Obesity affects graft function but not graft loss in kidney transplant recipients

Background: There is an ongoing debate regarding the suitability for transplantation of the high Body Mass Index (BMI) kidney transplant recipients (KTRs). Methods: Retrospective analysis of 370 consecutive KTRs stratified according to the World Health Organisation Body Mass Index categories. As a measure of allograft function eGFR was used. Results: Mean BMI was 26.2: 148 (40%) pre-obese, 47 (12.7%) class I obese, 11 (3%) class II obese, 9 (2.4%) class III obese. A linear trend from the normal BMI group moving through the progressively higher groups was observed for male sex and younger age. Overweight and obese KTRs had higher incidence of pre-transplant diabetes (P = 0.021), but there was no difference in new-onset hyperglycemia post-transplant (P = 0.35). Obesity was not a significant risk factor for lower eGFR at 1 year follow-up, but it became at 2 and 3 years follow up. No statistical difference in Delayed Graft Function and hospital length of stay was observed. 28 patients lost their grafts, and 25 patients died during follow-up. Kaplan-Meier analysis showed no difference in all-cause allograft loss between the different BMI groups (log rank P = 0.8) in a mean follow-up of 42 months (0-58). Conclusion: Obesity affects eGFR in the long-term. The allograft survival was lower but not significant

Technical considerations when designing a gene expression panel for renal transplant diagnosis

Gene expression analysis is emerging as a new diagnostic tool in transplant pathology, in particular for the diagnosis of antibody-mediated rejection. Diagnostic gene expression panels are defined on the basis of their pathophysiological relevance, but also need to be tested for their robustness across different preservatives and analysis platforms. The aim of this study is the investigate the effect of tissue sampling and preservation on candidate genes included in a renal transplant diagnostic panel. Using the NanoString platform, we compared the expression of 219 genes in 51 samples, split for formalin-fixation and paraffin-embedding (FFPE) and RNAlater preservation (RNAlater). We found that overall, gene expression significantly correlated between FFPE and RNAlater samples. However, at the individual gene level, 46 of the 219 genes did not correlate across the 51 matched FFPE and RNAlater samples. Comparing gene expression results using NanoString and qRT-PCR for 18 genes in the same pool of RNA (RNAlater), we found a significant correlation in 17/18 genes. Our study indicates that, in samples from the same routine diagnostic renal transplant biopsy procedure split for FFPE and RNAlater, 21% of 219 genes of potential biological significance do not correlate in expression. Whether this is due to fixatives or tissue sampling, selection of gene panels for routine diagnosis should take this information into consideration

Rituximab or Alemtuzumab Induction for ABO Incompatible Renal Transplantation?

Immunopathology of vascular and renal diseases and of organ and celltransplantatio

Mycophenolate mofetil therapy in immunoglobulin A nephropathy: histological changes after treatment

Background Endocapillary hypercellularity independently predicts renal outcome in immunoglobulin A nephropathy (IgAN). Mycophenolate mofetil (MMF) treatment is offered to patients presenting to the Imperial College Renal and Transplant Centre with IgAN and histological evidence of endocapillary hypercellularity. Clinical trials of MMF in IgAN have been inconclusive and have been limited by a lack of specific histological inclusion and exclusion criteria when recruiting patients. Evidence of histological improvement following MMF treatment would support its therapeutic use. We therefore reviewed histological changes after MMF therapy in a cohort of IgAN patients. Method Eighteen IgAN patients with native renal biopsies before and after repeated MMF treatment were identified. Patients were excluded if they had received any other immunosuppressive therapy, including corticosteroids. On the basis of the Oxford Classification of IgAN, we reviewed histological changes after MMF treatment. Results Nine patients (50%) were male. At diagnostic renal biopsy, the median age was 35 years [interquartile range (IQR) 30–41], serum creatinine was 97 µmol/L (IQR 79–153) and urine protein creatinine ratio (UPCR) was 146 mg/mmol (IQR 98–212). The median time between biopsies was 24 months (range 9–41). Following MMF treatment, repeat biopsy demonstrated statistically significant improvement in the mean percentage of glomeruli showing endocapillary hypercellularity and cellular/fibrocellular crescents. There was no change in mesangial hypercellularity, segmental sclerosis or tubular atrophy scores. Mesangial IgA deposition was also significantly reduced. Histopathological improvement persisted after the cessation of MMF therapy, suggesting that 2 years of treatment is adequate for benefit. The median serum creatinine remained stable at 3 years follow-up at 104 µmol/L (IQR 79–147). Conclusion MMF treatment is associated with histopathological improvement in IgAN