Dataset Information

Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis.

ABSTRACT:

Background and aims

Diabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chemical modification and functionality were analyzed in nondialysis subjects with DKD categorized according to the estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER).

Methods

Individuals with DKD were divided into eGFR> 60 mL/min/1.73 m² plus AER stages A1 and A2 (n = 10) and eGFR< 60 plus A3 (n = 25) and matched by age with control subjects (eGFR> 60; n = 8).

Results

Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more highly expressed in the eGFR< 60 + A3 group than in the controls: apolipoprotein D (apoD) and apoA-IV. HDL from the eGFR< 60 + A3 group presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability to remove ¹⁴C-cholesterol from macrophages (33%) in comparison to HDL from controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups, but HDL from the eGFR< 60 + A3 group presented a greater ability to inhibit the secretion of IL-6 and TNF-alpha (95%) in LPS-elicited macrophages in comparison to the control group.

Conclusion

The increase in apoD and apoA-IV could contribute to counteracting the HDL chemical modification by AGEs and carbamoylation, which contributes to HDL loss of function in well-established DKD.

SUBMITTER: Santana MFM

PROVIDER: S-EPMC7488728 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis.

Santana Monique F M MFM Lira Aécio L A ALA Pinto Raphael S RS Minanni Carlos A CA Silva Amanda R M ARM Sawada Maria I B A C MIBAC Nakandakare Edna R ER Correa-Giannella Maria L C MLC Queiroz Marcia S MS Ronsein Graziella E GE Passarelli Marisa M

Lipids in health and disease 20200914 1

<h4>Background and aims</h4>Diabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chem ...[more]

PMID: 32921312

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Project description:Rationale & objectiveChronic kidney disease (CKD) in patients with diabetes does not always equate to diabetic kidney disease (DKD). This study aims to delineate and compare the clinical characteristics, survival rates, and access to kidney transplantation among patients with type 2 diabetes commencing dialysis, who were classified by kidney biopsy as having either DKD or non-diabetic kidney disease (non-DKD).Study designWe used the comprehensive French Renal Epidemiology and Information Network registry to analyze baseline clinical characteristics at dialysis inception and outcomes defined as death and access to kidney transplantation.Outcomes & analytical approachWe employed a multivariate Cox proportional hazards model and the Fine-Gray competing risk model to assess the probabilities of mortality and transplantation.Settings & participantsAdults in the Renal Epidemiology and Information Network registry in France with a diagnosis of type 2 diabetes who initiated kidney replacement therapy from January 2009 to December 2015 and had a previous native kidney biopsy.ResultsWe analyzed data from 2,869 patients with diabetes, 45% of whom had a biopsy-confirmed diagnosis of DKD. Among these patients, half presented additional histopathological findings indicative of nephroangiosclerosis and focal segmental glomerulosclerosis. The clinical profiles of patients with DKD and non-DKD were largely comparable. There were no significant differences in dialysis survival rates or kidney transplantation access between the groups, even after adjusting for confounding variables and considering competing risks. At the 6-year mark, the mortality rate was 60.3% (95% CI: 55.5-64.5) for the DKD group and 60.3% (95% CI: 55.9-64.3) for the non-DKD group. Multivariable Cox analysis revealed no significant difference in mortality risk between the DKD and non-DKD groups.LimitationsThe study limitations include potential residual confounders, lack of predialysis data, kidney biopsies possibly outdated, nonrandom biopsy indications, and survival bias because of analysis at dialysis inception.ConclusionsIn patients with diabetes initiating dialysis, clinical characteristics and outcomes following dialysis initiation were similar in biopsy-proven DKD versus non-DKD. Our results suggest that the diabetic milieu has a more significant impact on outcomes in patients with diabetes treated with dialysis than the underlying pathological kidney diagnosis.

Dataset Information

Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis.

Background and aims

Methods

Results

Conclusion

Publications

Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis.

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