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Application of blood purification in the treatment of nephro

Dec 26, 2016
The treatment of nephrotic syndrome (NS) is the basic drugs (referred to as the glucocorticoid hormone????), for steroid resistant or dependent patients with NS, general use of hormones and immunosuppressive therapy, this scheme is not effective for patients with refractory NS likelihood of progression to end-stage renal failure is high. In refractory NS, the worst clinical outcome is focal glomerulosclerosis (FGS). Clinically, plasma exchange (PE), immune adsorption (IA), and immune purification (LDL-A) for low density lipoprotein (LDL) can be selected. This article focuses on the application of blood purification in FGS treatment.
One, PE, IA treatment of FGS in renal transplant cases accounted for 30%, of which, half of the recurrent cases of renal necrosis occurred in the transplantation of FGS. The recurrence of CPF mostly occurred in 1 weeks after renal transplantation, and the pathogenesis of FGS was related to vascular permeability factor (circoulatingpermeabilityfactors). According to reports, PE, IA can effectively treat or prevent FGS recurrence. Dantal reported the treatment of 8 patients with NS after renal transplantation by ELISA method for protein A column adsorption of lipoprotein (FGS2 cases, 6 cases of steroid resistant minimalchange), the urine protein decreased by 82%. The author put the adsorption liquid into rats, but increased urinary albumin 2.9~4.6 times. It has been proved that the molecular weight of the column dissolution factor causing proteinuria is below 100 thousand Dalton, so it is not directly related to immunoglobulin. Esnault et al. Reported that IA therapy can reduce proteinuria in patients with membranous nephropathy, IgA nephropathy, diabetic nephropathy, and amyloidosis nephropathy. The mechanism of IA may be related to the removal of non-specific vascular permeability enhancing factor. Feld reported that the treatment of 8 cases of primary steroid resistant FGS by PE method, among them, 2 cases of patients with proteinuria reduction, stable renal function; the remaining 6 cases of proteinuria in patients with no improvement, including 4 cases of patients with renal function deterioration. However, studies by Savin et al. Showed that albumin permeability (Palb), which represents glomerular capillary permeability, was improved in 6 cases of proteinuria without improvement. The author thinks that PE treatment of primary FGS effect than FGS after renal transplantation:?? FGS patients receiving PE therapy time is often late, progress is in the state of renal tissue injury;?? systemic pathogenic factors unrelated to glomerular permeability in patients with FGS.
Two 、 LDL-A treatment of refractory NS (mainly FGS)
Lipid metabolism disorders are associated with the onset and progression of FGS. Therefore, cholesterol lowering therapy (LDL-A), which is used to treat familial hypercholesterolemia (FH), has been used in the treatment of refractory FGS. The LDL-A therapy consisted of 2 primary filtration plasma exchange (doublefiltra-tionplasmapheresis, DFPP), and? LDL?. Among them, the use of LDL dextran sulfate cellulose column adsorption method, is widely used in clinical.
In 1988, Sakai et al. Reported that the use of LDL-A (including DFPP? And? LDL?) therapy for refractory NS patients results in remission as hyperlipidemia improves. In 1992, a multicenter study showed that 2 times a week LDL adsorption therapy refractory NS, in principle, continuous treatment for a total of 3 weeks, a total of 6 times. Of the 16 patients who received the treatment, proteinuria was reduced in all of the 9 patients (56,3%), of whom, in the 4 months after treatment, the urine protein decreased to below 1g for the first 1 months after treatment.
A group of multi center study of Muso in Kansai area showed that the adsorption of LDL therapy for 17 cases of patients with steroid resistant NS (FGS14 cases, MCNS3 cases), 2 times a week, after 3 weeks of continuous treatment, then changed to 1 times a week, for 6 weeks, a total of 12 times. The study and 10 cases (FGS9 cases, MCNS1 cases) hormone treatment of NS contrast, results, LDL adsorption treatment group urine protein, serum albumin rise, compared with the control group, the treatment group was significantly shortened NS state time.
According to reports, LDL-A therapy is also applicable in steroid resistant MCNS, and the effect is good. However, the efficacy of membranous nephropathy can not be sure. Sakai used this method to treat 13 cases of FGS cases, of which, there were 7 cases (54%) improved, while the disease in patients with membranous nephropathy in the 3 cases did not improve, only one case had a transient urinary protein reduction. Stenvinkel reported that in 4 cases of membranous nephropathy treated with LDL-A alone, there were improvement in NS in 3 patients. In the future, it is necessary to further explore the efficacy of LDL-A in the treatment of membranous nephropathy. Three, LDL-A treatment of FGS effective mechanism LDL-A therapy can adsorb LDL, very low density lipoprotein (VLDL) and Lp (a). However, there are still no clear answers to some questions. For example, the correlation between abnormal lipid composition and proteinuria, LDL adsorption therapy can remove CPF, etc.. The mechanism of LDL-A treatment of FGS is not very clear. Currently that may be related to the following. (1) to improve the expression of hormone receptor in hyperlipidemia and weaken the sensitivity of organism to hormone.
(2) because cyclosporin A (CYA) must be mediated by the LDL receptor (LDL-R) in the body to be absorbed by tissue cells. Because of the down-regulation of LDL-R expression in hyperlipidemia, the intracellular uptake of immunosuppressive agents will be affected. LDL-A improves the expression of LDL-R by improving hyperlipidemia, thereby promoting the intracellular uptake of immunosuppressive agents and improving clinical efficacy.
(3) by inhibiting the expression of inflammatory cytokines and chemokines, decrease the infiltration of macrophages in glomeruli.
(4) inhibition of thromboxane A2 (thromboxanA2) expression, improve renal vascular contraction.
(5) possible removal of CPF.

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