemical profiles of HHRH and CYP24A1 deficiency suggest elevated active vitamin D, and/or HC may be potential factors in cyst formation. Further studies are needed to evaluate the role of the SLC34A3 gene in cyst formation. (Figure Presented)

We recently encountered concern about the safety of bariatric surgery for a patient with cystinuria. Bariatric surgery procedures include those that cause malabsorption, like the Roux-en-Y gastric bypass procedure, and restrictive operations, such as the sleeve gastrectomy. These procedures produce beneficial effects on health and life expectancy, though whether kidney stones are prevented, as well as promoted, is not established. Although the importance of body weight to metabolic stone activity in patients with cystinuria is not established, the patient's physicians were concerned about whether any bariatric surgery procedure would affect her ability to drink sufficient quantities of water in order to reduce stone activity. Here we report the experience of a genetically defined patient with cystinuria who underwent a gastric sleeve procedure. In the months after the procedure, she lost 45 kg, though with time she regained 23 kg of that loss. She was able to maintain a urine volume of 4.0 L per day and has had no stone recurrence.XXCopyright

Background: Potassium citrate is a mainstay of treatment to prevent recurrent calcium-containing kidney stones. However, it can increase urine pH and calcium phosphate (CaP) supersaturation (SS). HCA, extracted from Garcinia cambogia, is a potent inhibitor of calcium oxalate crystal growth in vitro and should not provide "potential base", as citrate does. Urine excretion of HCA has not been well-studied.
Method(s): We enrolled 2 groups: calcium stone formers (SF; n = 9) and non-stone forming (NSF, n = 9) controls (after excluding 2 SF and 2 NSF whose urine creatinine excretion on the 2 collections differed by more than 20%). Mean age 49.3 years. Thiazides and citrate were held for 2 weeks prior to study. Participants recorded a self-selected diet for 2 days and performed 24-hour urine collection on day 2. HCA was purchased online from Amazon.com (Super CitriMax Garcinia Cambogia); 2 caps = 900 mg of HCA. Participants took 900 mg 3 times daily orally for 7 days. Diet from days 1 and 2 was replicated on day 6 and 7 of the HCA arm of the study. 24-hour urine was collected on day 7. Urine was sent to Litholink, Inc. (Chicago, IL) for analysis. Urinary excretion of hydroxycitrate and citrate were measured using LC/MS.
Result(s): According to label, 6 pills would provide 2700 mg (13.2 mmol) of HCA per day; we measured content as 3198 mg (15.6 mmol). Citrate content is supposed to be 0, but we found 126 mg (0.66 mmol) per day. Both NSF and SF had appearance of HCA in the urine: 1.86 +/- 0.80 and 2.07 +/- 0.67 mmol/day (p = 0.56). Urine chemistry seen in Table 1. In NSF, pH and citrate did not change. In SF, pH increased, citrate did not. K went up in both groups.
Conclusion(s): Administration of HCA, a potential inhibitor of Ca stone formation, leads to significant urinary HCA excretion. Citrate excretion was not affected. Urine pH increased, suggesting some alkalinizing effect. The difference in NSF and SF may be due to the lower starting pH in SF. The effect of HCA on stone formation remains to be determined. (Figure Presented)

Background:The COVID-19 pandemic strained hospital resources in New York City, including those for providing dialysis. New York University Medical Center and affiliations, including New York City Health and Hospitals/Bellevue, developed a plan to offset the increased needs for KRT. We established acute peritoneal dialysis (PD) capability, as usual dialysis modalities were overwhelmed by COVID-19 AKI. Methods:Observational study of patients requiring KRT admitted to Bellevue Hospital during the COVID surge. Bellevue Hospital is one of the largest public hospitals in the United States, providing medical care to an underserved population. There were substantial staff, supplies, and equipment shortages. Adult patients admitted with AKI who required KRT were considered for PD. We rapidly established an acute PD program. A surgery team placed catheters at the bedside in the intensive care unit; a nephrology team delivered treatment. We provided an alternative to hemodialysis and continuous venovenous hemofiltration for treating patients in the intensive-care unit, demonstrating efficacy with outcomes comparable to standard care. Results:From April 8, 2020 to May 8, 2020, 39 catheters were placed into ten women and 29 men. By June 10, 39% of the patients started on PD recovered kidney function (average ages 56 years for men and 59.5 years for women); men and women who expired were an average 71.8 and 66.2 years old. No episodes of peritonitis were observed; there were nine incidents of minor leaking. Some patients were treated while ventilated in the prone position. Conclusions:Demand compelled us to utilize acute PD during the COVID-19 pandemic. Our experience is one of the largest recently reported in the United States of which we are aware. Acute PD provided lifesaving care to acutely ill patients when expanding current resources was impossible. Our experience may help other programs to avoid rationing dialysis treatments in health crises.