What occurs in approximately one-third of patients with acute hepatic porphyria (AHP) that necessitates annual monitoring?

Chronic Kidney Disease in Acute Hepatic Porphyria

Chronic kidney disease (CKD) occurs in approximately one-third of patients with acute hepatic porphyria and requires annual monitoring with serum creatinine and estimated glomerular filtration rate. 1

Prevalence and Clinical Significance

The development of chronic kidney disease represents one of the most important long-term complications in AHP patients:

• CKD affects 29% of patients in the US Porphyrias Consortium longitudinal study, which included symptomatic, asymptomatic, and latent carriers of AHP 1
• Porphyria-associated kidney disease (PAKD) occurs in up to 59% of patients with symptomatic acute intermittent porphyria in French cohorts 1
• The annual decline in glomerular filtration rate approximates 1 mL/min per 1.73 m² in patients with PAKD 1
• In the EXPLORE natural history study, 68% of patients with recurrent attacks experienced reduced eGFR, with 28% meeting criteria for stage 3a, 3b, or 4 CKD 1

Pathophysiology

The mechanism of kidney injury in AHP is distinct from typical causes of CKD:

• ALA and PBG-mediated endoplasmic reticulum stress causes apoptosis and epithelial phenotypic changes in proximal tubular cells, leading to progressive renal injury 1
• A variant of the human peptide transporter 2 expressed by proximal tubular cells that mediates ALA reabsorption is an independent risk factor for developing PAKD 1
• Approximately 60% of patients with PAKD have concomitant hypertension, which further accelerates kidney disease progression 1

Monitoring Requirements

All patients with AHP should undergo annual surveillance for CKD, regardless of symptom severity 1, 2:

• Measure serum creatinine and eGFR at least annually in all AHP patients 1
• More frequent monitoring is required for patients on givosiran due to potential worsening of eGFR and renal function observed in clinical trials and real-world data 1
• Optimal control of systemic arterial hypertension is essential to decrease additional risk factors for CKD progression 1

Additional Complications Requiring Annual Monitoring

Beyond CKD, patients require surveillance for other long-term complications 1, 2:

• Hypertension occurs in 43% of patients and often develops during acute attacks, potentially becoming chronic 1
• Hepatocellular carcinoma surveillance should begin at age 50 years with liver ultrasound every 6 months, as HCC risk ranges from 1.5% to 1.8% 1
• Liver enzyme monitoring at least annually is necessary, as elevations occur in approximately 13% of patients during attacks and 28% of patients with recurrent attacks 1

Treatment Considerations for End-Stage Renal Disease

When CKD progresses to end-stage renal disease:

• Kidney transplantation is the treatment of choice for AHP patients with ESRD, as ALA and PBG levels can increase significantly between dialysis sessions 1
• Immunosuppressive therapy post-transplantation is generally well tolerated, with significant improvement in clinical AIP symptoms attributed to increased ALA and PBG clearance 1
• Combined liver-kidney transplantation may benefit patients with both recurrent attacks and end-stage renal disease 1, 2