Background Renal involvement in rheumatoid arthritis (RA) has not been fully understood. Chronic kidney disease (CKD) is now epidemic among the general population, and is not only a risk factor for end-stage renal disease (ESRD), but also for cardiovascular disease (CVD), anemia, bone disorders, and cancers. The recently-updated CKD classification, using a combination of proteinuria and estimated glomerular filtration rate (eGFR), has facilitated early and correct identification of CKD for general doctors.
Objectives To examine prevalence and incidence of CKD, and to explore risk factors for mortality and incident CKD in RA patients.
Methods RA patients who regularly visited our hospital from July 2004 to June 2014 were enrolled in the study. The following were excluded: those with visit frequency <3 times, age <18 years, observation period <3 months, lack of at least 2 consecutive laboratory data, and coexistence of acute renal failure. (1) Dipstick proteinuria was classified into 3 grades: (A1) – and +/-, (A2) 1+ and 2+, and (A3) 3+ or more. eGFR was classified into 6 grades: (G1) <90, (G2) 60-89, (G3a) 45-59, (G3b) 30-44, (G4) 15-29, and (G5) <15 ml/min/1.73m2. The whole participants were distributed into the 5 x 3 table, combining eGFR with proteinuria (e.g., G3bA2). CKD was defined as either eGFR <60 or 1+≤ proteinuria or both. Analyses were conducted on December in 2014. (2) Cumulative incidence of adverse outcomes including mortality and new CKD was analyzed by Kaplan-Meier method, using the longitudinal data obtained from some of RA patients. Multivariate Cox proportional hazards regression analysis was used to determine factors related to incidence of each outcome, adjusted for known risk factors at baseline.
Results (1) Prevalence of CKD: Of 2,064 Japanese RA patients enrolled, 1,313 (incl. 1,028 women) were eligible. Their mean age and follow-up period were 65.9±14.3 years and 44.3±43.0 months, respectively. Distribution of CKD was shown in Table. Among them, 354 (27%) had eGFR <60 ml/min/1.73m2 and 301 (23%) proteinuria. A total of 518 (39.5%) were diagnosed as having CKD at entry. CKD patients had the likelihood of anemia, hypertension, diabetes mellitus, CVD, and cancers, compared to those without CKD. (2) Incidence of death and new CKD: Longitudinal data (the mean follow-up period of 60.4±12.9 months) of 354 RA patients (incl. 96 with CKD), all of whom were enrolled in 2004, were available for this study. Forty-six patients (13.0%) died due to cancers (10), infections (9), CVD (5), interstitial pneumonia (4), and unknown causes (18). The cumulative mortality over time was 21.4%. Preexistence of both eGFR <60 and proteinuria (HR [95% CI], 3.82 [1.38 – 9.05]), coexisting cancers (5.18 [2.77 – 9.66]), and age (1.03 [1.01 – 1.07]) were significantly associated with mortality. Of 258 non-CKD patients, 82 patients (34.5%) developed new-onset CKD in the follow-up period. Cumulative incidence of CKD was 54.4%, as shown in Figure. Men (HR [95% CI], 2.25 [1.31 – 3.72]), age (1.04 [1.01 – 1.06]), and prevalent CVD (1.78 [1.08 – 2.84]) were risks linked with the incidence of CKD.
Conclusions The RA patients may have greater-than-expected prevalence and incidence of CKD. Prevalent CKD is a likely risk linked with increased mortality in RA patients. Older RA men with chronic heart failure are predisposed to incident CKD.
Disclosure of Interest None declared
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