J.A Zubimendi

Assessment of glomerular filtration rate in transplant recipients with severe renal insufficiency by Nankivell, Modification of Diet in Renal Disease (MDRD), and Cockroft-Gault equations

Measurement of glomerular filtration rate (GFR) is time consuming and cumbersome. Several formulas have been developed to predict creatinine clearance (CrCl) or GFR using serum creatinine (Cr) concentrations and demographic characteristics. However, few studies have been performed to discern the best formula to estimate GFR in kidney transplantation. In this study, Cockroft-Gault (CG), Nankivell, and Levey (MDRD) formulas were tested to predict GFR in 125 cadaveric renal transplant patients with severe renal insufficiency (GFR less than 30 mL/min per 1.73 m2). The GFR was estimated as the average Cr and urea clearances. The mean GFR estimated by averaged Cr and urea clearances (22.18+/-5.23 mL/min per 1.73 m2) was significantly different from the mean values yielded by the MDRD formula (20.42+/-6.65 mL/min per 1.73 m2, P=.000), the Nankivell formula (30.14+/-11.98 mL/min per 1.73 m2, P=.000), and the CG formula (29.42+/-8.64 mL/min per 1.73 m2, P=.000). The MDRD formula showed a better correlation (R=0.741, P=.000) than the CG (R=0.698, P=.000) and the Nankivell formulas (R=0.685, P=.000). Analysis of differences using the Bland-Altmann method demonstrated that MDRD gave the lowest bias (MDRD: -1.65+/-4.4 mL/min per 1.73 m2; CG: 7.33+/-6.24 mL/min per 1.73 m2; Nankivell: 8.05+/-9.23 mL/min per 1.73 m2) and narrower limits of agreement (Nankivell: -10.41-26.51 mL/min per 1.73 m2; CG: -5.15-19.81 mL/min per 1.73 m2; MDRD: -10.61-7.31 mL/min per 1.73 m2). In transplant patients with severe renal insufficiency, the MDRD equation seems better than the other formulas to estimate GFR.

Posttransplant diabetes is a cardiovascular risk factor in renal transplant patients

POSTTRANSPLANT DIABETES mellitus (PTDM) is a serious complication that is grossly under recognized. Prior to the advent of cyclosporine, immunosuppression with high doses of steroids caused PTDM in up to 40% of patients. With modern regimens, the incidence of PTDM has been shown to decrease. Depending on the criteria used to define PTDM and the immunosuppressive treatment regimen, the reported incidence varies from 3% to 20%. The relationship between glycemic control and microvascular and macrovascular complications of diabetes is well established. The aim of this study is to analyze the clinical impact of PTDM on the development of posttransplant cardiovascular disease (CVD).

Effect of early graft function on patient survival in renal transplantation

The influence of early graft function on long-term graft survival has been widely reported but its association with patient survival has received less attention. We investigated the effect of early renal function on patient survival and on cardiovascular disease after renal transplantation among 532 transplant patients who had grafts functioning for >1 year. Patients were classified into two groups, depending on the early creatinine clearance (< or >60 mL/min). We analyzed graft and patient survival, posttransplant cardiovascular disease, and the principal causes of death. Five- and 10-year graft and patient survival were lower among the group with worse early renal function. The main cause of death was vascular disease. Poorer early renal function increased the risk (RR) of patient death by 2.2-fold, and also the presence of posttransplant cardiovascular disease. In conclusion, patients with poor levels of early graft function are at an increased risk of death. These high-risk groups should be targeted for interventional studies to improve patient survival.

Association between the SstI polymorphism of the apolipoprotein C-III gene, glucose intolerance and cardiovascular risk in renal transplant recipients

CARDIOVASCULAR DISEASE (CVD) is the main cause of morbidity and mortality in renal transplant recipients. In addition to lipid abnormalities, insulin resistance may increase the risk of CVD. In the general population, the S2 allele of the SstI polymorphism of the apo C-III gene has been associated with hypertriglyceridemia, high blood pressure, and increased risk of coronary artery disease, all of which are characteristics of the transplant-related insulin-resistant state. However, the influence of apo C-III polymorphism on insulin resistance, dyslipemia, and the development of atherosclerosis in renal transplant recipients is not known.

Proteinuria as a useful clinical marker of cyclosporine nephrotoxicity in renal transplant patients

A SIGNIFICANT improvement in the success of organ transplantation during the last 20 years has been observed mainly due to the introduction of drugs like cyclosporine (CyA). Although nephrotoxicity (NT) is the major dose-limiting adverse event for this drug, most of immunosuppressive regimens continue to depend on CyA. CyA trough blood levels must be monitored to ensure that the concentration of this drug remains within its narrow therapeutic range. However, it has been questioned because of its inability to adequately reflect systemic exposure in terms of area under the curve. Unfortunately, drug monitoring may not always detect or prevent NT. NT is difficult to distinguish from chronic allograft rejection, which is a particular problem in renal transplantation. Although morphologic criteria for the differential diagnosis between chronic rejection (CR) and CyA-associated NT have been proposed, the risk of biopsy is limiting. Early biopsies are strongly recommended for patients whose serum creatinine levels increase from baseline values. When biopsies are performed too late, after months or years of severe impairment of renal function, they offer little change to decipher the morphologic lesions. CR is frequently associated with development of proteinuria. Because tubulointerstitial damage is one of the most important adverse effects when CyA is administrated chronically, proteinuria should not be present. The aim of the study was to analyze whether the development of proteinuria could be a useful clinical hallmark to distinguish CR from CyA NT.

Clinical relevance of posttransplantation HLA antibody monitoring by ELISA.

THE COMPLEMENT DEPENDENT cytotoxicity test had been the only useful method to measure alloimmunization; its use before renal transplantation has become routine to predict the risk of graft failure. Recently, new more sensitive and specific techniques have been developed, to measure HLA antibodies, such as flow cytometry or ELISA. This development has led to renewed interest in the measurement of HLA antibodies after transplantation, which was not performed routinely. The aim of the present study was to determine the role of ELISA, an easy and sensitive method to recognize donor-specific anti-HLA antibodies (HLA Abs), in the monitoring of renal graft recipients after kidney transplantation.