Clinicopathological characteristics of high-altitude polycythemia-related kidney disease in Tibetan inhabitants.

High-altitude polycythemia (HAPC) is a clinical syndrome that occurs in native inhabitants or long-term residents living at altitude. The kidney is one of the most affected organs. However, the clinical and kidney histopathological profiles of HAPC-related kidney disease have rarely been reported. Here, we report kidney biopsy-based clinicopathological study on this disease. HAPC was defined as excessive erythrocytosis [females, hemoglobin 190 g/L or more; males, 210 g/L or more] in patients living above an altitude of 2500 m for more than ten years. A total of 416 Tibetan patients underwent kidney biopsy between January 1, 2016, and November 31, 2020. Of these patients 17 met the diagnostic criteria for HAPC-related kidney disease. Clinically, these patients had a median urinary protein level of 2.5 g/24-hour (range 1.81-6.85). Twelve patients had hyperuricemia, nine had hypertension, and three had kidney insufficiency. On histopathology, glomerular hypertrophy, glomerular basement membrane thickening, podocyte foot process effacement, segmental glomerulosclerosis and global glomerulosclerosis were the main features. Extraglomerular arterial/arteriolar lesions were common, presenting as intimal fibrosis, hyalinosis and endothelial cell swelling/subintimal edema. Expansion of the arterial/arteriolar medial wall area characterized by smooth muscle cell proliferation was clearly observed, potentially indicating vascular remodeling. Hypoxia-inducible factor 2α was expressed in the kidney tissues of these patients. Thus, the pathological changes of HAPC-related kidney disease encompassed both glomerular and extraglomerular vascular lesions, suggesting a key role of both chronic hypoxia itself and secondary hemodynamic changes in the pathogenesis of this disease.

The Influence of Altitude on Erythropoietin Resistance Index in Maintenance Hemodialysis Patients: Data from Tibetan Plateau.

BACKGROUND: It is known that hypoxia influences many of the biologic processes involved in erythropoiesis; therefore, the high-altitude hypoxia may affect erythropoietin (EPO) responsiveness in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the impact of altitude on EPO responsiveness in MHD patients. METHODS: In this retrospective study, MHD patients from Tibet Autonomous Region People's Hospital (3,650 m above sea level) and Peking University People's Hospital (43.5 m above sea level) were recruited between May 2016 and December 2018. Patients were divided into 2 groups according to altitude. Variables including age, sex, dialysis vintage, dialysis modality, duration of EPO use, EPO doses, and laboratory tests were collected and analyzed. EPO responsiveness was measured in terms of the EPO resistance index (ERI). ERI was defined as the weekly weight-adjusted dose of EPO (IU/kg/week) divided by hemoglobin concentration (g/dL). The association between ERI and altitude was estimated using a multivariable linear regression model. RESULTS: Sixty-two patients from Tibet Autonomous Region People's Hospital (high-altitude [HA] group) and 102 patients from Peking University People's Hospital (low-altitude [LA] group) were recruited. The ERI for HA group and LA group was 6.9 ± 5.1 IU w-1 kg-1 (g/dL)-1 and 11.5 ± 6.4 IU w-1 kg-1 (g/dL)-1, respectively. After adjusting for covariates by multivariable regression, altitude was independently associated with ERI (R2 = 0.245, p < 0.001). CONCLUSION: Altitude had an independent negative correlation with ERI. This result supported the hypothesis that altitude-associated hypoxia improved EPO responsiveness in MHD patients.

Mineral and bone disorder in hemodialysis patients in the Tibetan Plateau: a multicenter cross-sectional study.

Background: Mineral and bone disorder (MBD) in hemodialysis patients is associated with increased morbidity and mortality. Studies on the MBD status of hemodialysis patients at high altitudes are extremely limited. Methods: A total of 146 hemodialysis patients from 5 local hospitals across all districts with hemodialysis centers in the Tibetan Plateau were enrolled in this cross-sectional study. Parameters related to MBD, including serum phosphorus (P), calcium (Ca), and intact parathyroid hormone (iPTH) levels, were measured. The achievement of MBD goals was compared with the achievement in the Dialysis Outcomes and Practice Study (DOPPS) 3, DOPPS 4 and a multicenter study of MBD in China. Factors associated with hyperphosphatemia were examined. Results: Altogether, 146 hemodialysis patients were recruited from the Tibetan Plateau. According to the K/DIGO guidelines, there were low achievement rates for serum Ca (40.4%), P (29.7%), and iPTH (47.1%). As for the (KDOQI) guidelines, the rates of achievement of defined targets were 38.4%, 33.7% and 16.4% for serum Ca, P and iPTH, respectively. The percentages of patients reaching the KDOQI targets for corrected Ca, P, and iPTH were significantly lower for Tibetan patients than the percentages found in DOPPS 3 (38.4% vs. 50.4%, 33.7% vs. 49.8%, and 16.4% vs. 31.4%, respectively, all p < .001) and DOPPS 4 (38.4% vs. 56.0%, 33.7% vs. 54.5%, and 16.4% vs. 35.3%, respectively, all p < .001). The percentage of patients reaching the KDOQI targets for iPTH was significantly lower in Tibet than in the plain areas of China (16.4% vs. 26.5%, p < .001). The proportion of patients with hypocalcemia was higher in Tibet than in the plain areas (44.5% vs. 19.4%, p < .001). The percentage of local patients with optimal P was significantly higher for patients with an activated vitamin D prescription than for patients without an activated vitamin D prescription (45.3% vs. 19.3%, p < .001). Age and the activated vitamin D prescription were independently associated with hyperphosphatemia. Conclusion: The MBD status of hemodialysis patients in Tibet is far from the ideal level. High altitude is one of the possible causes of the differences found, but not the principal one. It is necessary for medical staff in Tibet to improve the detection and treatment of MBD.