ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

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.