Urinary heme oxygenase-1 as a possible marker for early diagnosis of diabetic nephropathy and retinopathy

Abstract

Background Early detection of DN helps in primary prevention of this complication. Microalbuminuria has been proven as a useful biomarker for diagnosis of DN. Heme oxygenase-1 is an essential enzyme in heme catabolism induced by oxidative stress. It plays a pivotal role in maintaining renal function and protecting renal structure under conditions of oxidative stress such as proteinuria. Urinary heme oxygenase-1 may appear early before the development of microalbuminuria, so it can be used as a marker for early detection of DN. Patients and methods A total of 80 type 2 diabetic patients with and without DN were compared with 20 healthy control subjects matched in age and sex. They were divided into two groups: group I included 40 normoalbuminuric patients with albumin-to-creatinine ratio (ACR) less than 30 mg/g, and group II included 40 microalbuminuric patients with ACR 30–300 mg/g. For all studied groups, full history and clinical examination were done. Glycosylated hemoglobin, urinary ACR (mg/g), estimated glomerular filtration rate, urinary creatinine, and urine hemoxygnase-1 (UHO-1) and UHO-1/creat ratio by enzyme-linked immunosorbent assay were performed. Results Microalbuminuric patients had significantly higher levels of UHO-1 (5.02) compared with normoalbuminuric patients (3.01) and controls (0.3), with P less than 0.001, and normoalbuminuric patients had significantly higher levels of UHO-1 compared with control subjects, with P less than 0.001. UHO-1/Cr levels were significantly positively correlated with urinary ACR but significantly negatively correlated with glomerular filtration rate and systolic and diastolic blood pressures (P<0.001). By linear regression, there was a highly significant correlation between HO1and estimated glomerular filtration rate. Conclusion HO-1 was increased in patients with proteinuria and increased before the onset of microalbuminuria, indicating UHO-1 is more sensitive than albumin for the detection of early DN with no relation to diabetic retinopathy.