Comparison of outcomes with vancomycin or metronidazole for mild-to-moderate Clostridium difficile associated diarrhea among solid organ transplant recipients: A retrospective cohort study.

BACKGROUND: Current guidelines recommend oral vancomycin or fidaxomicin for the treatment of mild-to-moderate Clostridium difficile associated diarrhea (CDAD), while metronidazole is recommended as an alternative when oral vancomycin and fidaxomicin are unavailable. However, data are lacking among the solid organ transplant (SOT) population. METHODS: This single center, retrospective cohort study evaluated adult SOT recipients with mild-to-moderate CDAD. Analysis 1 evaluated patients receiving initial therapy with metronidazole vs oral vancomycin for at least 72 hours. Analysis 2 evaluated patients receiving metronidazole vs oral vancomycin for at least 70% of the treatment duration. The primary outcome was treatment failure. Secondary outcomes included CDAD recurrence and all-cause mortality. RESULTS: Analysis 1 included 71 patients (metronidazole n = 50, oral vancomycin n = 21) and analysis 2 included 75 patients (metronidazole n = 42, oral vancomycin n = 33). No significant differences in C. difficile risk factors were observed between groups in either analysis. However, in both analyses, more patients in the oral vancomycin arm received antibiotics during the CDAD episode (analysis 1, 52% vs 26%, P = .03; analysis 2, 55% vs 32%, P < .01). Neither analysis demonstrated differences in treatment failure (analysis 1, metronidazole 16%, oral vancomycin 10%, P = .71; analysis 2, metronidazole 2%, oral vancomycin 6%, P = .58). CDAD recurrence and all-cause mortality were similar across groups in both analyses. CONCLUSIONS: Results suggest that both metronidazole and oral vancomycin are reasonable options for the treatment of mild-to-moderate CDAD in patients with SOT. No difference in treatment failure was observed; however, oral vancomycin may be preferred for higher risk patients, such as those receiving concurrent antibiotics.

Antibody-Mediated Rejection: A Review.

BACKGROUND: Chronic antibody injury is a serious threat to allograft outcomes and is therefore the center of active research. In the continuum of allograft rejection, the development of antibodies plays a critical role. In recent years, an increased recognition of molecular and histologic changes has provided a better understanding of antibody-mediated rejection (AMR), as well as potential therapeutic interventions. However, several pathways are still unknown, which accounts for the lack of efficacy of some of the currently available agents that are used to treat rejection. METHODS: We review the current diagnostic criteria for AMR; AMR paradigms; and desensitization, treatment, and prevention strategies. RESULTS: Chronic antibody-mediated endothelial injury results in transplant glomerulopathy, manifested as glomerular basement membrane duplication, double contouring, or splitting. Clinical manifestations of AMR include proteinuria and a rise in serum creatinine. Current strategies for the treatment of AMR include antibody depletion with plasmapheresis (PLEX), immunoadsorption (IA), immunomodulation with intravenous immunoglobulin (IVIG), and T cell- or B cell-depleting agents. Some treatment benefits have been found in using PLEX and IA, and some small nonrandomized trials have identified some benefits in using rituximab and the proteasome inhibitor-based therapy bortezomib. More recent histologic follow-ups of patients treated with bortezomib have not shown significant benefits in terms of allograft outcomes. Furthermore, no specific treatment approaches have been approved by the US Food and Drug Administration. Other agents used for more difficult rejections include bortezomib and eculizumab (an anti-C5 monoclonal antibody). CONCLUSION: AMR is a fascinating field with ample opportunities for research and progress in the future. Despite the use of advanced techniques for the detection of human leukocyte antigen (HLA) or non-HLA donor-specific antibodies, alloimmune response remains an important barrier for successful long-term allograft function. Treatment of AMR with currently available therapies has produced a variety of results, some of them suboptimal, precluding the development of standardized protocols. New therapies are promising, but randomized controlled trials are needed to find surrogate markers and improve the efficacy of therapy.

Role of Special Coagulation Studies for Preoperative Screening of Thrombotic Complications in Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: Vascular thrombosis is a well-known complication after simultaneous pancreas-kidney (SPK) transplantation procedures. The role of preoperative special coagulation studies to screen patients at high risk for vascular thrombosis is unclear and not well studied. METHODS: This study reports a retrospective medical record review of 83 SPK procedures performed between April 2007 and June 2013 in a single institution. All SPK transplantation recipients underwent preoperative screening for hypercoagulable state. RESULTS: Eighteen of 83 patients (21.69%) were diagnosed with vascular thrombosis of the pancreas. Of the 23 patients with at least 1 positive screening test, only 4 had a thrombotic event (17.39%). On the other hand, 14 of 60 patients with negative screening tests developed vascular thrombosis (23.33%). The hypercoagulable screening workup had a positive predictive value of 17.39% and a negative predictive value of 76.67%. The workup also demonstrated low sensitivity (22.22%) and specificity (70.77%). CONCLUSION: No differences were seen in patient or graft survival between groups at 12 months. This retrospective study did not show any benefit of using special coagulation studies to rule out patients at risk for vascular thrombosis after SPK transplantation.

Posttransplant nephrocalcinosis is associated with poor renal allograft function: a single-center experience.

BACKGROUND: Nephrocalcinosis, characterized by intratubular and/or parenchymal deposition of calcium phosphate and calcium oxalate crystals, is frequently seen in renal allograft biopsies; however, the clinical consequence of this histologic finding remains unknown. Kidney transplant recipients with good allograft function usually demonstrate improvement in biochemical parameters; however, persistent hyperparathyroidism remains prevalent in this population of patients. We identified renal allografts with nephrocalcinosis and evaluated the effects on renal allograft function and survival. METHODS: We conducted a single-center, retrospective review of kidney allograft biopsies performed at our center from December 1, 2006 to November 30, 2012. Biopsies with nephrocalcinosis as the primary diagnosis were included in the final analysis. Biochemical parameters at the time of biopsy included serum creatinine, phosphate, calcium, intact parathyroid hormone (iPTH), 25-hydroxy vitamin D, and albumin. Serum creatinine was measured at 1, 3, 6, and 12 months after nephrocalcinosis was diagnosed. The use of calcimimetics, vitamin D analogs, active vitamin D, and bisphosphonates was also reviewed. RESULTS: We identified 12 patients with nephrocalcinosis as the primary diagnosis on renal biopsy. The average age of these patients was 52.2 ± 11.9 years, and the average time since transplantation was 2.3 ± 2.7 years. The baseline serum creatinine was 1.37 ± 0.4 mg/dL before the onset of acute kidney injury (AKI). Mean iPTH and 25-hydroxy vitamin D at the time of AKI were 495.66 ± 358.9 pg/mL and 19.9 ± 13.3 ng/mL, respectively. Renal function deteriorated in all patients, and mean serum creatinine at 12-month follow up was 2.37 ± 1.3 mg/dL (P=0.028). One patient progressed to end-stage renal disease at the end of the study period. CONCLUSION: The histologic finding of nephrocalcinosis is associated with poor renal allograft function. Metabolic abnormalities including hyperparathyroidism persist in renal allograft recipients despite normal allograft function and may be associated with the development of nephrocalcinosis in renal transplant recipients.

Late recurrence of light chain deposition disease after kidney transplantation treated with bortezomib: a case report.

BACKGROUND: Light chain deposition disease (LCDD) recurs frequently after renal transplantation with variable presentation. CASE REPORT: We report the case of a 67-year-old Caucasian female with recurrence of LCDD after living-donor kidney transplantation. Bone marrow biopsy revealed kappa light chain-restricted population of plasma cells, and the patient met the criteria for multiple myeloma. Her renal function progressively worsened and she became dialysis dependent. She received 1 cycle of bortezomib along with intravenous dexamethasone. She was able to discontinue dialysis within 2 months, and at 1 year follow-up her renal function was stable. CONCLUSION: Bortezomib has a role in the treatment of recurrent LCDD and multiple myeloma in kidney transplant patients. As opposed to traditional regimens, a short course may be beneficial.

Severe hepatitis C infection in a renal transplant recipient following hepatitis C genotype mismatch transplant.

We report a case of a 32-year-old female with histologically and clinically inactive chronic hepatic C infection, who received a cadaveric renal transplant from a hepatitis C-positive donor with a different genotype. The genotype mismatch (genotype 1 to genotype 2) and change to tacrolimus-based immunosuppression resulted in severe hepatitis C infection characterized by a 10-fold increase in transaminase levels and grade 3 inflammation histologically. Our report highlights the risk of genotype-mismatch transplants in solid organ transplantation.