Renal function in tyrosinaemia type I after liver transplantation: A long‐term follow‐up

Abstract

Hereditary tyrosinaemia type I is an autosomal recessive inborn error of tyrosine catabolism caused by a deficiency of the enzyme fumarylacetoacetase that results in liver failure, hepatocellular carcinoma, renal tubular dysfunction and acute intermittent porphyria. When treated with liver transplantation, tyrosinaemia type I was considered to be cured. Some years after the first liver transplantations in these patients, some reports focused on the renal function after transplantation. These reports showed that urinary succinylacetone excretion remained but that tubular function normalized. In this report we discuss the long-term renal follow-up (mean follow-up time 11 years, range 7-14 years) after liver transplantation in 9 patients with tyrosinaemia type I treated by liver transplantation in our centre. An evaluation was made of renal function and succinylacetone excretion in urine. In all patients we found a persistent excretion of succinylacetone in the urine. With respect to the glomerular function, we can conclude that there is no clear change in GFR. At the same time, tubulopathy persisted in some patients. We consider that excretion of metabolites such as succinylacetone will be an important contributing factor to tubular dysfunction after liver transplantation in patients with tyrosinaemia type I. Therefore, notwithstanding the major effect of liver transplantation on tyrosine metabolism, renal tubular dysfunction remains at risk and needs careful monitoring. Progressive tubular dysfunction can cause glomerular damage. The use of low-dose NTBC might be considered after liver transplantation in case of tubulopathy to prevent progression of tubular and glomerular dysfunction.

Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice

“…Patients with a high post-transplant tyrosine plasma level or urinary SA excretion may benefit from protein restriction and low-dose NTBC treatment [52],[53]. In our retrospective study, 6 patients from 3 different centres received NTBC and 4 of them were treated with a protein restricted diet after transplantation with a good outcome.…”

“…The tubulopathy associated with Tyr 1 was previously reported to be reversible [54], however progressive tubular dysfunction can lead to glomerular dysfunction [53]. According to the group’s experience, urinary testing should be performed once a year or until normal values are obtained using protein, glucose, beta1-albumin, alfa1-microglobuline and albumin.…”

Induced pluripotent stem cell–derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice

“…Cor rection of liver function improves tubular function by restoring liver tyrosine catabolism (19). Therefore, we analyzed plasma creatinine and urine amino acid levels in the chimeric mice to further define the functional capabilities of iPS cell-derived hepatocytes (for details see Supplemental Methods).…”

Nitisinone: a review

“…23,33,46 Early nitisinone treatment not only reduces the need for LT but also improves post-transplant renal function. [73][74][75] Glomerular function seems to remain stable on long-term follow-up under nitisinone therapy 74,75 Porphyria-like neurologic crises (PLNCs) and recurrent peripheral neuropathy have been reported in HT1 patients. 35,36,76,77 PLNCs are among the major causes of death in untreated HT1 patients.…”