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.

ЦЕЛЬ: оценить различия в панели цитокинов сыворотки крови, регулирующих воспаление и фиброз, у больных сахарным диабетом (СД) 2 типа и различными вариантами хронической болезни почек (ХБП).МАТЕРИАЛЫ И МЕТОДЫ: в исследование включено 130 больных СД 2 типа длительностью ≥10 лет, 48 мужчин и 92 женщины, от 42 до 88 лет (медиана 66 лет). Больные с расчетной скоростью клубочковой фильтрации (рСКФ) по CKD-EPI ≥60 мл/мин×1,73 м 2 и отношением альбумин/ креатинин мочи (АКМ)<3,0 мг/ммоль обозначены вошли в группу ХБП-(N=33). Группу нормоальбуминурической ХБП (НА-ХБП) составили больные с рСКФ<60 мл/мин×1,73 м 2 и АКМ<3,0 мг/ммоль (N=33). Больные с рСКФ ≥60 мл/мин×1,73 м 2 и АКМ ≥3,0 мг/ммоль сформировали группу альбуминурии без снижения СКФ (А-ХБП-). Пациенты с альбуминурической ХБП (А-ХБП+) имели рСКФ<60 мл/мин×1,73 м 2 и АКМ ≥3,0 мг/ммоль (N=32). Контрольную группу составили 30 человек (11 мужчин и 19 женщин) без нарушений углеводного обмена, ожирения и сердечно-сосудистых заболе-

BACKGROUND: A growing body of evidence demonstrates increasing prevalence of normoalbuminuric chronic kidney disease (NA-CKD) in subjects with type 2 diabetes (T2D), while proportion of albuminuric pattern is decreasing. AIMS: To determine the clinical and laboratory parameters associated with different patterns of CKD in patients with T2D. METHODS: This observational, single-center, cross-sectional study included 360 patients with T2D duration 10 years. Patients with urinary albumin/creatinine ratio (UACR) 3 mg/mmol and estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m2 were classified as no-CKD group (n=89). Patients with UACR 3 mg/mmol and eGFR 60 ml/min/1.73 m2 formed NA-CKD group (n=111). Individuals with eGFR 60 ml/min/1.73 m2 and UACR mg/mmol 3 were recorded as albuminuric with preserved renal function (A-CKD, n=87). Patients with eGFR 60 ml/min/1.73 m2 and UACR mg/mmol 3 mg/mmol were considered as albuminuric CKD group (A-CKD+, n=73). Urinary nephrin and podocin, the podocyte injury markers, and whey acidic protein four-disulfide core domain protein 2 (WFDC-2), a marker of tubulointerstitial involvement, was assessed by ELISA and compared to control (20 non-diabetic subjects). RESULTS: Age 65 years (p=0.0001), duration of T2D 15 years (p=0.0009), female sex (p=0.04), and therapy with diuretics (p=0.0005) were found as risk factors for NA-CKD. The risk factors for A-CKD were male sex (p=0.01), smoking (p=0.01), waist-to-hip ratio 1 (p=0.01) and HbA1c levels 8% (p=0.005). The duration of T2D 15 years (p=0.01) and the use of dihydropyridine calcium channel blockers (p=0.01) were associated with A-CKD+. In T2D groups, the urinary excretion of nephrin and podocin was increased (all p0.001), more markedly in albuminuric individuals (p0.01 vs. NA-CKD). WFDC-2 excretion was increased in men from all diabetic groups (p0.05) and in women with decreased eGFR only (p0.05 vs. the control and NA-CKD). CONCLUSIONS: The CKD patterns in T2D are heterogeneous according to their clinical and laboratory characteristics. The changes in the excretion of nephrin and podocin indicate the association of albuminuric patterns with podocyte injury. A decrease in eGFR in women with T2D is associated with an increase in urinary excretion of WFDC-2, tubulointerstitial fibrosis marker.