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Carbamylated Lipoproteins and Progression of Diabetic Kidney Disease.
Clin J Am Soc Nephrol. 2020 03 06; 15(3):359-366.CJ

Abstract

BACKGROUND AND OBJECTIVES

Protein carbamylation is a consequence of uremia and carbamylated lipoproteins contribute to atherogenesis in CKD. Proteins can also be carbamylated by a urea-independent mechanism, and whether carbamylated lipoproteins contribute to the progression of CKD has not been investigated.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS

A case-control study was performed to determine whether there were changes in plasma levels of carbamylated lipoproteins in individuals with type 2 diabetes with eGFR >60 ml/min per 1.73 m2 compared with a group of age- and sex-matched healthy controls. A cohort of 1320 patients with type 2 diabetes with baseline eGFR ≥30 ml/min per 1.73 m2 was longitudinally followed up to evaluate the association between carbamylated lipoproteins and progression of CKD. The primary kidney outcome was defined as doubling of serum creatinine and/or initiation of KRT during follow-up. Plasma carbamylated LDLs and HDLs was measured by ELISA.

RESULTS

In individuals with diabetes with eGFR >60 ml/min per 1.73 m2, both plasma carbamylated LDL and HDL levels were higher compared with healthy controls (P<0.001). After a mean follow-up of 9 years of the diabetic cohort, individuals in the top quartile of carbamylated LDL (hazard ratio, 2.21; 95% confidence interval, 1.42 to 3.46; P<0.001) and carbamylated HDL (hazard ratio, 4.53; 95% confidence interval, 2.87 to 7.13; P<0.001) had higher risk of deterioration of kidney function compared with those in the lowest quartile. On multivariable Cox regression analysis, plasma carbamylated LDL was no longer associated with kidney outcome after adjusting for baseline eGFR and potential confounding factors. However, the association between plasma carbamylated HDL and kidney outcome remained significant and was independent of HDL cholesterol.

CONCLUSIONS

Plasma carbamylated HDL but not carbamylated LDL was independently associated with progression of CKD in patients with type 2 diabetes.

Authors+Show Affiliations

Department of Medicine, University of Hong Kong, Hong Kong, China and kcbtan@hku.hk.Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China.Department of Medicine, University of Hong Kong, Hong Kong, China and.Department of Medicine, University of Hong Kong, Hong Kong, China and kcbtan@hku.hk.Department of Medicine, University of Hong Kong, Hong Kong, China and.Department of Medicine, University of Hong Kong, Hong Kong, China and.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32075807

Citation

Tan, Kathryn C B., et al. "Carbamylated Lipoproteins and Progression of Diabetic Kidney Disease." Clinical Journal of the American Society of Nephrology : CJASN, vol. 15, no. 3, 2020, pp. 359-366.
Tan KCB, Cheung CL, Lee ACH, et al. Carbamylated Lipoproteins and Progression of Diabetic Kidney Disease. Clin J Am Soc Nephrol. 2020;15(3):359-366.
Tan, K. C. B., Cheung, C. L., Lee, A. C. H., Lam, J. K. Y., Wong, Y., & Shiu, S. W. M. (2020). Carbamylated Lipoproteins and Progression of Diabetic Kidney Disease. Clinical Journal of the American Society of Nephrology : CJASN, 15(3), 359-366. https://doi.org/10.2215/CJN.11710919
Tan KCB, et al. Carbamylated Lipoproteins and Progression of Diabetic Kidney Disease. Clin J Am Soc Nephrol. 2020 03 6;15(3):359-366. PubMed PMID: 32075807.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carbamylated Lipoproteins and Progression of Diabetic Kidney Disease. AU - Tan,Kathryn C B, AU - Cheung,Ching-Lung, AU - Lee,Alan C H, AU - Lam,Joanne K Y, AU - Wong,Ying, AU - Shiu,Sammy W M, Y1 - 2020/02/19/ PY - 2019/09/27/received PY - 2020/01/07/accepted PY - 2020/2/23/pubmed PY - 2021/6/1/medline PY - 2020/2/21/entrez KW - HDL cholesterol KW - HDL2 lipoproteins KW - LDL lipoproteins KW - atherosclerosis KW - case-control studies KW - chronic renal insufficiency KW - cohort studies KW - creatinine KW - diabetic nephropathies KW - diabetic nephropathy KW - enzyme-linked immunosorbent assay KW - follow-up studies KW - glomerular filtration rate KW - humans KW - kidney KW - progression of renal failure KW - protein carbamylation KW - regression analysis KW - renal replacement therapy KW - type 2 diabetes mellitus KW - urea KW - uremia SP - 359 EP - 366 JF - Clinical journal of the American Society of Nephrology : CJASN JO - Clin J Am Soc Nephrol VL - 15 IS - 3 N2 - BACKGROUND AND OBJECTIVES: Protein carbamylation is a consequence of uremia and carbamylated lipoproteins contribute to atherogenesis in CKD. Proteins can also be carbamylated by a urea-independent mechanism, and whether carbamylated lipoproteins contribute to the progression of CKD has not been investigated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A case-control study was performed to determine whether there were changes in plasma levels of carbamylated lipoproteins in individuals with type 2 diabetes with eGFR >60 ml/min per 1.73 m2 compared with a group of age- and sex-matched healthy controls. A cohort of 1320 patients with type 2 diabetes with baseline eGFR ≥30 ml/min per 1.73 m2 was longitudinally followed up to evaluate the association between carbamylated lipoproteins and progression of CKD. The primary kidney outcome was defined as doubling of serum creatinine and/or initiation of KRT during follow-up. Plasma carbamylated LDLs and HDLs was measured by ELISA. RESULTS: In individuals with diabetes with eGFR >60 ml/min per 1.73 m2, both plasma carbamylated LDL and HDL levels were higher compared with healthy controls (P<0.001). After a mean follow-up of 9 years of the diabetic cohort, individuals in the top quartile of carbamylated LDL (hazard ratio, 2.21; 95% confidence interval, 1.42 to 3.46; P<0.001) and carbamylated HDL (hazard ratio, 4.53; 95% confidence interval, 2.87 to 7.13; P<0.001) had higher risk of deterioration of kidney function compared with those in the lowest quartile. On multivariable Cox regression analysis, plasma carbamylated LDL was no longer associated with kidney outcome after adjusting for baseline eGFR and potential confounding factors. However, the association between plasma carbamylated HDL and kidney outcome remained significant and was independent of HDL cholesterol. CONCLUSIONS: Plasma carbamylated HDL but not carbamylated LDL was independently associated with progression of CKD in patients with type 2 diabetes. SN - 1555-905X UR - https://www.unboundmedicine.com/medline/citation/32075807/Carbamylated_Lipoproteins_and_Progression_of_Diabetic_Kidney_Disease_ DB - PRIME DP - Unbound Medicine ER -