Association of admission, nadir, and terminal donor creatinine with kidney transplantation outcomes

Introduction: When assessing deceased kidney donors, a key factor in organ acceptance and allocation is donor kidney function. It is unclear whether terminal, admission, or the highest of terminal and admission donor estimated glomerular filtration rate (eGFR) most predicts recipient outcomes. Methods: We examined which measurement best predicts outcomes. Using data from the Australia and New Zealand Organ Donation and Dialysis and Transplant Registries, we included adult recipients of deceased donor kidney-only transplants over 2003 to 2019. We compared the 3 different exposure vari ables of admission, terminal, or highest eGFR. We created logistic regression models for delayed graft function (DGF), multilinear regression models for 6- and 12-month eGFR, and Cox proportional hazards models for graft loss, death censored graft failure and patient death. Results: A total of 8971 transplant recipients were included. There was strong evidence of an association between terminal, admission, and highest donor eGFR and DGF and recipient eGFR at 6 and 12 months. The eGFR was a strong predictor of graft and death censored graft failure, but not patient death. Terminal was a better predictor than admission and highest eGFR particularly for more contemporaneous outcomes. Conclusion: In assessing kidney donors, terminal eGFR were marginally better than admission and highest at predicting outcomes. Terminal eGFR should be used in risk equations to predict hard clinical endpoints.Georgina L. Irish, P. Toby Coates and Philip A. Clayto

Do patient decision aids help people who are facing decisions about solid organ transplantation? A systematic review

Published April 2023Background: Decisions about solid organ transplantation are complex.Patient decision aids (PDAs) enhance traditional education, by improving knowledge and supporting patients to align their values with treatments. There are increasing numbers of transplantation PDAs, however, it is unclear whether these are effective. We conducted a systematic review of studies assessing the impact of PDA use in transplantation. Methods:We searched the Cochrane Register of Controlled Trials, CINAHL, EMBASE, MEDLINE, and PsycINFO databases from database inception to October 26, 2020.We included primary studies of solid organ transplantation PDAs defined by the International Patient Decision Aids Standards. All comparators and reported outcomes were included. Mean difference in knowledge (before vs. after) was standardized on a 100-point scale. Pooled-effect for PDAs was calculated and compared to the standard of care for randomized controlled trials (RCTs) and meta-analyzed using random effects. Analysis of all other outcomes was limited due to heterogeneity (PROSPERO registration, CRD42020215940). Results: Seven thousand four hundred and sixty-three studies were screened, 163 underwent full-text review, and 15 studies with 4278 participants were included. Nine studies were RCTs. Seven RCTs assessed knowledge; all demonstrated increased knowledge withPDAuse (mean difference, 8.01;95%CI 4.69–11.34, p<.00001). There were many other outcomes, including behavior and acceptability, but these were too heterogenous and infrequently assessed for meaningful synthesis. Conclusions: This review found that PDAs increase knowledge compared to standard education, though the effect size is small. PDAs are mostly considered acceptable; however, it is difficult to determine whether they improve other decision-making components due to the limited evidence about non-knowledge-based outcomes.Georgina L. Irish, Alison Weightman, Jolyn Hersch, P. Toby Coates, Philip A Clayto

STrengthening the REporting of Genetic Association Studies (STREGA)— An Extension of the STROBE Statement

Julian Little and colleagues present the STREGA recommendations, which are aimed at improving the reporting of genetic association studies

Cancer post kidney transplant: the question of risk

Abstract not availableGeorgina L. Irish, P. Toby Coates and Philip A. Clayto

Urinary AASA excretion is elevated in patients with molybdenum cofactor deficiency and isolated sulphite oxidase deficiency

Analysis of α-aminoadipic semialdehyde is an important tool in the diagnosis of antiquitin deficiency (pyridoxine-dependent epilepsy). However continuing use of this test has revealed that elevated urinary excretion of α-aminoadipic semialdehyde is not only found in patients with pyridoxine-dependent epilepsy but is also seen in patients with molybdenum cofactor deficiency and isolated sulphite oxidase deficiency. This should be taken into account when interpreting the laboratory data. Sulphite was shown to inhibit α-aminoadipic semialdehyde dehydrogenase in vitro. © 2012 SSIEM and Springer

Mutations in SRD5B1 (AKR1D1), the gene encoding Delta(4)-3-oxosteroid 5 beta-reductase, in hepatitis and liver failure in infancy

A substantial group of patients with cholestatic liver disease in infancy excrete, as the major urinary bile acids, the glycine and taurine conjugates of 7alpha-hydroxy-3-oxo-4-cholenoic acid and 7alpha,12alpha-dihydroxy-3-oxo-4-cholenoic acid. It has been proposed that some (but not all) of these have mutations in the gene encoding delta(4)-3-oxosteroid 5beta-reductase (SRD5B1; AKR1D1, OMIM 604741). Our aim was to identify mutations in the SRD5B1 gene in patients in whom chenodeoxycholic acid and cholic acid were absent or present at low concentrations in plasma and urine, as these seemed strong candidates for genetic 5beta-reductase deficiency. Patients and subjects: We studied three patients with neonatal onset cholestatic liver disease and normal gamma-glutamyl transpeptidase in whom 3-oxo-delta(4) bile acids were the major bile acids in urine and plasma and saturated bile acids were at low concentration or undetectable. Any base changes detected in SRD5B1 were sought in the parents and siblings and in 50 ethnically matched control subjects. DNA was extracted from blood and the nine exons of SRD5B1 were amplified and sequenced. Restriction enzymes were used to screen the DNA of parents, siblings, and controls. Mutations in the SRD5B1 gene were identified in all three children. Patient MS was homozygous for a missense mutation (662 C>T) causing a Pro198Leu amino acid substitution; patient BH was homozygous for a single base deletion (511 delT) causing a frame shift and a premature stop codon in exon 5; and patient RM was homozygous for a missense mutation (385 C>T) causing a Leu106Phe amino acid substitution. All had liver biopsies showing a giant cell hepatitis; in two, prominent extramedullary haemopoiesis was noted. MS was cured by treatment with chenodeoxycholic acid and cholic acid; BH showed initial improvement but then deteriorated and required liver transplantation; RM had advanced liver disease when treatment was started and also progressed to liver failure. Analysis of blood samples for SRD5B1 mutations can be used to diagnose genetic 5beta-reductase deficiency and distinguish these patients from those who have another cause of 3-oxo-delta(4) bile aciduria, for example, severe liver damage. Patients with genetic 5beta-reductase deficiency may respond well to treatment with chenodeoxycholic acid and cholic acid if liver disease is not too advance