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


The Latest on Twitter

Kidney Week

Abstract: PO0467

Renal Injury Biomarkers Are Elevated in Acute Hepatic Porphyria

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism


  • Ticau, Simina, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Yucius, Kristina, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Karras, Alexandre, Department of Nephrology, Hopital Européen Georges Pompidou, APHP, Paris, France
  • Sardh, Eliane, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
  • Gouya, Laurent, CRMR Porphyries, Hôpital Louis Mourier, APHP, Paris, France
  • Simon, Amy, Beam Therapeutics, Cambridge, Massachusetts, United States
  • Borodovsky, Anna, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States

Acute hepatic porphyria (AHP) is a group of rare genetic diseases caused by defects in enzymes in the heme biosynthesis pathway. Acute intermittent porphyria (AIP) is the most common subtype. In patients with AHP, accumulation of heme pathway intermediates, delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), lead to acute attacks and long-term complications including hypertension and chronic kidney disease which is present in 30-60% of patients with biochemically active AIP. Chronic high excreters (CHE) are a group of patients that carry a genetic mutation and have elevated levels of ALA and PBG but are not experiencing acute attacks.


Proteomic analysis (Olink® platform) was used to measure 1196 proteins in plasma from consenting AHP patients with recurrent acute attacks (>90% AIP) in the EXPLORE natural history study, the ENVISION Phase 3 study, and CHE patients in the ALN-AS1-001 Phase 1 study at baseline. A separate cohort of healthy controls, age- and gender-matched to EXPLORE patients was also analyzed. Linear regression accounting for age, and sex was used to determine the proteins that were significantly different between AHP patients or CHE patients and controls.


212 plasma proteins were significantly different between healthy controls and patients with AHP. Two proteins with the largest effect sizes, kidney injury molecule-1 (KIM1; 3.4-fold; p-value= 8.0e-13) and matrix metalloproteinase-7 (MMP7; 5-fold; p-value= 1.5e-25) were previously described as biomarkers of renal injury. Three additional kidney injury biomarkers (neutrophil gelatinase-associated lipocalin, cystatin C (CST3) and chitinase-3-like protein 1) showed significant elevations in patients with AHP. Moderate to strong correlations were observed between each of these biomarkers and eGFR (correlation coefficients -0.33 to -0.54). AHP patients with a diagnosis of renal disease demonstrated significantly higher levels of each of these biomarkers than patients without such a diagnosis (p-values <0.01). KIM1, MMP7, and CST3 were also significantly elevated in CHE patients compared to controls.


Renal injury biomarkers may aid in diagnosing and managing kidney disease in patients with AHP suffering from recurrent acute attacks as well as chronic high excreters.


  • Commercial Support