Faculty Bibliography

The package inserts for products containing 5-aminosalicylic acid, or mesalamine, include the following language regarding the risk of adverse kidney effects: "renal impairment, including minimal change nephropathy, acute and chronic interstitial nephritis, and rarely renal failure, has been reported in patients given products such as mesalamine delayed-release tablets that contain mesalamine or are converted to mesalamine." In this article, we review the data regarding this nephrotoxicity and the recommendations regarding appropriate monitoring. Chronic interstitial nephritis is a rare occurrence in patients treated with these drugs for Crohn disease and ulcerative colitis. Patients often present with asymptomatic reductions in glomerular filtration rate, without accompanying pyuria, skin lesions, or eosinophilia, unlike cases of acute interstitial nephritis. Drug cessation is usually associated with improved kidney function. However, if left undetected, more prolonged exposure to the drug can lead to irreversible kidney failure and end-stage kidney disease. No convincing studies demonstrate efficacy of treatment with corticosteroids. Frequent monitoring of serum creatinine, especially in the first years after initiation of therapy, is recommended.

This review explores the relationship between vitamin D supplementation and lithogenesis. A causal relationship has been assumed despite myriad studies demonstrating that therapeutic doses of vitamin D do not increase lithogenic risk. Select stone formers may be at increased risk for recurrence with vitamin D supplementation, possibly from CYP24A1 gene mutations. Additionally, the evidence for who is vitamin D deficient, and the benefits of supplementation in those not at risk for rickets, is sparse. Concerns may be avoidable as vitamin D screening appears unnecessary in most patients, and superior pharmacology is available which increases bone density, while decreasing stone formation.

PURPOSE OF REVIEW/OBJECTIVE:Kidney stones are a common and preventable disorder. Certain occupations may increase risk for stone disease which will be discussed in this review. Few observational studies have examined this association. RECENT FINDINGS/RESULTS:Some occupations prevent individuals from drinking enough fluids to maintain a dilute urine or to void when they need to. People may have poor access to fluids or to bathroom facilities. These issues pose a risk for stone disease and are exacerbated by those who work in warmer climates. Individuals who do more activity while working, especially outdoors, perspire more, leading to more concentrated urine. In more sedentary jobs, individuals are at a higher risk of metabolic syndrome and therefore have a higher risk for stones. Astronauts, who work in environments without gravity, mobilize calcium from bone, leading to a higher risk of stone disease. SUMMARY/CONCLUSIONS:Proper fluid intake, more access to restrooms and increased use of potassium citrate may be the best options for those who encounter greater risk for stones because of their occupation.

Cystinuria comprises less than 1% of kidney stones and is associated with impaired health-related quality of life (HRQOL). Limited evidence is available regarding HRQOL of patients with cystinuria treated with tiopronin (Thiola^®). The objective of this study was to assess the HRQOL of patients with or without tiopronin treatment. For this cross-sectional survey, patients on tiopronin treatment were recruited through the "Thiola^® Total Care Hub," a specialty pharmacy used to dispense tiopronin, and compared with patients not taking tiopronin (non-tiopronin group) who were identified from the Cystinuria Contact Registry at New York University School of Medicine. Consented patients responded to a survey that included questions about their experiences with kidney stones, the Wisconsin stone quality of life (WISQOL) (disease-specific) questionnaire, and the short form-36 version 2 (SF-36v2) (generic) HRQOL questionnaire. Statistical analyses included independent-sample t tests, one-way analysis of variance (ANOVA), and correlations. The survey was completed by 312 patients: 267 in the tiopronin group (144 male, 123 female; mean 49 years) and 45 in the non-tiopronin group (10 male, 35 female; mean 48 years). Both groups utilized pain medications similarly (24% overall). Patients on tiopronin had a significantly better HRQOL than patients not on tiopronin for all WISQOL domains (p < 0.001) and all but the physical functioning SF-36v2 domain (p < 0.001), where both groups approached the US normative mean, when controlling for the last stone event. Compared with patients in the non-tiopronin group, patients taking tiopronin reported better HRQOL on both the WISQOL and SF-36v2.

PURPOSE OF REVIEW/OBJECTIVE:Men have more kidney stones compared with women; however, the difference is progressively decreasing. The reasons for higher prevalence of stones in men, as well as increasing prevalence in women, is a subject of ongoing speculation. In this review, we summarize the evidence of differences between men and women and expand on the speculative causes. RECENT FINDINGS/RESULTS:Stone incidence is rising in women and adolescent girls. Stone disease is more heritable among men than women, and women demonstrate greater influence of the unique environment. Women under the age of 50 years who have been pregnant, have more than double the odds of kidney stones compared with those who have never been pregnant. Women are more burdened with obesity, bariatric surgery and dieting, all associated with increased stones. Women have higher urinary pH because of greater absorption of dietary organic anions leading to increased urinary citrate, compared with men, and they differ in tubular calcium handling. SUMMARY/CONCLUSIONS:It is obvious that the cause of stones in men and women is complex and requires further study. Potential clues offered are in the change of the female environment, influencing increasing incidence in stones, particularly of younger women and female adolescents.

People with chronic kidney disease (CKD) are at increased risk of hyperkalemia, an electrolyte abnormality that can cause serious, sometimes fatal, cardiac arrhythmias. Muscle contraction causes potassium to be released from cells, increasing serum potassium concentrations. However, these effects are transient, and the long-term impact of exercise training on hyperkalemia risk in CKD patients is largely unknown. In this review, we examine the effects of exercise on factors affecting potassium balance in people with CKD, highlighting the potential benefits of regular exercise on hyperkalemia risk in this population. Although regular exercise is already recommended for people with CKD, research examining this hypothesis may lead to novel therapeutic treatments for this life-threatening condition.

BACKGROUND:A scarcity of organs has driven the transplant community to broaden selection criteria for both living and deceased donors. Living donor transplants offer better patient and allograft survival when compared with deceased donor transplants. Many transplant centers now allow complex living donors such as those with nephrolithiasis to undergo nephrectomy. METHODS:We conducted a survey of medical and surgical directors of kidney transplant programs in the United States to shed light on current practices pertaining to medical evaluation of living kidney donors with nephrolithiasis. 353 surveys were e-mailed to medical directors and surgical directors of transplant programs after contacts were obtained from UNOS. RESULTS:49 completed surveys were returned (13.9%). 77.7% (38/49) of survey participants said their centers will consider living kidney donor candidates with a history of symptomatic kidney stones, 69.4% (34/49) said their centers will consider candidates who are incidentally found to have kidney stones and 10.2% (5/49) said their centers decline all potential donors with nephrolithiasis. CONCLUSIONS:Several programs are still reluctant to allow potential donors with nephrolithiasis to donate. There is an unmet need to develop evidence-based guidelines to optimize outcomes in this population of kidney donors with nephrolithiasis and their recipients.

Previous studies assumed a uniform relationship between heat and kidney stone presentations. Determining whether sex and other characteristics modify the temperature dependence of kidney stone presentations has implications for explaining differences in nephrolithiasis prevalence and improving projections of the effect of climate change on nephrolithiasis. We performed an aggregated case-crossover study among 132,597 children and adults who presented with nephrolithiasis to 68 emergency departments throughout South Carolina from 1997 to 2015. We used quasi-Poisson regression with distributed lag non-linear models to estimate sex differences in the cumulative exposure and lagged response between maximum daily wet-bulb temperatures and emergent kidney stone presentations, aggregated at the ZIP-code level. We also explored interactions by age, race, payer, and climate. Compared to 10 °C, daily wet-bulb temperatures at the 99th percentile were associated with a greater increased relative risk (RR) of kidney stone presentations over 10 days for males (RR 1.73; 95% CI 1.56, 1.91) than for females (RR 1.15; 95% CI 1.01, 1.32; interaction P < 0.001). The shape of the lagged response was similar for males and females, with the greatest risk estimated for the 2 days following high temperatures. There were weak differences by age, race, and climatic zone, and no differences by payer status. The estimated risk of presenting emergently with kidney stones within 10 days of high daily wet-bulb temperatures was substantially greater among men than women, and similar between patients with public and private insurance. These findings suggest that the higher risk among males may be due to sexually dimorphic physiologic responses rather than greater exposure to ambient temperatures.