Our study revealed a higher prevalence of albuminuria among first-degree relatives of dialysis patients, and the positive association is independent of various potential confounders. Furthermore, we observed a lower prevalence of decreased renal function among spouses of dialysis patients compared with controls. A major strength of our study is the large sample size and the representativeness of controls.
The high prevalence of CKD among first-degree relatives of dialysis patients in our study is consistent with previous studies [19, 20]. Compared with previous screening programs for high-risk populations, the prevalence of albuminuria in relatives of dialysis patients (14.4%) in this study was lower than that from the Kidney Early Evaluation Program (KEEP) study (29%) , but similar to that from Tsai’s study (10.7%) . This figure was higher than the observed rate of albuminuria in a general population-based screening program in China (9.4%)3 and in Europe and the United States (5.9% – 7.4%) [22, 23]. One possible explanations might be familial clustering of metabolic disorders, such as hypertension and diabetes, which are known risk factors of albuminuria. Previous studies suggested that, of these renal risk factors, hypertension and diabetes mellitus are multifactorial disease under the influence of both genetic traits and environmental factors [10, 24]. Environmental factors, such as low socioeconomic status and lifestyle of inactivity and smoking, also should be considered as potential contributing for CKD [25, 26]. However, in our analyses, after adjusting for potential confounders, the positive association between being relatives of dialysis patients and albuminuria still exist, indicating that there might be genetic susceptibility of CKD for relatives.
Genetic traits may contribute to the development of CKD in relatives of dialysis patients. It is well known that familial focal segmental glomerulosclerosis (FSGS) is a significant and growing cause of CKD. Given the progress in understanding the biology and pathology of podocyte, mutation of associated genes, such as ACTN4, TRPC6 and NPHS2, contribute to the damage of podocyte and podocyte dysfunction [27, 28]. The latter was associated to the development of proteinuria and FSGS . These genes were recognized to be the genetic basis of FSGS. Meanwhile, more related genes or chromosomal regions were identified in diabetic (3q, 18q22.3-23), non-diabetic nephropathy (chromosome 10), systemic lupus erythematosus and familial IgA nephropathy (6q22-23) [30–32].
Spouses of patients with ESRD were considered to be nongenetic controls for studying the family clustering of CKD . Spousal concordance of health risks and behaviors such as cardiovascular disease, hypertension, metabolic syndrome and high fasting glucose levels has been observed in many disease [33–35]. In this study, we also found higher rates of some health risks in dialysis spouses compared with controls, such as dyslipidemia and use of nephrotoxic medications. However, this study demonstrated a significantly lower prevalence of low eGFR, but no differences in the prevalence of albuminuria and CKD in dialysis spouses compared with controls. Meanwhile, in our analyses, after adjusting for potential confounders, the negative association between being spouses of dialysis patients and low eGFR still exist. These results were enhanced by the sufficient number of participants from multicentric facilities and the ample representativeness of sex- and age- matched controls, which were randomly selected on a ratio of 2:1 from a representative sample of the general population of adults in Beijing . The exact reason was unknown. We assumed that for being spouses of dialysis patients, perceived and objective CKD knowledge are likely to impact risk-modifying behavior in different ways. Multi-component structured empowerment intervention is effective in pre-dialysis CKD patients and may lead to a delay in the progression of kidney disease [36–40].
Our study has limitations that deserve mention. Firstly, it was implemented on a voluntary bias within the dialysis units. Additionally, ESRD patients who didn’t start dialysis treatment were not included in present study. There were kinds of selecting bias in the study which limited the extension of the results from this study. Secondly, urine and blood results were based on a single measurement. It should be noticed that it might overestimate the prevalence of albuminuria based on one measurement. Finally, a cross-sectional study design has several inherent weaknesses, such as lack of long-term observation for outcome and difficulty interpreting the association of exposure with outcome.