Urinary neopterin and indices of renal involvement in rheumatoid arthritis

There is increasing evidence that renal disease is presumed to be one of the main
causes of mortality among rheumatoid arthritis (RA) patients. Thus, it is important to
periodically carryout sensitive and reliable measures for renal function to pickup the
earliest signs of renal dysfunction. In this regard, the aim of the present work is to
look for the most predictable urinary index for early renal involvement in RA.
Moreover, the study tried to find whether urinary neopterin levels give an indication
about the renal affection in RA.
Urine samples were obtained from 49 RA patients. Most of the studied RA
patients (91.84%) were on combined therapy [non-steroidal anti-inflammatory drugs
(NSAIDs), disease modifying anti-rheumatic drugs (DMARDs), and/or steroids]. The
activity of the disease was evaluated on the basis of clinical and routine
investigations. In addition, 15 urine samples were obtained from healthy controls.
For all the studied groups traditional kidney function tests were performed. Specific
urinary measures for renal function were determined namely, microalbuminuria,
beta-2-microglobulin (β2M), N-acetyl glucosaminidase (NAG), and gamma glutamyl
transferase (GGT). Furthermore, urinary neopterin levels were estimated in all the
studied groups. Receiver Operating Characteristics (ROC) curve was used to select
the best cutoff values for identifying the sensitivity and the specificity of the diagnostic
test.
The present study recorded 23 out of 49 (46.93%) RA patients had low creatinine
clearance (CrCl), 13 (26.53%) had macroalbuminuria, 17 (34.69%) had
microalbuminuria, and 9 (18.36%) had haematuria. A significant elevation of the
levels of microalbumin, β2M, and neopterin, and activities of NAG and GGT was
revealed in urine of RA patients as compared to control group. However, there were
only an increase in the levels of microalbuminuria and urinary neopterin in RA
patients with extra-articular manifestations as compared to RA patients without. On
the other hand, RA patients at risk of renal affection (with macroalbuminuria and/or
low CrCl) had high microalbuminuria and β2M levels. Also, the significant increase
of the activities of NAG and GGT was observedin those patients when compared to
those with normoalbuminuria and/or normal CrCl. Regarding the ROC plot, the area
under the curve (AUC)>0.7 indicates a discriminating strength of statistical
significance. ROC plot analysis showed that microalbuminuria, β2M, NAG, GGT and
neopterin had discriminating power for renal affection among RA patients (AUC
0.90, 0.956, 0.77, 0.92, and 0.71 respectively). Urinary neopterin was positively
correlated with ESR, urea, microalbumin, and urinary β2M (r=0.6, p<0.001; r=0.31,
p<0.05; r=0.51, p<0.001 and r=0.43, p<0.01 respectively).
In conclusion, the regular urine examination by simple and sensitive indices for
early identification of renal affection in RA could guide the clinicians for a suitable
line of therapy. The elevation of urinary neopterin levels was related to extra-articular manifestations as well as some kidney function tests. Such findings might
clarify to some extent the role of urinary neopterin as an indicator of renal
involvement in RA patients particularly those with active disease.