Post-transplant glomerulopathy impact in renal graft survival

Introduction: Primary glomerulopathy is cause of renal chronic disease in renal transplant recipients (30%-50%), being an important determinant in graft survival. Recent studies reveal that recurrence was the third most frequent cause of graft lost after 10 years post-transplant monitoring process. Objective: To analyze posttransplant glomerulopathy impact as a graft lost predictor. Methods: Between January 1990 and April 2013, 849 renal biopsies were carried out on 375 transplanted patients, 50 glomerulopathy cases were diagnosed. This population was compared with an historical renal transplant recipients group between 2000 to 2011, without glomerulopathy. Renal graft survival was analyzed in both populations. Results: 50 post-transplant glomerulopathies were diagnosed in 47 patients. We did not find statistically significant differences between this group and the historical one concerning recipient age, donor sex, donor type, miss match number, organ ischaemia time, acute rejection rate, delayed graft function, and neither in the recipient mortality. We did find significant differences in male sex, 88% vs 55% (p≤ 0.05). Renal graft lost rate was significantly more frequent among patients presenting glomerular disease 38 vs 8 % (p ≤ 0.01). Conclusion: In our population, post transplant glomerulopathy was associated to graft survival reduction and a higher membranoproliferative glomerulopathy lost rate was observed

Hyperuricemia, chronic kidney disease and kidney transplant (part II)

Post-transplant hyperuricemia has been defined with equal values to the ones of general population, its prevalence can reach 80% in those who have received a kidney transplant, and 5 to 25% can develop gout crisis. Advanced age at implant, history of hyperuricemia or gout, obesity, treatment with calcineurin inhibitors, use of diuretics and low glomerular filtration rate are some of the factors involved in its development. Hyperuricemia has been linked to decreased nitric oxide mediated vasodilation and proliferation of vascular smooth muscle through proinflammatory and profibrotic effects (mediated by T cells, macrophages, PDGF, TGF β among others). These effects have been associated, in turn, with hypertension, cardiovascular disease and renal damage progression (related tubulointerstitial fibrosis, arteriosclerosis of afferent tubular atrophy) factors that lead to a reduction in graft and patient survival. Indication for asymptomatic hyperuricemia treatment in this population is still under debate, both in terms of the indication in itself and the type of drug used, unlike what happens in stones, arthritis, or tophi where they must face treatment must be addressed, prioritizing the interaction with the drugs used in transplantation. It must be considered that most of the available information comes from the analysis of general population, therefore studies on this population group are particularly required

Hyperuricemia, chronic renal disease and renal transplant (part II)

Hyperuricemia (HU) in renal transplant (RT) has been defined, like general population, with KDIGO Guides, as over 6 mg/dl values in women and 7 mg/dl in men. HU incidence in some populations are 28%, reaching 80% in Cyclosporine era (CSA). HU is early observed after RT, risk factors associated with its development include: advanced age at the time of RT; gout history or preexisting HU; obesity; metabolic syndrome presence (MS); graft function deterioration; use of Inmunosuppression drugs, mainly cyclosporine (CSA); use of diuretics

Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants: An Analysis From the Randomized TRANSFORM Study

BACKGROUND: The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail. METHODS: TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids. RESULTS: Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R- subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA. CONCLUSIONS: De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.status: publishe