P1035urinary Heme Oxygenase 1 as a Marker for Early Diagnosis of Diabetic Nephropathy

Abstract

Background and Aims Heme oxygenase 1 is an essential enzyme in heme catabolism induced by oxidative stress.It induced in avariety of kidney substructres in response to injury, including proximal tubules, glomeruli and renal interstitium.We aimed to assess the possible role of heme Oxygenase-1 as a potential marker in early diagnosis of diabetic nephropathy. Method This case control study was conducted in Ain Shams university hospital, Cairo, Egypt. It included 80 type 2 diabetic patients diagnosed according to the American Diabetes Association (ADA) criteria, with and without DN ,and 20 healthy control subjects matched in age and sex .Patients were divided into two groups according to the value of the urinary albumin-to-creatinine ratio (ACR) : Group I: 40 normoalbuminuric patients(16 M and 24 F) with ACR<30 mg/g, and Group II: 40 microalbuminuric patients (18M and 22 F) with ACR 30-300mg/g. We excluded patients with history of diabetic ketoacidosis or hypoglycemic coma in the past 3 months preceding the study. Patients with glomerulonephritis, nephrolithiasis, tumors or any other renal diseases were excluded as well. For all studied groups,full history taking and clinical examination were done. We assessed glycosylated hemoglobin (HbA1C),blood urea, serum creatinine, urine creatinine, urinary albumin-to creatinine ratio (ACR mg/g) ,and urinary hemeoxygenase 1(UHO-1) by ELISA . Glomerular filtration rate (eGFR) was estimated by modification of diet in renal disease formula(MDRD)and uHO-1/cr was calculated. Results Group I patients were diabetic for 6.18±0.75 years, while group II patients for 6.05±0.81 years(p = 0.477). Normoalbuminuric patients had significantly higher levels of uHO-1 compared to control (3.01ng/ml vs 0.3 ng/ml,p<0.001).UHO-1 reached highest value among the microalbuminuric group (5.02 ng/ml) with P<0.001.UHO-1/cr ratio was significantly positively correlated with urinary ACR (r = 0.61,p<0.001) and significantly negatively correlated with eGFR(r = -0.71,p <0.001). There was highly significant correlation between uHO-1and eGFR by linear regression. ROC curves showed that AUC of uHO-1is comparable to uHO-1/ Cr ratio (0.957 vs 0.954) respectively with equivocal sensitivity 100 % and specificity 95% and cut off value of uHO-1 >0.46 ng/mland > 0.7 for uHO-1/ Cr ratio. Conclusion UHO-1 is increased in normoalbuminuric patients before the presence of any proteinuria and level increased with the progression of proteinuria and falling of eGFR as well as with the uncontrol of diabetes. UHO-1 is more sensitive than albumin for the detection of early diabetic nephropathy.

Evaluation of Maize Accessions for Drought Tolerance Through Principal Component Analysis

“…The biplot showed that almost all the variables and genotypes gave a high degree of variation. Previous studies enunciated that various crop genotypes revealed greater variation for most yield-related traits (Ravi et al, 2018;Worknesh et al, 2019;Ahmed et al, 2020). 13,5,18,1,12,33,11,2,26,9,17,26,38,37,20,39,3* 28,29,18,30,31,33,27,20,32,21,26,3* Quadrate II 11,30,44,6,21,15,22,35,36* 22,24,23,27,44,35,12,13,17,42,41* Quadrate III 23,34,31,28,25,40,32,19,24,45,47,…”

The roles of heme oxygenase-1 in renal disease

“…Inhibition of HO-1 by HO-1 inhibitors such as ZnPP showed an increase in the number of apoptotic cells, which also indicated the protective effect of HO-1. Ahmed et al., using Streptozotocin-induced diabetes as a model in spontaneously hypertensive rats (SHR), found that glomerular albumin permeability was higher and apoptosis was increased in diabetic SHR compared with the control group ( 48 ). After induction of HO-1 overexpression by COPP, the permeability of albumin and apoptosis decreased.…”

“…The protective role of HO-1 in DKD has also been demonstrated in relevant clinical studies. One study found that HO-1 can be used as an early biomarker of DKD ( 48 ). Urinary HO-1 levels were significantly higher in the diabetic nephropathy group than in the non-diabetic nephropathy group, and the increase in urinary HO-1 levels in these patients preceded significant proteinuria.…”

“…A cross-sectional study found that serum HO-1 levels were significantly elevated in sepsis patients with kidney damage, and were positively correlated with sepsis-induced AKI ( 61 ). Changes in the level of HO-1 are also seen in CKD such as diabetic nephropathy, which can reflect kidney damage ( 48 ).…”