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Background In kidney transplant recipients (KTR), the end-stage kidney disease (ESKD) risk dependent on the risk factors acting in native chronic kidney disease (CKD) remains undefined. Methods We compared risk and determinants of ESKD between 757 adult KTR and 1940 patients with native CKD before and after propensity-score (PS) analysis matched for unmodifiable risk factors [(age, sex, diabetes, cardiovascular disease and estimated glomerular filtration rate (eGFR)]. Results In unmatched cohorts, eGFR was lower in CKD versus KTR (45.9 ± 11.3 versus 59.2 ± 13.4 mL/min/1.73 m2, P < 0.001). During a median follow-up of 5.4 years, the unadjusted cumulative incidence of ESKD was consistently lower in unmatched KTR versus CKD. Conversely, in PS-matched analysis, the risk of ESKD in KTR was 78% lower versus CKD at 1 year of follow-up while progressively increased over time resulting similar to that of native CKD patients after 5 years and 2.3-fold higher than that observed in CKD at 10 years. R2 analysis in unmatched patients showed that the proportion of the outcome variance explained by traditional ESKD determinants was smaller in KTR versus native CKD (31% versus 70%). After PS matching, the risk of ESKD [hazard ratio (HR), 95% confidence interval (95% CI)] was significantly associated with systolic blood pressure (1.02, 1.01–1.02), phosphorus (1.31, 1.05–1.64), 24-h proteinuria (1.11, 1.05–1.17) and haemoglobin (0.85, 0.78–0.93) irrespective of KTR status. Similar data were obtained after matching also for modifiable risk factors. Conclusions In KTR, when compared with matched native CKD patients, the risk of ESKD is lower in the first 5 years and higher later on. Traditional determinants of ESKD account for one-third of the variability of time-to-graft failure. [ABSTRACT FROM AUTHOR]

Radiocontrast media (RCM) are widely used in clinical medicine but may lead to radiocontrast-induced nephropathy (RCIN). The pathogenesis of acute renal failure secondary to RCM is not fully understood, but direct toxic effects are believed to be a major cause of RCIN. We have investigated the effect of different types of RCM on signaling pathways known to play a role in cell death, survival, and inflammation. HK-2 cells were incubated with sodium diatrizoate and iomeprol (IOM) at a concentration of 75 mg I/ml for 2 h. Both RCM caused an increase in phosphorylation of p38 mitogen-activated protein kinase (MAPK) (p38) and c-Jun N-terminal kinases (JNKs) and NF-κB (at Ser 276), with sodium diatrizoate having a more drastic effect. Although cell viability was reduced significantly by both RCM, in cells pretreated with IOM the cell viability recovered over a 22-h time period after removal of the RCM. However, viability of diatrizoate-treated cells rose at 5 h but then fell at 22 h after removal of the RCM. The decrease in cell viability in diatrizoate-treated cells corresponded with an increase in phosphorylation of JNKs, p38, and NF-κB and a decrease in phosphorylation of Akt, signal transducer and activator of transcription 3, and forkhead box O3a, as well as poly (ADP-ribose) polymerase and caspase-3 cleavage. The recovery in viability of IOM-treated cells corresponded most notably with an increase in STAT3 phosphorylation and induction of Pim-1 kinase. There was also an increase in interleukin-8 release by diatrizoate-treated cells indicating the possibility of proinflammatory effects of RCM. A knowledge of the signaling pathways by which RCM exert their cytotoxic actions may help in finding future therapies for RCIN. [ABSTRACT FROM PUBLISHER]