Rhabdomyolysis may account for about 10% of all cases of acute renal failure (ARF). This study was performed to explore the protective influence of proanthocyanidins from seeds of grape in an experimental model of myoglobinuric ARF. Rats were injected with 50% glycerol (8 mL/kg, im) followed immediately and daily in the next three days by ip proanthocyanidins (20 mg/kg) or saline. After 96 h rats were sacrificed and kidney morphology, kidney cortex peptidase activities, and malondialdehyde (MDA) content were determined. A moderate renal failure was produced by glycerol injection with blood urea of 31.8+/-11.0 vs. 7.68+/-0.24 m mol/L, and serum creatinine of 153. +/-38.2 vs. 39.6+/-9.0 micromol/L, in glycerol-induced ARF vs. control rats, respectively. Rats that received proanthocyanidins in addition to glycerol had significantly lower (p < 0.01) blood urea and serum creatinine levels compared to those receiving glycerol alone. These functional differences between the glycerol and glycerol plus proanthocianidins groups were also confirmed histologically. Kidney cortex dipeptidylpeptidase IV (DPP IV) activity was not significantly changed in glycerol-induced ARF, however, markedly increased after proanthocyanidins treatment. Kidney cortex malondialdehyde content was found significantly increased in glycerol-induced ARF over control level, and was markedly reduced by proanthocyanidin treatment. Taken together, these results provide strong evidence for the protective role of proanthocyanidins from seeds of grape in glycerol-induced ARF. The effect is probably due to the antioxidant activity of proanthocyanidins and to increased expression of kidney cortex DPP IV with effective degradation of TNF-alpha. This may provide therapeutic opportunities of preventing and/or treating myoglobinuric ARF in humans.

Cellular immune disturbances, and T lymphocyte function in particular, have been previously implicated in idiopathic nephrotic syndrome (INS) of childhood. There are different patterns of cytokine expression in various forms of glomerulonephritis, which suggests that local production of these peptides plays an important role in the pathogenesis and progression of glomerulonephritis. To investigate T-cell and monocyte/macrophage cytokine production in INS, interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) of 11 children with steroid-sensitive nephrotic syndrome (SSNS), 9 with focal segmental glomerulosclerosis (FSGS), and 17 healthy controls was determined. Children with SSNS were studied in relapse, during corticosteroid treatment, and in stable remission, off corticosteroid treatment. IL-12 was not detected in serum, urine, and in supernatants of unstimulated PBMC. IL-12 production by concanavalin A (Con A)-stimulated PBMC of children with SSNS and FSGS was not different from controls. IFN-gamma production by Con A-stimulated PBMC was decreased in children with relapsing SSNS, both in relapse and and during corticosteroid treatment. However, in stable remission it was similar to controls. Markedly decreased IFN-gamma production (P<0.001) was observed by pokeweed mitogen-stimulated PBMC of relapsing SSNS patients and moderately decreased production by PBMC of FSGS patients. This study has established a decreased production of IFN-gamma by PBMC of relapsing SSNS and FSGS patients, but does not allow differentiation between these two different conditions. IL-12 did not have a pathogenic role in either SSNS or FSGS.

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The acute effects of acetaminophen, a commonly used as analgesic drug, upon the urinary excretion of some proteins and enzymes as markers of kidney damage, was investigated. Patients with chronic glomerulonephritis (GN) and Balkan endemic nephropathy (BEN), having kidney vulnerable to toxic drugs, were enrolled in the study. Timed urine specimens were collected: before drug administration, and in 3-hour periods for 24 hours after an oral dose of 2 g of acetaminophen. Urinary excretion of albumin before acetaminophen treatment was significantly higher in patients with GN and BEN than in healthy adults, however, beta 2-microglobulin excretion was increased in BEN patients only. Urinary excretion of creatinine markedly increased immediately after acetaminophen ingestion. Urinary excretion of total protein and albumin was not changed after acetaminophen administration. However, acetaminophen treatment produced a significant increase in beta 2-microglobulin excretion in patient with BEN and GN, and in clinically healthy members of nephropathic families. Excretion of aminopeptidase N (APN) activity before acetaminophen treatment was significantly higher in patients with GN, however, NAGA excretion was higher in both GN and BEN patients than in healthy controls. After acetaminophen administration urinary excretion of APN, dipeptidylpeptidase IV (DPP IV), gamma-glutamyltranspeptidase (GGT) and N-acetyl-beta-D-glucosaminidase (NAGA) did not increase significantly in any group studied. This study has shown that urinary excretion of APN, DPP IV, NAGA and GGT, as markers of kidney brush border and lysosomal damage, did not change after 2 g of acetaminophen taken orally. beta 2-microglobulin was a marker of acute acetaminophen nephrotoxicity in kidney disease patients and in clinically healthy adults from nephropathic families.

Balkan nephropathy (BN) has not been described in children. However, some previous studies have revealed abnormalities of the urinary tract in children from families with BN. In the present study, urinary excretion of albumin was studied in 703 healthy children, age 9-13 years, from endemic and non-endemic settlements around the South Morava River. Since BN is an environmentally induced disease, with possible seasonal variation of toxicant(s), children were studied three times a year: spring, autumn, and winter. After a water load of 15 ml/kg body weight, a 3-h urine sample was collected, from 7 to 10 a.m. Albumin excretion in urine was highest in children from families with BN in all three periods investigated. It was significantly different from excretion in children from the city, and in autumn it was also different ( P<0.01) from children in non-endemic families. Correlation analysis of albumin excretion with some urinary markers of tubular nephrotoxicity shows the highest correlation with both beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase in endemic villages in autumn. If the upper limit of albumin excretion is set at 8.5 mg/mmol creatinine, then in autumn increased albumin excretion was found in 15 of 229 children from endemic settlements and in only 5 of 454 children from non-endemic areas ( P<0.0001). Evidence is presented that in autumn children from families with BN excreted significantly more albumin than those from non-endemic families but living in the same settlements, or from children living outside of the endemic region in the city of Nis.