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Abstract: TH-PO893

Metabolic Differences in Diabetic Kidney Disease Patients with and Without Albuminuria

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Hallan, Stein I., Norwegian University of Science and Technology, Trondheim, Norway
  • Darshi, Manjula, University of Texas Health San Antonio, San Antonio, Texas, United States
  • Øvrehus, Marius Altern, Norwegian University of Science and Technology, Trondheim, Norway
  • Langlo, Knut Asbjørn Rise, Norwegian University of Science and Technology, Trondheim, Norway
  • Sharma, Kumar, University of Texas Health San Antonio, San Antonio, Texas, United States
Background

The classical paradigm describing diabetic kidney disease (DKD) as a linear progression with stages of glomerular hyperfiltration, progressive albuminuria, and subsequent declining GFR is being recently challenged. 25-50% of DKD with eGFR <60ml/min/1.73m2 do not have albuminuria, and the underlying pathology in this group is not well studied. We studied the metabolic differences in unselected well-matched DKD patients with (DKD A1+) and without (DKD A0) albuminuria.

Methods

41 patients with DKD, defined as diabetes mellitus with eGFR <60mL/min/1.73m2, and 60 healthy age- and sex-matched controls were randomly chosen from the general population (HUNT-3 study, 2006-08, Norway). Urine samples were analyzed and 75 organic acids quantified using gas chromatography-mass spectrometry (GC-MS, 4-6 calibration points, CV 10-20%). Kidney function was followed over 10 years.

Results

15 of 41 DKD patients (37%) had ACR <3.0mg/mmol. Age and sex were similar in the healthy control, DKD A0 and DKD A1+ groups (∼ 71 years, p=0.3; and 40% males, p=0.6). Baseline eGFR was identical in DKD A0 and A1+ (51 vs 51 ml/min/1.73m2). They also had similar BMI, BP, BP medication, physical activity and education (p>0.4 for all), while DKD A0 had more never-smokers (p=0.002). PLS-DA analysis of the organic acid metabolites showed that the three groups separated moderately, with DKD A0 positioned between controls and DKD A1+ patients (Figure 1). When comparing the two DKD groups, we found 22 metabolites with VIP scores ≥1.0, i.e. considered to contribute significantly to separation. Top metabolites were hexanol glycine, lactic acid and keto-glucatic acid. Enrichment analysis based on these metabolites showed that citric acid cycle, Warburg effect, glucose-alanine, keton body metabolism, and fatty acid biosynthesis were the most affected pathways (p<0.05 and ∼ 5-fold enriched for all).

Conclusion

DKD patients with and without albuminuria differ substantially in their metabolic disturbances and could represent different clinical phenotypes

Funding

  • Government Support - Non-U.S.