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Although renal transplantation improves survival, cardiovascular morbidity and mortality remain significantly elevated compared with nonrenal populations. The negative impact of traditional, uremia-related, and transplantation-related risk factors in this process remains, however, largely unexplored. Surrogate markers such as aortic stiffness and central wave reflections may lead to more accurate cardiovascular risk stratification, but outcome data in renal transplant recipients are scarce. We aimed to establish the prognostic significance of these markers for fatal and nonfatal cardiovascular events in renal transplant recipients. Carotid-femoral pulse wave velocity, central augmentation pressure, and central augmentation index were measured in a cohort of 512 renal transplant recipients using the SphygmoCor system. After a mean follow-up of 5 years, 20 fatal and 75 nonfatal cardiovascular events were recorded. Using receiver operating characteristic curves, the area under the curve for predicting cardiovascular events was 0.718 (95% CI 0.659-0.776) for pulse wave velocity, 0.670 (95% CI 0.604-0.736) for central augmentation pressure, and 0.595 (95% CI 0.529-0.660) for central augmentation index. When we accounted for age, gender, and C-reactive protein in Cox-regression analysis, pulse wave velocity (hazard ratio: 1.349 per 1 SD increase; 95% CI 1.104-1.649; P=0.003) and central augmentation pressure (hazard ratio: 1.487 per 1 SD increase; 95% CI 1.219-1.814; P<0.001) remained independent predictors of outcome. Aortic stiffness and increased wave reflections are independent predictors of cardiovascular events in renal transplant recipients. As single parameter of wave reflection, central augmentation pressure was better than central augmentation index. Combined measurement of pulse wave velocity and central augmentation pressure may contribute to an accurate cardiovascular risk estimation in this heterogeneous population.

Background and Objectives: The degree of chronic kidney disease (CKD) is currently expressed in terms of GFR, which can be determined directly or estimated according to different formulas on the basis of serum creatinine and/or cystatin C measurements (estimated GFR [eGFR]). The purpose of this study was to investigate whether eGFR values are representative for uremic toxin concentrations in patients with different degrees of CKD., Design, Setting, Participants, & Measurements: Associations between eGFR based on serum cystatin C and different uremic solutes (mol wt range 113 to 240 D; determined by colorimetry, HPLC, or ELISA) were evaluated in 95 CKD patients not on dialysis (CKD stage 2 to 5). The same analysis was also applied for six other eGFR formulas., Results: There was a substantial disparity in fits among solutes. In linear regression, explained variance of eGFR was extremely low for most solutes, with eGFR > 0.4 only for creatinine. The other eGFR formulations gave comparably disappointing results with regard to their association to uremic solutes. Relative similarity in R(2) values per solute for the different eGFR values and the strong disparity in values between solutes suggest that the differences in R(2) are mainly due to discrepancies in solute handling apart from GFR., Conclusions: eGFR is poorly associated with concentrations of all studied uremic toxins in patients with different degrees of CKD, correlates differently with each individual solute, and can thus not be considered representative for evaluating the accumulation of solutes in the course of CKD.

Background: In an attempt to reduce late referral and to improve the care of patients with chronic kidney disease (CKD), different organizations have issued guidelines on when to refer patients to the nephrologist. Most suggest referral of patients with a GFR below 60 ml/min/1.73 m2, and demand referral if the GFR is below 30 ml/min/1.73 m2. It is recommended to use the abbreviated MDRD equation to estimate GFR. This formula is, however, sensitive to the creatinine assay methodology. In addition, the impact of the implementation of such guidelines on the nephrology practice has never been evaluated. This study (i) identifies the true burden of CKD in a population and simulates the effects of a 100% implementation of the guidelines on the nephrology work load, and (ii) evaluates the validity of the estimated GFR using the abbreviated MDRD formula when routinely provided., Methods: Different laboratories (both hospital and private) in our region were asked to report on all the serum creatinine values performed during the first week of December 2004. If patients had more than one determination, only the lowest serum creatinine value was retained. Patients already known to a nephrology unit were not included. GFR was calculated using the abbreviated MDRD, using the serum creatinine as reported by these laboratories, or after correction to the MDRD-standard using different published equations., Results: 20,108 patients, with a mean age of 53.4+/-16.2 years, 48% females, had at least one serum creatinine determination in the observation period. According to the K/DOQI CKD classification, 20.2, 1.6 and 0.8% of females and 13.3, 1.6 and 0.6% of males were in stage 3, 4 and 5, respectively, when the abbreviated MDRD formula was used with the serum creatinine value as reported by the laboratories. Important differences in classifications were obtained when the different correction formulae for creatinine were applied. According to the current recommendations, this would lead to a mandatory referral of 1650-2400 CKD stage 4 patients per 100 000 inhabitants and a suggested referral of another 4100-15 360 CKD stage 3 patients per 100,000 inhabitants to a nephrology unit., Conclusion: Implementation of the current guidelines for referral of CKD patients to nephrologists would lead to an overload of the nephrology care capacities. Large differences in estimated GFRs with different corrections for serum creatinine are observed, resulting in important CKD classification differences. Standardization of serum creatinine assays is mandatory before guidelines, and especially the routine provision of the estimated GFR by the abbreviated MDRD formula, can be implemented in clinical practice.