Faculty Bibliography

Background: Our previous study showed that PH without a transplant (tx) had worse HRQoL compared to the US Standard Population and worsened with increased stone frequency. We now show the first longitudinal HRQoL profiles for PH patients with transplants.
Method(s): PH participants were enrolled from the Rare Kidney Stone Consortium registry. HRQoL was measured with a generic non-disease specific instrument (SF-36v2). Results were calculated as norm-based scores (NBS) based on US Standard Population (Mean domain score = 50). We created three groups based on the time of last stone event (<= 30 days, 31 - 365 days, >;366 days). The study compared HRQoL for participants with a kidney and/or liver transplant over 5 different time points.
Result(s): This sub-sample included 100 surveys of 32 PH participants (16 males and 16 females) with a tx. The mean age was 47 years for both males and females. This subsample includes 24 participants with liver/kidney tx (75%) and 8 with kidney tx only (25%). Participants with only a kidney tx reported significantly more stone events within a year (26% vs 13%, X2 =0.028). Two way ANOVA did not find a change in HRQoL profiles over time for PH participants with kidney or kidney/liver tx (figure). Most mean domain scores are 50 or above, except for the domain of General Health which was less. Participants with only a kidney tx scored significantly lower in role physical, bodily pain, general health, social function, and physical component score (data not shown) than participants with kidney/liver tx. There was no difference between male and female participants over time.
Conclusion(s): PH participants with kidney/liver tx achieve better HRQoL, measured with a non-disease specific generic instrument, than those with kidney alone; both are better when compared to the US Standard Population. The majority of PH participants with a tx are stone-free, with a direct beneficial impact on their HRQoL

Background: The COVID-19 pandemic was associated with a greater incidence of AKI than expected. At the NY Harbor VA we faced an overwhelming number of AKI patients who were critically ill with multi-organ failure. We needed to invoke new mechanisms of providing kidney replacement therapy (KRT).
Method(s): We obtained 3 Tablo systems in late March, 2019. The machines have selfcontained reverse osmosis capabilities and so do not require other equipment to operate. They can make dialysate from concentrate and tap water and so do not require special plumbing adaptation. Their self-contained step-by-step procedures are relatively simple to follow and allow rapid training of previously unskilled personnel. Tablo generates 300 ml dialysate per minute, and blood flow was increased to up to 400 ml/min as tolerated.
Result(s): Training was completed by 2 nephrologists and 2 RNs without previous dialysis experience. We used the Tablo Hemodialysis System to provide KRT to critically ill patients. In the first week we demonstrated that water cultures and endotoxin testing were negative, and that AAMI water tests were acceptable. We used the machines to provide KRT for ICU patients with double-lumen dialysis catheters. In addition we used the machines on hospital wards where KRT had not been provided before because of a lack of the plumbing needs of conventional HD machines. We provided multiple treatments 3-6 times per week for 15 AKI patients, mean age 65 years. The mean of the best urea reduction ratio achieved in the first 1-4 treatments, if available, was 41% (often limited by hypotension and fulfillment of ultrafiltration, UF, needs). Most treatments were successful and were slowed for hypotension or tachycardia. Some were aborted because of water pressure alarms if sediment filters needed replacement, or lines clotted due to hypercoagulability associated with COVID-19. Personnel availability dictated that most treatments were 3-4 hours (and up to 8h), and generally achieved UF goals. Later HD nurses cannulated arteriovenous fistulas in ESKD patients and left treatment to non-HD nurses to complete.
Conclusion(s): By incorporating a user-friendly platform and an accelerated training program including nephrologists and RNs without previous dialysis experience, we were able to nearly double our capacity to deliver KRT during the surge

It is a question many patients ask in stone clinic - does it matter what water I drink? Often patients cite scaling up of their water pipes or kettles as demonstrating the influence that the hardness of the water has on stone formation. This article is protected by copyright. All rights reserved.

Appropriate dosing of cystine-binding thiol drugs in the management of cystinuria has been based on clinical stone activity. When new stones form, the dose is increased. Currently, there is no method of measuring urinary drug levels to guide the titration of therapy. Increasing cystine capacity, a measure of cystine solubility, has been promoted as a method of judging the effects of therapy. In this study, we gave increasing doses of tiopronin or D-penicillamine, depending on the patients' own prescriptions, to ten patients with cystinuria and measured cystine excretion and cystine capacity. The doses were 0, 1, 2, 3 g per day, given in two divided doses, and administered in a random order. Going from 0 to 1 g/day led to an increase in cystine capacity from - 39.1 to 130.4 mg/L (P < 0.009) and decreased 24 h cystine excretion from 1003.9 to 834.8 mg/day (P = 0.039). Increasing the doses from 1 to 2 to 3 g/day had no consistent or significant effect to further increase cystine capacity or decrease cystine excretion. Whether doses higher than 1 g/day have additional clinical benefit is not clear from this study. Limiting doses might be associated with fewer adverse effects without sacrificing the benefit of higher doses if higher doses do not offer clinical importance. However, trials with stone activity as an outcome would be desirable.

PURPOSE OF REVIEW/OBJECTIVE:The effect of the intestinal microbiome on urine chemistry and lithogenicity has been a popular topic. Here we review the evidence for exposure to antibiotics increasing the risk of nephrolithiasis. RECENT FINDINGS/RESULTS:Studies of the intestinal microbiome have focused on Oxalobacter formigenes, an anaerobe that frequently colonizes the human colon. As a degrader of fecal oxalate its presence is associated with lower urinary oxalate, which would be protective against calcium oxalate stone formation. It also appears capable of stimulating colonic oxalate secretion. A recent study showed that antibiotics can eliminate colonization with O. formigenes. In a case-control study, exposure to sulfa drugs, cephalosporins, fluoroquinolones, nitrofurantoin/methenamine, and broad spectrum penicillins prospectively increased the odds of nephrolithiasis. The effect was greatest for those exposed at younger ages and 3-6 months before being diagnosed with nephrolithiasis. SUMMARY/CONCLUSIONS:Recent evidence suggests a possible, causal role of antibiotics in the development of kidney stones. A possible explanation for this finding includes alterations in the microbiome, especially effects on oxalate-degrading bacteria like O. formigenes. Ample reasons to encourage antibiotic stewardship already exist, but the possible role of antibiotic exposure in contributing to the increasing prevalence of kidney stones in children and adults is another rationale.

The most important variable leading to uric acid stones is low urine pH. Major causal conditions associated with low urine pH are metabolic syndrome and diabetes. In the study by Maalouf et al., treatment of uric acid stone formers with pioglitazone led to small but significant increases in urine pH. Pioglitazone will not supplant alkali administration to prevent uric acid stones, but the study helps confirm that insulin resistance is an important cause of low urine pH that causes uric acid stones.

Background/UNASSIGNED:Nephrolithiasis is a complex phenotype influenced by both genetic and environmental factors. Previously we found a genetic component to stone disease using a sample of male twin pairs. We now report on the genetic contribution to stones in a sample of female and male twin pairs. Methods/UNASSIGNED:We conducted a classic twin study of kidney stones using the Washington State Twin Registry. Data were collected by questionnaire to obtain self-reported history of kidney stones. Univariate structural equation modeling was used to determine the relative contributions of additive genetics, common environment, and unique environment. Results/UNASSIGNED: < 0.05). Conclusions/UNASSIGNED:Nephrolithiasis in women has a heritable component less than that we again demonstrate in men. This finding may in part explain why more stone formers are men than women. Women twins demonstrated a greater effect of the unique environment on stone prevalence. The specific environmental risk factors that account for this effect are not currently known.

PURPOSE/OBJECTIVE:The purpose of the study was to assess the differences in the concentration and function of urinary proteins between patients with cystine stones (CYS) and healthy controls (HC). We postulated that CYS and HC groups would demonstrate different proteomic profiles. METHODS:A pilot study was performed comparing urinary proteomes of 10 patients with CYS and 10 age- and gender-matched HC, using liquid chromatography-mass spectrometry. Proteins which met the selection criteria (i) ≥ 2 unique peptide identifications; (ii) ≥ twofold difference in protein abundance; and (iii) ≤ 0.05 p value for the Fisher's Exact Test were analyzed using Gene Ontology classifications. RESULTS:Of the 2097 proteins identified by proteomic analysis, 398 proteins were significantly different between CYS and HC. Of those, 191 were involved in transport processes and 61 in inflammatory responses. The majority were vesicle-mediated transport proteins (78.5%), and 1/3 of them were down-regulated; of those, 12 proteins were involved in endosomal transport (including 6 charged multivesicular body proteins (CHMP) and 3 vacuolar sorting-associated proteins) and 9 in transmembrane transport. Myosin-2 and two actin-related proteins were significantly up-regulated in the vesicle-mediated transport group. CONCLUSION/CONCLUSIONS:We provide proteomic evidence of impaired endocytosis, dysregulation of actin and myosin cytoskeleton, and inflammation in CYS. Endosomal transport proteins were down-regulated mainly through defective CHMP. These findings may contribute to further understanding of the pathogenesis of CYS, potentially affecting its management.

PURPOSE OF REVIEW/OBJECTIVE:Traditionally, nephrolithiasis was considered a relative contraindication to kidney donation because of a risk of recurrent stones in donors and adverse stone-related outcomes in recipients. However, the scarcity of organs has driven the transplant community to re-examine and broaden selection criteria for living donors with stones. In this review, we summarize and contrast the guidelines published by various prominent national and international societies on this topic. RECENT FINDINGS/RESULTS:Although recent iterations of living donor guidelines are less stringent with respect to nephrolithiasis than those published in the 1990s, there is little consensus among national and international transplant society guidelines regarding selection criteria for potential kidney donors with nephrolithiasis. SUMMARY/CONCLUSIONS:The lack of evidence-based guidelines deters transplant centers from implementing selection criteria to accept donors with nephrolithiasis and discourages studies of outcomes in donors with nephrolithiasis and their recipients. In addition to drawing attention to the disparities in prevailing guidelines, we put forth several questions that must be answered before generalizable criteria for selection of donor with nephrolithiasis can be developed.