A Study of Tubular Dysfunction in Indian Patients With Lupus Nephritis

Abstract

Most reports mention isolated tubular dysfunction in active lupus nephritis and, hence, the present study was designed to investigate varied functional defects in Indian patients with stable lupus nephritis. Twenty patients with lupus nephritis were evaluated for evidence of renal tubular functional abnormalities. Disease activity was studied using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Renal histology was available for 12 patients, including six with WHO class IV disease and three each with class III and class V disease. Analysis of activity and chronicity indices as well as severity of tubulointerstitial involvement was also done on these biopsy specimens. Estimation of fractional excretion (FE) of beta-2 microglobulin (β 2 μg), 24-hour urinary excretion of alkaline phosphatase (ALP), leucine aminopeptidase (LAP) and gamma-glutamyltransferase (GGT), as well as the short ammonium chloride (NH 4 Cl) test, were performed in all patients. Ten healthy volunteers served as controls. The mean creatinine clearance (Ccr) was 58.9 ± 19.1 mL/min (range, 24.5-104.3 mL/min). Serum β 2 μg and FE-β 2 μg were elevated in all patients (mean, 5.5 ± 1.4 mg/L and 1.6 ± 0.9%, respectively). Urinary ALP excretion was elevated in 65% of patients, with a mean of 6.88 ± 5.08 μmol/L/min, and urinary GGT excretion was elevated in 50% of patients, with a mean of 59.43 ± 33.70 μmol/L/min. There was no significant correlation of serum β 2 μg, FE-β 2 μg, and urinary ALP levels with Ccr or severity of proteinuria. Urinary GGT levels were increased proportionately to the decrease in Ccr. Only 20% of patients were unable to acidify their urine (pH < 5.3); the minimum urinary pH was higher in the lupus nephritis patients compared to controls (5.17 ± 0.58 vs 4.65 ± 0.26; p < 0.05). The mean baseline and peak titratable acidity were not significantly lower in lupus nephritis patients. There was significant correlation of all renal functional abnormalities with the severity of SLEDAI and tubulo-interstitial involvement. Both proximal and distal tubular functional abnormalities were seen in patients with lupus nephritis and can co-exist. FE-β 2 μg is the most sensitive indicator of proximal tubal dysfunction. Assessment of urinary enzymes may give an early indication of tubular dysfunction. Disease activity and severity of tubulo-interstitial involvement influence these abnormalities. [ Hong Kong J Nephrol 2003;5(2):90-7]