Effects of LDL apheresis on proteinuria in patients with diabetes mellitus, severe proteinuria, and dyslipidemia.
Apheresis
Diabetic kidney disease
Diabetic nephropathy
LDL
Proteinuria
Journal
Clinical and experimental nephrology
ISSN: 1437-7799
Titre abrégé: Clin Exp Nephrol
Pays: Japan
ID NLM: 9709923
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
22
02
2020
accepted:
11
08
2020
pubmed:
29
8
2020
medline:
6
10
2021
entrez:
29
8
2020
Statut:
ppublish
Résumé
Patients with diabetes mellitus and severe proteinuria present with poor renal prognoses, despite improvements in diabetes and kidney disease therapies. In this study, we designed a low-density lipoprotein (LDL)-cholesterol apheresis treatment for patients with diabetic nephropathy (DN)/diabetic kidney disease and severe proteinuria. This was a multicenter prospective LICENSE study to confirm the impact of LDL apheresis on proteinuria that exhibited hyporesponsiveness to treatment. In addition, we sought to determine the efficacy and safety of LDL apheresis by comparing the outcomes to those of historical controls in patients with diabetes, refractory hypercholesterolemia, and severe proteinuria. This was a prospective, multicenter study, including 40 patients with diabetes, severe proteinuria, and dyslipidemia. LDL apheresis was performed 6-12 times over a 12-week period. The primary endpoint was the proportion of patients with a decrease in proteinuria excretion of at least 30% in the 6 months after starting therapy. The secondary endpoints included serum creatinine levels and laboratory variables, which were evaluated 4, 6, 12, 18, and 24 months after therapy initiation. LDL apheresis was performed on 40 registered patients with diabetes. The proportion of cases in which proteinuria decreased by 30% or more after 6 months of LDL apheresis was 25%, which was similar to that of historical controls. The overall survival and end-stage kidney disease-free survival rates were significantly higher in the LICENSE group compared to those in historical controls. Our results suggest that LDL apheresis may be effective and safe for patients with diabetes, proteinuria, and dyslipidemia. Trial registration number: jRCTs042180076.
Sections du résumé
BACKGROUND
BACKGROUND
Patients with diabetes mellitus and severe proteinuria present with poor renal prognoses, despite improvements in diabetes and kidney disease therapies. In this study, we designed a low-density lipoprotein (LDL)-cholesterol apheresis treatment for patients with diabetic nephropathy (DN)/diabetic kidney disease and severe proteinuria. This was a multicenter prospective LICENSE study to confirm the impact of LDL apheresis on proteinuria that exhibited hyporesponsiveness to treatment. In addition, we sought to determine the efficacy and safety of LDL apheresis by comparing the outcomes to those of historical controls in patients with diabetes, refractory hypercholesterolemia, and severe proteinuria.
METHODS
METHODS
This was a prospective, multicenter study, including 40 patients with diabetes, severe proteinuria, and dyslipidemia. LDL apheresis was performed 6-12 times over a 12-week period. The primary endpoint was the proportion of patients with a decrease in proteinuria excretion of at least 30% in the 6 months after starting therapy. The secondary endpoints included serum creatinine levels and laboratory variables, which were evaluated 4, 6, 12, 18, and 24 months after therapy initiation.
RESULTS
RESULTS
LDL apheresis was performed on 40 registered patients with diabetes. The proportion of cases in which proteinuria decreased by 30% or more after 6 months of LDL apheresis was 25%, which was similar to that of historical controls. The overall survival and end-stage kidney disease-free survival rates were significantly higher in the LICENSE group compared to those in historical controls.
CONCLUSION
CONCLUSIONS
Our results suggest that LDL apheresis may be effective and safe for patients with diabetes, proteinuria, and dyslipidemia.
TRIAL REGISTRATION
BACKGROUND
Trial registration number: jRCTs042180076.
Identifiants
pubmed: 32857255
doi: 10.1007/s10157-020-01959-9
pii: 10.1007/s10157-020-01959-9
doi:
Substances chimiques
Cholesterol, LDL
0
Creatinine
AYI8EX34EU
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-8Références
Kobayashi S. Applications of LDL-apheresis in nephrology. Clin Exp Nephrol. 2008;12:9–15. https://doi.org/10.1007/s10157-007-0003-8 .
doi: 10.1007/s10157-007-0003-8
pubmed: 18175056
Kobayashi S, Oka M, Moriya H, Maesato K, Okamoto K, Ohtake T. LDL-Apheresis reduces P-selectin, CRP and fibrinogen—possible important implications for improving atherosclerosis. Ther Apher Dial. 2006;10:219–23. https://doi.org/10.1111/j.1744-9987.2006.00332.x .
doi: 10.1111/j.1744-9987.2006.00332.x
pubmed: 16817784
Wada T, Muso E, Maruyama S, et al. Rationale and study design of a clinical trial to assess the effects of LDL apheresis on proteinuria in patients with diabetes and severe proteinuria and dyslipidemia. Clin Exp Nephrol. 2018;22:591–6. https://doi.org/10.1007/s10157-017-1488-4 .
doi: 10.1007/s10157-017-1488-4
pubmed: 29080119
Shimizu M, Furuichi K, Toyama T, et al. Research Group of Diabetic Nephropathy, the Ministry of Health, Labour, and Welfare of Japan and Japan Agency for Medical Research and Development. Decline in estimated glomerular filtration rate is associated with risk of end-stage renal disease in type 2 diabetes with macroalbuminuria: an observational study from JDNCS. Clin Exp Nephrol. 2018;22:377–87. https://doi.org/10.1007/s10157-017-1467-9 .
doi: 10.1007/s10157-017-1467-9
pubmed: 28889347
Sato E, Amaha M, Nomura M, Matsumura D, Ueda Y, Nakamura T. LDL-apheresis contributes to survival extension and renal function maintenance of severe diabetic nephropathy patients: a retrospective analysis. Diabetes Res Clin Pract. 2014;106:241–6. https://doi.org/10.1016/j.diabres.2014.08.012 .
doi: 10.1016/j.diabres.2014.08.012
pubmed: 25306260
Wada T, Haneda M, Furuichi K, Babazono T. Clinical impact of albuminuria and glomerular filtration rate on renal and cardiovascular events, and all-cause mortality in Japanese patients with type 2 diabetes. Clin Exp Nephrol. 2014;18:613–20. https://doi.org/10.1007/s10157-013-0879-4 .
doi: 10.1007/s10157-013-0879-4
pubmed: 24132561
Ninomiya T, Perkovic V, de Galan BE, ADVANCE Collaborative Group, et al. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol. 2009;20:1813–21. https://doi.org/10.1681/ASN.2008121270 .
doi: 10.1681/ASN.2008121270
pubmed: 2723977
pmcid: 2723977
Yamanouchi M, Furuichi K, Hoshino J, et al. Research Group of Diabetic Nephropathy, the Ministry of Health, Labour and Welfare, and the Japan Agency for Medical Research and Development. Nonproteinuric versus proteinuric phenotypes in diabetic kidney disease: a propensity score-matched analysis of a nationwide, biopsy-based cohort study. Diabetes Care. 2019;42:891–902. https://doi.org/10.2337/dc18-1320 .
doi: 10.2337/dc18-1320
pubmed: 30833372
Yokoyama H, Araki S, Honjo J, et al. Association between remission of macroalbuminuria and preservation of renal function in patients with type 2 diabetes with overt proteinuria. Diabetes Care. 2013;36:3227–333. https://doi.org/10.2337/dc13-0281 .
doi: 10.2337/dc13-0281
pubmed: 23780946
pmcid: 3781501
Perkovic V, Jardine MJ, Neal B, CREDENCE Trial Investigators, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380:2295–306. https://doi.org/10.1056/NEJMoa1811744 .
doi: 10.1056/NEJMoa1811744
pubmed: 30990260
pmcid: 30990260
Toyama T, Neuen BL, Jun M, et al. Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and meta-analysis. Diabetes Obes Metab. 2019;21:1237–50. https://doi.org/10.1111/dom.13648 .
doi: 10.1111/dom.13648
pubmed: 30697905
Heerspink HJL, Greene T, Tighiouart H, et al. Chronic Kidney Disease Epidemiology Collaboration. Change in albuminuria as a surrogate endpoint for progression of kidney disease: a meta-analysis of treatment effects in randomised clinical trials. Lancet Diabetes Endocrinol. 2019;7:128–39. https://doi.org/10.1016/S2213-8587(18)30314-0 .
doi: 10.1016/S2213-8587(18)30314-0
pubmed: 30635226
Kobayashi S. LDL-apheresis for diabetic nephropathy: a possible new tool. Nephron. 1998;79:505–6. https://doi.org/10.1159/000045113 .
doi: 10.1159/000045113
pubmed: 9689183
Nakamura T, Kawagoe Y, Ogawa H, et al. Effect of low-density lipoprotein apheresis on urinary protein and podocyte excretion in patients with nephrotic syndrome due to diabetic nephropathy. Am J Kidney Dis. 2005;45:48–53. https://doi.org/10.1053/j.ajkd.2004.09.013 .
doi: 10.1053/j.ajkd.2004.09.013
pubmed: 15696443
Muso E. Beneficial effect of LDL-apheresis in refractory nephrotic syndrome. Clin Exp Nephrol. 2014;18:286–90. https://doi.org/10.1007/s10157-013-0930-5 .
doi: 10.1007/s10157-013-0930-5
pubmed: 24535024
pmcid: 3994285
Wada T, Furuichi K, Sakai N, et al. Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions in human diabetic nephropathy. Kidney Int. 2000;58:1492–9. https://doi.org/10.1046/j.1523-1755.2000.00311.x .
doi: 10.1046/j.1523-1755.2000.00311.x
pubmed: 11012884
de Zeeuw D, Remuzzi G, Parving HH, et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004;65:2309–20. https://doi.org/10.1111/j.1523-1755.2004.00653.x .
doi: 10.1111/j.1523-1755.2004.00653.x
pubmed: 15149345