RESUMO
BACKGROUND/AIMS: We aimed to determine if soluble α-klotho level was an indicator of chronic kidney disease (CKD) progression and whether α-klotho interacted with aldosterone during the course of further renal damage. METHODS: 112 adults with stages 1-5 CKD were enrolled into our cohort study. All of the patients were followed up for 6 years (from January 2010 to December 2015). Serum soluble α-klotho and aldosterone were measured at baseline and at 1.5-years follow-up. The primary outcome was the initiation of renal replacement therapy (RRT) and the secondary outcome was the occurrence of cardio-cerebrovascular events. Long-term progression to RRT and cardio-cerebrovascular events in patients was analyzed with a risk-adjusted Cox proportional hazards regression model. Adjustment included age, gender, eGFR, mean arterial pressure, 24-h protein excretion and the change in α-klotho level from baseline at 1.5-years follow-up. RESULTS: Baseline circulating α-klotho levels were positively associated with baseline estimated glomerular filtration rate (eGFR; r = 0.224, p = 0.017), but not age, calcium, phosphate, or parathyroid hormone levels. The change in α-klotho level from baseline at 1.5-years follow-up (p = 0.002) was independently associated with renal replace treatment (RRT) initiation after adjustment for age, gender, eGFR, mean arterial pressure, and 24-h protein excretion in Cox regression analysis. Aldosterone levels were positively associated with CKD stage, and were inversely correlated with circulating α-klotho levels. CONCLUSION: The change in concentration of soluble α-klotho during the 1.5-years follow-up was an indicator of CKD progression. Renal damage associated with a reduction of α-klotho may involve the upregulation of plasma aldosterone. Future studies are needed to validate our findings, and to investigate the underlying mechanism by which α-klotho and aldosterone may cause renal damage.
Assuntos
Aldosterona/sangue , Glucuronidase/sangue , Insuficiência Renal Crônica/diagnóstico , Aldosterona/metabolismo , Progressão da Doença , Seguimentos , Taxa de Filtração Glomerular , Glucuronidase/metabolismo , Humanos , Proteínas Klotho , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/terapia , Terapia de Substituição RenalRESUMO
To determine whether -344T/C CYP11B2 promoter polymorphism affects serum aldosterone levels and whether this polymorphism is an indicator of eGFR decline in patients with chronic kidney disease. -344 C/T CYP11B2 gene polymorphism analysis was performed in 96 adults with stages 1-5 CKD by using polymerase chain reaction. Serum aldosterone levels were measured at baseline and at 1.5-year follow-up. The primary outcome was the annual eGFR decline and the secondary outcome was the occurrence of cardio-cerebrovascular events. The genotype distribution of -344T/C SNP in the patients with CKD was: CC (9.4%), CT (53.1%), and TT (37.5%), nearly similar to the healthy non-CKD individuals as reported. Mean aldosterone levels were highest in the TT group and lowest in CC group (p = 0.036). Serum aldosterone level also showed a negative correlation with baseline eGFR in patients with eGFR >60 mL/min (r = -0.403, p < 0.001). The mean annual eGFR decline ratio was highest in the TT group and lowest in the CC group (p = 0.011). The incidence of cardio-cerebrovascular accidents was significantly higher in the TT group than in the CC and CT groups (p = 0.033). -344T/C promoter polymorphism of CYP11B2 modulated aldosterone levels in patients with all stages of CKD and was predictive of annual eGFR decline in CKD stages 3-4. In addition, the -344 T allele appeared to be an independent predictor of cardio-cerebrovascular events.