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ECPB 2015, 72(4): 47–55
https://doi.org/10.25040/ecpb2015.04.047
Clinical physiology and biochemistry

State of metabolic-hypoxic disorders in children with diabetic nephropathy

MAIDANNYK V., BURLAKA Ye.
Abstract

Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects ~40 % of type 1 patients. It increases the risk of death, mainly of cardiovascular causes, and is defined by increased urinary albumin excretion. Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Several key mechanisms are involved in the development of diabetic nephropathy – advanced glycation products formation, inflammation, oxidative stress, disturbances in the Vitamin D3 regulatory system. The purpose of the study was to investigate the links and level of metabolic disorders in children with DM type I and diabetic nephropathy. The study involved 34 children with DM type I and diabetic nephropathy (aged 10 to 16 years). The affinity of hemoglobin to oxygen and lipid oxidation ratio were determined using spectrophotometric method.

The level of the marker of cellular hypoxia HIF-1α was measured using Western Blotting technique.

In the group of children with newly diagnosed DM type I low rate of affinity of hemoglobin to oxygen as compared to the control group has been recorded. In the group of children with DM type I and developed diabetic nephropathy the level of the marker was significantly higher as compared to the control grouP. Children from control group developed the affinity of hemoglobin to oxygen at level 3.05 ± 0.23 a.u. In the group of children with newly diagnosed diabetes an increased level of the index was recorded as compared to the control group – 3.61 ± 0.25 a.u. (p < 0.05). In the group of children with diabetes and diabetic nephropathy an index was at the level 1.76 ± 0.27 a.u. (p < 0.01, as compared to the control group). High level of intracellular hypoxia has been documented in all patients as compared to the control. The level of HIF-1α was significantly higher in patients with diabetic nephropathy in comparison to the diabetic grouP. In patients with newly diagnosed diabetes mellitus the level of HIF-1α exceeded the control group by 30.03 ± 3.75 % (p < 0.01). Index in the group of diabetic nephropathy exceeded the records from the group with the diabetes mellitus (118.44 ± 1.76 % and 130.04 ± 3.75 %, respectively (p < 0.01)). Stage-dependent increase of the level of lipids oxidation coefficient depending on the efficacy of control of DM has been documented. Children from control group have the index at the level 1.25 ± 0.03 a.u. In the group of children with newly diagnosed diabetes – 1.01 ± 0,05 a.u. (p < 0.05 as compared to control). In the group of children with diabetes and diabetic nephropathy and – 0.76 ± 0.07 a.u. (p < 0.01) in comparison to control group.

Specific inhibitors of the various pathways having place in diabetic nephropathy development are now available, enabling to prevent and treat diabetic nephropathy. The mainstay of therapy remains attaining optimum glycaemic control. Antihypertensive therapy has a major role in slowing the progression of diabetic nephropathy. Agents that interrupt the renin-angiotensin system such as angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists may be particularly useful as renoprotective agents in both the hypertensive and normotensive context. However, the basic therapeutic effects based on the ability to recover already existing cellular damage remains to be unknown. Further investigations of the studied markers and their interrelation in the network of disorders due to Vitamin D3 deficiency and apoptosis controlling system, including the pathogenesis of progression of diabetic nephropathy is a promising direction to create schemes of prevention and treatment of diabetic kidney disease.

Keywords: diabetes mellitus type I, diabetic nephropathy, metabolic disorders, hypoxia

Full text: PDF (Ukr) 1.62M

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