Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

BACKGROUND: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. METHODS: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). FINDINGS: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. INTERPRETATION: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. FUNDING: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.

Endothelial failure and rejection in recipients of corneas from the same donor.

OBJECTIVE: To determine whether patients who receive corneas from the same donor have similar risks of endothelial failure and rejection. METHODS AND ANALYSIS: Patients with Fuchs endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK) who received their first corneal transplant between 1999 and 2016 were analysed. Patients receiving corneas from donors who donated both corneas for the same indication were defined as 'paired'. Gray's test was used to compare the cumulative incidence of endothelial failure and rejection within 5 years post-transplant for 'paired' and 'unpaired' groups. Cox regression models were fitted to determine whether there was an association between recorded donor characteristics (endothelial cell density (ECD), age and sex and endothelial graft failure and rejection. RESULTS: 10 838 patients were analysed of whom 1536 (14%) were paired. The unpaired group comprised 1837 (69%) recipients of single corneal donors and 7465 (69%) donors who donated both corneas for another indication. ECD was lower for unpaired single cornea donors (p<0.01). There was no significant difference in endothelial graft failure or rejection between paired and unpaired groups for FED (p=0.37, p=0.99) or PBK (p=0.88, p=0.28) nor for donor ECD, age, sex and paired donation after adjusting for transplant factors (across all models p>0.16 for ECD, p>0.32 for donor age, p>0.14 for sex match and p>0.17 for the donor effect). CONCLUSION: The absence of a significant difference in graft outcome for corneal transplants for FED and PBK between paired and unpaired donors may reflect a homogeneous donor pool in the UK.

Corneal Transplant Follow-up Study II: a randomised trial to determine whether HLA class II matching reduces the risk of allograft rejection in penetrating keratoplasty.

PURPOSE: A randomised trial to test the hypothesis that human leucocyte antigen (HLA) class II matching reduces the risk of allograft rejection in high-risk penetrating keratoplasty (PK). METHODS: All transplants were matched for HLA class I antigens (≤2 mismatches at the A and B loci) and corneas were allocated to patients by cohort minimisation to achieve 0, 1 or 2 HLA class II antigen mismatches. The corneal transplants (n=1133) were followed for 5 years. The primary outcome measure was time to first rejection episode. RESULTS: Cox regression analysis found no influence of HLA class II mismatching on risk of immunological rejection (HR 1.13; 95% CI 0.79 to 1.63; p=0.51). The risk of rejection in recipients older than 60 years was halved compared with recipients ≤40 years (HR 0.51; 95% CI 0.36 to 0.73; p=0.0003). Rejection was also more likely where cataract surgery had been performed after PK (HR 3.68; 95% CI 1.95 to 6.93; p<0.0001). In univariate analyses, preoperative factors including chronic glaucoma (p=0.02), vascularisation (p=0.01), inflammation (p=0.03), ocular surface disease (p=0.0007) and regrafts (p<0.001) all increased the risk of rejection. In the Cox model, however, none of these factors was individually significant but rejection was more likely where≥2 preoperative risk factors were present (HR 2.11; 95% CI 1.26 to 3.47; p<0.003). CONCLUSIONS: HLA class II matching, against a background of HLA class I matching, did not reduce the risk of allograft rejection. Younger recipient age, the presence of ≥2 preoperative risk factors and cataract surgery after PK all markedly increased the risk of allograft rejection. TRIAL REGISTRATION NUMBER: ISRCTN25094892.

6†The impact of COVID-19 on corneal transplantation in England.

INTRODUCTION/BACKGROUND: At the beginning of the COVID-19 pandemic, eye banks around the world had to assess the impact of SARS-CoV-2 infection in potential ocular tissue donors and decide how to characterise donors to meet ongoing demand for tissue for transplantation.NHSBT eye banks normally issue cornea grafts for over 4000 transplants per annum (pre-pandemic). SARS-CoV2 RNA screening is not a requirement for eye donor characterisation. Donor authorisation is based on review of donor medical and contact history and any available COVID test results (e.g. from hospital testing or as part of organ donor characterisation). After retrieval, globes are disinfected with PVP-iodine, and corneas stored in organ culture.This presentation explores the impact of COVID-19 on corneal donation and transplantation in England. METHODS: UK Transplant Registry data were analysed on all corneal donors and transplants in England from 1 January 2020 to 2 July 2021. All laboratory confirmed SARS CoV-2 infections were collected by Public Health England from 16 March 2020. Information was available until mid-November 2021.To assess the possibility of transmission through a transplanted graft, cases with a diagnosis of infection within 14 days post transplant were identified for further review. RESULTS: 4130 corneal grafts were performed in England. We are aware of 222 recipients who tested positive for SARS-CoV2. 2 of these have been reported to have died within 28 days of testing positive. The diagnosis of SARS-CoV2 infection in these 2 recipients had been made beyond 30 days post transplant.In 3 of the 222 infected recipients, the interval between transplant and infection was within 14 days (all 3 recipients alive). 2 of the 3 donors were fully characterised organ donors (universally screened for SARS-CoV-2 RNA in upper and lower respiratory tract samples), and one was an eye only donor who had tested negative in hospital 2 days prior to death. CONCLUSIONS: The linkage of large registries allows collection of useful data in a large cohort of patients transplanted during the COVID-19 pandemic. The incidence of COVID-19 and characteristics of corneal transplant recipients who tested positive for SARS-CoV2 were found to be similar to those for the general population of England.These data have not identified any epidemiological evidence for transmission of COVID-19 through corneal transplantation, and offer reassurance about the safety and quality systems that are in place to allow ongoing corneal transplantation during the pandemic.

Graft Survival After Penetrating and Endothelial Keratoplasty in Iridocorneal Endothelial Syndrome.

PURPOSE: To compare the survival of a first penetrating keratoplasty (PK) or endothelial keratoplasty (EK) for iridocorneal endothelial (ICE) syndrome with transplant survival in Fuchs endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK). METHODS: We compared graft survival of PK and EK for ICE syndrome for 2 time periods. We then compared graft survival in ICE syndrome with graft survival in FED and PBK. Kaplan-Meier estimates of graft survival up to 5 years posttransplant were calculated with 95% confidence intervals (CI), whereas comparisons between the groups were performed using the log-rank test. RESULTS: We included 86 first transplants for ICE syndrome. There was no difference in graft survival between the 58 PKs and the 28 EKs for up to 5 years after surgery (P = 0.717). For the period from 2009 to 2017, the 5-year graft survival rates for ICE syndrome were 64.3% (CI, 21.8%-88.0%) for the 16 PKs and 66.8% (CI, 41.8%-83.0%) for the 26 EKs (P = 0.469). Between 2009 and 2017, the 5-year survival rate for 42 grafts with ICE syndrome was 62.7% (CI, 39.6%-79.0%), which was lower than 75.9% (CI, 74.2%-77.4%) in 7058 transplants for FED but higher than 55.1% (CI, 52.0%-58.0%) in 3320 transplants for PBK, although the numbers of ICE transplants are too small to tell whether this difference was by chance. CONCLUSIONS: The results indicate no difference in graft survival between PK and EK for ICE syndrome. Graft survival in ICE syndrome is intermediate between that of FED and PBK.