Recurrent glomerulonephritis after kidney transplantation: a practical approach.

PURPOSE OF REVIEW: This review will provide a practical approach in the assessment of kidney failure patients with primary glomerulonephritides (GN) being considered for kidney transplantation, focusing on high-risk subtypes of immunoglobulin A nephropathy, focal segmental glomerulosclerosis, idiopathic membranous glomerulonephritis and membranoproliferative glomerulonephritis. RECENT FINDINGS: Recurrent glomerulonephritis remains one of the most common causes of allograft loss in kidney transplant recipients. Although the epidemiology and clinical outcomes of glomerulonephritis recurrence occurring after kidney transplantation are relatively well-described, the natural course and optimal treatment strategies of recurrent disease in kidney allografts remain poorly defined. With a greater understanding of the pathophysiology and treatment responses of patients with glomerulonephritis affecting the native kidneys, these discoveries have laid the framework for the potential to improve the management of patients with high-risk glomerulonephritis subtypes being considered for kidney transplantation. SUMMARY: Advances in the understanding of the underlying immunopathogenesis of primary GN has the potential to offer novel therapeutic options for kidney patients who develop recurrent disease after kidney transplantation. To test the efficacy of novel treatment options in adequately powered clinical trials requires a more detailed understanding of the clinical and histological characteristics of kidney transplant recipients with recurrent glomerulonephritis.

Kidney Donor Profile Index and allograft outcomes: interactive effects of estimated post-transplant survival score and ischaemic time.

Background: The Kidney Donor Profile Index (KDPI) is routinely reported by the donation agencies in Australia. We determined the association between KDPI and short-term allograft loss and assessed if this association was modified by the estimated post-transplant survival (EPTS) score and total ischaemic time. Methods: Using data from the Australia and New Zealand Dialysis and Transplant Registry, the association between KDPI (in quartiles) and 3-year overall allograft loss was examined using adjusted Cox regression analysis. The interactive effects between KDPI, EPTS score and total ischaemic time on allograft loss were assessed. Results: Of 4006 deceased donor kidney transplant recipients transplanted between 2010 and 2015, 451 (11%) recipients experienced allograft loss within 3 years post-transplant. Compared with recipients of kidneys with a KDPI of 0-25%, recipients who received donor kidneys with a KDPI >75% experienced a 2-fold increased risk of 3-year allograft loss {adjusted hazard ratio [HR] 2.04 [95% confidence interval (CI) 1.53-2.71]}. The adjusted HRs for kidneys with a KDPI of 26-50% and 51-75% were 1.27 (95% CI 0.94-1.71) and 1.31 (95% CI 0.96-1.77), respectively. There were significant interactions between KDPI and EPTS scores (P-value for interaction <.01) and total ischaemic time (P-value for interaction <.01) such that the associations between higher KDPI quartiles and 3-year allograft loss were strongest in recipients with the lowest EPTS scores and longest total ischaemic time. Conclusion: Recipients with higher post-transplant expected survival and transplants with longer total ischaemia who received donor allografts with higher KDPI scores experienced a greater risk of short-term allograft loss compared with those recipients with reduced post-transplant expected survival and with shorter total ischemia.

Global Epidemiology, Health Outcomes, and Treatment Options for Patients With Type 2 Diabetes and Kidney Failure.

The burden of type 2 diabetes and related complications has steadily increased over the last few decades and is one of the foremost global public health threats in the 21st century. Diabetes is one of the leading causes of chronic kidney disease and kidney failure and is an important contributor to the cardiovascular morbidity and mortality in this population. In addition, up to one in three patients who have received kidney transplants develop post-transplant diabetes, but the management of this common complication continues to pose a significant challenge for clinicians. In this review, we will describe the global prevalence and temporal trend of kidney failure attributed to diabetes mellitus in both developing and developed countries. We will examine the survival differences between treated kidney failure patients with and without type 2 diabetes, focusing on the survival differences in those on maintenance dialysis or have received kidney transplants. With the increased availability of novel hypoglycemic agents, we will address the potential impacts of these novel agents in patients with diabetes and kidney failure and in those who have developed post-transplant diabetes.

Theoretical versus Ex Vivo Assessment of Radiation Damage Repair: An Investigation in Normal Breast Tissue.

In vivo validation of models of DNA damage repair will enable their use for optimizing clinical radiotherapy. In this study, a theoretical assessment was made of DNA double-strand break (DSB) induction in normal breast tissue after intraoperative radiation therapy (IORT), which is now an accepted form of adjuvant radiotherapy for selected patients with early breast cancer. DSB rates and relative biological effectiveness (RBE) were calculated as a function of dose, radiation quality and dose rate, each varying based on the applicator size used during IORT. The spectra of primary electrons in breast tissue adjacent to each applicator were calculated using measured X-ray spectra and Monte Carlo methods, and were used to inform a Monte Carlo damage simulation code. In the absence of repair, asymptotic RBE values (relative to (60)Co) were approximately 1.5. Beam-quality changes led to only minor variations in RBE among applicators, though differences in dose rate and overall dose delivery time led to larger variations and a rapid decrease in RBE. An experimental assessment of DSB induction was performed ex vivo using pre- and postirradiation tissue samples from patients receiving breast intraoperative radiation therapy. Relative DSB rates were assessed via γ-H2AX immunohistochemistry using proportional staining. Maximum-likelihood parameter estimation yielded a DSB repair halftime of 25.9 min (95% CI, 21.5-30.4 min), although the resulting model was not statistically distinguishable from one where there was no change in DSB yield among patients. Although the model yielded an in vivo repair halftime of the order of previous estimates for in vitro repair halftimes, we cannot conclude that it is valid in this context. This study highlights some of the uncertainties inherent in population analysis of ex vivo samples, and of the quantitative limitations of immunohistochemistry for assessment of DSB repair.