In this large prospective study of 1,427 Chinese HD patients, we reported the all-cause mortality rate and explored related risk factors. The overall mortality rate was 8.8 per 100 patient-years in our patients. Cardiovascular death was the leading cause of death, which account for more than half of all deaths. Patients that were older, with lower Alb, blood platelets, higher PP and had a history of CHF had a higher risk of all-cause mortality.
We reported a lower overall mortality rate compared with other western DOPPS countries, such as North America (14.3 per 100 patient-years) and Europe countries (13.1 per 100 patient-years)[9]. But it was a little higher than that in Japan (7.87 per 100 patient-years)[10]. Prior DOPPS analyses noted that many beneficial dialysis practices (such as high use of arteriovenous fistula, longer or more frequent dialysis sessions, more effective volume management, good patient compliance, mineral and bone disorder control) were more common in Japan than in other countries[11]. However, in European and North American countries, kidney transplantation was more common among ESKD patients than Asian countries, such as China and Japan. In other words, many healthier and younger patients have opted for kidney transplantation instead of maintenance dialysis treatment in those countries. Therefore, transplantation may deplete the dialysis pool of healthier patients in North America and Europe, but not in China and Japan[11]. Although this may have impact on mortality rate among countries, mortality rate differences among countries may still exist after this factor adjusted.
Some widely recognized risk factors found in our results were consistent with previous researches, such as aging, low Alb, comorbidities. Not surprisingly, aging was known to be a significant risk factor for death. And the guideline of Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that the optimal serum Alb level of chronic kidney disease (CKD) patients was equal to or greater than the lower limit of the normal range (approximately 4.0 g/dL)[12]. We had 42.0% of our patients with serum Alb ≥ 4g/l, and 83.6% patients ≥ 3.5g/l. Patients with Alb ≥ 4g/l also have survival benefits, compared with patients with Alb in 3.5–3.9 g/l. Serum Alb was regarded as the reflection of visceral protein stores, so it can act as a marker of protein malnutrition. Malnutrition was a strong contributor for increasing mortality in HD patients[13, 14]. Deaths due to cardiovascular and infectious causes were increased with malnutrition and hypoalbuminemia[15, 16]. Therefore, for most patients, they should try to make serum Alb meet the target of 4 g/l, and for patients with Alb < 3.5g/l, special attention should be paid to improving their nutritional status. Comparing the clinical data of the 2 groups of patients, we found that patients who died combined with more comorbidities than those who survived. In the Cox model, patients with a history of CHF had higher mortality risk. As more than half of our patients died from cardiovascular causes, patients with a history of cardiovascular disease have a higher risk of death than other patients.
In our results, patients with low platelet counts (< 100*109/L) had a higher risk of all-cause mortality. Thrombocytopenia may have serious consequences, such as increasing the risk of internal and external bleeding, delaying in wound healing and coagulation defects. Previous studies have reported that thrombocytopenia was associated with an increased risk of all-cause death and cardiovascular death in general populations and patients with lung disease[17–19]. In one study about the association about mean platelet volume (MPV) and mortality in incident HD patients, the author also showed that lower baseline platelet counts were associated with higher mortality risk across all multivariable models, which was in line with our findings[20]. Furthermore, there was a prothrombotic adverse drug reaction called Heparin-induced thrombocytopenia (HIT)[21]. Heparin is a common anticoagulant used during HD period to prevent clotting. Some patients may produce platelet-activating antibodies when they received heparin[22], and show unusual clinical features, such as thrombocytopenia, sometimes accompanied by disseminated intravascular coagulation and microvascular thrombosis. Several studies showed that HD patients with HIT were at a higher risk of cardiovascular mortality and arteriovenous fistula thrombosis than patients without HIT[23, 24].
And high PP was an independent predictor of all-cause mortality. Compared with PP < 63mmHg, PP ≥ 63mmHg was associated with a 64.8% increase in hazard ratio for death. Regarding blood pressure control, PP was not widely considered as a risk factor in ESKD patients. But several studies reported that PP was associated with all-cause mortality and/or cardiovascular mortality in HD patients[25, 26]. Meanwhile, cardiac dysfunction was a widespread problem in ESKD patients, and cardiovascular death was the major cause in those patients. Elevated PP was usually due to increased central aortic stiffness and accompanied by increased pulse-wave velocity. Said et al found that PP was associated with an increased risk of developing cardiovascular disease and cardiovascular mortality in a large community-based population[27]. Elevated pressure during systole induce left ventricular hypertrophy, then lead to left ventricular failure, whereas lower pressure throughout diastole had the possibility to limit coronary perfusion and lead to ischemia[25]. This may contribute to the high prevalence of cardiovascular disease in ESKD patients[28].
Overall, the mortality rate of our HD patients was comparatively low compared with other countries. Among China and other countries, especially developed countries, there were obvious differences in race, lifestyle, economic status, medical insurance policies and so on. Whether the risk of mortality is affected by these factors and how they affect need further investigation. Therefore, it was important to explore the risk factors related to death in Chinese HD patients and the modifiable dialysis patterns.
However, our study had several limitations. Firstly, this is an observational study which might has inherent shortcomings such as selection bias and confounding factors. Secondly, the limited number of deaths in our study makes it impossible for us to perform some more detailed subgroup analysis. Thirdly, the China DOPPS study only included patients from three major cities. We didn’t include patients receiving HD treatment in smaller cities or rural areas, and their conditions may be worse than what we reported. Therefore, the results can not represent for the whole country. Even though, the results of this study have irreplaceable significance for us to understand the current situation of Chinese HD patients and to explore modifiable practice patterns to improve patients’ survival.
In conclusion, results in this study were important and complement to previous findings and added new knowledge to the understanding of mortality risks for prevalent HD patients globally. Our analysis highlighted that there were some modifiable risk factors for Chinese patients’ survival. Attention should also be paid to patients who were older, with lower Alb, low platelet counts, higher PP, and had a history of CHF.