What causes reflux-nephropathy?

Currently, there are four possible mechanisms for the development of focal nephrosclerosis: the collaptoid lesion of the parenchyma (ischemia); autoimmune lesion of kidney tissue; humoral theory of reflux-nephropathy; immune renal damage.

The question of the role of urinary system infection (IMI) in the formation of reflux-nephropathy continues to be debated. However, the diagnosis of reflux-nephropathy, before the debut of the urinary tract infection, indicates the possibility of the formation of reflux-nephropathy under the influence of sterile vesicoureteral reflux, even in the antenatal and neonatal period. The main reason for the assumption of the leading role of the infectious process in the formation of sclerosis of kidney tissue is that the cause for nephro-urological examination of patients is very often the infection of the urinary tract and the attack of pyelonephritis.

It has now been established that changes in cellular energy play a big role in the pathology of the kidneys, in particular, in tubulopathy, kidney failure, tubulointerstitial component. Disturbances in cellular energy can be determined by changes in mitochondrial activity. Renal tissue with reflux-nephropathy is in a state of hypoxia, which can be caused by both renal blood flow disorders and mitochondrial instability.

At the heart of the formation of reflux-nephropathy is the retrograde current of urine from the pelvis to the collecting system of the kidneys with an increase in intra-local pressure. Intra-neural reflux (pyelotubular, pyelointerstitial, pyelosubkapsular, pyelovenous, pyeloparvazal, pyelosinus), also called pyelotubular reverse current, is considered as one of the main factors contributing to the development of nephrosclerosis. The emergence of bipolar sclerosis in children with reflux-nephropathy is also explained by the anatomical features of the papillae. Complex or compound papillae are located in the region of the poles of the kidneys. They have multiple channels in the central concave part of the papilla, along which both physiological and reverse urine flow is possible. These channels (Bellini's ducts) are widely open in the central part of the complex papilla. Simple papillae localized along the central part of the pelvis, thanks to the conical form and the sipes of Bellini, are a barrier to retrograde urine flow. This is also the role of damage to the wall of the pelvis, leading to a disorder of its "suction" function. Under the influence of intracranial reflux, morphological changes occur in virtually all structural and functional elements of the renal parenchyma: lymphoplasmocytic or macrophage infiltration of interstitial tissue of the kidneys with proliferation of connective tissue; changes in proximal and distal tubules (focal atrophy and dystrophy with ruptures of their basal membranes); thickening of the walls of blood vessels, narrowing of their lumen, phenomena of obliterating endarteritis and thrombosis of veins; changes in glomerulus in the form of periglomerular sclerosis, segmental hyalinosis, and glomerular subsidence against the background of immaturity of the glomeruli. Progression of irreversible changes in the kidney occurs due to an increase in the zones of connective tissue transformation of the renal parenchyma, located around the "primary" scars.

Three histological markers of reflux-nephropathy are distinguished: dysplastic elements, which are considered as a consequence of an abnormality of the embryonic development of the kidney; abundant inflammatory infiltrates, which are a reflection of the transferred inflammations of the kidney tissue, that is, a sign of chronic pyelonephritis; detection of the Tamm-Horsfall protein, the presence of which indicates intracellular reflux.

The results of light-optical and electron microscopic studies of the kidneys in patients with vesicoureteral reflux show that reflux-nephropathy is characterized by retardation of kidney growth and differentiation of the nephron with ultrastructural signs of dysplasia, expressed by signs of nephrosclerosis involving the parenchyma and capillary vessels of the glomeruli and stroma in the sclerotic process. The picture of nephrohydrosis is also characteristic.

Features of the pathogenesis of reflux-nephropathy in young children. The most severe lesion of the parenchyma was revealed in children of the first year of life with vesicoureteral reflux of the 3rd and especially the 4th degree.

The presence of sclerotic changes in the kidney parenchyma occurs in 60-70% of patients with vesicoureteral reflux. The greatest risk of nephrosclerosis formation is observed in the first year of life and is 40% compared with the older age groups (25%). This feature is due to a high incidence of intravenous reflux (BP) at an early age, due to the immaturity of the papillary apparatus and a high level of intra-lateral pressure. In neonates reflux-nephropathy is diagnosed in 20-40% of cases of development of vesicoureteral reflux. And 30-40% of them show different types of renal dysplasia / hypoplasia, segmental hypoplasia, cystic dysplasia). With age, as the papillary apparatus matures, there is a decrease in the frequency of intrarenal reflux and the formation of reflux-nephropathy. The development of reflux-nephropathy until two years is observed more often, especially with bilateral reflux and vesicoureteral reflux of high degrees. The above regularity is explained by the high frequency of reflux-nephropathy at grade 3-4 vesicoureteral reflux, which correlates with the level of intra-local pressure and the severity of urodynamics disturbance, as well as the high probability of embryogenesis of the renal tissue.

Thus, it is possible to single out the risk factors for the development of reflux-nephropathy: bilateral high-grade vesicoureteral reflux, developmental malformations and renal dysplasia, recurrent UTI, NDMP, especially in the hyporeflexive type.

Risk factors for the development of vesicoureteral reflux and reflux nephropathy: a burdened genealogical anamnesis of renal pathology, a small birth weight, a large number of stigmas of dysembryogenesis, neurogenic dysfunction of the bladder, leukocyturia without clinical manifestations, unreasonable recurring temperature rises, abdominal pains, especially related with the act of urination, the expansion of the calyx and pelvic system of the fetus and the newborn according to ultrasound of the kidneys.