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. 2024 Jan 15;12(1):190.
doi: 10.3390/biomedicines12010190.

Circulating Lipoprotein Sphingolipids in Chronic Kidney Disease with and without Diabetes

Maria F Lopes-Virella  1   2 , Samar M Hammad  3 , Nathaniel L Baker  4 , Richard L Klein  1   2 , Kelly J Hunt  2   4
Affiliations

Circulating Lipoprotein Sphingolipids in Chronic Kidney Disease with and without Diabetes

Maria F Lopes-Virella et al. Biomedicines. .

Abstract

Abnormalities of sphingolipid metabolism play an important role in diabetes. We compared sphingolipid levels in plasma and in isolated lipoproteins between healthy control subjects and two groups of patients, one with chronic kidney disease without diabetes (ND-CKD), and the other with type 2 diabetes and macroalbuminuria (D-MA). Ceramides, sphingomyelins, and sphingoid bases and their phosphates in LDL were higher in ND-CKD and in D-MA patients compared to controls. However, ceramides and sphingoid bases in HDL2 and HDL3 were lower in ND-CKD and in D-MA patients than in controls. Sphingomyelins in HDL2 and HDL3 were lower in D-MA patients than in controls but were normal in ND-CKD patients. Compared to controls, lactosylceramides in LDL and VLDL were higher in ND-CKD patients but not in D-MA patients. However, lactosylceramides in HDL2 and HDL3 were lower in both ND-CKD and D-MA patients than in controls. Plasma hexosylceramides in ND-CKD patients were increased and sphingoid bases decreased in both ND-CKD and D-MA patients. However, hexosylceramides in LDL, HDL2, and HDL3 were higher in ND-CKD patients than in controls. In D-MA patients, only C16:0 hexosylceramide in LDL was higher than in controls. The data suggest that sphingolipid measurement in lipoproteins, rather than in whole plasma, is crucial to decipher the role of sphingolipids in kidney disease.

Keywords: albuminuria; ceramide; diabetes; dihydrosphingosine; glycosphingolipid; hexosylceramide; lactosylceramide; macroalbuminuria; sphingolipid; sphingomyelin; sphingosine.

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Conflict of interest statement

None of the authors has any conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Between-group effect sizes for lipoprotein ceramide species (A) comparing the group of normal controls (Control) and the group of patients with type 2 diabetes and macroalbuminuria (D-MA) to non-diabetic patients with chronic kidney disease (ND-CKD). (B) Between-group effect sizes are presented for lipoprotein sphingomyelin species levels comparing the group of normal controls (Control) and the group of patients with type 2 diabetes and macroalbuminuria (D-MA) to non-diabetic patients with chronic kidney disease (ND-CKD). Mean difference in log10 transformed data and pooled standard deviations were used to calculate between-group effect sizes, and they are presented as Cohen’s d on the x-axis. The magnitude of the geometric mean level of the sphingolipid species carried by the corresponding lipoproteins (LDL and HDL3) in the ND-CKD group are reflected by the bubble size. Higher levels have larger bubble sizes. Yellow (LDL), blue (HDL), solid color (Control), stripes (D-MA).
Figure 2
Figure 2
Between-group differences are presented for (A) lactosylceramide and (B) hexosylceramide species levels comparing the group of normal controls (Control) and the group of patients with type 2 diabetes and macroalbuminuria (D-MA) to non-diabetic patients with chronic kidney disease (ND-CKD). Mean difference in log10 transformed data and pooled standard deviations were used to calculate between-group effect sizes, and they are presented as Cohen’s d on the x-axis. The magnitude of the geometric mean level of the sphingolipid species carried by the corresponding lipoproteins (LDL and HDL3) in the ND-CKD group is reflected by the bubble size. Higher levels have larger bubble sizes. Yellow (LDL), blue (HDL), solid color (Control), stripes (D-MA).
Figure 3
Figure 3
Between-group effect sizes are presented for the levels of sphingoid bases and their phosphates comparing the group of normal controls (Control) and the group of patients with type 2 diabetes and macroalbuminuria (D-MA) to non-diabetic patients with chronic kidney disease (ND-CKD). Mean difference in log10 transformed data and pooled standard deviations were used to calculate between-group effect sizes, and they are presented as Cohen’s d on the x-axis. The magnitude of the geometric mean level of the sphingolipid species carried by the corresponding lipoproteins (LDL and HDL3) in the ND-CKD group are reflected by the bubble size. Higher levels have larger bubble sizes. Sphingoid bases: sphingosine (Sph) and dihydrosphingosine (dhSph), and their phosphates: sphingosine 1-phosphate (Sph-1P), and dihydrosphingosine 1-phosphate (dhSph-1P). Yellow (LDL), blue (HDL), solid color (Control), stripes (D-MA).
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