Urinary N-acetyl-beta-D-glucosaminidase (NAG) in lupus nephritis and rheumatoid arthritis.

Increased activity of urinary N-acetyl-beta-D-glucosaminidase (NAG) can be used as an early indicator of damage to the tubular epithelium. Systemic lupus erythematosus (SLE) is a multisystem autoimmune rheumatic disease. Nephritis is known as the most serious complication of SLE and the strongest predictor of poor outcome. In this study urinary NAG excretion was investigated in 24 SLE patients with normal renal function (serum creatinine < or =1.2 mg/dL) and the results were compared with those from 26 untreated patients with rheumatoid arthritis (RA) and 27 healthy controls. The SLE patients were divided into two groups according to their urinary total protein levels: group A consisted of 16 patients with < or =3.5 g/day proteinuria, and group B consisted of eight patients with nephrotic-range proteinuria (>3.5 g/day). Serum and urinary creatinine, total urinary protein levels, and urinary NAG excretion were measured in patients with SLE and RA. In addition, serum C3 and C4 levels were determined in the SLE patients. Renal biopsies were performed in all of the SLE patients. Glomerular lesions were classified according to WHO criteria for lupus nephritis (LN) I-V. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was used to assess disease activity. Urinary NAG excretion was significantly higher in the SLE groups than in the healthy controls (P<0.001). In urinary NAG excretion there was also significant difference between SLE groups and RA patients (P<0.001). However, there was no significant difference in NAG excretion between the RA and control groups (P=0.062). Urinary NAG excretion was significantly higher (P<0.05) in group B compared to group A. There were no differences in SLEDAI scores, ages, and serum creatinine levels between study groups (P=0.601, P=0.285, P=0.669, respectively). Elevated SLEDAI values and hypocomplementemia were detected more often in younger patients (P<0.010, r=-0.529 and P<0.010, r=-0.569, respectively). There was a strong positive correlation between proteinuria and urinary NAG activity (P<0.001, r=0.759). These results suggest that the determination of urinary NAG activity may be a useful supplement to the routine biochemical analysis performed on the urine in cases of SLE.

Increased excretions of glycosaminoglycans and heparan sulfate in lupus nephritis and rheumatoid arthritis.

Urinary glycosaminoglycans (GAG) and heparan sulfate (HS) are considered to be markers of early renal involvement. This study was undertaken to demonstrate their excretion patterns in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) with and without arthritis. Serum creatinine and urinary GAG, HS, microalbumin, and creatinine measurements were made in 51 biopsy-proven lupus nephritis (LN) cases, 12 RA patients, and 21 healthy controls. Urinary GAG and HS levels were higher in the LN and RA groups than in controls. Heparan sulfate excretions and SLE disease activity index (SLEDAI) scores were no different between SLE patients with classes 1 and 2 (group A) and those with classes 3, 4, and 5 (group B) renal involvement. However, GAG and microalbumin excretions were significantly high in the latter. There were no differences in GAG and HS excretions between normoalbuminuric, microalbuminuric, and macroproteinuric SLE patients or between those with and without arthritis. In conclusion, urinary GAG and HS, being unrelated to the presence of arthritis, are independent markers of LN. Extrarenal causes or subclinical renal involvement may be responsible in RA due to their increased excretion in these patients.

Effect of carbon monoxide on dopamine and glutamate uptake and cGMP levels in rat brain.

After the recognition of nitric oxide (NO) as a messenger molecule in the nervous system, carbon monoxide (CO) has received attention with similar properties. The present study aims to elucidate the effects of CO on synaptosomal dopamine ((3)H-DA) and glutamate ((3)H-Glu) uptake and on cGMP levels; possible interaction between NO and CO systems was also evaluated. Our results provide evidence for the inhibition of DA and Glu uptake by CO in a time-, dose-, and temperature-dependent manner in rat striatum and hippocampus, respectively; the inhibition observed was sexually dimorphic with more pronounced effects in females. Basal cGMP levels were higher in female rats than males in the striatum and exogenous CO increased striatal cGMP levels only in males; no effect of CO was observed in the hippocampus. In vivo nitric oxide synthase (NOS) inhibition increased DA and Glu uptake; however, CO was still effective in inhibiting uptake following NOS inhibiton. Taken together, these findings suggest a role for CO in trans-synaptic regulation through modulation of DA and Glu transporters and of cGMP levels; the effect on cGMP levels is independent of NOS activity and appears to be sexually dimorphic and region specific.