In this large prospective cohort study, we investigated relationship of commonly available blood cell indices and rapid kidney function decline in general population. In consistence with study in CKD patients, low hemoglobin was significantly associated with rapid kidney function loss. Besides, we demonstrated several novel associations. Participants with high monocyte and platelet count exhibited high risk of rapid kidney function decline. These observations provide helpful information to slow the kidney function loss in general population.
Anemia is a common complication and well-known risk factor for disease progression in patients with CKD [15, 19, 20], however, it has not been recognized in general population. In our study, both low hemoglobin and low hematocrit were risk factors for the rapid kidney function loss in general population. Interestingly, we also observed that hemoglobin and hematocrit level increased with a decrease in eGFR at baseline. In a study enrolled 145,865 adults who visited a health center in Korea, Oh et al reported that hemoglobin level was higher in participants with a subtle decline in renal function [21]. The Atherosclerosis Risk in Communities (ARIC) study showed that the peak value of hemoglobin was observed at eGFR of 75–89 mL/min/1.73m2 [22]. These data indicated that hemoglobin and hematocrit level increase in population with minor kidney function insufficiency, presumably due to a compensation mechanisms. Moreover, this compensatory increase might slow the rate of kidney function decline in general population.
Our study demonstrated that monocyte count might be a predictor of rapid kidney function decline in general population. Previous studies about the association of monocyte and kidney function were restricted to patients with CKD. Some epidemiologic studies observed that high monocyte count was as associated with low kidney function in patients with CKD [23, 24]. Moreover, Bowe et al. reported a significant association between higher monocyte count and risk of CKD progression to ESRD in a large longitudinal observational cohort [10]. We demonstrated the relationship of high monocyte count and rapid kidney function loss in general population, which indicated that monocyte may participate in kidney damage at early stage. In recent years, studies have proposed a pathogenic role of monocyte/macrophage in kidney disease. Animal experiment proved that monocytes can differentiate into macrophages in kidney and promote inflammation and renal fibrosis [25]. Blockade of monocyte/macrophage related chemokine can reduced recruitment of monocyte and abrogates the development of kidney injury in various animal models, including unilateral ureteral obstruction, adriamycin-induced nephrotic syndrome and diabetic kidney injury [26-28]. More studies are necessary to investigate the mechanism underlying the association of monocytes and kidney injury in future.
This is the first study indicated that platelet count has the ability to predict rapid kidney function decline in general population. Due to its important roles in the hemostasis and thrombosis, platelet was reported to be associated with high incidence of atherosclerotic cardiovascular disease (CVD) [29]. Also, a few studies have observed that high platelet count was associated with high CVD mortality in patients on hemodialysis [30, 31]. However, the research regarding the relationship of platelet and kidney function loss is limited. Our study demonstrated that platelet may also participate in kidney damage. Platelets was anucleate megakaryocyte fragmentation in circulating blood, it can interact with other types of immune cells, including T-cells, neutrophils, and mononuclear phagocytes. These interactions might initiate and exacerbate the inflammation [32]. Therefore, high platelet count could reflect chronic inflammatory status in population with relative normal kidney function. In addition, platelet is correlated with established kidney injury risk factors, such as hypertension, diabetes and metabolic syndrome [33, 34]. These may explain the observed association between high platelet count and rapid kidney function decline in our study.
The main strengths of our study are the prospective design, the relatively large sample size, and adjustment for a number of potential confounders. However, several limitations should be considered in the present study. Firstly, we did not collected data about urinary protein at baseline, thus, we were not able to exclude participants with eGFR ≥ 60 mL/min/1.73 m2 but abnormal urinary protein levels in our analysis. Secondly, most participants of our study were middle-aged and older Chinese, thus the results may not be generalized to populations of all ages or other ethnicities. Finally, despite including a wide range of potential confounding factors, there may exist confounders either unmeasured or unknown that could explain the rapid kidney function loss seen.