Clinicopathologic features of antineutrophil cytoplasm autoantibody (ANCA)-associated acute renal failure in Chinese patients

Summary: The clinical course and renal pathologic features of anti-neutrophil cytoplasm auto-antibody (ANCA)-associated renal disease were studied among Chinese patients from a single centre. Eight ANCA positive patients with acute renal impairment were studied, four of whom required dialysis shortly after presentation. Their mean age at presentation was 61.6 ± 4.2 years. Renal histology, obtained in seven patients, showed paucummune crescentic glomerulonephritis in five patients, interstitial nephritis in two patients, and small vessel vasculitis in one patient. Pulmonary baemorrhage was the other common disease manifestation, present in four of the eight patients, necessitating ventilatory support in three patients. Neurologic, cutaneous, and gastrointestinal involvement were also observed. Seven of the eight patients tested positive for pANCA and anti-myeloperoxidase, while cANCA was detected in one patient of the eight patients, six (75%) responded to therapy, consisting of prednisolone and cyclophosphamide in five patients, and antibacterial therapy alone in one patient, who had interstitial nephritis but no evidence of vasculitis. Two patients died from sepsis and severe debilitation one month after presentation. of the other six patients, five had significant improvement of renal function, while one became dialysis-dependent. the levels of ANCA and C-reactive protein remained normal, and disease reactivation was not observed during follow-up for 32.4 ± 6.1 months. Patient and renal survival rates at one year were 75% and 62.5%, respectively. It was concluded that the clinical and pathologic features of ANCA-associated renal disease in Chinese patients are, in general, similar to those described in Caucasians. Nevertheless, cANCA-positivity is distinctly uncommon. the demonstration of interstitial nephritis in two of the eight patients underlines the importance of renal biopsy for correct histologic diagnosis. Early institution of aggressive immunosuppression and supportive therapies are essential for the achievement of favourable outcome in patients with vasculitis.     

Purification and characterization of the human neutrophil NADH- cytochrome b5 reductase

NADH-cytochrome b5 reductase is the predominant NADH-diaphorase found in the human neutrophil (Blood 62:152, 1983). Although this reductase segregates with the light membranes of nitrogen-cavitated neutrophils separated on Percoll gradients (which include the plasma membrane markers alkaline phosphatase and NADPH-oxidase), it is approximately 95% excluded from plasma membrane-enriched phagocytic vacuoles. The reductase constitutes approximately 5% of the light membrane fraction FAD-flavoprotein (14.8 +/- 5.5 pmol/mg protein) and was found in equimolar concentration with a high potential b cytochrome also present in this light membrane fraction and tentatively identified as cytochrome b5. Isolation of the reductase from human neutrophils was accomplished by Triton X-114 solubilization of the light Percoll gradient membranes, followed by temperature-dependent phase separation and then affinity chromatography on AMP-Sepharose. The active preparation contained 1.3 mol FAD/mol protein, migrated on sodium dodecyl sulfate-polyacrylamide gels as a single band corresponding to an apparent mol wt of 45,000 daltons, exhibited a pl of 5.7 on chromatofocusing and was obtained in greater than 70% yield, with an overall purification of almost 900-fold. The purified enzyme was characterized by a high specificity for NADH as electron donor (Km = 6.4 mumol/L v Km greater than 1.6 mmol/L for NADPH) and exhibited a maximal turnover of ca. 30,000 min-1 at 22 degrees C with either ferricyanide or cytochrome b5 (Km = 10 nmol/L) as electron acceptor. Although the physical characterization and biochemical properties described here demonstrate that this neutrophil NADH b5 reductase is similar to the corresponding liver and erythrocyte enzymes, its unique function in the neutrophil has yet to be determined.     

High human exposure to cobalt and other metals in Katanga, a mining area of the Democratic Republic of Congo

Background and objectives

The human health impact of the historic and current mining and processing of non-ferrous metals in the African Copperbelt is not known. This study assessed the exposure to metals in the population of Katanga, in the south east of the Democratic Republic of Congo, using biomonitoring.

Methods

Seventeen metals (including Cd, Co, Cu, Pb, U) and non-metals (including As) were measured by ICP-MS in urine spot samples from 351 subjects (32% women), aged 2-74 yr (mean 33 yr). Forty subjects (controls) lived 400 km outside the mining area; 311 subjects lived in the mining area, either very close (<3 km) (n=179; 6 communities) or moderately close (3-10 km) (n=132; 4 communities) to mines or smelting plants.

Results

For all metals (except Ni) urinary concentrations were significantly higher in subjects from the mining area than in control subjects. In subjects living very close to mines or smelting plants, the geometric means (25th-75th percentile) of urinary concentrations, expressed as μg/g creatinine, were 17.8 (10.9-29.0) for As, 0.75 (0.38-1.16) for Cd, 15.7 (5.27-43.2) for Co, 17.1 (8.44-43.2) for Cu, 3.17 (1.47-5.49) for Pb and 0.028 (0.013-0.065) for U, these values being significantly higher than those of subjects living 3-10 km from mines or industrial operations. Urinary Co concentrations were markedly elevated, exceeding 15 μg/g creatinine in 53% of the subjects, and even 87% of children (<14 yr), living very close to the mining areas. Urinary As was also high (79% above 10 μg/g creatinine in subjects living very close to the mining areas). Compared with background values from the US general population, subjects living very close to areas of mining or refining had 4-, 43-, 5- and 4-fold higher urinary concentrations of Cd, Co, Pb and U, respectively.

Conclusions

This first biomonitoring study of metal exposure in the African Copperbelt reveals a substantial exposure to several metals, especially in children. The urinary Co concentrations found in this population are the highest ever reported for a general population. The pathways of exposure and health significance of these findings need to be further investigated.