RESUMO
A decreased expression of the fibroblast growth factor (FGF)-23 coreceptor Klotho was postulated as an early alteration in chronic kidney disease mineral and bone disorder, resulting in a compensatory increase in plasma FGF-23 levels. Klotho exists in both membrane-bound and secreted (sKlotho) forms, the latter of which may exert vasculoprotective effects. Here we analyzed plasma sKlotho levels in a large cohort of 312 patients with stage 2-4 chronic kidney disease, and assessed plasma levels of FGF-23, sKlotho, parathyroid hormone, and urinary fractional phosphate excretion. Patients were prospectively followed for an average of 2.2 years for the occurrence of death or initiation of renal replacement therapy. The levels of sKlotho were significantly associated with age, but not with the glomerular filtration rate or other parameters of calcium-phosphate metabolism. Moreover, while patients with high FGF-23 levels faced worst outcome even after adjustment for confounders, we found no prognostic impact of sKlotho. Thus, plasma levels of sKlotho were not related to kidney function and did not predict adverse outcome in patients with chronic kidney disease. Future studies are needed to understand how tissue expression, urinary excretion, and plasma levels of Klotho diverge in progressive chronic kidney disease.
Assuntos
Glucuronidase/sangue , Rim/fisiopatologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Índice de Gravidade de Doença , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Seguimentos , Humanos , Proteínas Klotho , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/mortalidade , Terapia de Substituição Renal , Taxa de SobrevidaRESUMO
PURPOSE: To determine whether the difference of resistive indexes (RIs) in spleen and kidney (DI-RISK) is a more specific ultrasonographic (US) marker of intrarenal parenchymal damage than intrarenal RI alone. MATERIALS AND METHODS: The study was approved by the local ethics committee. All study participants provided informed consent. The authors defined standard values for renal RI, splenic RI, and DI-RISK in 152 healthy subjects; carotid intima media thickness (IMT) was assessed as a marker of systemic vascular disease. Next, the authors measured these US parameters and collected echocardiographic data in 290 patients with chronic kidney disease (stage 2-4) recruited between September 2008 and February 2011 to evaluate the DI-RISK across the spectrum of stages of kidney function. Correlation coefficients were calculated with the Spearman test, and multivariate linear regression was used to analyze independent predictors of renal RI, splenic RI, and DI-RISK. RESULTS: Healthy subjects had a mean age of 34.3 years ± 8.7, and patients with chronic kidney disease had a mean age of 65.0 years ± 12.3 (P < .001). In healthy subjects, both renal and splenic RIs were associated with IMT (renal RI: r = 0.19, P = .022; splenic RI: r = 0.23, P = .005); there was no correlation between DI-RISK and IMT (r = -0.10, P = .215). Similarly, in patients with chronic kidney disease, renal and splenic RIs correlated with IMT (renal RI: r = 0.33, P < .001; splenic RI: r = 0.30, P = .001). DI-RISK was associated with the estimated glomerular filtration rate (eGFR; r = -0.19, P = .001) but not with IMT (r = 0.08, P = .174). At multivariate regression analysis, DI-RISK was independently associated with eGFR but not with extrarenal factors. CONCLUSION: In patients with chronic kidney disease, renal RIs do not selectively indicate organ damage, but also mirror systemic vascular disease. The authors introduced DI-RISK as a potential US marker that may more specifically reflect kidney damage.
