Mary Ann Lim

Successful Treatment of Hepatitis C in Renal Transplant Recipients With Direct-Acting Antiviral Agents.

The direct‐acting antivirals (DAAs) constitute an emerging group of small molecule inhibitors that effectively treat hepatitis C virus (HCV) infection, a common comorbidity in end‐stage renal disease patients. To date, there are no data to guide use of these agents in kidney transplant patients. The authors collected data from 20 consecutive kidney recipients treated with interferon‐free treatment regimens for HCV at their center: 88% were infected with genotype 1; 50% had biopsy‐proved advanced hepatic fibrosis on their most recent liver biopsy preceding treatment (Metavir stage 3 fibrosis [F3] or F4); and 60% had failed treatment pretransplantation with interferon‐based therapy. DAA treatment was initiated a median of 888 days after renal transplantation. All patients cleared the virus while on therapy, and 100% have achieved a sustained virologic response at 12 weeks after completion of DAA therapy. The most commonly used regimen was sofosbuvir 400 mg daily in combination with simeprevir 150 mg daily. However, four different treatment approaches were used, with comparable results. The DAAs were well tolerated, and less than half of patients required calcineurin inhibitor dose adjustment during treatment. Eradication of HCV infection with DAAs is feasible after kidney transplantation with few treatment‐related side effects.

Determinants of the Decision to Accept a Kidney from a Donor at Increased Risk for Blood-Borne Viral Infection

BACKGROUND AND OBJECTIVES The use of kidneys from donors at increased risk for viral infections (DIRVI) such as HIV could increase the number of transplants and decrease waiting times. This study aimed to identify the proportion of kidney transplant candidates that would accept a kidney from a DIRVI and the factors that influenced this decision. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Conjoint analysis was used to assess the conditions in which renal transplant candidates would accept a DIRVI kidney. Candidates completed 12 scenarios in which the waiting time for a kidney, the donor age as a surrogate for kidney quality, and the risk of contracting HIV were systematically varied. RESULTS Among 175 respondents, 42 (24.0%) rejected DIRVI kidneys under all conditions, 103 (58.9%) accepted DIRVI kidneys under some conditions, and 31 (17.7%) always accepted DIRVI kidneys. In multivariable logistic regression, patients were more likely to accept a DIRVI kidney when waiting time was longer, the donor was younger, and HIV risk was lower (P < 0.01 for each variable). Patients on dialysis (P < 0.01) and older patients (P = 0.04) more commonly accepted DIRVI kidneys, but self-rated sense of health was not associated with DIRVI kidney acceptance. CONCLUSIONS Most renal transplant candidates would accept a DIRVI kidney under some circumstances. These findings suggest that recipients can be allowed to make prospective choices regarding DIRVI kidney acceptance without hindering placement of these organs.

Immunosuppression for kidney transplantation: Where are we now and where are we going?

Advances in immunosuppression have propelled kidney transplantation from a scientific curiosity to the optimal treatment for patients with end stage kidney disease. Declining rates of acute rejection have led to improvements in short term kidney transplant survival, culminating in incrementally better long term patient and allograft outcomes. Contextualized around established immune-suppressing drug targets, this review summarizes the history of the clinical science and highlights the pivotal trials that have led to present-day treatment standards at the level of both individual agents and multidrug regimens for kidney recipients. Finally, recently approved and emerging therapies are discussed, with an emphasis on challenges faced by clinicians managing this increasingly complex patient population.

Development of proteinuria and focal segmental glomerulosclerosis during direct-acting antiviral therapy for hepatitis C virus infection

Focal segmental glomerulosclerosis (FSGS) is a clinicopathologic diagnosis made in patients with proteinuria who exhibit focal glomerular scarring and podocyte injury on kidney biopsy and is associated with high rates of renal disease progression over time. We recently observed 3 patients with hepatitis C virus (HCV) infection, solid organ transplantation, and normal baseline kidney function who developed proteinuria during treatment with direct-acting antiviral (DAA) therapies and whose kidney biopsies demonstrated FSGS without immune complex or cryoglobulinemic glomerulonephritis (Table 1).

Comparing Outcomes between Antibody Induction Therapies in Kidney Transplantation

Kidney transplant recipients often receive antibody induction. Previous studies of induction therapy were often limited by short follow-up and/or absence of information about complications. After linking Organ Procurement and Transplantation Network data with Medicare claims, we compared outcomes between three induction therapies for kidney recipients. Using novel matching techniques developed on the basis of 15 clinical and demographic characteristics, we generated 1:1 pairs of alemtuzumab-rabbit antithymocyte globulin (rATG) (5330 pairs) and basiliximab-rATG (9378 pairs) recipients. We used paired Cox regression to analyze the primary outcomes of death and death or allograft failure. Secondary outcomes included death or sepsis, death or lymphoma, death or melanoma, and healthcare resource utilization within 1 year. Compared with rATG recipients, alemtuzumab recipients had higher risk of death (hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 1.03 to 1.26; P<0.01) and death or allograft failure (HR, 1.18; 95% CI, 1.09 to 1.28; P<0.001). Results for death as well as death or allograft failure were generally consistent among elderly and nonelderly subgroups and among pairs receiving oral prednisone. Compared with rATG recipients, basiliximab recipients had higher risk of death (HR, 1.08; 95% CI, 1.01 to 1.16; P=0.03) and death or lymphoma (HR, 1.12; 95% CI, 1.01 to 1.23; P=0.03), although these differences were not confirmed in subgroup analyses. One-year resource utilization was slightly lower among alemtuzumab recipients than among rATG recipients, but did not differ between basiliximab and rATG recipients. This observational evidence indicates that, compared with alemtuzumab and basiliximab, rATG associates with lower risk of adverse outcomes, including mortality.

Should living kidney donors with hypertension be considered for organ donation

Purpose of reviewThe large number of end-stage kidney disease patients waiting for a kidney transplant often means years of delay before a suitable organ becomes available. Living kidney donors are one way to circumvent such long waiting times, and the desire to increase the pool of living kidney donors has allowed the selection of donors with hypertension. Recent findingsHypertensive kidney donors, despite having larger glomeruli, and fewer glomeruli, particularly when over the age of 50 years, do well in follow-up. The data are mainly in white living kidney donors whose preexisting hypertension has been well controlled [blood pressure (BP) <140/90 mmHg] on one or two antihypertensive medications. Those selected for donation do as well as nonhypertensive donors as long they are older (age >50 years), nonobese (BMI 26–30 kg/m2), and have no evidence of end-organ damage prior to donation. SummaryAlthough the data supporting long-term safety of nephrectomy in hypertensive donors are modest, small studies with short-term follow-up suggest no increase in the incidence of kidney disease or worsening of the control of hypertension in donors with a history of high BP.

Histopathologic changes in anti-angiotensin II type 1 receptor antibody-positive kidney transplant recipients with acute rejection and no donor specific HLA antibodies

OBJECTIVE To determine the association of antibodies against angiotensin II type 1 receptor (AT1R Ab) and histopathologic changes seen in patients with kidney allograft rejection and negative donor specific HLA antibodies (DSA). METHODS Stored sera from 27 patients who had biopsy-proven rejection in the absence of DSA were tested for AT1R Ab. Biopsy slides of all patients were re-examined and classified according to Banff 2013 criteria. Histopathologic changes were compared between AT1R positive and negative patients. RESULTS 75% of patients with positive pre-transplant AT1R Ab had antibody mediated rejection (AMR) compared to 37% of AT1R Ab-negative patients. A trend towards increased interstitial inflammation was observed in the AT1R Ab positive group (p=0.08). More patients in the AT1R Ab positive group had microcirculation inflammation (88% vs 58% with glomerulitis scores ≥1; 75% vs 58% with peritubular capillaritis scores ≥1). CONCLUSION In kidney transplant recipients with rejection and no DSA, a higher incidence of AMR and worse inflammation scores are observed in the presence of positive pre-transplant AT1R antibodies.

Safety and Feasibility of Outpatient Rabbit Antithymocyte Globulin Induction Therapy Administration in Kidney Transplant Recipients

Kidney transplant induction therapy often includes inpatient administration of rabbit antithymocyte globulin (rATG) over multiple days. To reduce hospital length of stay (LOS) and drug expenditures, the rATG induction course was completed in the outpatient setting via peripheral intravenous administration. The present study assesses early readmission trends ascribable to an outpatient rATG administration protocol to ensure initial reduction in hospital LOS is sustained early after discharge.

Evaluation of allergy to tacrolimus in kidney transplant candidates and recipients with a history of macrolide antibiotic allergy

Concern has been raised over using tacrolimus for maintenance immunosuppression in kidney transplant recipients with known allergies to macrolide antibiotics, such as azithromycin, clarithromycin and erythromycin. Allergic reactions to macrolide antibiotics are rare and are reported in 0.4%-3% of treatments.1 While tacrolimus is a macrolide drug, the chemical structure substantially differs from that of macrolide antibiotics (23-versus 14 or 15-membered lactone ring, respectively). 1 Only one case of cross-sensitivity between tacrolimus and clarithromycin has been reported.2 The study aim was to determine if kidney transplant candidates and recipients with a reported macrolide antibiotic allergy also display an allergic reaction to oral tacrolimus. This article is protected by copyright. All rights reserved.