Pathogenesis of acute renal failure

Acute renal failure develops over a period of several hours to several days in response to various injuries and is manifested by azotemia, oligoanuria, acid-base imbalance and electrolyte imbalance. It occurs with a sudden, potentially reversible decrease in SCF.

Normal glomerular filtration rate and maximum urine osmolality values

Indicators	Newborns	1-2 weeks of life	6-12 months of life	1-3 years	Adults
SCF, ml/min per 1.73 m2	2b,2±2	54.8±8	77±14	96±22	118±18
Maximum urine osmolality, mosmol/kg H20	543+50	619±81	864±148	750±1330	825±1285

It remains controversial at what level a decrease in SCF by 50% or more, persisting for at least 24 hours, indicates the onset of acute renal failure. This is accompanied by an increase in the concentration of creatinine in the blood plasma of 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 and electrolyte disturbances, metabolic acidosis, accumulation of carbon dioxide, increased ventilation, lung damage and pathological breathing.

Acute renal failure syndrome is rarely isolated; it often develops as part of multiple organ failure. The peculiarity of the course 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%. The wide range of survival is associated with the different nature of diseases that cause the development of acute renal failure.

In the neonatal period, the risk of developing acute renal failure is increased due to the immaturity of the kidneys. The main distinguishing feature of a full-term newborn is a low SCF and minimal renal blood flow. In newborns, the physiological ability of the kidneys to both concentrate and dilute urine is also very limited, therefore, the ability to regulate hemostasis disorders is minimal. At the same time, their functioning nephrons are located in the juxtamedullary layer and are relatively well protected from hypoxia. This is why transient renal ischemia in newborns occurs quite often (with an unfavorable course of labor, the development of asphyxia), but rarely leads to true cortical necrosis. In fact, the kidneys respond to changes in hemodynamics and hypoxia only by reducing the filtration rate. After normalization of hemodynamics and elimination of the damaging agent, renal dysfunctions also disappear.

When renal perfusion or vascular volume decreases, the reabsorption of dissolved substances, including urea, increases. Under physiological conditions, 30% of the urea filtered in the glomeruli is reabsorbed. This percentage increases with decreased renal perfusion. Since creatinine is not reabsorbed, increased urea reabsorption leads to an increase in the urea/creatinine ratio in the blood. This condition is often referred to as prerenal azotemia.

In some cases, progression of general hemodynamic and blood circulation disorders, sharp depletion of renal blood flow cause renal afferent vasoconstriction with redistribution of renal blood flow. In severe ischemia of the renal cortex, the SCF falls to critical values, almost to zero, with subsequent ischemic necrosis of the epithelium of the convoluted tubules of the kidneys. The main clinical sign of acute tubular necrosis is the development of oliguria.

Acute renal failure syndrome may be caused by inflammation in the renal parenchyma and interstitium (glomerulonephritis or tubulointerstitial nephritis). Along with ischemia, parenchymatous kidney damage is promoted by endogenous intoxication (microbial toxins, proinflammatory mediators, biologically active substances, free oxygen radicals, etc.), which affect the blood coagulation system.

In patients with pure nephrotic syndrome, acute renal failure may be associated with interstitial tissue edema, increased hydrostatic pressure in the proximal tubules and Bowman's capsule, and, accordingly, with a decrease in filtration pressure and the value of SCF. Hemodialysis with massive ultrafiltration or the introduction of albumin, which eliminates interstitial edema, can restore renal function.

In some cases, anuria in glomerular kidney disease may be a consequence of tubular obstruction by protein masses or blood clots, for example, in patients with IgA nephropathy with episodes of macrohematuria.

A decrease in SCF may be due to 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 plasmapheresis.

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

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

• renal vasoconstriction causing tissue ischemia;
• decreased permeability of glomerular capillaries, leading to a drop in SCF;
• obstruction of tubules by cellular debris;
• transepithelial reverse flow of filtrate into the peri-tubular space.

The hemodynamic factor plays a dominant role in the pathogenesis of the syndrome. It is described by a well-known phenomenon (tubuloglomerular feedback), the essence of which is damage to the epithelial cells of the proximal tubules due to the influence of some factors, leading to a decrease in the reabsorption of salts and water in the initial part of the nephron. Increased flow of Na ⁺ ions and water into the distal parts of the nephron serves as a stimulus for the release of vasoactive substances (renin) by the juxtaglomerular apparatus. Renin causes and maintains spasm of the afferent arterioles with redistribution of renal blood flow, desolation of the arterioles and a decrease in the SCF. All this leads to a decrease in the excretion of salts and water. The feedback signal sent by the tubules to reduce blood flow and SCF under conditions of excessive excretion of solutions is called tubuloglomerular feedback. Under physiological conditions, it provides a safety mechanism to limit SCF when tubular capacity is overloaded. However, in acute kidney injury, activation of this mechanism further reduces renal blood flow, limiting nutrient delivery and worsening tubular injury.

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 the SCF and do not improve the course of acute renal failure.

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

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

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

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