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The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34-70 years), median creatinine of 1.2 mg/dL (0.66-1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post-kidney transplant patients with chronic HCV infection.

“In the long run,” the economist John Maynard Keynes wryly observed in his 1923 A Tract on Monetary Reform , “we are all dead.” Given the logistic barriers to performing long-term studies of immunosuppression in kidney-transplant recipients, as well as the associated expense, many transplant professionals are similarly pessimistic about how to determine adequate long-term regimens in the current era, in which short-term results are excellent but late transplant loss remains a vexing problem. More than 14,000 of the 101,000 patients listed for kidney transplantation are awaiting repeat transplantation. 1 Mechanisms of late transplant loss remain under investigation; toxic effects of . . .

Among patients with short bowel syndrome who commonly have kidney disease, kidney transplantation remains challenging. We describe the clinicopathologic course of a 59-year old man with short bowel syndrome secondary to Crohn’s disease who underwent a deceased donor kidney transplant that was complicated by recurrent acute kidney allograft injury due to volume depletion from diarrhea, ultimately requiring the placement of permanent intravenous access for daily volume expansion at home resulting in the recovery of allograft function. Teduglutide treatment at 1.8 years post-transplant led to a dramatic decrease in diarrhea. A literature review of similar cases yielded 18 patients who underwent 19 kidney transplants. Despite high rates of complications, at the time of last follow-up (median 2.1 years [0.04-7]), 94% of the patients were still alive and 89% had functioning allografts, with a median eGFR of 37.5 [14-122] ml/min/1.73m2. In conclusion, despite high rates of complications, kidney transplantation in patients with short bowel syndrome is associated with acceptable short- and midterm outcomes. Further, we report for the first time the effects of the glucagon-like peptide-2 analogue teduglutide for short bowel syndrome in a kidney transplant recipient.

BackgroundRenal transplantation is the optimal treatment for selected patients with end-stage renal disease (ESRD). However, the survival benefit of renal transplantation among patients with ESRD attributed to granulomatosis with polyangiitis (GPA) is unknown.MethodsWe identified patients from the United States Renal Data System with ESRD due to GPA (ESRD-GPA) between 1995 and 2014. We restricted our analysis to waitlisted subjects to evaluate the impact of transplantation on mortality. We followed patients until death or the end of follow-up. We compared the relative risk (RR) of all-cause and cause-specific mortality in patients who received a transplant versus non-transplanted patients using a pooled logistic regression model with transplantation as a time-varying exposure.ResultsDuring the study period, 1525 patients were waitlisted and 946 received a renal transplant. Receiving a renal transplant was associated with a 70% reduction in the risk of all-cause mortality in multivariable-adjusted analyses (RR=0.30, 95% CI 0.25 to 0.37), largely attributed to a 90% reduction in the risk of death due to cardiovascular disease (CVD) (RR=0.10, 95% 0.06–0.16).DiscussionRenal transplantation is associated with a significant decrease in all-cause mortality among patients with ESRD attributed to GPA, largely due to a decrease in the risk of death to CVD. Prompt referral for transplantation is critical to optimise outcomes for this patient population.

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Background: Intradialytic hypotensive events are common among hemodialysis patients and are associated with a variety of patient- and procedure-related factors, including intradialytic decline in plasma osmolality. Prior studies and practice have suggested that administration of osmotically active drugs may ameliorate blood pressure decline during chronic hemodialysis. Methods: Clinical and treatment data were collected for 102 consecutive patients requiring initiation of renal replacement therapy in 2 major teaching hospitals. Routine administration of mannitol differed according to institutional protocols, allowing its examination as the primary exposure of interest. Generalized linear models were fit to estimate associations of mannitol use during dialysis initiation with intradialytic blood pressure, as assessed by: (1) intradialytic blood pressure decline; (2) nadir intradialytic blood pressure; (3) absolute systolic blood pressure <90 mm Hg or decline >20 mm Hg. Results: Mean age was 62 years (±16), 70% were male and 44% were diabetic. Mean predialysis and nadir systolic blood pressure were 142 mm Hg (±29) and 121 mm Hg (±26), respectively. Mannitol administration was associated with a lesser decline in intradialytic blood pressure, a higher nadir blood pressure and fewer hypotensive events requiring intervention. No effect modification was evident according to diabetes or acuity of kidney disease (chronic vs. acute). Conclusions: Mannitol administration appears to preserve hemodynamic stability during hemodialysis initiation. Randomized controlled trials are needed to confirm these findings and identify optimal management strategies to prevent intradialytic hypotension.

Primary mitochondrial diseases (MD) are complex, heterogeneous inherited diseases caused by mutations in either the mitochondrial or nuclear DNA. Glomerular diseases in MD have been reported with tRNA mutation m.3243A>G causing a syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). We describe here a case of focal segmental glomerulosclerosis (FSGS) associated with a new tRNA mutation site. A 34-year-old man with a history of living related kidney transplantation, diabetes, hearing loss, and developmental delay presented to the outpatient clinic with complaints of new behavioral difficulties, worsening symptoms, and brain involvement on imaging. Physical examination was remarkable for difficulty hearing, a pattern of dysarthric speech, and cerebellar gait. Laboratory investigations including lactate levels were unremarkable. Based on this set of clinical circumstances, concern for an underlying genetic abnormality was raised. Multiple metabolic tests were unremarkable. Whole exome sequencing revealed a mitochondrial MT-TW tRNA change at position m.5538G>A. Genotype-phenotype correlations are consistent with this tRNA mutation as a cause of his symptoms. To the best of our knowledge, this is the first case describing FSGS-associated MD caused by an m.5538 G>A mutation. Consideration of an underlying MD should be made in patients presenting with deafness, neurologic changes, diabetes, and renal failure.

Hydroxocobalamin is a recently approved antidote for the treatment of cyanide poisoning. The case presented involves a young patient administered empiric hydroxocobalamin due to suspected cyanide overdose. Due to the development of acute kidney injury and severe metabolic derangement, emergent hemodialysis was initiated. Unfortunately, hemodialysis was confounded by a recurrent \"blood leak\" alarm. This unforeseen effect was secondary to interference from hydroxocobalamin. Hydroxocobalamin causes orange/red discoloration of bodily fluids and permeates the dialysate. This leads to defraction of light in the effluent path of the blood leak detector from discolored dialysate, which can result in activation of the blood leak alarm and an inability to continue hemodialysis treatment. This case highlights several new and emerging critical concerns with this medication, including the potential consequence of delayed initiation of emergent renal replacement therapy with empiric administration, the need for increased awareness among clinicians of various disciplines, and the need for multidisciplinary communication.

Although many expatriates find overseas assignments exciting, all of them experience some degree of disorientation, confusion and anxiety as they adjust to their host country's culture. In addition to the challenges of a foreign language and society, expatriates often find themselves on a journey of self-discovery. HR professionals should be aware of the challenges of expatriate life and help prepare employees for these challenges by offering a full employee assistance program (EAP) with specialized counseling for expatriates. HR professionals can expect the following stages of cultural adjustment: 1. honeymoon, 2. rejection, 3. regression, and 4. cultural adjustment. By being well-prepared and maintaining a positive attitude, employees and their families can experience a joyful and satisfying assignment. HR professionals need to be aware of the stages of culture adjustment, as well as ways to help employees during their transitions.