Study identifies potential early biomarkers of kidney, liver damage

Biomarkers may be valuable for monitoring AIP-related organ damage

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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People with acute intermittent porphyria (AIP) have high levels of three markers of kidney and liver injury in their blood, suggesting these could potentially serve as early biomarkers to mitigate damage, a recent study reports.

Levels of these markers — KIM-1, FABP-1, and alpha-GST — were found to be associated with the presence of porphyrin precursors, namely porphobilinogen (PBG) and delta-aminolevulinic acid (ALA), which are often found at high levels in the urine of AIP patients.

“Our findings can hopefully promote further research with the aim of better understanding kidney disease, [and] liver disease … in AIP,” researchers wrote.

The study, “Potential Biomarkers for the Earlier Diagnosis of Kidney and Liver Damage in Acute Intermittent Porphyria,” was published in the journal Life.

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AIP is the most common form of acute porphyria, which is a group of genetic disorders caused by disruptions in the production of heme, a molecule that enables red blood cells to transport oxygen throughout the body.

Heme is produced through a stepwise process, and when a given step is disrupted, there is an accumulation of intermediate molecules, called porphyrins and their precursors, in the body. This can lead to symptoms such as pain, gastrointestinal issues, urinary problems, and changes in mental status.

AIP patients may develop porphyria-associated kidney and liver diseases

AIP patients may also develop porphyria-associated kidney and liver diseases, likely due to the accumulation of porphyrin precursors, such as PBG or ALA.

To prevent and treat AIP-related kidney and liver diseases, early detection is crucial. However, traditionally used markers are insufficient to detect early kidney and liver damage, according to the researchers.

To identify modern biomarkers, a research team in Norway conducted an exploratory study to detect differences in modern biomarkers between 50 patients with a genetically confirmed AIP diagnosis, and 50 individuals without the disease who were matched by age, sex, and place of residence.

To that end, the researchers analyzed urine PBG levels, as well as kidney and liver injury marker panels, including both routine and modern biomarkers, on blood and urine samples collected from AIP patients and matched controls.

Although there were no significant differences in conventional kidney function parameters between the two groups, AIP patients were found to have significantly higher levels of kidney injury marker-1 (KIM-1), a marker of kidney damage, in the bloodstream (median of 92 vs. 50 picograms per milliliter, or pg/mL).

Moreover, the investigators found higher KIM-1 levels in the blood were associated with higher levels of PBG in the urine. This may indicate PBG and KIM-1 may be associated and involved in the mechanisms underlying the development of chronic kidney disease in people with AIP.

As expected, KIM-1 levels correlated with commonly used markers of kidney damage, such as serum creatinine and cystatin C.

Similarly, blood levels of fatty acid binding protein-1 (FABP-1), a marker of both kidney and liver injury, were higher in AIP patients compared with matched controls (median of 36 vs. 21 pg/mL). The levels of alpha-glutathione S-transferase (alpha-GST), a marker of liver damage, were also higher in the blood of AIP patients compared with controls (median of 3,626 vs. 1,982 pg/mL).

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High FABP-1 levels may put patients at higher risk of liver cancer

AIP patients with high urine PBG levels tended to have increased levels of FABP-1, both in the blood and urine. Considering FABP-1 levels are elevated in hepatocellular carcinoma, a type of liver cancer and a known complication of AIP, patients with higher levels of this marker may be at higher risk of developing the cancer, according to the researchers.

Blood levels of KIM-1 and alpha-GST were also found to be significantly correlated with the levels of certain cytokines, which are molecules that regulate communication between immune cells and inflammation.

“In conclusion, KIM-1, FABP-1, and [alpha]-GST could represent potential early indicators of renal and hepatic damage in AIP, demonstrating associations with porphyrin precursors and inflammatory markers,” the researchers wrote.

In the future, these biomarkers may be used to differentiate patients with distinct AIP clinical manifestations.

“Furthermore, these sensitive and early markers of organ damage may be valuable for monitoring for AIP-related organ damage, both for patients on and off treatment,” the researchers wrote.