Porphyria and kidney diseases

Abstract

The kidneys, after the bone marrow and liver, are third in terms of the amounts of haem synthesized daily. Haem is incorporated into haemoproteins that are critical to renal physiology. In turn, disturbances in haem metabolism interfere with renal physiology and are tightly interrelated with kidney diseases. Acute intermittent porphyria causes kidney injury, whereas medical situations associated with end-stage renal disease, such as porphyrin accumulation, iron overload and hepatitis C, participate in the inhibition of uroporphyrinogen decarboxylase and predispose the individual to porphyria cutanea tarda. Even if some of these interactions have been known for a long time, the clinical situations associated with these interrelations have strikingly evolved over time with the advent of new therapeutic strategies for dialysis therapy and a better understanding of the pathophysiological mechanisms of porphyria-associated kidney disease. Physicians should be aware of these interactions. The aim of this review is to summarize the complex interactions between kidney physiology and pathology in the settings of porphyria and to emphasize their often-underestimated importance.

EXPLORE: A prospective, multinational natural history study of patients with acute hepatic porphyria with recurrent attacks

“…CKD is reported to impact 30%-60% of patients with AHP and may be due to the toxic effects of chronic, high levels of ALA and PBG on the kidney and influenced by genetic variation in the ALA transporter peptide transporter 2. (13,20,40,41) As has been observed in other studies, disease activity in patients with AIP was detectable through increased biomarker levels during and between attacks. (31,42) At baseline, there were marked elevations in levels of urinary ALA and PBG compared with the ULN in healthy individuals (35) and in ALAS1 mRNA compared with normal levels.…”

“…(26) The most common comorbid conditions reported in the medical history at baseline were consistent with the known natural history of patients with AHP. (13,40) Although renal disorders were reported in ~10% of patients in the medical history, approximately 70% had an abnormal eGFR (<90 mL/min/1.73 m 2 ), and 30% met the criteria for stage 3a, 3b, or 4 CKD. CKD is reported to impact 30%-60% of patients with AHP and may be due to the toxic effects of chronic, high levels of ALA and PBG on the kidney and influenced by genetic variation in the ALA transporter peptide transporter 2.…”

EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks

“…The most common comorbid conditions reported in the medical history at baseline were consistent with the known natural history of patients with AHP . Although renal disorders were reported in ~10% of patients in the medical history, approximately 70% had an abnormal eGFR (<90 mL/min/1.73 m 2 ), and 30% met the criteria for stage 3a, 3b, or 4 CKD.…”

“…Although renal disorders were reported in ~10% of patients in the medical history, approximately 70% had an abnormal eGFR (<90 mL/min/1.73 m 2 ), and 30% met the criteria for stage 3a, 3b, or 4 CKD. CKD is reported to impact 30%‐60% of patients with AHP and may be due to the toxic effects of chronic, high levels of ALA and PBG on the kidney and influenced by genetic variation in the ALA transporter peptide transporter 2 …”

Delivery of oligonucleotides to bone marrow to modulate ferrochelatase splicing in a mouse model of Erythropoietic Protoporphyria

“…With over 80 % of heme produced in red blood cells progenitors, the bone marrow is the major site of biosynthesis. Kidneys and liver are also minor sites of heme biosynthesis (4). A lack of FECH means that PPIX continuously accumulates during erythroid maturation, resulting in PPIX circulating in red blood cells of the bloodstream.…”