Drug-induced prerenal acute kidney injury (AKI) is characterized by a decrease in glomerular filtration rate and associated oliguria resulting from a decrease in renal blood flow, or in intraglomerular pressure caused by the administration of the drug. Fewer drugs are known to cause this type of AKI than those known to cause renal AKI. Attention must be paid to the increasing incidence of drug-induced prerenal AKI in patients with risk factors for renal ischemia, such as hemorrhage, dehydration, shock, heart failure, arteriosclerosis and advanced age. For patients with these risk factors who are treated with nephrotoxic drugs, it is important to distinguish between renal and prerenal AKI. In addition to increased serum creatinine and decreased urinary output (which are used as diagnostic criteria for both types of AKI), prerenal AKI can be differentiated from renal AKI based on a fractional excretion of sodium (FENa) of less than 1%, decreased urine sodium concentration and/or increased urine osmotic pressure. However, it should be noted that these tests are not routinely performed in clinical practice and consequently prerenal AKI is often misdiagnosed as renal AKI. This review describes the causative drugs of prerenal AKI, focusing particularly on non-steroidal anti-inflammatory drugs (NSAIDs), calcineurin inhibitors, renin-angiotensin system inhibitors and diuretics.
The number of patients with chronic kidney disease (CKD) has been continuously increasing in Japan. Therefore, proper use of renally eliminated drugs and potential nephrotoxic drugs has become more important. In Ehime University Hospital, pharmaãsts visit inpatients after their admission and check any drugs brought to hospital, and prevent over-dose administrating renally eliminated drugs in CKD patients. However, pharmacists cannot become involved with outpatients. There are concerns that outpatients may be at increased risk of over-dose administration of renally eliminated drugs. Therefore, in this study, we examined the prescription of renally eliminated drugs for outpatients. The subjects were 2969 outpatients prescribed renally eliminated drugs during July 2012. In 792 of the outpatients, serum creatinine levels and estimated glomerular filtration rate (eGFR) were measured. These 792 patients were classified by stage of CKD based on their eGFR. The eGFR was calculated as: 194 ✕ Cr-1.094 ✕ age-0.287 ✕ (female:0.739). Patients and dosages were retrospectively investigated. There were 295 patients with CKD stages 3 to 5 (37.2%), many of whom were prescribed renally eliminated drugs, such as silodosin, allopurinol, levofloxaãn, and famotidine. In 6 patients prescribed silodosin (40%), 7 patients prescribed allopurinol (9%), 5 patients prescribed levofloxaãn (8%), and 17 patients prescribed famotidine (7%), the drug had been overdose administration based on their renal function. In this study, we determined the use of renally eliminated drugs for outpatients. Our results indicate that CKD outpatients may have an increased risk of over-dose administration of renally eliminated drugs. Hospital pharmaãsts are working closely with health insurance pharmaães to prevent overdose administration of renally eliminated drugs for outpatients with CKD.
As an index of renal function in patients, the concentration of serum cystatin C (CysC) is known to be superior to serum creatinine. Recently, the estimated glomerular filtration rate calculated from CysC (eGFRcys) has been more frequently used than that calculated from serum creatinine (eGFRcreat) or than the estimated creatinine clearance (CCr). However, few reports have compared these parameters in many patients. The present study compares eGFRcys vs eGFRcreat and eGFRcys vs CCr in 1,163 in-patients of Hokkaido Gastroenterology Hospital, to clarify the reasons for the differences among these parameters and to specify the factor that most influences evaluation of renal function. The average eGFRcreat and average CCr of the 1,163 patients was found to be roughly the same, but eGFRcys was found to be higher than those parameters; the mean of difference between eGFRcyc and eGFRcreat, and that between eGFRcys and CCr was 27.6 and 21.4, respectively. To divide patients whose difference between eGFRcys and eGFRcreat or CCr was larger or smaller than the mean (27.6, 21.4), we used multiple logistic regression analysis to assess which factor most affects the renal function of patients. A significant correlation was found between [eGFRcys - CCr] and serum albumin level. Moreover, correlations were found between [eGFRcys - eGFRcreat] and gender, body mass index and serum albumin. These data suggest that the value of eGFRcreat and CCr were lower than eGFRcys, and that it changed enough to affect the renal function values. The factor influenãng this difference would not be muscle mass, but rather nutritional status.
[Purpose] It is assumed that the dose of febuxostat does not need to be adjusted even in patients with renal dysfunction. On the other hand, its package insert describes that it should be carefully administered to such patients because of limited experience. We therefore examined its clinical efficacy and adverse events in such patients. [Methods] We retrospectively reviewed the clinical records of 70 patients with chronic kidney disease (CKD) who received febuxostat, excluding those who concomitantly received anti-neoplastic agents and telaprevir, at our hospital between June 2011 and June 2013. Patients were divided into two groups based on the estimated glomerular filtration rate (eGFR) at the time of initiation of febuxostat: the mild-to-moderate group (MM group) consisting of 32 patients with CKD stage 1 to 3, and the severe group (S group) consisting of 38 patients with CKD stage 4 to 5.We compared febuxostat doses, serum uric aãd levels, and other laboratory data including AST, ALT, and CPK levels, drugs administered before febuxostat and concomitantly-administered drugs, and adverse events between the two groups at the initiation of febuxostat and 24 weeks. [Results] The mean dose of febuxostat at 24 weeks was 16.9 and 13.7 mg/day in the MM and S groups, respectively. The mean uric aãd level significantly decreased from 8.7 (before febuxostat) to 6.6 mg/dL (at 24 weeks) and from 9.4 to 6.8 mg/dL in the MM and S groups, respectively. The goal of uric aãd level under 7.0 mg/dL was achieved by 73.3% and 56.5% of the MM and S groups, respectively. Ten patients in the S group experienced adverse events such as CPK elevation or other abnormal laboratory data. However, most of them were mild and transient. [Discussion] Febuxostat could reduce the uric aãd level in the 38 patients with severe CKD and 32 patients with mild-tomoderate CKD at similar doses. No patient had to discontinue febuxostat due to severe adverse effects. Our results suggest that febuxostat at varying dosages can be administered to reduce the uric aãd level even in patients with severe renal dysfunction.