Low-density lipoprotein apheresis retards the progression of hyperlipidemic overt diabetic nephropathy

Nakao, Toshiyuki; Yoshino, Maki; Matsumoto, Hiroshi; Okada, Tomonari; Han, Myongi; Hidaka, Hiromi; Shino, Tamami; Yamada, Chikayuki; Nagaoka, Yume; Miyahara, Tadashi

doi:10.1046/j.1523-1755.1999.07153.x

Cited by 16 publications

(9 citation statements)

References 12 publications

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“…Since then, there has been accumulating evidence that LA reduces proteinuria in diabetic nephropathy [14,50,51]. Interestingly, Nakamura et al [51] reported that LA reduces proteinuria in patients with diabetic nephropathy in association with a reduction in urinary podocyte excretion.…”

Section: La In Diabetic Nephropathymentioning

confidence: 99%

“…Podocyte are believed to have a key role in maintaining the integrity of the glomerular filtration barrier, and podocyte loss occurs in patients with type 2 diabetic nephropathy, and this is related to increased proteinuria [53]. Nakao et al [50] studied the effect of long-term intermittent LA therapy on the progression of overt diabetic nephropathy by an estimation of decline rates of reciprocal serum creatinine for an average duration of 8.2 months. Long-term intermittent LA therapy appeared to retard the progression of diabetic nephropathy.…”

Section: La In Diabetic Nephropathymentioning

confidence: 99%

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Applications of LDL-apheresis in nephrology

Kobayashi

2008

Clin Exp Nephrol

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LDL-apheresis (LA) was originally used for familial hyperlipidemia, and then in Japan extended to use for the treatment of patients with peripheral arterial disease (PAD) and nephrotic syndrome due to steroid-resistant focal glomerular sclerosis (FGS). The reason why this treatment is applicable for these disorders is due to the fact that LA exerts its favorable effects beyond the lipid-lowering effect. The main underlying mechanisms, for example, in the case of LA application in patients with PAD are: (1) improvement of hemorheology, (2) improvement of endothelial dysfunction, (3) elevations of serum levels of NO and bradykinin, (4) increase in serum levels of vascular endothelial growth factor, and (5) reduction of adhesion molecules on monocytes. Furthermore, we have reported that LA could have anti-inflammatory effects because LA reduces serum levels of P-selectin, which is known to play an important role in the development of atherosclerosis as well as a reduction of serum C-reactive protein levels as standard biomarker of atherosclerosis. Massive proteinuria is also an important challenge in nephrology. The possible mechanisms besides removal of toxic lipids are the reduction of the vasoconstrictive prostanoid and thromboxane A2 (TXA2) and an improvement in macrophage function evidenced by a significant amelioration of interleukin-8 production by lipopolysaccharide-stimulated peripheral blood mononuclear cells. It is intriguing to note that in terms of pharmacodynamics, LA improves steroid and cyclosporine uptake into lymphocytes. Although there are no randomized controlled trials, it is clear that LA has various effects beyond lowering lipids. Making the device more concise and changing it into a whole blood adsorption type, we need to collect more clinical cases and to study the underlying mechanisms further.

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Section: La In Diabetic Nephropathymentioning

confidence: 99%

Section: La In Diabetic Nephropathymentioning

confidence: 99%

Applications of LDL-apheresis in nephrology

Kobayashi

2008

Clin Exp Nephrol

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“…Second, increases in serum lipids have been associated with a faster decline of renal function (23,24). Third, there is also increasing evidence that inhibition of cholesterol synthesis by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors (statins), inhibition of triglyceride synthesis by peroxisome proliferator-activated receptor-␣ (PPAR-␣) agonists (fibrates), or a decrease in LDL achieved by LDL apheresis protect against diabetic and nondiabetic renal disease (25)(26)(27). A meta-analysis of several small-scale interventional studies in diabetic and nondiabetic human subjects with glomerulosclerosis and proteinuria in fact indicate that long-term treatment with statins and/or fibrates significantly prevents the decline in glomerular filtration rate (25).…”

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confidence: 99%

Regulation of Renal Lipid Metabolism, Lipid Accumulation, and Glomerulosclerosis in FVBdb/db Mice With Type 2 Diabetes

et al. 2005

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Diabetic kidney disease has been associated with the presence of lipid deposits, but the mechanisms for the lipid accumulation have not been fully determined. In the present study, we found that db/db mice on the FVB genetic background with loss-of-function mutation of the leptin receptor (FVB-Lepr db mice or FVB db/db ) develop severe diabetic nephropathy, including glomerulosclerosis, tubulointerstitial fibrosis, increased expression of type IV collagen and fibronectin, and proteinuria, which is associated with increased renal mRNA abundance of transforming growth factor-␤, plasminogen activator inhibitor-1, and vascular endothelial growth factor. Electron microscopy demonstrates increases in glomerular basement membrane thickness and foot process (podocyte) length. We found that there is a marked increase in neutral lipid deposits in glomeruli and tubules by oil red O staining and biochemical analysis for cholesterol and triglycerides. We also detected a significant increase in the renal expression of adipocyte differentiation-related protein (adipophilin), a marker of cytoplasmic lipid droplets. We examined the expression of sterol regulatory element-binding protein (SREBP)-1 and -2, transcriptional factors that play an important role in the regulation of fatty acid, triglyceride, and cholesterol synthesis. We found significant increases in SREBP-1 and -2 protein levels in nuclear extracts from the kidneys of FVB db/db mice, with increases in the mRNA abundance of acetyl-CoA carboxylase, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-CoA reductase, which mediates the increase in renal triglyceride and cholesterol content. Our results indicate that in FVB db/db mice, renal triglyceride and cholesterol accumulation is mediated by increased activity of SREBP-1 and -2. Based on our previous results with transgenic mice overexpressing SREBP-1 in the kidney, we propose that increased expression of SREBPs plays an important role in causing renal lipid accumulation, glomerulosclerosis, tubulointerstitial fibrosis, and proteinuria in mice with type 2 diabetes.

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“…In humans using univariate statistical models, hyperlipidemia significantly correlated to the progression of renal disease [11,111,117,132,132,133,134,135,136]. However, in multivariate models, which include the degree of renal failure and proteinuria, the correlation of hyperlipidemia and progression was minimal or absent [11,111,117,134].…”

Section: Fatmentioning

confidence: 99%

Nutrition in children with preterminal chronic renal failure. Myth or important therapeutic aid?

Wingen¹,

Mehls

2002

Pediatric Nephrology

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Nutrition has been believed to be an important therapeutic instrument in children with chronic renal failure (i) for improving growth, and (ii) for slowing down the deterioration of renal function. The therapeutic strategies for both targets may be conflicting, at least in part, since a high calorie intake is needed for optimal growth, whereas a low protein diet, which was believed to protect renal function, places patients at risk of low calorie intake. Dietary manipulations for optimal growth are mainly effective in infants with chronic renal failure. However, growth remains suboptimal even with an energy intake above 80% of RDA. Although a low protein diet is able to slow down the rate of deterioration in renal function in rodent studies, the results of prospective clinical studies were disappointing at least for an observation period up to three years. The conclusions out of meta-analyses of these clinical studies in adults are contradictory. The progression rate was not significantly influenced by protein restriction, whereas renal replacement therapy could be postponed. However, the latter seems to be the effect of weakening uremic symptoms during the phase of end-stage renal failure. According to our present knowledge it is not justified to prescribe special diets to children early in the course of chronic renal failure, but the composition of their nutrition should follow the general concept of an optimal mixed diet.

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Low-density lipoprotein apheresis retards the progression of hyperlipidemic overt diabetic nephropathy

Cited by 16 publications

References 12 publications

Applications of LDL-apheresis in nephrology

Applications of LDL-apheresis in nephrology

Regulation of Renal Lipid Metabolism, Lipid Accumulation, and Glomerulosclerosis in FVBdb/db Mice With Type 2 Diabetes

Nutrition in children with preterminal chronic renal failure. Myth or important therapeutic aid?

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