Symmetric dimethyl arginine and N-acetyl- β-D-glucosaminidase lysosimyria of proximal renal tubules as a target for nephrotoxicity in patients with rheumatoid arthritis treated with disease modifying antirheumatic drugs.

Dejan Spasovski,Vesna Janevska,Sonja Alabakovska,Irena Kafedziska,Trajan Balkanov,Goce Spasovski,Svetlana Krstevska-Balkanov,Beti Dejanova,Jordan Calovski,Nada Marina,Maja Slaninka-Micevska,Snežana Percinkova,Gjorgi Božinovski,Arif Latifi

doi:10.5812/nephropathol.8989

Abstract

The aim of this study was to determine the effect of initial therapy with some disease modifying antirheumatic drugs (DMARDs) (Methotrexate and Ketoprofen) on glomerular and tubular integrity in patients with Rheumatoid arthritis (RA). To determine whether there is a change in clinical and laboratory indicators of renal function in course of the follow up of treatment and whether that change correlates with the dynamics of the quantity of enzymes excreted in urine and reactants of the acute phase. Using colorimetric method for determination of NAG, samples of 70 participants were examined (35 RA patients treated with Ketoprofen only, 35 RA patients treated with combined use of Methotrexate and Ketoprofen). The follow up was 5 time-intervals in the course of 24 weeks. There was moderate correlation between NAG and microalbuminuria (r=0,34) in the group of patients treated with Ketoprofen only, while statistically significant correlation (r=0,21) was seen in group of patients with combined use of Methotrexate and Ketoprofen. NAG enzymuria in size, number of patients registered, and time of appearance were greater and appears earlier in the group with the combined use of Methotrexate and Ketoprofen compared with the mono-therapy with Ketoprofen. Mean urinary NAG induction was increasing with the concomitant use of Methotrexate and Ketoprofen. Methotrexate is more potent NAG inductor than Ketoprofen and provokes greater tubular enzymuria than Ketoprofen.

Highlights

The aim of this study was to determine the effect of initial therapy with some disease modifying antirheumatic drugs (DMARDs) (Methotrexate and Ketoprofen) on glomerular and tubular integrity in patients with Rheumatoid arthritis (RA)
Analyzing the group of patients treated with combined use of Methotrexate and Ketoprofen, in relation with the distribution of patients according to the values of NAG in the five probes, one could conclude that elevated values of NAG are registered in 31 (89%) of patients in the 8th week (3rd probe), when the degree of mean urinary NAG induction is highest (1.99±1.00)
It shows that Methotrexate is more potent NAG inductor compared with Ketoprofen, but during their combined use, the mean urinary NAG induction is increased considering size and time of appearance (Table 1, Figures 1 and 2)

Summary

Introduction

The aim of this study was to determine the effect of initial therapy with some disease modifying antirheumatic drugs (DMARDs) (Methotrexate and Ketoprofen) on glomerular and tubular integrity in patients with Rheumatoid arthritis (RA). Objectives: To determine whether there is a change in clinical and laboratory indicators of renal function in course of the follow up of treatment and whether that change correlates with the dynamics of the quantity of enzymes excreted in urine and reactants of the acute phase. NAG enzymuria in size, number of patients registered, and time of appearance were greater and appears earlier in the group with the combined use of Methotrexate and Ketoprofen compared with the mono-therapy with Ketoprofen. Lysosomal system of the tubules is dynamic system, and low level of lysosomal enzymes, found in normal urine, is result of normal exocytotic and pinocytotic activity of the tubular endothelial cells [1]. With the absence of the toxic stimulus, decrease of the urinary enzyme activity will be followed by regeneration of tubular cell function

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