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Effect of increasing doses of cystine-binding thiol drugs on cystine capacity in patients with cystinuria
Malieckal, Deepa A; Modersitzki, Frank; Mara, Kristin; Enders, Felicity T; Asplin, John R; Goldfarb, David S
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.
PMID: 30980122
ISSN: 2194-7236
CID: 3809492
Water to prevent kidney stones: Tap vs. bottled; Soft vs. hard - Does it matter? [Letter]
Willis, S; Goldfarb, D S; Thomas, K; Bultitude, M
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.
PMID: 31310699
ISSN: 1464-410x
CID: 3977792
Recurrent Calcium Kidney Stones
Beara-Lasic, Lada; Goldfarb, David S
PMID: 31221735
ISSN: 1555-905x
CID: 3939382
The use of antibiotics and risk of kidney stones
Joshi, Shivam; Goldfarb, David S
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.
PMID: 31145705
ISSN: 1473-6543
CID: 3957952
Effect of thiazolidinedione therapy on the risk of uric acid stones
Asplin, John R; Goldfarb, David S
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.
PMID: 31010476
ISSN: 1523-1755
CID: 3821402
Urine proteomic profiling in patients with nephrolithiasis and cystinuria
Kovacevic, Larisa; Caruso, Joseph A; Lu, Hong; Kovacevic, Natalija; Lakshmanan, Yegappan; Carruthers, Nicholas J; Goldfarb, David S
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.
PMID: 30519981
ISSN: 1573-2584
CID: 3520752
A Twin Study of Genetic Influences on Nephrolithiasis in Women and Men
Goldfarb, David S; Avery, Ally R; Beara-Lasic, Lada; Duncan, Glen E; Goldberg, Jack
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:Â < 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.
PMCID:6451147
PMID: 30993229
ISSN: 2468-0249
CID: 3808072
Controversies in kidney stones and other chronic kidney disease topics
Goldfarb, David S
PMID: 30585853
ISSN: 1473-6543
CID: 3560392
Differences in national and international guidelines regarding use of kidney stone formers as living kidney donors
Tatapudi, Vasishta S; Goldfarb, David S
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.
PMID: 30531468
ISSN: 1473-6543
CID: 3537002
Blood volume analysis as a guide for dry weight determination in chronic hemodialysis patients: a crossover study
Malha, Line; Fattah, Hasan; Modersitzki, Frank; Goldfarb, David S
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.
PMID: 30744587
ISSN: 1471-2369
CID: 3656112