Potential Biomarkers for the Earlier Diagnosis of Kidney and Liver Damage in Acute Intermittent Porphyria

Author:

Storjord Elin1,Wahlin Staffan2ORCID,Karlsen Bård Ove13ORCID,Hardersen Randolf I.45ORCID,Dickey Amy K.67,Ludviksen Judith K.3,Brekke Ole-Lars15ORCID

Affiliation:

1. Department of Laboratory Medicine, Nordland Hospital Trust, 8092 Bodø, Norway

2. Hepatology Division, Department of Upper GI Diseases, Porphyria Centre Sweden, Karolinska Institute and Karolinska University Hospital, 14186 Stockholm, Sweden

3. Research Laboratory, Nordland Hospital Trust, 8092 Bodø, Norway

4. Department of Nephrology, Nordland Hospital Trust, 8092 Bodø, Norway

5. Department of Clinical Medicine, UiT-The Arctic University of Norway, 9019 Tromsø, Norway

6. Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA

7. Harvard Medical School, Boston, MA 02115, USA

Abstract

Acute intermittent porphyria (AIP) is an inherited metabolic disorder associated with complications including kidney failure and hepatocellular carcinoma, probably caused by elevations in the porphyrin precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA). This study explored differences in modern biomarkers for renal and hepatic damage between AIP patients and controls. Urine PBG testing, kidney injury panels, and liver injury panels, including both routine and modern biomarkers, were performed on plasma and urine samples from AIP cases and matched controls (50 and 48 matched pairs, respectively). Regarding the participants’ plasma, the AIP cases had elevated kidney injury marker-1 (KIM-1, p = 0.0002), fatty acid-binding protein-1 (FABP-1, p = 0.04), and α-glutathione S-transferase (α-GST, p = 0.001) compared to the matched controls. The AIP cases with high PBG had increased FABP-1 levels in their plasma and urine compared to those with low PBG. In the AIP cases, KIM-1 correlated positively with PBG, CXCL10, CCL2, and TCC, and the liver marker α-GST correlated positively with IL-13, CCL2, and CCL4 (all p < 0.05). In conclusion, KIM-1, FABP-1, and α-GST could represent potential early indicators of renal and hepatic damage in AIP, demonstrating associations with porphyrin precursors and inflammatory markers.

Funder

Somatic Research Fund at Nordland Hospital Trust and the Northern Norway Regional Health Authorities

Publisher

MDPI AG

Subject

Paleontology,Space and Planetary Science,General Biochemistry, Genetics and Molecular Biology,Ecology, Evolution, Behavior and Systematics

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