Published online Nov 15, 2019. doi: 10.4239/wjd.v10.i11.517
Peer-review started: August 26, 2019
First decision: September 21, 2019
Revised: October 6, 2019
Accepted: October 18, 2019
Article in press: October 18, 2019
Published online: November 15, 2019
A 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.
To identify the risk factors and biomarkers of albuminuric and non-albuminuric patterns of CKD in patients with T2D.
Three 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.
Non-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.
The data provide further evidence that albuminuric and non-albuminuric CKD phenotypes correspond to different pathways of diabetic kidney disease progression.
Core tip: In this study, we demonstrate the differences in clinical and laboratory characteristics between albuminuric and non-albuminuric phenotypes of chronic kidney disease (CKD) in patients with long-term type 2 diabetes. Different risk factors are found for three different CKD phenotypes. We also show the diversity in the urinary excretion of nephrin and podocin, two slit diaphragm proteins, and of WAP-four-disulfide core domain protein 2, a tubulointerstitial fibrosis marker, between different CKD phenotypes. The results further support the notion that albuminuric and non-albuminuric CKD phenotypes are different in their pathophysiology and clinical characteristics.