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

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

Altered activity of plasma hemopexin in patients with minimal change disease in relapse

Since an active isoform of plasma hemopexin (Hx) has been proposed to be a potential effector molecule in minimal change disease (MCD), we tested plasma and urine samples from subjects with MCD in relapse (n =18) or in remission (n =23) (after treatment with prednisolone) for presence or activity of Hx. For comparison, plasma or urine from proteinuric subjects with focal and segmental glomerulosclerosis (FSGS, n =11), membranoproliferative glomerulonephritis (MPGN, n =9), IgA nephropathy (n =5) or healthy control donors (n =10), were incorporated into the study. Electrophoresis and Western blotting methods were used for evaluation of the Hx status, whereas protease activity of Hx was tested upon kidney tissue in vitro according to standard methods. The results show (1) a decreased mean titer of plasma Hx exclusively in MCD relapse subjects as compared with MCD in remission (0.21 +/- 0.14 mg/ml vs 0.44 +/- 0.06 mg/ml; p <0.01). Mean Hx titers in other proteinuric subjects ranged from 0.38 +/- 0.05 mg/ml to 0.40 +/- 0.06 mg/ml, whereas, the mean titer of healthy controls was 0.59 +/- 0.03 mg Hx/ml; (2) an increased Hx activity (expressed in arbitrary units) exclusively in plasma from MCD relapse subjects (3.3 +/- 0.72 vs 1.16 +/- 0.56, MCD remission; p <0.01); (3) different Western blot patterns in MCD relapse vs remission plasma; (4) reduced stainability or virtual absence of the 80-kD Hx band in blots of urine from MCD relapse in contrast to urine samples from other proteinuric subjects with FSGS, MPGN, or IgA nephropathy. It is concluded that Hx in MCD relapse subjects may exist in an altered isoform, showing enhanced protease activity as compared with subjects in remission, subjects with other forms of primary glomerulopathy, or healthy control individuals

Searches for Gravitational Waves from Known Pulsars at Two Harmonics in the Second and Third LIGO-Virgo Observing Runs

We present a targeted search for continuous gravitational waves (GWs) from 236 pulsars using data from the third observing run of LIGO and Virgo (O3) combined with data from the second observing run (O2). Searches were for emission from the l = m = 2 mass quadrupole mode with a frequency at only twice the pulsar rotation frequency (single harmonic) and the l = 2, m = 1, 2 modes with a frequency of both once and twice the rotation frequency (dual harmonic). No evidence of GWs was found, so we present 95% credible upper limits on the strain amplitudes h (0) for the single-harmonic search along with limits on the pulsars' mass quadrupole moments Q (22) and ellipticities epsilon. Of the pulsars studied, 23 have strain amplitudes that are lower than the limits calculated from their electromagnetically measured spin-down rates. These pulsars include the millisecond pulsars J0437-4715 and J0711-6830, which have spin-down ratios of 0.87 and 0.57, respectively. For nine pulsars, their spin-down limits have been surpassed for the first time. For the Crab and Vela pulsars, our limits are factors of similar to 100 and similar to 20 more constraining than their spin-down limits, respectively. For the dual-harmonic searches, new limits are placed on the strain amplitudes C (21) and C (22). For 23 pulsars, we also present limits on the emission amplitude assuming dipole radiation as predicted by Brans-Dicke theory

Searches for gravitational waves from known pulsars at two harmonics in the second and third LIGO-Virgo observing runs

We present a targeted search for continuous gravitational waves (GWs) from 236 pulsars using data from the third observing run of LIGO and Virgo (O3) combined with data from the second observing run (O2). Searches were for emission from the l = m = 2 mass quadrupole mode with a frequency at only twice the pulsar rotation frequency (single harmonic) and the l = 2, m = 1, 2 modes with a frequency of both once and twice the rotation frequency (dual harmonic). No evidence of GWs was found, so we present 95% credible upper limits on the strain amplitudes h0 for the single-harmonic search along with limits on the pulsars' mass quadrupole moments Q22 and ellipticities ε. Of the pulsars studied, 23 have strain amplitudes that are lower than the limits calculated from their electromagnetically measured spin-down rates. These pulsars include the millisecond pulsars J0437−4715 and J0711−6830, which have spin-down ratios of 0.87 and 0.57, respectively. For nine pulsars, their spin-down limits have been surpassed for the first time. For the Crab and Vela pulsars, our limits are factors of ∼100 and ∼20 more constraining than their spin-down limits, respectively. For the dual-harmonic searches, new limits are placed on the strain amplitudes C21 and C22. For 23 pulsars, we also present limits on the emission amplitude assuming dipole radiation as predicted by Brans-Dicke theory