Background and aims: Diabetic kidney disease (DKD) is associated with lipid derangements worsening kidney function and enhancing cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications bringing up the participation of untraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in HDL proteome and functionality. We analyzed HDL composition, proteome, chemical modification and functionality in non-dialytic DKD subjects categorized according to estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods: DKD individuals were divided in 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 expressed in eGFR<60+A3 group in comparison to controls: apolipoprotein D (apoD) and apoA-IV. HDL from eGFR<60+A3 presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability in removing 14C-cholesterol from macrophages (33%) in comparison to controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups but HDL from eGFR<60+A3 presented a higher ability in inhibiting the secretion of IL6 and TNF alpha (95%) in LPS-elicited macrophages in comparison to control group. Conclusion: The increment in ApoD and ApoA-IV seems to counteract the HDL chemical modification by AGE and carbamoylation that contributes for HDL loss of function in well-established DKD.

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Background and aims: Diabetic kidney disease (DKD) is associated with lipid derangements worsening kidney function and enhancing cardiovascular ( CVD ) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications bringing up the participation of untraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in HDL proteome and functionality. We analyzed HDL composition, proteome, chemical modification and functionality in non-dialytic DKD subjects categorized according to estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods: DKD individuals were divided in eGFR>60 mL/min/1.73 m 2 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 expressed in eGFR<60+A3 group in comparison to controls: apolipoprotein D ( apoD ) and apoA-IV . HDL from eGFR<60+A3 presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability in removing 14 C-cholesterol from macrophages (33%) in comparison to controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups but HDL from eGFR<60+A3 presented a higher ability in inhibiting the secretion of IL6 and TNF alpha (95%) in LPS-elicited macrophages in comparison to control group. Conclusion: The increment in ApoD and ApoA-IV seems to counteract the HDL chemical modification by AGE and carbamoylation that contributes for HDL loss of function in well-established DKD.

Background and aims: Diabetes mellitus kidney disease (DKD) is associated with lipid derangements worsening kidney function and enhancing cardiovascular (CV) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CV complications bringing up the participation of untraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in HDL proteome and functionality. We analyzed HDL composition, proteome, chemical modification and functionality in non-dialytic DKD subjects categorized according to glomerular filtration rate (GFR) and urinary albumin excretion rate (AER). Methods: DKD individuals were divided in GFR > 60 mL/min/1.73 m2 plus AER stages A1 and A2 (n = 10) and GFR < 60 plus A3 (n = 25) and matched by age with control subjects (GFR > 60; n = 8). Results: Targeted proteomic analyses quantified 29 proteins associated with HDL in all groups, although only 2 were more expressed in GFR < 60 + A3 group in comparison to controls: apolipoprotein D (apo D) and apo A-IV. HDL from GFR < 60 + A3 presented higher levels of total AGEs, pentosidine and carbamoylation (1.2, 1.1 and 4.2 times, respectively) and a reduced ability in removing 14C-cholesterol from macrophages (33%) in comparison to controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups but HDL from GFR < 60 + A3 presented a higher ability in inhibiting the secretion of IL6 and TNF alpha (95%) in LPS-elicited macrophages in comparison to control group. Conclusion: The increment in apo A-IV that presents many antiatherogenic actions seems to counteract the HDL chemical modification by AGE and carbamoylation and its increment in apo D that occurred in well-established DKD.

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.