Pathogenesis of acute renal failure

Acute renal failure develops over a period of several hours to several days in response to various injuries manifested by azotemia, oligoanuria, a violation of acid-base balance and electrolyte balance. Occurs when there is a sudden, potentially reversible decrease in GFR.

Normal parameters of the glomerular filtration rate and indicators of maximum osmolality of urine

Indicators	Newborns	1-2 weeks of life	6-12 months of life	1-3 years	Adults
GFR, ml / min at 1.73 m 2	2b, 2 ± 2	54.8 ± 8	77 ± 14	96 ± 22	118 ± 18
Maximum osmolality of urine, mosmole / kg H 2 0	543 + 50	619 ± 81	864 ± 148	750 ± 1330	825 ± 1285

It remains controversial, at what level the reduction of GFR by 50% or more, persisting for at least 24 hours, indicates the occurrence of acute renal failure. This is accompanied by an increase in the concentration of creatinine in the blood plasma more than 0.11 mmol / L in newborns and proportionally higher in older children. An additional diagnostic sign is oliguria. The leading pathophysiological links in the development of symptoms of acute renal failure are water-electrolyte disorders, metabolic acidosis, accumulation of carbon dioxide, increased ventilation, lung damage and pathological respiration.

The syndrome of acute renal failure is rarely isolated, more often it develops as a part of multiple organ failure. The peculiarity of this syndrome is its cyclicity with the possibility of complete restoration of impaired renal functions. Nevertheless, mortality in acute renal failure is 10-75%. A wide range of survival is associated with the different nature of the diseases that cause the development of acute renal failure.

In the neonatal period, the risk of developing acute renal failure is increased because of the immaturity of the kidneys. The main distinguishing feature of the full term newborn is low GFR and minimal renal blood flow. Neonates also have very limited physiological ability of the kidneys both to concentrate and to urine dilution, hence, the possibility of regulating hemostasis is minimal. The functioning nephrons are located in the juxtamendullar layer and are relatively well protected from hypoxia. That is why transient ischemia of kidneys in newborns occurs quite often (with unfavorable course of childbirth, development of asphyxia), but rarely leads to true cortical necrosis. In fact, the kidneys respond to changes in hemodynamics and hypoxia only by a decrease in the rate of filtration. After the normalization of hemodynamics and the elimination of the damaging agent, renal dysfunction also disappears.

With a decrease in renal perfusion or vascular volume, reabsorption of dissolved substances, including urea, increases. Under physiological conditions, 30% of the urea filtered in the glomeruli is reabsorbed. This percentage increases with decreasing renal perfusion. Since creatinine is not reabsorbed, an increase in the reverse absorption of urea leads to an increase in the urea / creatinine ratio in the blood. This condition is often defined as prerenal azotemia.

In a number of cases, progression of violations of general hemodynamics and blood circulation, sharp depletion of renal blood flow causes renal afferent vasoconstriction with redistribution of renal blood flow. With severe ischemia of the cortical layer of the kidney, the GFR falls to critical values, practically to zero, followed by ischemic necrosis of the epithelium of the convoluted tubule of the kidneys. The main clinical sign of acute tubular necrosis is the development of oligoanuria.

The syndrome of acute renal failure may be due to inflammation in the parenchyma and interstitium of the kidneys (glomerulonephritis or tubulointerstitial nephritis). Along with ischemia, parenchymal damage to the kidneys is facilitated by endogenous intoxication (microbial toxins, proinflammatory mediators, biologically active substances, free radicals of oxygen, etc.) that affect the blood clotting system.

In patients with a purely nephrotic syndrome of acute renal failure may be associated with edema of the interstitial tissue, increased hydrostatic pressure in the proximal tubules and the Bowman capsule, and, respectively, with a decrease in filtration pressure and GFR. Hemodialysis with massive ultrafiltration or the introduction of albumin, which removes interstitial edema, can restore kidney function.

In some cases anuria in glomerular lesions of the kidneys can be a consequence of tubular obturation with protein masses or blood clots, for example, in patients with IgA-nephropathy with episodes of macrohematuria.

Reduction of GFR may be due to the processes of rapidly developing proliferation in the glomeruli with compression of capillary loops and / or tubulointerstitial changes, as well as the release of vasoactive substances and cytokines from monocytes and other cells, which serves as a direct indication for conducting plasmapheresis.

In septic conditions, the pathogenetic link is a severe anaerobic bacterial shock and hemolysis associated with it.

Despite the diversity of the etiological factors of organic acute renal failure, its pathogenesis consists of the following main pathological processes:

• renal vasoconstriction causing tissue ischemia;
• reducing the permeability of glomerular capillaries, leading to a fall in GFR;
• obstruction of tubules by cellular detritus;
• of the transepithelial backflow of the filtrate into the near-canal space.

The hemodynamic factor plays a dominant role in the pathogenesis of the syndrome. It is described by a well-known phenomenon (tubulohlomerular feedback), the essence of which is the damage to the epithelial cells of the proximal tubules due to the action of any factors, leading to a decrease in the reabsorption of salts and water in the initial part of the nephron. The increased intake of Na ⁺ and water ions in the distal sections of the nephron serves as a stimulus for the release of vasoactive substances (renin) by the juxtaglomerular apparatus. Renin induces and maintains a spasm of leading arterioles with redistribution of renal blood flow, arterioles disuse and a decrease in GFR. All this leads to a decrease in the excretion of salts and water. The feedback signal supplied by the tubules to reduce blood flow and GFR in conditions of excessive excretion of solutions is called tubulohlomerular feedback. In physiological conditions, it provides a safety mechanism for limiting GFR when the functional capacity of the tubules is overloaded. However, with acute renal damage, activation of this mechanism further reduces renal blood flow, limiting the delivery of nutrients, exacerbating tubular damage.

In the oligoanuric stage of acute renal failure, the hemodynamic factor does not play a dominant role. When renal damage has already occurred, attempts to increase renal blood flow do not significantly increase GFR and do not improve the course of acute renal failure.

Due to a significant damage to the reabsorption capacity of nephrons, changes in the normal corticomedullary osmotic gradient, under conditions of a decrease in the filtration rate, there is an increase in fractional or absolute water excretion. All the above mechanisms explain the development of the polyuric stage of acute renal failure.

In the stage of recovery, the role of the hemodynamic factor again comes to the fore. Increased renal blood flow in parallel increases GFR and increases diuresis. The duration of the recovery stage is determined by the residual mass of the active nephrons. The rate of recovery of the kidneys is directly dependent on the renal blood flow in the recovery phase.

Pathological changes in acute renal failure are in most cases limited to varying degrees of dystrophic changes in the nephron. Timely use at the present stage of conservative methods of detoxification, renal replacement therapy makes it possible to treat the syndrome of acute renal failure as a reversible condition.

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