C.D Garcia

Induction of Renal Tubular Cell Apoptosis in Focal Segmental Glomerulosclerosis: Roles of Proteinuria and Fas-Dependent Pathways

The hypothesis that apoptosis represents a proximate mechanism by which tubule cells are damaged in FSGS was tested. Thirty kidney biopsy specimens from children with idiopathic early FSGS were studied retrospectively. Unexpected, apoptosis was evident in both proximal and distal tubule cells. There was a significant correlation between the degree of proteinuria and the number of apoptotic cells. Fas protein was detected predominantly in the tubule cells that underwent apoptosis. When compared with patients with other chronic proteinuric states, those with FSGS displayed a proliferation/apoptosis ratio in favor of proliferation in the glomerulus but dramatically in favor of apoptosis in the tubules. When both proteinuria and apoptosis were included in a stepwise logistic regression procedure, only apoptosis was found to predict independently the development of ESRD. Prolonged incubation of cultured Madin-Darby canine kidney (distal/collecting) cells with albumin also resulted in a dose- and duration-dependent induction of apoptosis and activation of the Fas pathway, lending support to the novel finding of distal tubule cell apoptosis in patients with FSGS. The results indicate that an elevated tubule cell apoptosis rate at the time of initial biopsy represents an independent predictor of progression to ESRD in patients with early FSGS.

Kidney graft failure due to noncompliance

RENAL transplantation is the treatment of choice for end-stage renal failure. However, the recipient needs a lifelong intake of immunosuppressive medication for the long-term success of the transplantation. There is a growing awareness of patient noncompliance with immunosuppression, which can result in rejection and graft loss. Recent data show rates of noncompliance ranging from less than 5% to more than 45%; it depends on time posttransplant and evaluation method. Noncompliance is one of the major causes of graft failure among renal transplant recipients. The objective of this study was to evaluate the present rate of graft loss due to noncompliance among our patients and to identify factors associated with noncompliance.

Collaborative Brazilian Pediatric Renal Transplant Registry (CoBrazPed-RTx): A Report From 2004 to 2013

BACKGROUNDnThe Collaborative Brazilian Pediatric Renal Transplant Registry started in 2004 as a multicenter initiative aiming to analyze, report, and share the results of pediatric kidney transplantation in Brazil. Data from all pediatric kidney transplants performed between January 2004 and December 2013 were recorded electronically and periodically updated. All patients under 18 years old from the participating centers were enrolled. Demographic data, etiology of chronic kidney disease, and patient and graft survival were analyzed. From a total of 2443 pediatric kidney transplants performed in Brazil during the study period, we report data from 1751 pediatric renal transplants performed in 13 centers enrolled in the collaborative study. Median age at transplantation was 12.4 years, and most of recipients were male (56%). The most common underlying renal etiologies were obstructive uropathy (31%) and glomerulopathy (26%).nnnMETHODSnAccording to donor source, 1155 (66%) of transplants were performed with deceased donors (DD). Initial immunosuppression consisted mainly of tacrolimus, mycophenolate, steroids, and induction therapy with anti-IL-2R antibodies.nnnRESULTSnOne-year graft survival (death-censored) was 93% and 90% (log rank test, P < .01), respectively, for living donor (LD) and DD. Graft losses (15%) were most frequently caused by vascular thrombosis, chronic allograft nephropathy, death with functioning kidney, acute rejection, and recurrent renal disease. Recipients of DD had 2.02 (95% confidence interval: 1.14-3.59) times the hazard of graft loss compared with those of LD (P = .015). Patient survival rates at 1 and 5 years were 98% and 97% for LD and 97% and 93% for DD, respectively. The mortality rate was 3.8%, mainly as the result of infection and cardiovascular disease.nnnCONCLUSIONSnThe results of this collaborative pediatric transplant study are comparable to international registries. Our effort has been able to maintain an exchange of information, both among the participating centers and with other international registries.

Pre-Emptive Pediatric Kidney Transplantation or Not?

BACKGROUNDnKidney transplantation prior to dialysis (pre-emptive kidney transplantation, PKT) has been controversial because of the paucity of clinical evidence to clarify the risks and benefits of PKT. Several authors have confirmed a significant advantage of PKT in the treatment of patients with end-stage renal disease (ESRD). The aim of this study was to examine the characteristics of patients who received PKT or non-pre-emptive kidney transplant (NPKT).nnnMETHODSnWe used a cohort of 323 consecutive kidney-transplanted children (53% boys) from Hospital da Criança Santo Antonio, Porto Alegre, Brazil, who underwent transplantation between January 2000 and December 2010.nnnRESULTSnThe main causes of ESRD were congenital anomalies of the kidney and urinary tract (CAKUT) (39%) and glomerulopathies (27.5%). The 12-, 36-, 60-, and 90-months death-censored graft survival rates were 97%, 92%, 86%, and 76%, respectively, in the PKT group, and 87%, 79%, 72%, and 65% in the NPKT group (P < .05).nnnCONCLUSIONSnThe results of this study suggest that pre-emptive transplantation is beneficial (hazard ratio = 0.37; 95% confidence interval: 0.18-0.82). The main causes of graft loss (n = 67) were recurrence of primary disease (21%), chronic allograft injury (17%), and death with a functioning graft (16%). We recommend PKT as a better choice for transplantation whenever possible to minimize ESRD morbidity and provide better long-term patient and graft survival.