Acute intermittent porphyria and chronic renal failure

Marsden, Joanne; Chowdhury, Paramit; Wang, J; Deacon, A C; Dutt, Neelanjana; Peters, T. J.; Macdougall, Iain C.

doi:10.5414/cnp69339

Cited by 36 publications

(37 citation statements)

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“…Renal impairment in patients, usually associated with hypertension and active porphyria, is well documented (Marsden et al 2008;Frei et al 2012). The causal factors are unclear although it may be due to toxicity of the precursor 5-aminolaevulinic acid or other haem precursors filtered in the urine that are formed in excess in the body during periods of activity; it is also possible in some patients that the effect is compounded by the use of nonsteroidal anti-inflammatory drugs.…”

Section: Stopping Prophylactic Haem Arginate Treatmentmentioning

confidence: 99%

Audit of the Use of Regular Haem Arginate Infusions in Patients with Acute Porphyria to Prevent Recurrent Symptoms

et al. 2015

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The National Acute Porphyria Service (NAPS) provides acute care support and clinical advice for patients in England with active acute porphyria requiring haem arginate treatment and patients with recurrent acute attacks.This audit examined the benefits and complications of regular haem arginate treatment started with prophylactic intent to reduce the frequency of recurrent acute attacks in a group of patients managed through NAPS. We included 22 patients (21 female and 1 male) and returned information on diagnosis, indications for prophylactic infusions, frequency and dose, analgesia, activity and employment and complications including thromboembolic disease and iron overload.The median age at presentation with porphyria was 21 years (range 9-44), with acute abdominal pain as the predominant symptom. Patients had a median of 12 (1-400) attacks before starting prophylaxis and had received a median of 52 (0-1,350) doses of haem arginate. The median age at starting prophylaxis was 28 years (13-58) with a median delay of 4 years (0.5-37) between presentation and prophylaxis. The frequency of prophylactic haem arginate varied from 1 to 8 per month, and 67% patients were documented as having a reduction in pain frequency on prophylaxis. Only one patient developed clinically significant iron overload and required iron chelation, but the number of venous access devices required varied from 1 to 15, with each device lasting a median of 1.2 years before requiring replacement. Six patients stopped haem arginate and in three this was because their symptoms had improved. Prophylactic haem arginate appears to be beneficial in patients with recurrent acute porphyria symptoms, but maintaining central venous access may prove challenging.

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Section: Stopping Prophylactic Haem Arginate Treatmentmentioning

confidence: 99%

Audit of the Use of Regular Haem Arginate Infusions in Patients with Acute Porphyria to Prevent Recurrent Symptoms

et al. 2015

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“…The association of CKD with AIP has been described, and few reports have documented a chronic tubulointerstitial nephropathy with mild hypertension. [10][11][12][13] No large-scale follow-up study of CKD associated with AIP has been conducted to date, and the biological mechanisms that promote kidney injury are not known. We conducted this population-based, observational study to provide a comprehensive survey of the clinical, biological, and pathological characteristics of CKD associated with AIP (hereafter referred to as PAKD, for porphyria associated kidney disease), and we used in vitro models to provide mechanistic insights into how porphyrin precursors might promote kidney injury.…”

mentioning

confidence: 99%

High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria

Pallet

Mami

Schmitt

et al. 2015

Kidney International

100

113

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Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of ~1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis.

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“…9,10 In our cohort, 2 patients had preexisting renal impairment, and 1 of these patients required renal transplantation 39 months after LT. The progression to end-stage renal failure in this case was attributed to tacrolimus nephrotoxicity on clinical grounds.…”

Section: Complicationsmentioning

confidence: 99%

Hepatic Artery Thrombosis

2010

High-Yield Imaging: Interventional

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Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the UK Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation.

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Acute intermittent porphyria and chronic renal failure

Cited by 36 publications

References 0 publications

Audit of the Use of Regular Haem Arginate Infusions in Patients with Acute Porphyria to Prevent Recurrent Symptoms

Audit of the Use of Regular Haem Arginate Infusions in Patients with Acute Porphyria to Prevent Recurrent Symptoms

High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria

Hepatic Artery Thrombosis

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