Higher rates of rejection in HIV-infected kidney transplant recipients on ritonavir-boosted protease inhibitors: 3-year follow-up study.

Rejection rates in HIV-infected kidney transplant (KTx) recipients are higher than HIV-negative recipients. Immunosuppression and highly active antiretroviral therapy (HAART) protocols vary with potentially significant drug-drug interactions, likely influencing outcomes. This is an IRB-approved, single-center, retrospective study of adult HIV-infected KTx patients between 5/2009 and 12/2014 with 3-year follow-up, excluding antibody-depleting induction. A total of 42 patients were included; median age was 52 years, 81% male, 50% African American, 29% Hispanic, 17% Caucasian. The most common renal failure etiology was hypertensive nephrosclerosis (50%) with 5.8 median years of pre-transplant dialysis. All patients received IL-2 receptor antagonist, were maintained on tacrolimus (76%) or cyclosporine (17%), and 40% received ritonavir-boosted PI-based HAART (rtv+) regimen. Patient and graft survival at 3 years were 93% and 90%. At 1-, 2-, and 3-year time points, median serum creatinine was 1.49, 1.35, and 1.67; treated biopsy-proven rejection was 38%, 38%, and 40.5%; and 92% of episodes were acute rejection. At these time points, rejection rates were significantly higher with boosted PI HAART regimens compared to other HAART regimens, 59% vs 24% (P = 0.029), 59% vs 24% (P = 0.029), and 68% vs 24% (P = 0.01). Despite higher rejection rates, HIV-infected KTx recipients have reasonable outcomes. Given significantly higher rejection rates using rtv+ regimens, alternative HAART regimens should be considered prior to transplantation.

Transplant renal artery stenosis: clinical manifestations, diagnosis and therapy.

Transplant renal artery stenosis (TRAS) is a well-recognized vascular complication after kidney transplant. It occurs most frequently in the first 6 months after kidney transplant, and is one of the major causes of graft loss and premature death in transplant recipients. Renal hypoperfusion occurring in TRAS results in activation of the renin-angiotensin-aldosterone system; patients usually present with worsening or refractory hypertension, fluid retention and often allograft dysfunction. Flash pulmonary edema can develop in patients with critical bilateral renal artery stenosis or renal artery stenosis in a solitary kidney, and this unique clinical entity has been named Pickering Syndrome. Prompt diagnosis and treatment of TRAS can prevent allograft damage and systemic sequelae. Duplex sonography is the most commonly used screening tool, whereas angiography provides the definitive diagnosis. Percutaneous transluminal angioplasty with stent placement can be performed during angiography if a lesion is identified, and it is generally the first-line therapy for TRAS. However, there is no randomized controlled trial examining the efficacy and safety of percutaneous transluminal angioplasty compared with medical therapy alone or surgical intervention.

Histopathology of renal failure after heart transplantation: a diverse spectrum.

BACKGROUND: Chronic kidney disease occurs frequently after heart transplantation and is associated with significant morbidity and mortality. Herein we describe the histopathology associated with renal failure in a cohort of heart transplant recipients. METHODS: Over a 4-year period all patients with an estimated GFR <30 ml/min/1.73 m(2) or significant proteinuria were referred to the kidney transplant clinic for clinical evaluation. A percutaneous renal biopsy was performed as part of a standardized evaluation. RESULTS: Eighteen patients underwent renal biopsy 5.8 ± 4.1 years after transplantation. Hypertension (88.9%), Type 2 diabetes (55.6%) and allograft vasculopathy (38.9%) were prevalent. All patients were receiving calcineurin inhibitors. Mean creatinine was 2.9 ± 1.2 mg/dl with an estimated GFR 27.9 ± 9.1 ml/min/1.73 m(2). Eight patients (44%) had proteinuria >1 g per 24 hours. The major histologic findings were nephrosclerosis plus diabetic glomerulopathy (50%), nephrosclerosis and focal segmental glomerulosclerosis (22.2%) and nephrosclerosis alone (22.2%). One patient had direct CNI toxicity consisting of nodular sub-adventitial hyalinosis. Eleven patients (61.1%) had glomerular disease and 11 patients (61.1%) had moderate or severe tubular atrophy. During follow-up, 5 patients (27.8%) started hemodialysis, 4 (22.2%) died, and 2 (11.1%) received a renal transplant. CONCLUSIONS: We observed diverse histologic patterns in this series of renal biopsies suggesting that chronic kidney disease after heart transplantation has a complex and varied pathologic basis. Further defining the renal injuries that precede heart transplantation and predispose to the progression of kidney disease after transplant may assist in treating this population.

Antibodies reactive to non-HLA antigens in transplant glomerulopathy.

Although T and B cell alloimmunity contribute to transplant injury, autoimmunity directed at kidney-expressed, non-HLA antigens may also participate. Because the specificity, prevalence, and importance of antibodies to non-HLA antigens in late allograft injury are poorly characterized, we used a protein microarray to compare antibody repertoires in pre- and post-transplant sera from several cohorts of patients with and without transplant glomerulopathy. Transplantation routinely induced changes in antibody repertoires, but we did not identify any de novo non-HLA antibodies common to patients with transplant glomerulopathy. The screening studies identified three reactivities present before transplantation that persisted after transplant and strongly associated with transplant glomerulopathy. ELISA confirmed that reactivity against peroxisomal-trans-2-enoyl-coA-reductase strongly associated with the development of transplant glomerulopathy in independent validation sets. In addition to providing insight into effects of transplantation on non-HLA antibody repertoires, these results suggest that pretransplant serum antibodies to peroxisomal-trans-2-enoyl-coA-reductase may predict prognosis in kidney transplantation.

Rapidly progressive recurrent hepatitis C virus infection starting 9 days after liver transplantation.

Early histological recurrence of hepatitis C after liver transplantation (LT) has a negative impact on patient and graft survival. We report a case of histological recurrence of HCV occurring in the second week after LT. A 75-year-old woman with chronic HCV and hepatocellular carcinoma underwent LT with an organ from a 75-year-old HCV-negative deceased donor. After an uneventful early postoperative period, an increase in the transaminases was observed, and on postoperative day 9 day, the alanine aminotransferase (ALT) was 673 IU/mL and aspartate aminotransferase (AST) 300 IU/mL, with normal alkaline phosphatase and bilirubin. Analysis of liver biopsy samples showed diffuse necroinflammatory changes with acidophilic bodies and concomitant mild acute cellular rejection. Subsequently there was a further increase in the transaminases, and on postoperative day 13, the AST rose to 445 IU/mL and ALT to 992 IU/mL. Repeat biopsy was performed, and analysis of the samples revealed lymphocytic portal inflammation with lymphoid aggregates and mild interface hepatitis, parenchymal necrosis, activation of sinusoidal lining cells, and mild steatosis. The biopsy sample was characteristic for HCV recurrence. The HCV RNA level was 84,000,000 copies/mL, and markers for other viral causes were not present. The patient became jaundiced and her course progressively worsened. She died on day 87 after transplantation. To our knowledge, this is the earliest reported case of histological recurrence of HCV after LT. It illustrates the importance of older donor and recipient age in the same patient as cofactors for early HCV recurrence and poor outcome.

Recurrent hepatic sarcoidosis post-liver transplantation manifesting with severe hypercalcemia: a case report and review of the literature.

Sarcoidosis is a systemic granulomatous disease primarily involving the lungs, lymph nodes, skin, eyes and nervous system; liver involvement is asymptomatic in most cases. However, once the patient develops clinical symptoms liver disease is usually progressive and may necessitate orthotopic liver transplantation. There are a few reports of asymptomatic recurrent sarcoidosis developing within the liver allograft. We report a case of early recurrence of sarcoidosis in the liver allograft diagnosed on biopsy in a patient who presented with severe hypercalcemia, kidney dysfunction, and increase in size of abdominal lymph nodes. The liver chemistry tests were within normal limits. The patient responded well to steroid treatment by normalizing serum calcium and creatinine levels and reducing lymph node size. To date, there has been no report in the literature of symptomatic recurrence of hepatic sarcoidosis following orthotopic liver transplantation.