What causes reflux nephropathy?

Currently, four possible mechanisms for the development of focal nephrosclerosis are distinguished: collapse-like damage to the parenchyma (ischemia); autoimmune damage to renal tissue; humoral theory of reflux nephropathy; immune damage to the kidneys.

The role of urinary tract infection (UTI) in the development of reflux nephropathy continues to be debated. However, diagnostics of reflux nephropathy before the onset of urinary tract infection indicates the possibility of developing reflux nephropathy under the influence of sterile vesicoureteral reflux even in the antenatal and neonatal periods. The main reason for the assumption of the leading role of the infectious process in the development of renal tissue sclerosis is that the reason for nephro-urological examination of patients is very often urinary tract infection and an attack of pyelonephritis.

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

The formation of reflux nephropathy is based on the retrograde flow of urine from the renal pelvis into the collecting system of the kidneys with an increase in intrapelvic pressure. Intrarenal reflux (pyelotubular, pyelointerstitial, pyelosubcapsular, pyelovenous, pyeloparavasal, pyelosinus), also called pyelotubular reverse flow, is considered one of the main factors contributing to the development of nephrosclerosis. The occurrence 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, through which both physiological and reverse urine flow are possible. These channels (Bellini ducts) are widely open in the central part of the complex papilla. Simple papillae located along the central part of the pelvis, due to their conical shape and slit-like Bellini ducts, are a barrier to retrograde urine flow. Damage to the renal pelvis wall also plays a role, leading to a disorder of its "suction" function. Under the influence of intrarenal refluxes, morphological changes occur in almost all structural and functional elements of the renal parenchyma: lymphoplasmocytic or macrophage infiltration of the interstitial tissue of the kidneys with proliferation of connective tissue; changes in the proximal and distal tubules (focal atrophy and dystrophy with ruptures of their basement membranes); thickening of the vascular walls, narrowing of their lumen, phenomena of obliterating endarteritis and venous thrombosis; changes in the glomeruli in the form of periglomerular sclerosis, segmental hyalinosis, collapse of the glomeruli against the background of immaturity of the glomeruli. The progression of irreversible changes in the kidneys occurs due to the increase in the zones of connective tissue degeneration of the renal parenchyma, located around the “primary” scars.

There are three histological markers of reflux nephropathy: dysplastic elements, which are considered to be a consequence of anomalies in the embryonic development of the kidney; abundant inflammatory infiltrates, which are a reflection of previous inflammation of the renal tissue, i.e. a sign of chronic pyelonephritis; detection of the Tamm-Horsfall protein, the presence of which indicates intrarenal 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 renal growth retardation and nephron differentiation with ultrastructural signs of dysplasia, pronounced signs of nephrosclerosis with involvement of the parenchyma vessels and glomerular capillaries and stroma in the sclerotic process. The picture of nephrohidrosis is also characteristic.

Peculiarities of the pathogenesis of reflux nephropathy in young children. The most severe parenchyma damage was detected in children of the first year of life with vesicoureteral reflux of the 3rd and especially 4th degree.

The presence of sclerotic changes in the renal parenchyma occurs in 60-70% of patients with vesicoureteral reflux. The highest risk of nephrosclerosis development is observed in the first year of life and is 40% compared to older age groups (25%). This feature is due to the high frequency of intrarenal reflux (VR) at an early age, caused by the immaturity of the papillary apparatus and high intrapelvic pressure. In newborns, reflux nephropathy is diagnosed in 20-40% of cases of vesicoureteral reflux, with various types of renal dysplasia (hypoplasia, segmental hypoplasia, cystic dysplasia) observed in 30-40%. With age, as the papillary apparatus matures, a decrease in the frequency of intrarenal reflux and the formation of reflux nephropathy is observed. The development of reflux nephropathy before the age of two is observed more often, especially with bilateral reflux and high-grade vesicoureteral reflux. The above-mentioned pattern is explained by the high frequency of reflux nephropathy with grades 3-4 vesicoureteral reflux, which correlates with the level of intrapelvic pressure and the severity of urodynamic disorders, as well as the high probability of renal tissue embryogenesis disorders.

Thus, it is possible to identify risk factors for the development of reflux nephropathy: high-grade bilateral vesicoureteral reflux, renal malformations and dysplasia, recurrent UTI, low urinary tract infection, especially of the hyporeflexive type.

Risk factors for the development of vesicoureteral reflux and reflux nephropathy: a burdened family history of renal pathology, low birth weight, a large number of stigmas of dysembryogenesis, neurogenic dysfunction of the bladder, leukocyturia without clinical manifestations, unreasonable repeated increases in temperature, abdominal pain, especially associated with urination, dilation of the calyceal-pelvic system of the fetus and newborn according to ultrasound of the kidneys.