Faculty Bibliography

BACKGROUND:Volume overload and depletion both lead to high morbidity and mortality. Achieving euvolemia is a challenge in patients with end stage kidney disease on hemodialysis (HD). Blood volume analysis (BVA) uses radiolabeled albumin to determine intravascular blood volume (BV). The measured BV is compared to an ideal BV (validated in healthy controls). We hypothesized that BVA could be used in HD to evaluate the adequacy of the current clinically prescribed "estimated dry weight" (EDW) and to titrate EDW in order to improve overall volume status. We were also interested in the reproducibility of BVA results in end stage kidney disease. METHODS:Twelve adults on chronic HD were recruited; 10 completed the study. BVA (Daxor, New York, NY, USA) was used to measure BV at baseline. EDW was kept the same if the patient was deemed to be euvolemic by BVA otherwise, the prescribed EDW was changed with the aim that measured BV would match ideal BV. A second BVA measurement was done 1-3 months later in order to measure BV again. RESULTS: = 0.08). CONCLUSIONS:This pilot study is the first longitudinal measurement of BVA in HD patients. It revealed that changing weight did not proportionally change intravascular BV. BV remained stable for 1-3 months. BVA may not be helpful in clinically stable HD patients but studies on patients with hemodynamic instability and uncertain volume status are needed. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov (NCT02717533), first registered February 4, 2015.

Cystinuria, a genetic disorder of cystine transport, is characterized by excessive excretion of cystine in the urine and recurrent cystine stones in the kidneys and, to a lesser extent, in the bladder. Males generally are more severely affected than females. The disorder may lead to chronic kidney disease in many patients. The cystine transporter (b^0,+) is a heterodimer consisting of the rBAT (encoded by SLC3A1) and b^0,+AT (encoded by SLC7A9) subunits joined by a disulfide bridge. The molecular basis of cystinuria is known in great detail, and this information is now being used to define genotype-phenotype correlations. Current treatments for cystinuria include increased fluid intake to increase cystine solubility and the administration of thiol drugs for more severe cases. These drugs, however, have poor patient compliance due to adverse effects. Thus, there is a need to reduce or eliminate the risks associated with therapy for cystinuria. Four mouse models for cystinuria have been described and these models provide a resource for evaluating the safety and efficacy of new therapies for cystinuria. We are evaluating a new approach for the treatment of cystine stones based on the inhibition of cystine crystal growth by cystine analogs. Our ongoing studies indicate that cystine diamides are effective in preventing cystine stone formation in the Slc3a1 knockout mouse model for cystinuria. In addition to crystal growth, crystal aggregation is required for stone formation. Male and female mice with cystinuria have comparable levels of crystalluria, but very few female mice form stones. The identification of factors that inhibit cystine crystal aggregation in female mice may provide insight into the gender difference in disease severity in patients with cystinuria.

Careful phenotyping of patients to classify those with kidney stones has a long and important history in revealing the chemical basis for stone formation. Advances in our genetic understanding of kidney stones will lead to incredible insights regarding the pathophysiology of this common disorder. At this time, both evaluation of urine chemistry and genotyping of patients are extremely useful in the setting of a university and research-based kidney stone clinic. For much of the world, in a more clinically focused setting, these techniques are neither available nor absolutely necessary. Careful implementation of an empiric prescription based on stone composition would have an important effect to reduce stone recurrence in the world's many stone formers. Increased fluid intake, generic dietary manipulations, and prescription of potassium citrate and thiazides are all appropriate empiric therapies for people with calcium and uric acid kidney stones.

Objective/UNASSIGNED:Lesinurad (LESU) is a selective urate reabsorption inhibitor approved at 200 mg daily for use with a xanthine oxidase inhibitor (XOI) to treat hyperuricaemia in gout patients failing to achieve target serum urate on XOI. The aim of the study was to investigate the long-term safety of LESU + XOI therapy. Methods/UNASSIGNED:Safety data were pooled from three 12-month phase III (core) trials evaluating LESU 200 and 400 mg/day combined with an XOI (LESU200+XOI and LESU400+XOI), and two 12-month extension studies using descriptive statistics. To adjust for treatment duration, treatment-emergent adverse events (TEAEs) were expressed as exposure-adjusted incidence rates (patients with events per 100 person-years). Results/UNASSIGNED:In the core studies, exposure-adjusted incidence rates for total and total renal-related TEAEs were comparable for XOI alone and LESU200+XOI but higher with LESU400+XOI. Exposure-adjusted incidence rates for serum creatinine (sCr) elevations ⩾1.5×baseline were 2.9, 7.3 and 18.7, respectively. Resolution (sCr ⩽1.2×baseline) occurred in 75-90% of all events, with 66-75% occurring without any study medication interruption. Major adverse cardiovascular events were 3, 4 and 9 with XOI, LESU200+XOI and LESU400+XOI, respectively. Longer exposure in core+extension studies did not increase rates for any safety signals. Conclusion/UNASSIGNED:At the approved dose of 200 mg once-daily combined with an XOI, LESU did not increase renal, cardiovascular or other adverse events compared with XOI alone, except for sCr elevations. With extended exposure in the core+extension studies, the safety profile was consistent with that observed in the core studies, and no new safety concerns were identified.

Protein-energy wasting (PEW) is a major diet-related complication in hemodialysis (HD) patients. Nutrient-based dietary guidelines emphasize animal-based protein foods for preventing and managing PEW in HD patients. Although dietary protein intake is important for protein anabolism, other dietary factors contribute to PEW. In this article, we examine the diet-related etiologies of PEW in HD patients, and discuss how they may be affected differently by animal- and plant-based protein foods. In general, animal foods are superior sources of protein, but may contribute more to metabolic derangements that cause PEW. Given the potential mixed effects of animal-based protein foods on PEW, human research studies are needed to determine the impact of liberalizing the diet to allow plant-based protein foods on protein status.

Introduction: This study examines the use of dialysis services by end-stage renal disease (ESRD) patients following the Superstorm Sandy-related, months-long closure of the New York campus of the US Department of Veterans Affairs (VA) New York Harbor VA Healthcare System (NYHHS, Manhattan VAMC). Methods: Outpatient visits, dialysis care, emergency department visits, and hospitalizations at VA and non-VA facilities for 47 Manhattan VAMC ESRD patients were examined 12 months pre- and post-Sandy using VA administrative and clinical data. Results: The Brooklyn campus of NYHHS, which is within ten miles of Manhattan VAMC, experienced the largest increase in the number of dialysis encounters after the closure. Dialysis encounters for VA patients also increased at non-VA facilities, rising on average, to 106 per month. For the James J Peters Bronx VAMC, the number of total dialysis encounters for Manhattan VAMC patients fluctuated between 39 and 43 per month, dropping to less than 30 after the Manhattan VAMC dialysis unit reopened. Conclusion: Manhattan VAMC ESRD patients used nearby alternate VA sites and non-VA clinics for their care during the closure of the Manhattan VAMC dialysis unit. The VA electronic health records played an important role in ensuring continuity of care for patients who exclusively used VAMC facilities post-Sandy because patient information was immediately accessible at other VA facilities. The events related to Superstorm Sandy highlight the need for dialysis providers to have a comprehensive disaster plan, including nearby alternate care sites that can increase service capacity when a dialysis facility is closed because of a disaster.

Background: Potassium citrate is a mainstay of treatment to prevent calcium 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 (CaOx) crystal growth in vitro and may not yield HCO3. It is "generally regarded as safe" and available over the counter. We studied how HCA supplementation affects urine chemistry.
Method(s): We enrolled 2 groups: calcium stone formers (SF) and non-stone forming (NSF) controls. Thiazides and potassium 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 300 mg 3 times daily was taken orally for 7 days, and 24-hour urine collected on day 7 while the patient replicated the initial, self-selected diet.
Result(s): 13 people, aged 26-76 years, participated. There were 6 SF and 7 NSF, combined into 1 group of 13. Patients replicated their diets well, as urine Na, volume, and creatinine were similar (data not shown). Results presented in Table. HCA increased urine K and citrate (P < 0.001 and 0.013 respectively). Mean urine pH was unchanged (6.25 to 6.47, P=0.14), while urinary NH4 fell (P = 0.017). 24h excretion of Ca and Ox did not change. SS of CaOx and CaP did not change. Serum values did not change: baseline HCO3 and K were 23.5 +/- 2.5 and 4.0 +/- 0.2 meq/L and 23.7 +/- 1.8 and 4.4 +/- 0.6 meq/L after HCA.
Conclusion(s): Urine K excretion rose by 29 meq/day compared with an expected increase based on the label of 14 meq, suggesting the label was not accurate. Increased citrate and lower NH4 suggest some K is in the form of alkali salts or that some HCA is metabolized to bicarbonate. There was no change in CaP or CaOx SS. The lack of effect on SS may not reflect the potential ability of HCA to inhibit calcium crystallization, as it inhibits Ca crystal growth in vitro in supersaturated media