P0854THE ENDOGENOUS ERYTHROPOIETIN EXPRESSION IN CKD PATIENTS AT HIGH ALTITUDE: DATA FROM TIBETAN PLATEAU

Abstract

Abstract Background and Aims Some studies have shown that higher altitude was associated with lower EPO doses and higher hematocrit levels in HD patients. Our pre-study also confirmed that the higher the altitude, the lower the EPO resistance index [weekly weight-adjusted dose of erythropoietin (IU/kg/week) divided by Hb concentration (g/dl)]. Possible explanations included that patients at higher altitude produce more endogenous EPO or they respond more efficiently to EPO than patients at lower altitude. The aim of this study was to determine whether endogenous EPO production was up-regulated in CKD patients at high altitude. Method Three cohorts from different altitude were compared. Among them, 58 CKD patients were from Tibet Autonomous Region People's Hospital (3650m above sea level, recruited between March 2019 and July 2019. The other two cohorts were from the literatures. [1,2] The exclusion criteria included patients under EPO substitution or those with acute renal failure, polycystic kidney disease, renal carcinoma or polycythemia. The subjects were then stratified into groups according to the CKD stage. EPO concentrations were determined by using electrochemiluminescent immunoassay. Change of endogenous EPO levels with altitude by CKD stage was studied. Results The characteristics of the Tibet cohort were shown in table 1, the other two can be found in references. In Tibet cohort, there was a significant correlation between serum EPO concentrations and CKD stages as well as eGFR. The equation derived from liner regression analysis was EPO (mIU/ml) =-1.941*CKD stage+17.67 (r2 = 0.093, P = 0.020) and log EPO (mIU/ml) =-0.0002311*eGFR (ml/min/1.73m2) + 1.025 (r2 = 0.097, P = 0.017). Serum EPO concentrations dropped with decreasing of eGFR, see in Figure 1. Normally there was an exponential relation between hemoglobin and endogenous EPO in healthy people. The correlation was attenuated and even absent in CKD patients. In Tibet cohort, there was no linear relation between hemoglobin and endogenous EPO (r2 < 0.001, P =0.907), see in Figure 2. Compared with the other two cohorts at lower altitude, the average EPO concentration of Tibetan patients was higher in CKD stage one, however, it decreased quickly with increasing stages of CKD. The average EPO concentration were even lower in CKD stage two to five, see in Figure 3. Conclusion Endogenous EPO production was only up-regulated in patients with normal renal function at high altitude, those with impaired renal function failed to produce more EPO. Our results suggest that the possible explanation for CKD patients at high altitude had better EPO responsiveness is that they respond more efficiently to EPO other than they produce more endogenous EPO.