Fertility Management in Cystinosis: A Clinical Perspective.

Cystinosis is a rare, inherited, lysosomal storage disorder characterized by the progressive accumulation of intralysosomal cystine and subsequent organ and tissue damage. The kidneys are the first and most severely impacted organ. Although cystinosis was once considered a fatal pediatric disease, patients with cystinosis are living well into adulthood with advances in medical care, including kidney transplant and early and continuous use of cysteamine therapy. This increase in life expectancy has revealed an extrarenal phenotype of cystinosis that emerges in adolescence and adulthood, affecting nearly all body systems, including the endocrine and reproductive systems. As individuals with cystinosis are planning for the future, reproductive health and fertility have become areas of increased focus. This narrative review aims to summarize the current understanding of reproductive health and fertility in patients with cystinosis and discuss practical considerations for monitoring and managing these complications.

Sitagliptin Versus Placebo to Reduce the Incidence and Severity of Posttransplant Diabetes Mellitus After Kidney Transplantation-A Single-center, Randomized, Double-blind Controlled Trial.

BACKGROUND: Postkidney transplant diabetes mellitus (PTDM) affects cardiovascular, allograft, and recipient health. We tested whether early intervention with sitagliptin for hyperglycemia (blood glucose >200 mg/dL) within the first week of transplant and discontinued at 3 mo could prevent development of PTDM in patients without preexisting diabetes. METHODS: The primary efficacy objective was to improve 2-h oral glucose tolerance test (OGTT) by > 20 mg/dL at 3 mo posttransplant. The secondary efficacy objective was to prevent new onset PTDM, defined as a normal OGTT at 3 mo. RESULTS: Sixty-one patients consented, and 50 patients were analyzed. The 3-mo 2-h OGTT (end of treatment) was 141.00 ± 62.44 mg/dL in the sitagliptin arm and 165.22 ± 72.03 mg/dL ( P = 0.218) in the placebo arm. The 6-mo 2-h OGTT (end of follow-up) was 174.38 ± 77.93 mg/dL in the sitagliptin arm and 171.86 ± 83.69 ng/dL ( P = 0.918) in the placebo arm. Mean intrapatient difference between 3- and 6-mo 2-h OGTT in the 3-mo period off study drug was 27.56 + 52.74 mg/dL in the sitagliptin arm and -0.14 + 45.80 mg/dL in the placebo arm ( P = 0.0692). At 3 mo, 61.54% of sitagliptin and 43.48% of placebo patients had a normal 2-h OGTT ( P = 0.2062), with the absolute risk reduction 18.06%. There were no differences in HbA1c at 3 or 6 mo between sitagliptin and placebo groups. Participants tolerated sitagliptin well. CONCLUSIONS: Although this study did not show a significant difference between groups, it can inform future studies in the use of sitagliptin in the very early posttransplant period.

Effect of Frequent Dialysis on Renal Recovery: Results From the Acute Renal Failure Trial Network Study.

INTRODUCTION: The optimal frequency of intermittent hemodialysis (IHD) in the treatment of acute kidney injury (AKI) remains unclear. Increasing the frequency of IHD, while offering the possible advantage of reduced ultrafiltration requirement and less hemodynamic instability per session, amplifies patient contact with an extracorporeal circuit with possible deleterious cardiovascular and immunological consequences. A recent study suggested that intensive renal replacement therapy (RRT) is associated with a decrease in urine output during AKI. We hypothesized that increased frequency of IHD may be associated with delayed renal recovery. METHODS: This is a post hoc analysis of the Acute Renal Failure Trial Network (ATN) study. The ATN study was a large randomized multicenter trial of intensive versus less-intensive RRT in critically ill patients with AKI. This study used either continuous RRT or IHD, depending on the hemodynamic status of the patient. Of 1124 patients, 246 were treated solely with IHD during the study period and were included in this analysis. The participants were randomized to receive IHD 3 days per week (L-IntRRT) or 6 days per week (IntRRT). The primary outcome of interest was renal recovery at day 28. RESULTS: L-IntRRT was associated with higher number of RRT-free days through day 28 than IntRRT (mean difference 2.5 days; 95% confidence interval [CI]: -4.79 to -0.27 days; P = 0.028). The likelihood for renal recovery at day 28 was lower in the IntRRT group (OR: 0.49; 95% CI: 0.28-0.87; P = 0.016). CONCLUSION: In hemodynamically stable patients with AKI, intensifying the frequency of IHD from 3 to 6 days per week may be associated with impaired renal recovery.

Single-dose rituximab for recurrent glomerulonephritis post-renal transplant.

BACKGROUND/AIMS: Post-renal transplant recurrent glomerulonephritis (GN) contributes to allograft loss. Rituximab treatment has been used in a multidose strategy with variable efficacy and toxicity. We investigated a novel single-dose approach. METHODS: A single center, retrospective, cohort study was conducted between January 1998 and April 2012 among renal allograft recipients with recurrent GN treated with rituximab (cases) or without (controls). The primary outcome was complete response (CR, urine protein/creatinine ratio (UP/C) <0.3). Secondary outcomes included partial response (PR >50% reduction in UP/C), response relapse, treatment-response by GN type, acute rejection incidence, time to graft loss, and infection incidence. RESULTS: The median dose of rituximab was 200 mg per patient. Of 20 rituximab cases and 13 controls, CR was achieved in eight (40%) versus four (31%), respectively (p = 0.72). Three subjects in each group achieved PR (p = 0.66). Response relapse was similar between the two groups (p = 0.47). Significantly more subjects with recurrent membranous nephropathy (MN) achieved CR with rituximab treatment (p = 0.029). Acute rejection was lower in the rituximab group versus controls (n = 0 vs. 4; p = 0.046). The mean time to graft loss was much later in the rituximab group (35 months, (95% CI 33-37)) versus controls (29 months, (95% CI 24-35)) at 36 months (p = 0.04). There was no infection increase in rituximab-treated subjects (p = 0.16). CONCLUSION: Single-dose rituximab for treatment of recurrent GN was associated with less subsequent rejection and longer time to graft loss without increased infection, but was no more effective than regimens not using rituximab at 36-months except those with recurrent membranous GN.

Cardiac evaluation prior to kidney transplantation.

Kidney transplantation is the treatment of choice for most patients with stage 5 chronic kidney disease and end-stage renal disease (ESRD), offering improved quality of life and overall survival rates. However, the limited supply of available organs makes this a scarce resource. Cardiovascular complications continue to be the leading cause of mortality in the kidney transplant population, accounting for over 30% of deaths with a functioning allograft. Thus, preoperative cardiac risk assessment is critical to optimize patient selection and outcomes. Currently there is no consensus for cardiovascular evaluation in the chronic kidney disease and ESRD population prior to kidney transplantation; the recommendations of the American Society of Nephrology and American Society of Transplantation differ from those of the American Heart Association and the American College of Cardiology. Previously developed risk scores have also been used to risk stratify this population. In this review, we discuss two cases that illustrate the difficulties of interpreting the prognostic value of current testing strategies. We also discuss the importance of different tests for cardiovascular evaluation as well as previous nonkidney transplant specific risk scores used in the pre-kidney transplant population.