Ascorbic acid ameliorates renal injury in a murine model of contrast-induced nephropathy.

BACKGROUND: Contrast induced nephropathy (CIN) is the commonest cause of iatrogenic renal injury and its incidence has increased with the advent of complex endovascular procedures. Evidence suggests that ascorbic acid (AA) has a nephroprotective effect in percutaneous coronary interventions when contrast media are used. A variety of biomarkers (NGAL, NGAL:creatinine, mononuclear cell infiltration, apoptosis and RBP-4) in both the urine and kidney were assayed using a mouse model of CIN in order to determine whether AA can reduce the incidence and/or severity of renal injury. METHODS: Twenty-four BALB/c mice were divided into 4 groups. Three groups were exposed to high doses of contrast media (omnipaque) in a well-established model of CIN, and then treated with low or high dose AA or placebo (saline). CIN severity was determined by measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL):creatinine at specific time intervals. Histological analysis was performed to determine the level of mononuclear inflammatory infiltration as well as immunohistochemistry to determine apoptosis in the glomeruli by staining for activated caspase-3 and DNA nicking (TUNEL assays). Reverse transcriptase PCR (rtPCR) of mRNA transcripts prepared from mRNA extracted from mouse kidneys was also performed for both lipocalin-2 (Lcn2) encoding NGAL and retinol binding protein-6 (RBP4) genes. NGAL protein expression was also confirmed by ELISA analysis of kidney lysates. RESULTS: Urinary NGAL:creatinine ratio was significantly lower at 48 h with a 44% and 62% (204.3µg/mmol versus 533.6µg/mmol, p = 0.049) reduction in the low and high dose AA groups, respectively. The reduced urinary NGAL:creatinine ratio remained low throughout the time period assessed (up to 96 h) in the high dose AA group. In support of the urinary analysis ELISA analysis of NGAL in kidney lysates also showed a 57% reduction (12,576 ng/ml versus 29,393 ng/ml) reduction in the low dose AA group. Immunohistochemistry for apoptosis demonstrated decreased TUNEL and caspase-3 expression in both low and high dose AA groups. CONCLUSIONS: Ascorbic acid reduced the frequency and severity of renal injury in this murine model of CIN. Further work is required to establish whether AA can reduce the incidence of CIN in humans undergoing endovascular procedures.

Treatment of serious gram-negative infections with aztreonam.

Aztreonam (SQ 26,776) is the first parenteral monobactam agent to be used in patient trials. The agent has significant activity in vitro against facultative aerobic gram-negative bacteria but not against gram-positive or anaerobic bacteria. Aztreonam was used for a year to treat 106 hospitalized patients with a total of 131 documented gram-negative infections. Important exclusion criteria included granulocytopenia, hyperbilirubinemia, meningitis, patients less than 13 years of age, pregnancy, and history of anaphylaxis to penicillin. In this study of 35 men and 71 women, there were 67 cases of pyelonephritis (25% bacteremic), 19 of pneumonia (16% bacteremic), 10 of skin or soft-tissue infections, 9 cases of osteomyelitis, and 6 cases of postpartum endometritis. During the study period, 159 facultative aerobic gram-negative bacteria were tested for aztreonam susceptibility, and 144 (91%) were found to be susceptible. Eighty percent of infections were cured by both clinical and microbiological criteria and each of the other 26 infections showed clinical improvement. Eradication of the infecting organism was achieved in 89% of infections without adverse reaction or drug toxicity.