Progression Of Nephrosclerosis Research Articles

The role of matrix metalloproteinases and their inhibitors in physiopathological processes in children with kidney diseases

The review of studies of international and national researchers on the impact of matrix metalloproteinases (matrix metalloproteinases, ММРs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) on physiological and pathological processes in children with kidney diseases. It is shown that MMPs play a significant role in organogenesis, i.e. nephrogenesis. Thus, MMP-2, MMP-9 and TIMPs play a large role in basal membranes remodeling associated with epithelial structures in a developing kidney. Immunohistochemistry assay showed that MMP-2 was localized in structures of immature nephrons undergoing epithelial differentiation, MMP-9 – only in vascular structures included in immature glomeruli. Decreased activity of MMP and /or increased synthesis of TIMPs in nephrocytes contribute to the reduction of intercellular substance components catabolism and serve as a basis for glomerular fibrosis and renal interstitium. MMPs are the major group of proteases which regulate metabolism in extracellular matrix and serve as the most important parameters in tissue remodeling observed in acute and chronic inflammatory processes in kidneys. The literature review gives an opportunity to assess the importance of drug design preventing and delaying the progression of nephrosclerosis.

Approaches to kidney anti-ischemic protection in organ-preserving surgical treatment of patients with renal cell cancer

The advantages of organ-preserving kidney operations are the improvement of functional results, the reduction in the number of patients with end-stage chronic renal failure in long-term follow up and related cardiovascular complications along with overall patients quality of life improvement. On the one hand, a dry surgical field is necessary for visualizing the resection margin and on the other hand, its creation starts the process of acute ischemic damage to the tissue of the operated kidney. Each minute of kidney ischemia proportionally increases the risk of developing renal failure in the long-term postoperative period. It is especially important to consider the duration of ischemia during operations on a single kidney, with bilateral tumor lesions of the kidneys, as well as in the presence of chronic renal failure. After resection of the kidney, its residual function depends on the preoperative level of glomerular filtration, the amount of parenchyma retained during surgery, and the duration of renal ischemia. The predicted functional insufficiency of the healthy contralateral kidney in the postoperative period is 18%. The possibility of the chronic renal failure onset or worsening of the existing one due to the progression of nephrosclerosis reaches almost 80%. The development of chronic renal failure stage III and above in the long term after renal resection is more than 30%. Thus, there is a need for the development of precision surgery, as well as the search for anti-ischemic kidney protection, aimed at maintaining the maximum volume of functioning renal parenchyma.

ИЗУЧЕНИЕ СИСТЕМЫ IL-1 И G-CSF ПРИ ГИДРОНЕФРОЗЕ, КАК ПЕРСПЕКТИВА СОЗДАНИЯ НОВЫХ ДИАГНОСТИЧЕСКИХ ТЕСТОВЫХ СИСТЕМ

Hydronephrosis refers to diseases of the urinary system, which are characterized by high prevalence. Moreover, this pathology of all obstructive uropathies, leading to a decrease in the function of the renal parenchyma, accounts for up to 15% of cases. Therefore, the search for various markers involved in the development and progression of kidney damage is particularly relevant, since in the literature there are very contradictory data. Our article presents the results of a survey of 40 patients with established and confirmed diagnosis of stage I hydronephrosis (according to the classification of N. A. Lopatkin), and 20 completely healthy people (control group). All patients initially and at the end of the study determined the levels of cytokines: IL-1a, IL-1b, IL-1ra and G-CSF. We found that patients with hydronephrosis had higher rates of pro-inflammatory components of the IL-1β system: IL-1β — 104.42 (75% CI [111.8–151.4]) pg/ml, which was significantly higher than in the control group 3.7 times. In patients with hydronephrosis, there is an increase in the levels of IL-1β, IL-1a, and G-CSF against the background of a decrease in IL-1ra. The study of the IL-1 and G-CSF systems in dynamics during hydronephrosis is a very promising direction, opening up enormous opportunities in creating effective diagnostic markers of hydronephrosis in the very early stages of the formation of this pathology. Thus, analysis of the literature indicates that damage to the renal tissue in obstructive uropathies is an extremely complex process, and the initiation of fibrogenesis processes with partial inhibition of resorption leads to remodelling of connective tissue and progression of nephrosclerosis.

VITAMIN D NEPHROPROTECTIVE STRATEGY OF CHILDREN WITH CHRONIC RENAL DISEASE

According to current conception, the process of forming of nephrosclerosis despite the origins is detected by the force of the same cellular and molecular mechanisms. Hence primary triggers cause elevated production of range of cellular response mediators, cytokines and growth factors such as transforming plateled-derived growth factor, fibroblast growth factor, interferon gamma, nuclear factor and others, by means of sequential processes, is followed by the replacement of kidney tissue. One of the most studied aspects of the process of nephrosclerosis is the influence of anginotensin II. Therefore, despite the triggering factors, development and progression of nephrosclerosis all children with chronic renal disease are in a risk group with predisposition for renal insufficiency and it is required to prescribe nephroprotective therapy, i.e. the drugs that will influence one of the links of the nephrosclerosis, in order to slow down its progression. Currently, with nephroprotective goal in early age are used the following elements - angiotensin converting enzyme inhibitors and angiotensin receptors, antogonists (blockers). Lately, the active search for effective and safe drugs with nephroprotective effect on one side and great interest towards undiscovered before qualities of Vitamin D caused a huge amount of works that support the effect of Vitamin D. Prescription of Vitamin D to animals with uremia was followed by the drop of apoptosis of podocides and loss of the protein that is contained in the split diaphragm that caused decrease in proteinuria. Vitamin D suppresses protophibrotic TGF-B1 in tubular epithelial cells. The regression of tubulointerstitial phibrosis under the influence of Vitamin D was confirmed based on the cases of animals with obstruction of urethra. Along with the use of the mentioned above groups of drugs, which effectiveness was proved experimentally and clinically, we strongly believe the more thorough study of the Vitamin D drug use is needed, especially to study the prevention and slowing down of the progression of nephrosclerosis in the cases of children with chronic renal disease. It is crucial to detect the exact dosage of the drug, the prescription period and the methods for the control of the effective concentration of the drug.

Kidneys: The Victim Of Hypertension: Review

Background & objectives: Our review discuss the relation between hypertension and the renal system ,and show the cyclic effect of both hypertension and chronic kidney damage on each other, our objectives are to control the high blood pressure with minimal renal affection due to side effects of medications. Materials & methods: many studies and trials compare between different antihypertensive drugs and their effects on kidneys which may decrease their efficiency. Results: Angiotensin converting enzyme inhibitor (ACE-Is), angiotensin II receptor blocker (ARBs), Beta-blockers and calcium channel blockers are identified to be the second line of treatment of hypertension according to a network meta-analysis conducted in 2003, ACE-Is were found to show a significant effect in slowing the progression of nephrosclerosis and slower declining of GFR more than β-blocker or calcium channel blocker. Conclusion: Kidney is indispensable organ in the body that we must protect it from the irreversible macroscopic and microscopic changes pathological as : macroscopic (small size, finely granular surface, adherent and difficulty stripped capsule, fibrotic, atrophic, not demarcated cortex on cut section, thick prominent arterioles and increased peripelvic fat) and microscopic (afferent and efferent arterioles show benign arteriosclerosis, gradual ischemic atrophy and fibrosis of the glomeruli, atrophy of non-functioning tubules related to atrophic glomeruli, may undergo compensatory cystic dilatation of tubule related to functioning glomeruli). ACE-Is is considered the drug of choice in hypertensive patients complicated with chronic kidney disease, In hypertensive patients that are refractory to medical treatment, renal sympathetic denervation is a safe alternative.

Improvement in treatment of hypertension has not reduced incidence of end-stage renal disease.

Hypertension is an important cause of end-stage renal disease (ESRD) in the USA and in Sub-Saharan Africa. Antihypertensive therapy has led to a substantial decrease in incidence of stroke (42%) and to a lesser extent of myocardial infarction (16%), yet there has been an increase in hypertension related ESRD. In 1991, about 190 000 persons in the USA either underwent dialysis or received a transplant for ESRD. Hypertension was found to be the underlying cause in 29% of these patients, second only to diabetes mellitus (36%). Both in the USA and South Africa hypertension was found to be the most common cause of ESRD, but it is not clear whether this is related to the higher incidence and severity of hypertension in black people. Moreover blood pressure (BP) control in black patients does not necessarily lead to improved renal function. These findings suggest that factors other than BP elevation participate in the progression of nephrosclerosis. They include misdiagnosis, black race (socio-economic status, physiologic differences, severity of hypertension), BP control (adequate control of BP and type of antihypertensive therapy), and possibly other factors like genetics. The lack of reduction in ESRD may be that currently accepted standards for BP control are not adequate and that different antihypertensive agents affect glomerular haemodynamics in different ways. These factors need an in-depth analysis to improve the important public health issue of increasing morbidity and mortality from ESRD.

Renal responses to angiotensin receptor antagonist and angiotensin-converting enzyme inhibitor in partially nephrectomized spontaneously hypertensive rats.

To investigate the role of the renin-angiotensin system (RAS) on nephrosclerosis in salt-loaded, partially nephrectomized spontaneously hypertensive rats (SHR), we evaluated the effects of angiotensin II (ANGII) blockade on the progression of nephrosclerosis with an angiotensin type 1 receptor (AT1rec) antagonist [TCV-116 (TCV)] and an angiotensin-converting enzyme (ACE) inhibitor (enalapril) at the doses equivalent in reducing systemic blood pressure (BP). SHR were five/sixths nephrectomized and were fed a high-salt diet. In addition to being significantly preventive against an increase in systolic BP, both TCV and enalapril significantly attenuated the increases in proteinuria and the renal histopathological alterations. Transcription of AT1rec mRNA in the remnant kidney was enhanced with the progression of nephrosclerosis, but was inhibited by TCV as well as enalapril. In these aspects, there were no apparent differences between effects of TCV and enalapril. The RAS system plays an important role in nephrosclerosis in partially nephrectomized SHR despite a high-salt diet, and direct ANGII blockade certainly protected the kidney against hypertensive injury in this model.

Light-chain-induced renal tubular acidosis: effect of sodium bicarbonate on sodium-proton exchange

We measured sodium-proton (Na+/H+) exchange in lymphocytes and platelets of a 46-year-old woman with the adult Fanconi syndrome before, during, and after treatment with NaHCO3. Kappa light chains in her urine and unique but rarely observed crystalline structures confirmed the presence of light-chain nephropathy. Her glomerular filtration rate was only moderately impaired at 72 ml/min. NaHCO3 at 1, 3, and 5 mmol/kg/day for 5 days increased her serum HCO3 and pH from 17 to 21 mmol/l and 7.28 to 7.39 respectively. Plasma renin and aldosterone values were decreased by NaHCO3. Na+/H+ exchange (delta Hi/min) was measured with the fluorescent marker BCECF after acidification of lymphocytes and platelets with sodium propionate at five (10-50 mM) doses. Na+/H+ exchange was accelerated in this patient compared to normal controls. NaHCO3 treatment significantly decreased Na+/H+ exchange in lymphocytes, but not in platelets. These findings suggest that Na+/H+ exchange can be influenced by NaHCO3 ingestion at doses that only modestly affect systemic pH. Since Na+/H+ exchange is involved in stimulus response coupling, cell growth regulation, cell differentiation, and perhaps the progression of nephrosclerosis, these observations may have clinical relevance.