Risk factors and urinary biomarkers of non-albuminuric and albuminuric chronic kidney disease in patients with type 2 diabetes

Abstract

BACKGROUNDA number of recent studies indicate a transformation in the natural course of chronic kidney disease (CKD) in type 2 diabetes (T2D) patients: an increasing prevalence of declined renal function without proceeding to the accompanying elevation of albuminuria. It has been suggested that albuminuric and non-albuminuric CKD patterns could be different in their phenotypes and pathogenic mechanisms.AIMTo identify the risk factors and biomarkers of albuminuric and non-albuminuric patterns of CKD in patients with T2D.METHODSThree hundred sixty patients with T2D duration ≥ 10 years were included in this observational cross-sectional study. The associations of a panel of demographic and clinical characteristics, complications, comorbidities, and metabolic and hematology parameters with albuminuric and non-albuminuric CKD patterns were analyzed. The urinary excretion of nephrin and podocin, two podocyte-specific markers, and WAP-four-disulfide core domain protein 2 (WFDC-2), a marker of tubulointerstitial fibrosis, was determined by ELISA in comparison with healthy controls.RESULTSNon-albuminuric CKD was associated with age ≥ 65 years (P = 0.0001), female sex (P = 0.04), diabetes duration ≥ 15 years (P = 0.0009), and the use of diuretics (P = 0.0005). Male sex (P = 0.01), smoking (P = 0.01), waist-to-hip ratio >1.0 (P = 0.01) and hemoglobin A1c (HbA1c) > 8.0% (P = 0.005) were risk factors for elevated albuminuria not accompanied by a decrease in estimated glomerular filtration rate (eGFR). Duration of diabetes ≥ 15 years and the use of calcium channel blockers were risk factors for albuminuria with decreased eGFR (both P = 0.01). In multivariate logistic regression analysis, age, HbA1c, female sex and diuretics were significant predictors for reduced eGFR, while waist-to-hip ratio, HbA1c and male sex were associated with elevated urinary albumin-to-creatinine ratio (UACR). Excretion of nephrin and podocin was increased in patients with albuminuria, regardless of decline in renal function (P < 0.001), correlating positively with UACR. The urinary excretion of WFDC-2 was markedly higher in men than in women (P < 0.000001). Men with T2D demonstrated increased WFDC-2 levels independently of the CKD pattern (all P < 0.05). In T2D women, WFDC-2 excretion was increased in those with reduced renal function (P ≤ 0.01), correlating negatively with eGFR.CONCLUSIONThe data provide further evidence that albuminuric and non-albuminuric CKD phenotypes correspond to different pathways of diabetic kidney disease progression.

Risk Prediction for Early Chronic Kidney Disease: Results from an Adult Health Examination Program of 19,270 Individuals

“…The findings of this study were consistent with those of previous reports, including the most recent report of the National Health Research Institutes Annual Report on Kidney Disease in the urine protein to creatinine ratio (UPCR) [ 4 ] and the red blood cell count (RBC) [ 5 ], and Xiao’s report on the prediction of chronic kidney disease in proteinuria (PRO) [ 35 ]. The findings of the albumin (ALB) and fasting glucose level (GLU) are consistent with previous studies following Korbut et al [ 36 ] and Kshirsagar et al [ 37 ]. Similarly, Xue et al [ 38 ], Mahmood et al [ 39 ], and Kshirsagar et al [ 37 ] reported that triglycerides (TG), age, and gender are critical for prediction of chronic kidney disease.…”

Associations between Sex and Risk Factors for Predicting Chronic Kidney Disease

“…Previous studies revealed that gender is associated with CKD deterioration [3,22,23]. The urine protein (PRO)-to-urine creatinine ratio (UPCR) is the most important risk factor this consequence [24][25][26]. The UPCR is used for the next section of analyzing the impact of gender differences to predict the risk factors for CKD.…”

Empagliflozin alleviates podocytopathy and enhances glomerular nephrin expression in db/db diabetic mice

“…Mutation-caused abnormalities of the nephrin gene result in congenital nephrotic syndrome of the Finnish type[ 18 ]. The increased urinary excretion of nephrin is associated with the albuminuric pattern of CKD in patients with T2D[ 19 ]. Since the slit diaphragm provides the most selective barrier for albumin[ 20 ], it can be assumed that the anti-albuminuric action of SGLT2 inhibitors could be mediated by an effect on podocytes.…”