Estimated Glomerular Filtration Rate in Renal Transplantation: The Nephrologist in the Mist.

BACKGROUND: Formulas do not estimate renal function with acceptable precision and accuracy. METHODS: We compared 51 creatinine-based and/or cystatin c-based formulas with a gold standard (iohexol plasma clearance) in 193 renal transplant recipients using concordance correlation coefficient, total deviation index, coverage probability and the error in chronic kidney disease (CKD) stage classification. RESULTS: No formula showed a concordance correlation coefficient greater than 0.90 (average for creatinine-based formulas: ∼0.70 and for cystatin c-based formulas: ∼0.85). A wide total deviation index was observed: approximately 70% (creatinine-based) and approximately 50% (cystatin c-based), indicating that 90% of the estimations showed bounds of error of ±70% or ±50%, respectively, compared with the gold standard. No formula included 90% of the estimations within a coverage probability of ±10%. Half the CKD stages classified by creatinine-based formulas were incorrect, mainly due to overestimation of renal function. One of 3 CKD stages diagnosed by cystatin c-based formulas was incorrect, with both overestimation and underestimation. Overall, the formulas showed very low precision and accuracy and a high degree of error in reflecting real renal function. CONCLUSIONS: In conclusion, formulas do not properly reflect renal function in kidney transplantation, which makes their use in clinical practice unreliable. Moreover, their use in clinical trials should be avoided.

The combined effect of pre-transplant triglyceride levels and the type of calcineurin inhibitor in predicting the risk of new onset diabetes after renal transplantation.

BACKGROUND: Insulin resistance precedes overt diabetes in the general population and hypertriglyceridemia is a reliable marker of the disorder. Thus, patients in the waiting list with hypertriglyceridemia may be at risk for new-onset diabetes after transplantation (NODAT). Objectives. We investigate whether pre-transplant triglyceride (TG) levels are a risk factor for NODAT and whether they exert a combined effect with the type of calcineurin inhibitor (CNI). METHODS: We analysed 314 consecutive non-diabetic recipients [215 cyclosporine A (CsA); 99 tacrolimus (Tacro)] transplanted between 1999 and 2003 with a mean follow-up of 34 months. Outcome was NODAT defined by ADA criteria. RESULTS: NODAT developed in 81 recipients (25.8%). Multivariate analysis which included a propensity score for factors determining CNI allocation showed that age (OR: 1.06; 95% CI: 1.03-1.09), pre-transplant BMI (OR: 1.1; 95% CI: 1.02-1.17),TG levels (OR: 1.3 per 50 mg/dl increment, 95% CI: 1.07-1.6) and treated acute rejection (OR: 4.8, 95% CI: 3-11), but not the type of CNI, were independent risk factors for NODAT. A significant interaction between pre-transplant TG and type of CNI was observed. Using CsA as the reference, the combination of Tacro plus pre-transplant hypertriglyceridemia (>/=200 mg/dl) showed an OR of 3.26 (1.4-7.8) to develop NODAT, contrasting with an OR of 0.75 (0.34-1.6) in Tacro recipients with pre-transplant TG levels <200 mg/dl. CONCLUSION: Pre-transplant hypertriglyceridemia was a risk factor for NODAT only in recipients treated with Tacro; it highlights the importance of pre-transplant insulin resistance in the pathogenesis of NODAT.

Interleukin-2 receptor antagonist induction in modern immunosuppression regimens for renal transplant recipients.

Addition of interleukin-2 receptor antagonist (IL-2RA) induction to calcineurin inhibitor (CNI)-based regimens reduces biopsy-proven acute rejection by 30-40%. IL-2RA induction facilitates early withdrawal of steroids, and supports the safe use of reduced-exposure CNI or delayed CNI introduction. IL-2RAs and rabbit antithymocyte globulin (Thymoglobulin) show comparable efficacy in patients at standard or low immunologic risk, but the adverse event profiles of lymphocyte-depleting agents are less favorable. IL-2RAs, uniquely, provide effective immunosuppression with similar tolerability to placebo.