Background: 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. Materials and Methods: 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. Results: 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. Conclusions: Methotrexate is more potent NAG inductor than Ketoprofen and provokes greater tubular enzymuria than Ketoprofen. www.nephropathol.com DOI:10.5812/nephropathol.8989 J Nephropathology. 2013; 2(1): 36-52 Original Article Journal of NephropathologyImplication for health policy/practice/research/medical education: Determination of the urinary N-acetyl-β-D-glucosaminidase together with the urinary creatinine excretion could serve as a more sensitive test for renal lesions in patients suffering from rheumatoid arthritis, as an additional diagnostic tool, and the information for the status of the disease.

The Diagnostic Value of N-Acetyl-β-D-Glucosaminidase and Microalbumin Concentrations in Rheumatoid ArthritisThe purpose of this research was to compare the diagnostic values of laboratory variables, to present quantitative evaluations of the diagnostic sifted test with reference to sensitivity and specificity, the predictive value of the positive and negative test and precision of the test for N-acetyl-β-D-glucosa-minidase (NAG), microalbumin, rheumatoid factor (RF), Creactive protein (CRP), DAS 28 index, in early diagnosis of untreated rheumatoid arthritis (RA), and to define the effect of untreated rheumatoid arthritis on glomerular and tubular function. Using a colorimetric assay for the determination of Nacetyl-β-D-glucosaminidase and an immunoturbidimetric assay for the determination of urinary albumin, the samples of serum and urine have been examined in 70 participants (35 RA who were not treated, 35 healthy controls). RF was defined with the test for agglutination (Latex RF test) in the same participants. Out of 35 examined patients with RA, in 13 we found the presence of NAG enzymuria (sensitivity of the test 37.14%), while microalbuminuria appeared in 4 patients (sensitivity of the test 11.42%). RF appeared in 17 patients (sensitivity of the test 48.57%). Four patients were NAG and RF positive, while 3 patients were microalbuminuria and RF positive. Among 18 RF negative patients, 9 patients were NAG positive, and 1 patient presented with microalbuminuria. Among 17 RF positive RA, the presence of NAG was found in 4 patients, and the presence of microalbuminuria in 3 patients. Among 18 RF negative RA, NAG enzymuria appeared in 9 patients. Microalbuminuria was present in 1 patient. In the healthy control group, 8 patients were NAG positive, 2 patients were positive for microalbuminuria. RF appeared in 2 patients. NAG has higher sensitivity than microalbuminuria in the detection of asymptomatic renal lesions in untreated RA.

Effect of abdominal aorto-venocaval shunt (AVS) on the automaticity of the pulmonary-vein myocardium was studied in the rat. Spontaneous electrical activity was observed in one third of the isolated pulmonary-vein preparations from the AVS rats, but scarcely in those from sham-operated rats; the activity was induced by tertiapin and suppressed by carbachol or chelation of intracellular Ca(2+). The evoked action potentials in AVS rats had less negative resting membrane potential and longer action potential duration than those in sham-operated rats. These results suggest that the automaticity of the rat pulmonary-vein myocardium is manifested under chronic volume overload.

Ten patients, mean age 51.50 +/- 3.03 years, with degenerative rheumatism on NSAID treatment without any sign of renal disease, and 11 control subjects, mean age 43.50 +/- 1.51 years, were studied. NSAID treatment was of 11.30 +/- 5.60 weeks duration in average, with ibuprofen, naproxen, or indomethacin. Urinary excretion of three specific renal tubular enzymes--AAP: alanine-amino-peptidase, GGT: gamma-glutamyl-transpeptidase, and beta-NAG: beta-N-acetyl-glucosaminidase, were determined in 8-h overnight urine samples, as well as GFR creatinine clearance/1.73 m2, urinary volume/8 h, specific gravity of the urine, proteinuria and glucosuria. In the group treated with NSAIDs, urinary excretion of the enzymes was significantly higher than in the control group--AAP: 1414.20 +/- 317.60, 864.20 +/- 94.42, p < 0.00001; GGT: 8034.6 +/- 1378.55, 5095.64 +/- 614.40, p < 0.00001, and beta-NAG: 1644.60 +/- 299.97, 964.82 +/- 142.00, p < 0.00001. Patients on NSAID treatment showed abnormal urinary excretion of AAP in 7/10 cases, of GGT in 6/10, and of beta-NAG in 7/10 cases. Duration of the treatment did not correlate with the urinary excretion of the enzymes. Age was in correlation with the urinary excretion of the enzymes only in the control group, r = 0.52, p < 0.005 for AAP, r = -0.43, p < 0.02 for GGT, and r = -0.23, p < 0.05 for beta-NAG.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Aminopeptidase, γ-Glutamyl Transferase and β2-microglobulin as Diagnostic Markers in Patients with Rheumatoid Arthritis The purpose of this research is to evaluate the values of alanine aminopeptidase (AAP), γ-glutamyl transferase (γ-GT), and β2-Microglobulin in urine (β2-M), in untreated rheumatoid arthritis (RA) and to define the effect of untreated rheumatoid arthritis on the tubular function and brush border region. We used a kinetic assay for AAP, standard methods by the IFCC for γ-glutamyl transferase and MEIA for the determination of β2-Microglobulin in urine in 70 participants (35 untreated RA patients, 35 healthy individuals). From the total of 35 RA patients, 24 patients had AAP (sensitivity of the test 68.57%), 16 patients had γ-GT enzymuria (sensitivity of the test 45.71%), while the presence of β2-Microglobulin in urine was found in a very low percentage. Out of 18 RF negative patients, 14 patients are AAP positive, 10 patients were γ-GT positive, while the presence of β2-Microglobulin in urine was not detected. Among 17 RF positive RA patients, the presence of AAP was noticed in 10, the presence of γ-GT in 6 patients, while the presence of β2-Microglobulin in urine was not detected. AAP has higher sensitivity than γ-GT and β2-Microglobulin in the detection of asymptomatic renal lesions in untreated RA.