FEATURES OF METABOLIC AND INFLAMMATORY MARKERS IN DIFFERENT CLINICAL AND LABORATORY PHENOTYPES OF CHRONIC KIDNEY DISEASE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Keywords:
type 2 diabetes mellitus; chronic kidney disease; diabetic nephropathy; BMP-7; cystatin C; albuminuria; glomerular filtration rate; C-reactive proteinAbstract
Objective. To evaluate the clinical and laboratory characteristics of four chronic kidney disease (CKD) phenotypes in patients with type 2 diabetes mellitus (T2DM) according to estimated glomerular filtration rate (eGFR) and albuminuria status.
Materials and Methods. This prospective cross-sectional study included 153 patients with T2DM stratified into four groups: NRF/NA (normal renal function/normoalbuminuria, n=35), DRF/NA (decreased renal function/normoalbuminuria, n=35), NRF/EA (normal renal function/elevated albuminuria, n=35), and DRF/EA (decreased renal function/elevated albuminuria, n=30). The control group consisted of 18 healthy individuals. Demographic, anthropometric, glycemic, lipid, inflammatory, and coagulation parameters were assessed.
Results. The groups differed significantly in age (p<0.001), blood pressure levels, markers of renal function, carbohydrate metabolism indices, and inflammatory parameters. The highest C-reactive protein (CRP) levels (24.5±13.1 mg/L) were observed in the NRF/EA group. In the same group, cystatin C reached 5.79±2.0 mg/L despite formally normal eGFR values. The prothrombin index was significantly elevated in groups with albuminuria. BMP-7 levels did not differ significantly between the groups (p=0.080); however, BMP-7 showed a positive correlation with C-peptide (ρ=0.176; p=0.030).
Conclusion. CKD phenotyping in T2DM based on two axes (eGFR and albuminuria) reveals heterogeneity of pathogenic mechanisms, which has practical implications for personalized nephroprotective therapy. The NRF/EA phenotype is characterized by a predominance of pro-inflammatory and procoagulant features accompanied by subclinical tubular dysfunction.
References
Afkarian M, Zelnick LR, Hall YN, et al. Clinical manifestations of kidney disease among US adults with diabetes, 1988-2014. JAMA. 2016;316(6):602-610.
de Boer IH, Bangalore S, Benetos A, et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care. 2017;40(9):1273-1284.
Fioretto P, Caramori ML, Mauer M. The kidney in diabetes: dynamic pathways of injury and repair. The Camillo Golgi Lecture 2007. Diabetologia. 2008;51(8):1347-1355.
Molitch ME, Steffes M, Sun W, et al. Development and progression of renal insufficiency with and without albuminuria in adults with type 1 diabetes in the diabetes control and complications trial and the epidemiology of diabetes interventions and complications study. Diabetes Care. 2010;33(7):1536-1543.
Penno G, Solini A, Bonora E, et al. Gender differences in cardiovascular disease risk factors, treatments and events in type 2 diabetes: the RIACE Italian multicentre study. J Intern Med. 2013;274(2):176-191.
Perkins BA, Ficociello LH, Silva KH, et al. Regression of microalbuminuria in type 1 diabetes. N Engl J Med. 2003;348(23):2285-2293.
Pugliese G, Penno G, Natali A, et al. Diabetic kidney disease: new clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology. J Nephrol. 2020;33(1):9-35.
Stevens LA, Schmid CH, Greene T, et al. Factors other than glomerular filtration rate affect serum cystatin C levels. Kidney Int. 2009;75(6):652-660. 1. Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care. 2014;37(10):2864-2883.
Wang SN, Lapage J, Bhatt R. Loss of tubular bone morphogenetic protein-7 in diabetic nephropathy. J Am Soc Nephrol. 2001;12(11):2392-2399.
