Faculty Bibliography

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.

Concerns regarding protein and amino acid deficiencies with plant-based proteins have precluded their use in chronic kidney disease (CKD) patients. Many of these concerns were debunked years ago, but recommendations persist regarding the use of "high-biological value" (animal-based) proteins in CKD patients, which may contribute to worsening of other parameters such as blood pressure, metabolic acidosis, and hyperphosphatemia. Plant-based proteins are sufficient in meeting both quantity and quality requirements. Those eating primarily plant-based diets have been observed to consume approximately 1.0 g/kg/day of protein, or more. CKD patients have been seen to consume 0.7-0.9 g/kg/day of mostly plant-based protein without any negative effects. Furthermore, those substituting animal-based proteins for plant-based proteins have shown reductions in severity of hypertension, hyperphosphatemia, and metabolic acidosis. Plant-based proteins, when consumed in a varied diet, are not only nutritionally adequate but have pleiotropic effects which may favor their use in CKD patients.

Kidney transplantation significantly improves patient survival, and is the most cost effective renal replacement option compared with dialysis therapy. Living kidney donors provide a valuable societal gift, but face many formidable disincentive barriers that include not only short- and long-term health risks, but also concerns regarding financial expenditures and health insurance. Other than governmental coverage for their medical evaluation and surgical expenses, donors are often asked to personally bear a significant financial responsibility due to lost work wages and travel expenses. In order to alleviate this economic burden for donors, we advocate for the consideration of tax credits, lifelong health insurance coverage, and an outcomes registry as societal reciprocity to reward their altruistic act of kidney donation.

INTRODUCTION/BACKGROUND:To evaluate the potential significance of cystoscopy findings following neoadjuvant chemotherapy (NAC) as prognostic indicator in patients undergoing radical cystectomy for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS/METHODS:Patients who received NAC prior to radical cystectomy for MIBC were analyzed. Patients were divided into two groups according to cystoscopy performed after two cycles of NAC: responders and non-responders. Univariate analysis was performed to analyze associations between observed response to chemotherapy and pT stage, pN stage and tumor downstaging. Logistic regression modeling was fitted to evaluate predictors for extravesical disease and pathologic downstaging. Kaplan-Meier analysis was used to evaluate disease specific survival. RESULTS:We identified 101 patients who received neoadjuvant chemotherapy prior to radical cystectomy. According to the cystoscopy findings, 60 patients (59%) were identified as responders to NAC. Stage pT0 at cystectomy was confirmed in 22 patients (36.5%) in the responder group versus only 1 patient (2.5%) in the non-responder group. Univariate analysis showed statistically significant association between response to chemotherapy observed on cystoscopy and pT stage as well as tumor downstaging. Multivariate regression modeling revealed that cystoscopy findings were an independent predictor of extravesical disease and pathologic downstaging. There was a distinct survival benefit in NAC responder group (p < 0.001). Cox proportional hazard model identified cystoscopy findings as an independent predictor of survival (OR 0.38, 95% CI 0.20-0.74, p = 0.004). CONCLUSIONS:Observed response to NAC on follow up cystoscopy is associated with favorable pathological outcomes and is a significant predictor of survival in patients undergoing radical cystectomy for MIBC.

BACKGROUND:In adult kidney transplantation, there is no clear consensus on the incidence of graft failure-due-to noncompliance (GFNC), with some reporting it as relatively uncommon and others as a major cause of late graft failure. We suspected that GFNC was a major cause of late graft loss at our center but did not know the extent of this problem. METHODS:In our prospectively followed cohort of 628 adult, primary kidney-alone transplant recipients with long-term follow-up, GFNC and other graft loss causes were determined from our ongoing clinical evaluations. Using competing risks methodology, we determined the overall percentage of patients developing GFNC and the significant prognostic factors for its hazard rate and cumulative incidence (via Cox regression). RESULTS:Cumulative incidence estimates (± standard error) of GFNC (n=29), GF-with-compliance (n=46), receiving a never-functioning graft (n=7), and death-with-a-functioning-graft (n=53) at 101 months after transplant (last-observed-graft loss) were as follows: 9.8%± 2.4%, 10.9%± 1.7%, 1.1%± 0.4%, and 13.0%± 1.9%, respectively. Only three patients experienced GFNC during the first 24 months; GFNC represented 48.1% (26/54) of death-censored GFs beyond 24 months. Two baseline variables were jointly associated with a significantly higher GFNC hazard and cumulative incidence: younger recipient age (P<0.000001 each) and non-white recipient (P=0.004 and P=0.02). Estimated percentages of ever developing GFNC were 28.4%± 6.5% among 79 non-whites younger than 35 years versus 0.0% (0/144) among whites 50 years or older. Among 302 recipients younger than 50 years, 18.1%± 4.1% developed GFNC, representing 67.6% (25/37) of its death-censored graft failures observed beyond 24 months after transplant. CONCLUSIONS:GFNC is a major cause of late GF at our center, with younger and non-white recipients at a significantly greater GFNC risk. Interventional approaches to eliminate GFNC could dramatically improve long-term kidney graft survival.