RESUMO
The lecture considers a number of molecular and cellular mechanisms underlying the structural and functional rearrangement and development of renal and cardiac fibrosis in chronic kidney disease (CKD). It details the key component of disadaptative organ remodeling (the formation of myofibroblasts via epithelial-mesenchymal and endothelial-mesenchymal transdifferentiation) and the role of leading angiofibrogenic mediators (angiotensin II, transforming growth factor-beta type 1, a plasminogen activator inhibitor type 1, etc.) in the regulation of these processes. Investigation of the molecular and cellular bases of organ fibrosis, including the factors of dysregulated activation, differentiation and survival of microfibroblasts, makes it possible to specify the mechanisms of action of traditional nephro- and cardioprotective agents, to offer a possibility for a goal-oriented (target) effect on individual fibrogenic components, and to expand the arsenal of medications suppressing renal and cardiac remodeling.
Assuntos
Rim/efeitos dos fármacos , Miocárdio , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Remodelação Ventricular/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Biomarcadores/sangue , Biomarcadores/urina , Cardiotônicos/uso terapêutico , Fibrose , Humanos , Rim/metabolismo , Rim/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Miofibroblastos/patologia , Insuficiência Renal Crônica/tratamento farmacológico , Tetrazóis/uso terapêutico , Valina/análogos & derivados , Valina/uso terapêutico , ValsartanaRESUMO
AIM: To determine clinical significance of urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis in essential hypertension (EH). MATERIAL AND METHODS: Examination of the kidneys was made in 71 patients with EH degree 1-3. Renal function was assessed by 24-h albuminuria, calculated glomerular filtration rate (GFR) by Cockroft-Golt. Early signs of renal damage were microalbuminuria--MAU (diurnal albuminuria 30-300 mg/day), reduction of GFR (< 90 ml/min/1.73 m2). EH patients with hypercreatininemia and GFR under 60 ml/min/1.73m2 corresponding to stage III of chronic kidney disease were not included in the study. An additional nephropathy marker was an elevated index of resistance of interlobular renal arteries (RI > 0.65) as shown by dopplerometry. ELISA examined urinary biomarkers of intercellular and cell-matrix interactions in the kidney in EHpatients and healthy controls (n = 12). RESULTS: MAU was detected in 54 (76%) of 71 EH patients, elevated RI > 0.65--in 37 (52%) patients. Urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis were higher in EH patients then in the controls. Urinary excretion of PAI-1, TGF-beta1, VEGF and collagen of type IV in EH patients with MAU was significantly higher than in patients with normoalbuminuria. A strong direct correlation between MAU and the rest above urinary biomarkers was found as well as between urinary excretion of collagen IV and RI. An inverse negative relationship was seen between RI and GFR. CONCLUSION: Renal impairment in EHpatients is a progressive disorder. Each stage of this process has its own clinicodiagnostic markers. Urinary biomarkers ofproteolysis/fibrinolysis and fibroangiogenesis in the kidney are informative for monitoring of early HNP.
Assuntos
Albuminúria/urina , Fibrinólise , Hipertensão/fisiopatologia , Nefropatias/urina , Neovascularização Patológica/urina , Adolescente , Adulto , Idoso , Albuminúria/etiologia , Biomarcadores/urina , Colágeno Tipo IV/urina , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Neovascularização Patológica/etiologia , Inibidor 1 de Ativador de Plasminogênio/urina , Fator de Crescimento Transformador beta/urina , Fator A de Crescimento do Endotélio Vascular/urina , Adulto JovemRESUMO
AIM: To determine early criteria of renal affection in hypertensive patients for improvement of diagnosis and treatment of hypertensive nephropathy. MATERIAL AND METHODS: 148 patients with essential hypertension (EH) were examined (82 males, 66 females, mean age 43.64 +/- 11.35 years). Of them, 46 patients (24 young males among them) had EH of new onset (NOH) and 102 patients had EH of long duration (LDEH). The examination included investigation of lipid, carbohydrate, uric acid metabolism, renal function, microalbuminuria, intrarenal hemodynamics (color dopplerography on ALOKA SSD-2000 MultiView. RESULTS: 50% of NOH and 90% of LDEH patients had metabolic disorders: excessive body weight, hypercholesterolemia, hypertriglyceridemia, uric acid disbolism, impaired glucose tolerance. These disorders, except uric acid metabolism, correlated in severity with duration and severity of EH. Intensity of microalbuminuria depends on EH duration, severity of concomitant metabolic defects. Markers of early renal damage in EH patients are increased intrarenal peripheral vascular resistance and microalbuminuria. These alterations are detectable in 30% NOH patients (at the disease onset). Treatment with ACE inhibitors eliminates microalbuminuria, diminished hyperfiltration and improved intrarenal circulation. This justifies use of ACE inhibitors for nephroprotection in EH patients. CONCLUSION: Monitoring of the above early markers of renal damage and metabolic shifts is essential for assessing progression of hypertensive nephropathy and control over efficacy of antihypertensive treatment including ACE inhibitors.
Assuntos
Hipertensão/complicações , Nefropatias/diagnóstico , Adulto , Biomarcadores/análise , Feminino , Humanos , Hipertensão/fisiopatologia , Nefropatias/etiologia , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ultrassonografia Doppler em CoresRESUMO
To study humoral antistreptococcal immunity, 29 patients with acute glomerulonephritis (AGN), 211 patients with chronic glomerulonephritis (CGN) and 30 healthy donors were examined. According to EIA, blood sera of the indicated groups demonstrated antibodies (AB) to structural components of Streptococcus--A-polysaccharide (A-ps) and hyaluronic acid (HA) and to its extracellular products--streptokinase (SK) and streptolysin-O (ASLO). It has been shown that in the blood of AGN patients, the levels of AB to A-ps, SK and ASLO were high. The highest level of AB and SK was detected in 55% of the patients with the disease standing of up to half a year. In patients of all the clinical groups of CGN, the levels of AB to A-ps, SK and HA were elevated. The degree of the rise of the levels of all AB depended on the disease activity. Of prognostic importance in the chronicity of AGN and progression of CGN are high titers of AB and SK. The etiological role of streptococcus in glomerulonephritis and its importance in CGN exacerbation and prognosis are under discussion.