Urinary excretion of renal brush border membrane enzymes in leprosy patients--effect of multidrug therapy.

Renal function at the brush border membrane level has been studied using characteristic enzymes, such as alkaline phosphatase, leucine-aminopeptidase and gamma-glutamyl transpeptidase. Urinary enzyme studies were performed using leprosy patients, classified on the basis of bacteriological index (BI>3; n=20, BI<3; n=12, BI-ve; n=10) and compared with control subjects (n=10). The role of enzymuria in monitoring WHO-recommended multidrug therapy (MDT) has been evaluated in these patients. A significant increase in the enzyme activities (p<0.01), as well as significant (p<0.01) proteinurea in 24-hour urine samples of both the smear positive groups (BI>3, BI<3) prior to therapy compared to control subjects, indicates proximal tubular functional impairment at brush border membrane level. In the smear negative (BI-ve) group, no significant difference was observed in enzyme activities as compared with the control group. In a follow-up study (BI>3;n=13, BI<3; n=4) the activities of all the enzymes decreased significantly in all the groups when compared to a corresponding untreated group. The follow-up study was not carried out on the smear negative group. The surprising finding was the differential behaviour of r-glutamyl transpeptidase, whose activity increased significantly (p<0.01) even after therapy in BI>3 group when compared with untreated patients. However in a detailed work-up including hepatic and renal function tests, the serum biochemistry was found to be normal both before and after therapy. Urinary excretion of brush border enzymes seems to be related to bacterial load, and their potential in studying the effect of MDT remains unclear.

Role of reactive oxygen species in renal damage in experimental leprosy.

Renal involvement is known to occur in leprosy. In the present study the possible role of reactive oxygen species (ROS) in causation of renal damage in mice infected with Mycobacterium leprae has been investigated. At least six animals from each group (control and infected) were killed at 0 day, 3, 6 and 9 months postinfection. The results showed a significant increase in the chemiluminescence (CL) response of peritoneal macrophages which was maximum between 3 and 6 months. No significant increase was observed in CL response of blood neutrophils. A significant increase in lipid peroxidation was observed at 3 and 6 months as evident by an increase in malondialdehyde levels. The increased ROS production might be the cause of lipid peroxidation. The renal damage is alos evident by decrease in the activity of renal brush border membrane enzymes, namely, alkaline phosphatase, leucine aminopeptidase and r-glutamyl transpeptidase. Thus ROS might play a role during early stages of M. leprae infection but in the later stages other immunological mechanisms may overpower the effect of ROS.

Detection of rifampicin-induced nephrotoxicity by N-acetyl-3-D-glucosaminidase activity.

The objective of the present study was to assess renal damage, if any, by non-invasive technique, viz NAG activity in urine and GFR in patients on continuous and intermittent rifampicin therapy. Eighty-four tuberculosis patients for cross-sectional study and six subjects for longitudinal study on antitubercular therapy and ten patients on withdrawal of rifampicin participated in the investigation; 13 leprosy patients intermittently treated with rifampicin were also included. Twenty-seven normal subjects served as controls. Rifampicin on continuous use resulted in a progressive increase in enzymuria with no change in GFR. An additive toxic effect was obvious in patients receiving streptomycin; when the treatment was withdrawn the urinary NAG activity stabilized within 15-21 days. However, patients receiving rifampicin intermittently did not show any evidence of renal damage. The results suggest that there is a need for monitoring renal damage, particularly on antitubercular therapy, when nephrotoxic agents are administered together.

Serum lactate dehydrogenase in murine leprosy: source and isozymes.

The bulk of the lactate dehydrogenase (LDH) that increases in the serum of mice infected with Mycobacterium lepraemurium (MLM) derives from the liver and corresponds to the isozyme V. MLM-induced granulomas continuously arise in the liver and steadily increase in size until the animal's death. Growing granulomas push the adjacent hepatocytes away and cause them to disrupt and to release their cytoplasmic contents, including LDH. The LDH is then picked up by the infiltrating phagocytes and/or admixed with the circulating blood. Other LDH-containing organs (including the testis with its additional isozyme LDH-X) in the infected or normal animals do not seem to significantly contribute to the serum levels of LDH. The study of the liver-associated histochemical and biochemical changes in this controlled model of murine leprosy allows us to gain insight into the overall pathology of this mycobacteriosis. In some respects this sheds light on the liver involvement in human leprosy; a subject on which results of all sorts have been published.

Urinary excretion of renal brush-border enzymes in lepromatous leprosy--a preliminary investigation.

Activities of the brush-border enzymes, alkaline phosphatase, maltase, leucine aminopeptidase, and gamma-glutamyl transpeptidase, were measured in urine samples of 25 lepromatous leprosy patients and an equal number of age-matched healthy controls. None of the patients were shown to be suffering from any other systematic disease. The enzymatic activities were shown to be significantly elevated in leprosy patients when compared to controls.