Predictive value of serum Klotho protein level in assessing: cardiovascular risk, achievement of the end stage of CKD, and overall survival of patients with initial CKD C3-4: a prospective clinical analysis (follow-up period of 8 years)

BACKGROUND. Cardiovascular complications (CVС) are the leading cause of death in a cohort of CKD patients, including young working age people. The search for a prognostic marker that allows predicting and preventing the risk of CVС is an important not only medical but also socioeconomic task.

THE AIM OF THE STUDY: To determine the predictive value of baseline serum Klotho levels in assessing cardiovascular risk, risk of developing end-stage renal disease (ESRD), and overall survival among patients with stage 3-4 CKD, during an 8-year follow-up period.

PATIENTS AND METHODS: The study included 75 patients with CKD C3-4, mean age 54+9 years. The initial serum Klotho level was divided into quartiles (1 quartile Klotho – 148-336 pg/ml; 2-3 quartile – 337-580 pg/ml; 4 quartile – 580-812 pg/ml). The overall survival of patients over a period of 8 years, the cause of death, and the achievement of ESRD, depending on the Klotho quartile, were assessed. RESULTS: During the observation period, 22 patients died, of which 12 (54.5 %) died from CVC, 7 (31.8 %) from covid infection, 3 (13.6 %) from other causes. When assessed by quartiles, patients with the 1st quartile prevailed among the deceased patients, including those from CVC: the 1st quartile was – 9 (75.0 %), the 2nd-3rd quartile -3 (25.0 %), the 4th quartile – 0 ( 0 %), (chi-square = 8.2, p=0.023). Among patients who achieved ESRD and started dialysis (n=30), patients with 1 quartile were 12 (63.2 %), 2-3 quartile -16 (43.2 %), 4 quartile – 2 (10.5 % ), (chi-square = 11.3, p = 0.01). Among the surviving patients (n=53) with CVC on the moment of end study (n=28), patients with 1 quartile were 19 (67.9 %), 2-3 quartile 9 (32.1 %), 4 quartile – 0 % (chisquare=19.9, p<0.001). At the same time, among the entire sample of patients, there was no correlation of the Klotho level with age (r=-0.067, p=0.570), CKD stage (r=-0.281, p=0.06). In the same time, there was a statistically significant correlation of Klotho level with the achievement of ESRD by the patient and the beginning of dialysis (r=-0.465, p<0.001), the development of CVC (r=-0.512, p<0.001), overall survival (r=-0.368, p=0.001).

CONCLUSION: According to our data, the serum level of Klotho did not depend on the age of patients or the stage of CKD (in the sample of patients with 3-4 stages of CKD), however, it was clearly associated with the risk of cardiovascular events, the risk of progression of CKD to ESRD, overall survival of patients and can be considered as prognostic marker in patients with pre-dialysis stages of CKD.

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