I. The integrated treatment of chronic renal failure refers to the comprehensive treatment of patients with chronic renal failure, which mainly includes four major parts: intervention in the progression of CRF, prevention of uremic complications, reduction of comorbidities and preparation for renal replacement therapy.
(1) In the intervention of progression, we should achieve the control of blood pressure and proteinuria;
(2) Prevention of uremic complications by correcting malnutrition and anemia and controlling secondary hyperparathyroidism and metabolic acidosis;
(3) In the reduction of CRF comorbidities, attention should be paid to the prevention and treatment of cardiac and cerebral conditions and neurological and retinal pathologies;
(4) For future renal replacement therapy, patient education should be done to prepare for the selection of appropriate replacement therapy options in the future and to pay attention to timely dialysis.
The significance of blocking the renin-angiotensin system for the treatment of chronic renal failure
The methods of blocking the renin-angiotensin system (RAS) include angiotensin-converting enzyme inhibitors (ACEI) and angiotensin I receptor antagonists (ARB). The mechanism of renal protection by blocking the RAS depends on its hemodynamic effects, i.e., hypotensive and nonhypertensive effects.
The hemodynamic renoprotective effects of blocking RAS.
(1) Decrease in intra-glomerular pressure by lowering systemic blood pressure;
(2) Selective dilatation of the small glomerular efferent arteries, thereby reducing glomerular capillary transmembrane pressure;
(3) The decrease in intra-glomerular pressure decreases the pressure on glomerular thylakoid cells and endothelial cells, thereby reducing damage to them;
(4) The decrease of glomerular transmembrane pressure and the improvement of glomerular capillary filtration barrier can reduce proteinuria and prevent proteinuria-induced kidney damage.
The non-hypertensive renoprotective effect of blocking RAS is mainly related to the role of making angiotensin II (Ang II) in renal remodeling by.
(1) Reducing renal ammonia production, thereby preventing renal damage caused by ammonia itself and by activation of complement;
(2) Inhibition of renal tubular interstitial monocyte-macrophage and fibroblast aggregation;
(3) Promote extracellular matrix protease activity and reduce the activity of its inhibitors, thus promoting matrix degradation;
(4) Inhibit the expression of transforming growth factor-b, platelet-derived growth factor and monocyte chemotactic protein-1 in renal tissues;
(5) Improve lipid glucose metabolism and prevent kidney damage caused by disorders of lipid glucose metabolism;
(6) Inhibit plasma aldosterone levels, which are now receiving increasing attention in the progression of renal disease.
Third, low protein diet
Protein diet can significantly affect renal hemodynamics, and then change glomerular filtration, the mechanism of which is partly because some amino acids in protein, especially arginine, can expand the small arteries into the glomerulus, but the main thing is done by excitation of the RAS. Protein diet increases the secretion of insulin and glucagon. Excessive glucagon and insulin can increase GFR, and in addition, excessive insulin can cause further damage to the kidney by stimulating sympathetic nerves, affecting lipid metabolism, and promoting the function of GluT1.
The nitrogenous metabolites from protein diet cause the progression of nephropathy by increasing the renal burden. The well-known MDRD study and several other studies have confirmed that a low protein diet (LPD) slows the rate of renal decompensation.
Does LPD cause malnutrition in patients with chronic kidney disease itself due to protein leakage or decreased appetite due to renal failure. This is because patients with CRF often have a negative nitrogen balance, especially a significant decrease in the synthesis of branched-chain amino acids and essential amino acids, and a positive nitrogen balance with an increased rate of protein synthesis after conversion to LPD.
Data from the MDRD study showed that although some nutritional indicators were lower in LPD patients than in the regular diet group, they did not affect survival or the incidence of complications. There are still some clinical observations showing no significant difference in survival of pre-dialysis LPDers entering dialysis compared to those on the regular diet.
LPD is now considered to have some impact in slowing the progression of CRF, but still does not address the underlying essential amino acid deficiency. Studies have shown greater superiority of alpha-keto acid supplementation on top of a very low protein diet (VLPD), as evidenced by.
(1) increased intake of some essential amino acids without a corresponding increase in ammonia intake and has been shown to improve the nutritional status of CRF patients;
(2) It still has the advantage of LPD in delaying renal decompensation, or even better;
(3) It has the effect of preventing secondary PTH increase in CRF and improving renal bone disease;
(4) Improving abnormal insulin metabolism;
(5) improve cellular Na+-K+-ATPase function, reduce lipid peroxidation and mitigate tissue damage;
(6) Affect the role of IGF and TGFβ in the mechanism of CRF progression;
(7) Partial correction of acidosis during CRF.
IV. New understanding of renal anemia
With the application of recombinant erythropoietin (EPO) in the treatment of renal anemia, the setting of target has been a controversial issue. It should be recognized that although the current increase in Hct to 30-33% has resulted in significant improvements in various aspects such as self-conscious symptoms, return to work, death from all causes, and hospitalization compared to Hct <30%, a further increase in Hct to about 35% could further reduce the relative risk of mortality and hospitalization, while a Hct of 40% would be closer to the physiological A further increase in Hct to about 35% would further reduce mortality and the relative risk of hospitalization, while a Hct of 40% would be closer to physiological status and would have a leap forward in improving quality of life.
As EPO therapy for renal anemia is still problematic in terms of tolerance, hypertension, and high cost, newer drugs such as EPO receptor agonists will show their superiority.
Iron supplementation is also a difficult issue in the treatment of renal anemia. Nowadays, oral iron does not meet the need, while intravenous iron supplementation has some problems including oxidative stress damage caused by iron overload. Therefore, new dosage forms of oral iron may dominate in the near future because of their advantages in iron absorption and utilization, reduction of EPO dosage, and gastrointestinal side effects.
V. Effect of acidosis on the progression of renal lesions
It is not only one of the clinical manifestations of CRF, but it is also clear that acidosis itself is one of the important mechanisms of CRF progression. Due to the prevalence of acidosis, the organism needs to mobilize a series of compensatory mechanisms that are mobilized at the cost of promoting the progression of renal lesions. These compensatory mechanisms include.
(1) promotion of increased PTH secretion to facilitate the release of skeletal calcium salts as a buffer for acidosis ;
(2) Increased ammonia synthesis by residual renal tissue to promote excretion of NH4+, which can stimulate interstitial adsorption of complement to accelerate nephropathy;
(3) Increased synthesis of ubiquitin and enhanced muscle catabolism to provide more ammonia, while promoting negative nitrogen balance;
(4) Increased renal citrate reabsorption, which contributes to the deposition of calcium-containing stones in the renal tubules, which can lead to tubular obstruction and infection;
(5) Increased transfer of intracellular K+ to the extracellular compartment, and low intracellular potassium can lead to the formation of small renal cysts;
(6) Chronic acidosis can increase TGFβ expression, upregulate G-Srs gene and promote tyrosine phosphorylation, activate complement, and lead to the formation of renal fibrosis;
(7) Promote the secretion of PTH;
(8) Promote insulin resistance;
(9) Inhibits the production of active vitamin D;
(10) cause abnormal state of GH/IGH axis, inhibit thyroxine and affect growth and development and produce some uremic related symptoms.
Therefore, more attention should be paid to the correction of acidosis both before dialysis and in patients already on dialysis. The ideal serum HCO3- level should be no less than 21 mmol/L before dialysis and no less than 24 mmol/L for CAPD patients.
VI. Rational dialysis treatment
Compared with peritoneal dialysis, patients with uremia often experience rapid loss of residual renal function after entering hemodialysis. Based on this, for patients entering dialysis for the first time, unless there are contraindications, peritoneal dialysis should generally be used first. For patients with hemodialysis, the maintenance of arteriovenous fistula function is significantly different in terms of age, i.e., patients younger than 65 years of age have longer maintenance of internal fistula function than those older than 65 years of age, while the maintenance of artificial vascular access is significantly lower than that of arteriovenous fistula, and there is no difference in patient age, so patients entering hemodialysis for the first time should try to choose their own vascular access Endovascular fistula.
Loss of endovascular function can occur for a variety of reasons, with thrombosis and atherosclerosis caused by proliferation of vascular smooth muscle cells (VSMC) being important factors. Pansentin is significantly more effective than aspirin in long-term antiplatelet aggregation and prevention of thrombosis, and fish oil supplementation also has a role to play. Factors that promote VSMC proliferation include basic fibroblast growth factor (bFGF), and pansentin has an inhibitory effect on the pro-VSMC proliferative effect of bFGF.