{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:35:14Z","timestamp":1791477314553,"version":"4.3.4"},"reference-count":90,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Porphyrias are a group of rare disorders originating from an enzyme dysfunction in the pathway of heme biosynthesis. Depending on the specific enzyme involved, porphyrias manifest under drastically different clinical pictures. The most dramatic presentation of the four congenital acute hepatic porphyrias (AHPs: acute intermittent porphyria\u2014AIP, ALAD deficiency, hereditary coproporphyria\u2014HCP, and porphyria variegata\u2014VP) consists of potentially life-threatening neurovisceral attacks, for which givosiran, a novel and effective siRNA-based therapeutic, has recently been licensed. Nonetheless, the clinical manifestations of acute porphyrias are multifaceted and do not limit themselves to acute attacks. In particular, porphyria-associated kidney disease (PAKD) is a distinct, long-term degenerating condition with specific pathological and clinical features, for which a satisfactory treatment is not available yet. In PAKD, chronic tubule-interstitial damage has been most commonly reported, though other pathologic features (e.g., chronic fibrous intimal hyperplasia) are consistent findings. Given the relevant role of the kidney in porphyrin metabolism, the mechanisms possibly intervening in causing renal damage in AHPs are different: among others, \u03b4-aminolevulinic acid (ALA)-induced oxidative damage on mitochondria, intracellular toxic aggregation of porphyrins in proximal tubular cells, and derangements in the delicate microcirculatory balances of the kidney might be implicated. The presence of a variant of the human peptide transporter 2 (PEPT2), with a greater affinity to its substrates (including ALA), might confer a greater susceptibility to kidney damage in patients with AHPs. Furthermore, a possible effect of givosiran in worsening kidney function has been observed. In sum, the diagnostic workup of AHPs should always include a baseline evaluation of renal function, and periodic monitoring of the progression of kidney disease in patients with AHPs is strongly recommended. This review outlines the role of the kidney in porphyrin metabolism, the available evidence in support of the current etiologic and pathogenetic hypotheses, and the known clinical features of renal involvement in acute hepatic porphyrias.<\/jats:p>","DOI":"10.3390\/diagnostics11122324","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T08:17:58Z","timestamp":1639124278000},"page":"2324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Kidney Involvement in Acute Hepatic Porphyrias: Pathophysiology and Diagnostic Implications"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4812-3750","authenticated-orcid":false,"given":"Andrea","family":"Ricci","sequence":"first","affiliation":[{"name":"Internal Medicine Unit, Department of Medical and Surgical Science for Children and Adults, Regional Reference Centre for Diagnosing and Management of Porphyrias, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico of Modena, Largo del Pozzo 71, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2514-8469","authenticated-orcid":false,"given":"Claudio Carmine","family":"Guida","sequence":"additional","affiliation":[{"name":"Interregional Reference Center for the Prevention, Surveillance, Diagnosis and Treatment of Porphyria, Nephrology and Dialysis Unit, Scientific Institute for Research and Health Care, Viale Cappuccini, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0385-9123","authenticated-orcid":false,"given":"Paola","family":"Manzini","sequence":"additional","affiliation":[{"name":"Transfusion Medicine and Blood Establishment, Regional Reference Centre for Diagnosis and Management of Porphyrias, University Hospital City of Science and Health of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Cuoghi","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, Department of Medical and Surgical Science for Children and Adults, Regional Reference Centre for Diagnosing and Management of Porphyrias, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico of Modena, Largo del Pozzo 71, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-1914","authenticated-orcid":false,"given":"Paolo","family":"Ventura","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, Department of Medical and Surgical Science for Children and Adults, Regional Reference Centre for Diagnosing and Management of Porphyrias, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico of Modena, Largo del Pozzo 71, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1056\/NEJMra1608634","article-title":"Porphyria","volume":"377","author":"Bissell","year":"2017","journal-title":"N. 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