In this retrospective cohort study, 14.8% of patients with RA had a GFR < 60 ml/min/1.73 m2, evaluated using the CKD-EPI formula. Our data are roughly in consistence with findings in previous studies. In a cohort of 400 subjects with RA in England, 13% had a GFR < 60 ml/min /1.73 m2, estimated by the Modification of Diet in Renal Disease (MDRD) equation [3, 4]. Another cross-sectional study of 107 RA patients and 76 patients with serum-negative arthritis observed renal impairment (GFR < 60 ml/min /1.73 m2) in 17.48% of the patients with RA . A multicenter cross-sectional survey involving 970 patients in France found that approximately 9% of patients with RA had impaired renal function, indicated by a GFR < 60 ml/min/1.73 m2 .
In this investigation, we found that neutrophil count > 7.5 × 10^9/L was associated with an increased risk of renal damage in RA patients. To our knowledge, this was the first survey to report the relationship between neutrophils and renal damage in RA patients. The property of neutrophils to release extracellular traps was not conducive to the clinical development of RA . It is well-known that a large number of neutrophils accumulate in the synovial tissue of RA, which spontaneously released neutrophil extracellular traps (NETs) . NETs, a network structure consisted of DNA and granulose, could indirectly impair the endothelial function,promote blood vessel and glomerular damage, thus it would induce renal failure and even death . Several previous studies respectively reported that the imbalance between the emergence and removal of NETs adversely affected kidney health [22, 23].
Another finding of our present study was that UA > 360umol/l and hemoglobin < 120 g/L significantly associated with a higher risk of renal impairment in RA patients. Similarly, Daoussis et al. also indicated that an elevated UA level was a strong predictor of renal damage in RA patients [3, 4]. A possible explanation for this relationship may be the reduction of uric acid excretion due to renal dysfunction . Previous studies supported the fact that elevated UA levels affect kidney function by causing renal cortical vasoconstriction, intrarenal vascular disease (hypertension), and renal organ damage . Hyperuricemia played a role in renal vascular injury in healthy rats and kidney-damaged rats, as observed in animal experiments . However, Wolfe et al found that decreased hemoglobin levels were weakly associated with renal impairment . Previous studies have demonstrated that decreased hemoglobin levels were more common in patients with CKD , which may be due to shortened red blood cell lifespan and iron loss in hemodialysis patients [29, 30], erythropoietin (EPO) deficiency , inflammation , iron and vitamin deficiency [33, 34], or multiple organ dysfunctions .
Chiu et al followed more than 12,000 RA patients for five years in a cohort study, and they observed that diabetes, hypertension, hyperlipidemia, and cardiovascular disease were related to renal damage , which was consistent with the observations of Couderc et al. and Vansijl et al . Unfortunately, we failed to find an independent link between cardiovascular risk factors and kidney damage. This discrepancy was likely due to the smaller sample size and lack of long-term follow-up in our study. As was found by Haroon et al , this study found that corticosteroids, DMARDs and NASIDs usage were not independently associated with kidney damage. Previous evidence showed that the use of NASIDs, methotrexate, tumor necrosis factor (TNF) and DMARDs (such as etanercept) did not add to burden of kidney function of RA patients[37–38], but only long-term use of cyclosporine A and cyclophosphamide caused renal damage in patients with RA [39–40].
Several limitations in this study should be discussed. GFR, estimated by various quantitative equations, has been determined to be the optimal indicator of renal function in recent years. The CKD-EPI SCr/CysC equation recommended as a GRF equation by the KDIGO guidelines , has the advantage of more accurate calculated results, narrower calculation error, and broader clinical application [42, 43]. Therefore, the CKD-EPI equation was chosen to estimate renal function. However, the development of the CKD-EPI SCr/CysC equation did not take into account differences in race, region, and medical facilities amongst patient cohorts, resulting in potential errors in this study’s Chinese cohort in this study . Moreover, the SCr component of the CKD-EPI equation was linked to total muscle mass, and some RA patients also present with sarcopenia. Consequently, CKD-EPI SCr/CysC equations that depend on SCr to assess eGFR may overestimate kidney function in RA patients . Information on the disease progression of RA and the composition of specific medications (such as DMARDs) prescribed to each patient would have improved the estimation of renal function in the cohort of this study, however, missing data disqualified any analysis regarding these two factors in this cohort. In addition, data on urinary protein levels and hematuria, both of which are markers of renal dysfunction, were not collected in the data set. Finally, the vast majority of study participants were Chinese, so the results of this study may not be generalizable to other races. Finally, our survey was a retrospective analysis, and we were unable to clarify the causality.