Tubular dysfunction in patients with rheumatoid arthritis

Abstract

Background The leading causes of premature mortality in rheumatoid arthritis (RA) are cardiovascular complications [1]. Even the earliest subclinical renal dysfunction is an important independent risk factor for cardiovascular disease [2]. One of the methods of early diagnosis of renal disease can be the assessment of tubular damage. Objectives To examine of the urinary excretionsof the markers of tubular dysfunction in patients with rheumatoid arthritis. Methods The study included 73 patients with RA at the age 18 to 60 years, who were treated at the rheumatology department of Saratov Regional Hospital. Exclusion criteria were an associated kidney diseases, hypertension stage III, any kind of secondary nephropathy and pregnancy. We investigated the urinary excretionsof alpha1-microglobulin (alpha1-Mg) and albumin (Al) by immunoturbidimetric method and urine enzymes (gamma glutamattranspeptidase (GGT) and lactatedehydrogenase (LDH)) by the kinetic method in a morning urine sample. The content of alpha1-Mg and Al was recalculated per 1 g of creatinine, GGT and LDH - per 1mmol urine creatinine. Results In patients with RA compared with a control group matched for age, sex, body mass index, blood pressure, increased urinary excretionofalpha1-Mg (26.6 [18.69, 37.57] mg / g and 13.75 [10.91, 18.69] mg / g, respectively, p <0.001), GGT (2.59 [1.26, 5.12] U / mmol, and 1.89 [1.22, 2.65] U / mmol, p = 0.045) and LDH (3.14 [1.47, 5.92] and 1.93 [0.82, 3.31], respectively, p = 0.008) was detected. Even in patients with normal urinary albumin excretion (<25 mg / g for women and 17 mg / g in men, n = 21) urinary excretionofalpha1-Mg was higher than in controls (18.69 [11.93, 19.9] mg/g and 12,85 [9,52; 18,69], p = 0.037). Correlation was found out of alpha1-Mg level with the duration of morning stiffness (r = 0.354; p = 0.002), the multiplicity of nonsteroid anti-inflammatory drugs (NSAIDs) in the month prior to the survey (r = 0.318; p = 0.009), duration of NSAID history (r = 0.270; p = 0.021), the dose of methotrexate at the time of examination (r = -0.452; p = 0.004), the indices HAQ (r = 0.447; p = 0.004) and PAS (r = 0.450; p = 0.004), triglycerides (r = 0.247; p = 0.048), in patients older than 40 years - with radiologic stage of RA (r = 0.407; p = 0.005). GGT level correlates with systolic (r = 0.338; p = 0.006) and diastolic (r = 0.301; p = 0.023) blood pressure at the time of the survey, the concentration of triglycerides (r = 0.374; p = 0.019), the index scale SCORE (r=0.222; p=0.048); LDH level correlates with the multiplicity of NSAIDs in the month prior to the survey (r = 0.374; p=0.004), the index scale SCORE (r=0.252; p=0.031), concentration of low-density lipoprotein (r=0.366; p=0.006). Conclusions The urinary excretion of markers of tubulointerstitial dysfunction in patients with RA is higher than in healthy individuals. The most sensitive marker of tubulointerstitial dysfunction is alpha1-Mg. The severity of tubular damage correlates with the presence and degree of hypertension and dyslipidemia, the index scale SCORE, the multiplicity of NSAIDs, the radiological stage, the functional status of patients.