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KIDNEY FUNCTIONAL RESERVE IN PATIENTS WITH CHRONIC RENAL DISEASE AND NONALCOHOLIC STEATOHEPATITIS IN THE BACKGROUND OF OBESITY, THERAPEUTIC CORRECTION OPPORTUNITIES

Аuthors: A. A. Antoniv

Pages: 371–381

Abstract

         

Introduction. The increase in the frequency of nonalcoholic steatohepatitis (NASH) comorbid course on the background of obesity and chronic kidney disease (CKD) cases in people of working age in Ukraine and in the world necessitates conducting research on mechanisms of mutual burden and finding new factors for the progression pathogenesis of this comorbidity.

The aim of the study: to establish changes in the functional status of the kidneys and the functional reserve of the kidneys depending on the stage of chronic kidney disease (pyelonephritis) for comorbidity with nonalcoholic steatohepatitis and obesity.

Material and methods of research. 240 patients with CKD (chronic bilateral pyelonephritis) of I–III stage were examined, 145 of them had comorbid NASH and obesity of the 1st degree (1 group), 95 patients were diagnosed with CKD І–ІІІ stage without comorbid pathology. Depending on the stage of the CKD, the groups of patients was distributed as follows: 1st group – into 3 subgroups: CKD I stage – 51 patients, CKD II stage – 53 patients, CKD III stage – 41 patients. The 2nd group was divided into 3 subgroups: CKD I stage – 32 patients, CKD II stage – 35 patients, CKD III stage – 28 patients. The control group consisted of 30 practically healthy persons (PHPs). The average age of patients was (49.8 ± 5.8) years. The diagnosis of CKD was made according to the recommendations of the clinical guidelines of the Institute of Nephrology of the National Academy of Medical Sciences of Ukraine (2012). The study included patients with CKD І–ІІІ stage without a nephrotic syndrome with chronic uncomplicated pyelonephritis in the phase of exacerbation. The glomerular filtration rate (GFR) was investigated by creatinine clearance, calculated using the Cockroft-Gaulta formula, as well as by the universal automatic calculator CKD-EPI. In addition to standard research methods (blood creatinine, urea, proteinograms, ionograms, urinalysis, urine analysis by Nechyporenko, Zimnytsky, urine culture with the identification of the pathogen, its amount and sensitivity to antibiotics, etc.), the kidney function was studied after water-salt loading. For aqueous salt loading 0.5 % sodium chloride solution was used in the volume of 0.5 % of the body weight of the patient, and the urine was collected after one hour, the research was conducted as follows: at 7 am, the patient completely cleared the bladder, after which he was offered to drink 0.5 % sodium chloride solution at a rate of 0.5 % of body weight, then for an hour the patient was in a state of rest, after an hour, urine was collected, the volume measured and the creatinine concentration determined according to the standard procedure. Creatinine excretion was calculated by water-salt loading, urine output per minute, GFR by creatinine clearance (CC). The increase in excretion of creatinine after aqueous-salt loading relative to the excretion of creatinine at daily diuresis was the magnitude of functional renal reserve (FRR). For the determination of FRR, the presence and magnitude of growth of GFR after saline loading was determined by the Cockroft-Gaul formula.

Research results. Features of the functional state of the kidneys for the comorbidity of chronic kidney disease (CKD): chronic pyelonephritis with obesity and nonalcoholic steatohepatitis (NASH), depending on the stage of CKD, is characterized by a higher degree of reduction of glomerular filtration rate (GFR), degree of hypoalbuminemia, proteinuria than in isolated course. Patients with CKD in І–ІІ stages without comorbid conditions have established a significantly higher functional renal reserve (FRR) in response to water-electrolyte stimulation, which is sufficient in both categories of patients (GFR increase in the range of 28–37 % versus 19–31 % for comorbidity with NASH). Patients with CKD in stage III with nonalcoholic steatohepatitis have significantly reduced FRR, and 4.9 % of patients with comorbidity FRR is absent, which proves the syndrome of the interconnection of NASH with CKD, which is the interdependence of the decrease in GFR with increasing intensity of oxidative stress, decrease in the potential of antioxidant factors protection and hyperproduction of the components of the connective tissue: collagen, hexosamines, sialic acids, cytokeratin-18 against the background of decreased activity of collagenolysis (p < 0.05).

Conclusions: Non-alcoholic steatohepatitis significantly aggravates the course of CKD I–III stages with a possible decrease in nitrogen function, glomerular filtration rate, hypopalbuminemia than in the isolated course of CKD only. Patients with CKD of the I–II stages without comorbid conditions have established a significantly higher functional reserve of the kidneys in response to water-saline stimulation, which, at the same time, is sufficient in both categories of patients (GFR increase in the range of 28–37 % versus 19–31 % for comorbidity with NASH) regarding the possibility of improving the function of the kidneys by developing appropriate therapeutic and rehabilitation programs. Patients with CKD stage III with nonalcoholic steatohepatitis have significantly reduced the FRR (growth of GFR by 8.9 % versus 17.5 % in patients without NASH), and 4.9 % of patients with comorbidity had no functional renal reserve (an increase of 3,2 %), which proves the syndrome of the interaction of NASH with the CKD of stage III in the form of almost irreversible changes in the functional state of the kidneys and the need for constant monitoring and prevention of its progression. Correlation analysis of the indices obtained in patients with comorbidity of CKD І–ІІІ stage and NASH indicates significant interdependence of reduction of GFR with increasing intensity of oxidative stress, decrease in the potential of antioxidant defense factors (content of reduced glutathione), hyperproduction of connective tissue components (collagen (protein-bound oxyproline), hexosamines, sialic acids), cytokeratin-18 against the background of collagenolysis decrease (p < 0.05), which correlate with the intermediate and high power interactions with the index of GFR (p < 0.05).

Keywords: chronic kidney disease, nonalcoholic steatohepatitis, glomerular filtration rate, functional renal reserve.

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