Omeprazole-induced acute interstitial nephritis is not related to CYP2C19 genotype or CYP2C19 phenotype.

AIM: Omeprazole-induced acute interstitial nephritis (OIAIN) is a rare adverse event. It is unknown if this is an idiosyncratic immune mediated reaction or if it relates to direct drug toxicity. Individuals who are homozygous for the variant alleles of CYP2C19 are poor metabolizers of omeprazole and have a greater exposure to the drug. The aim of this study was to determine the prevalence of the CYP2C19 poor metabolizer genotype and phenotype in patients with OIAIN. METHODS: Twenty patients were genotyped for the CYP2C19 variant alleles (2, 681G>A and 3, 636G>A) by RFLP-PCR analysis and eighteen phenotyped for CYP2C19 metabolizer status. RESULTS: The frequency of the CYP2C19 2 allelic variant was 12.5%, no 3 allelic variants were detected and no patient was a homozygous variant genotype. This was not different from the expected frequency. 33% of subjects were phenotypically CYP2C19 poor metabolizers. CONCLUSIONS: There was discordance between CYP2C19 genotype and phenotype. However, up to 45% of healthy elderly subjects have a poor metabolizer phenotype. Thus neither CYP2C19 poor metabolizer genotype nor phenotype is a risk factor for OIAIN.

Proton pump inhibitors and acute interstitial nephritis: report and analysis of 15 cases.

AIM: Although proton pump inhibitors (PPI) are usually safe and effective therapeutic agents, serious adverse effects can occur. The aim of the present study was to report and analyse the clinical features of 15 patients with acute interstitial nephritis (AIN) and acute renal failure from PPI that were referred to renal services in Auckland over a period of 3 years. METHODS: The clinical presentation, therapeutic drugs, demographic details and renal outcome of the patients were considered. The population at risk and total PPI exposure were able to be defined. The diagnosis of AIN was made by renal biopsy in 12 cases. In all patients, the time-course of drug exposure and improvement of renal function on withdrawal suggested PPI were causal. RESULTS: The median patient age was 78 years. The mean baseline serum creatinine level was 83 micromol/L, peak level 392 micromol/L, and recovery level 139 micromol/L. The erythrocyte sedimentation rate (ESR) and C-reactive protein were elevated at the time of diagnosis in the 11 and 12 patients, respectively, where this information was collected (ESR mean 85 mm/h, and C-reactive protein mean 81 mg/L). AIN occurred at 8 per 100 000 patient years (95% confidence level 2.6-18.7 per 100 000 patient years). Although four patients presented with an acute systemic allergic reaction, 11 were asymptomatic with an insidious development of renal failure. CONCLUSION: PPI are now the most commonly identified cause of AIN in the Auckland area. Recovery occurs after withdrawal of the drug but is often incomplete. Early diagnosis may be facilitated by clinician awareness of the insidious onset of renal failure, and an elevated erythrocyte sedimentation rate and C-reactive protein.