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      Beneficial effect of LDL-apheresis in refractory nephrotic syndrome

      Clinical and Experimental Nephrology

      Springer Japan

      LDL-apheresis, Nephrotic syndrome, Secondary hyperlipidemia, Lipid nephrotoxicity, Cohort study

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          Abstract

          LDL-apheresis is a method to correct dyslipidemia rapidly. It is expected to alleviate the tissue toxicity of persistent dyslipidemia in not only primary, but also in secondary dyslipidemia associated with refractory nephrotic syndrome, and to have a protective effect against glomerular and tubular injury as expected in atherosclerosis. In addition, the effectiveness of LDL-apheresis to promote the remission of nephrotic syndrome has been recognized. In Japan, LDL-A to control hyperlipidemia in patients with refractory nephrotic syndrome associated with focal segmental glomerulosclerosis is covered by national health insurance. Here, the hypothetical mechanism behind its effect and the evidence for its effectiveness over a long period are reviewed.

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          Most cited references 10

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          Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease.

          It is hypothesised that chronic progressive kidney disease may be mediated by abnormalities of lipid metabolism. A series of self-perpetuating secondary events follows an initial glomerular injury. Increased glomerular basement membrane permeability leads to loss of lipoprotein lipase activators, resulting in hyperlipidaemia. Circulating low-density lipoprotein binds with glycosaminoglycans in the glomerular basement membrane and increases its permeability. Filtered lipoprotein accumulates in mesangial cells and stimulates them to proliferate and produce excess basement membrane material. The proximal tubular cells metabolise some of the filtered lipoprotein and the remainder are altered on passage down the nephron. Luminal apoprotein precipitates, initiating or aggravating tubulo-interstitial disease, if the intraluminal pH is close to the isoelectric point of the apoprotein. The hypothesis offers new approaches to the study of chronic progressive kidney disease by proposing a major pathogenetic role for lipid abnormalities.
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            Effect of plasma protein adsorption on protein excretion in kidney-transplant recipients with recurrent nephrotic syndrome.

            Among patients with the idiopathic nephrotic syndrome who have focal and segmental glomerulosclerosis and undergo renal transplantation, 15 to 55 percent have recurrent nephrotic syndrome. The recurrence may be caused by a plasma factor or factors that increase glomerular permeability, because plasma exchange transiently decreases or abolishes proteinuria in some patients. We studied the effect on proteinuria of the removal of protein (mostly immunoglobulins) by adsorption onto protein A from the plasma of patients with recurrent nephrotic syndrome. Eight patients were treated with one to three cycles of two to seven 1-day sessions of protein adsorption, and the patients' urinary protein excretion was measured repeatedly. Their immunosuppressive regimens were not changed during the treatment. The adsorbed proteins were eluted from the protein A and injected into rats, and the urinary albumin excretion of the rats was measured. The protein-adsorption treatment consistently decreased urinary protein excretion by an average of 82 percent at the end of a cycle (P < 0.001). In one patient proteinuria disappeared, and in another urinary protein excretion remained below 2.5 g per day with repeated cycles of protein adsorption. In all but one patient the effect of adsorption was limited in time, with a return to the preadsorption level of protein excretion within a maximum of two months. The administration to rats of material eluted from the protein A increased urinary albumin excretion 2.9- to 4.6-fold (P < 0.001 and P = 0.005, respectively). Although protein A primarily binds immunoglobulins, the active fraction of the eluted proteins had a molecular weight below 100,000, indicating that immunoglobulin was not directly involved. Adsorption of plasma protein decreases urinary protein excretion in patients with recurrence of the nephrotic syndrome after renal transplantation. Studies of the adsorbed proteins should provide information about the mechanism of this disease.
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              Significantly Rapid Relief from Steroid-Resistant Nephrotic Syndrome by LDL Apheresis Compared with Steroid Monotherapy

              Rapid amelioration of hypercholesterolemia by LDL apheresis (LDL-A) was performed for long-standing nephrotic syndrome (NS) with hyperlipidemia due to focal segmental glomerulosclerosis (FGS) and the clinical data and prognosis were compared between LDL-A-treated and nontreated groups. Seventeen steroid-resistant NS patients treated with LDL-A (LDL-A group) and 10 NS patients treated with steroids only (steroid-monotherapy (SM) group) were compared. Serum cholesterol and phospholipid levels were significantly lowered only in the LDL-A group (p < 0.01, respectively). The LDL-A group showed a significant decrease of urinary protein (UP, p < 0.01) and increase of serum albumin (p < 0.05). Average time needed to achieve a decrease of UP to less than nephrotic range (< 3.5 g/day) was significantly shorter in the LDL-A group than in the SM group (p < 0.01). Although this is not a prospective study, it is highly expected that a rapid improvement of hypercholesterolemia by LDL-A in steroid-resistant NS will provide more rapid relief from NS than steroid therapy alone.
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                Author and article information

                Contributors
                +81-6-63128824 , +81-6-63128867 , muso@kitano-hp.or.jp
                Journal
                Clin Exp Nephrol
                Clin. Exp. Nephrol
                Clinical and Experimental Nephrology
                Springer Japan (Tokyo )
                1342-1751
                1437-7799
                18 February 2014
                18 February 2014
                2014
                : 18
                : 286-290
                Affiliations
                Center of nephrology and Urology, Division of Nephrology and Dialysis, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka, 530-8480 Japan
                Article
                930
                10.1007/s10157-013-0930-5
                3994285
                24535024
                © The Author(s) 2014

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                Categories
                Review Article
                Custom metadata
                © Japanese Society of Nephrology 2014

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