Comparison of Outcomes of In-Centre Haemodialysis Patients between the 1st and 2nd COVID-19 Outbreak in England, Wales, and Northern Ireland: A UK Renal Registry Analysis.

INTRODUCTION: This retrospective cohort study compares in-centre haemodialysis (ICHD) patients' outcomes between the 1st and 2nd waves of the COVID-19 pandemic in England, Wales, and Northern Ireland. METHODS: All people aged ≥18 years receiving ICHD at 31 December 2019, who were still alive and not in receipt of a kidney transplant at 1 March and who had a positive polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 31 January 2021, were included. The COVID-19 infections were split into two "waves": wave 1 from March to August 2020 and wave 2 from September 2020 to January 2021. Cumulative incidence of COVID-19, multivariable Cox models for risk of positivity, median, and 95% credible interval of reproduction number in dialysis units were calculated separately for wave 1 and wave 2. Survival and hazard ratios for mortality were described with age- and sex-adjusted Kaplan-Meier plots and multivariable Cox proportional models. RESULTS: 4,408 ICHD patients had COVID-19 during the study period. Unadjusted survival at 28 days was similar in both waves (wave 1 75.6% [95% confidence interval [CI]: 73.7-77.5], wave 2 76.3% [95% CI 74.3-78.2]), but death occurred more rapidly after detected infection in wave 1. Long vintage treatment and not being on the transplant waiting list were associated with higher mortality in both waves. CONCLUSIONS: Risk of death of patients on ICHD treatment with COVID-19 remained unchanged between the first and second outbreaks. This highlights that this vulnerable patient group needs to be prioritized for interventions to prevent severe COVID-19, including vaccination, and the implementation of measures to reduce the risk of transmission alone is not sufficient.

Increasing trends in hemodialysis and living donor kidney transplantation for children and young people in the United Kingdom.

BACKGROUND: The UK Renal Registry is responsible for the national collection and reporting of data on all children receiving long-term kidney replacement therapy [KRT], including kidney transplantation. METHODS: All 13 UK pediatric nephrology centers contributed to providing individual patient data from the pediatric population incident to and prevalent to KRT as per the date 31 December 2018. Data for children aged 16-<18 years were presented separately as some were managed under adult care settings with different methods of data collection. Demographics and biochemical data, including kidney function and prevalence of cardiovascular risk factors [hypertension, hypercholesterolemia, BMI] were reported. RESULTS: Eight hundred and twenty-six children (65.4 per million age-related population [pmarp]) and 199 young people (139.4pmarp) in the United Kingdom were prevalent to KRT on 31 December 2018. Overall, the incidence of KRT during 2018 was 9.1 pmarp and 12.6 pmarp in children and young people, respectively. Congenital anomalies of the kidney and urinary tract (CAKUT) were the most prevalent primary diagnoses (52%). Living and deceased donor transplantation was the most common treatment modality (78%). Patients on dialysis had lower age standardized mean height and weight ranges recorded in comparison to transplant patients [median height z score -1.8 vs. -1.1]. 73.1% patients had one or more cardiovascular disease risk factors. CONCLUSIONS: This study highlights increasing prevalence of hemodialysis and living donor transplantation as modalities for KRT. Of those incident to KRT, the highest patient survival was seen among 8-12 years and lowest <2 years. Moreover, there was a demographic shift from Caucasian toward Asian/other ethnicity and from CAKUT to other primary kidney diseases.

Outcomes of patients with COVID-19 on kidney replacement therapy: a comparison among modalities in England.

BACKGROUND: Chronic kidney disease is a recognized risk factor of poor outcomes from coronavirus disease 2019 (COVID-19). METHODS: This retrospective cohort study used the UK Renal Registry database of people on kidney replacement therapy (KRT) at the end of 2019 in England and who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 March 2020 and 31 August 2020 to analyse the incidence and outcomes of COVID-19 among different KRT modalities. Comparisons with 2015-2019 mortality data were used to estimate excess deaths. RESULTS: A total of 2783 individuals on KRT tested positive for SARS-CoV-2. Patients from more-deprived areas {most deprived versus least deprived hazard ratio [HR] 1.20 [95% confidence interval (CI) 1.04-1.39]} and those with diabetes compared with those without [HR 1.51 (95% CI 1.39-1.64)] were more likely to test positive. Approximately 25% of in-centre haemodialysis and transplanted patients died within 28 days of testing positive compared with 36% of those on home therapies. Mortality was higher in those ≥80 years of age compared with those 60-79 years [odds ratio (OR) 1.71 (95% CI 1.34-2.19)] and much lower in those listed for transplantation compared with those not listed [OR 0.56 (95% CI 0.40-0.80)]. Overall, excess mortality in 2020 for people on KRT was 36% higher than the 2015-2019 average. Excess deaths peaked in April 2020 at the height of the pandemic and were characterized by wide ethnic and regional disparities. CONCLUSIONS: The impact of COVID-19 on the English KRT population highlights their extreme vulnerability and emphasizes the need to protect and prioritize this group for vaccination. COVID-19 has widened underlying inequalities in people with kidney disease, making interventions that address health inequalities a priority.

Sociodemographic features and mortality of individuals on haemodialysis treatment who test positive for SARS-CoV-2: A UK Renal Registry data analysis.

Kidney disease is a recognised risk factor for poor COVID-19 outcomes. Up to 30 June 2020, the UK Renal Registry (UKRR) collected data for 2,385 in-centre haemodialysis (ICHD) patients with COVID-19 in England and Wales. Overall unadjusted survival at 1 week after date of positive COVID-19 test was 87.5% (95% CI 86.1-88.8%); mortality increased with age, treatment vintage and there was borderline evidence of Asian ethnicity (HR 1.16, 95% CI 0.94-1.44) being associated with higher mortality. Compared to the general population, the relative risk of mortality for ICHD patients with COVID-19 was 45.4 and highest in younger adults. This retrospective cohort study based on UKRR data supports efforts to protect this vulnerable patient group.

The Challenges of Using UK Renal Registry Data to Audit the Care of Patients with Diabetes on Renal Replacement Therapy.

INTRODUCTION: Diabetes is a major cause of CKD and of mortality in patients on renal replacement therapy (RRT). Auditing the care of patients with diabetes on RRT against published guidelines relies on robust data collection. OBJECTIVE: This article assesses the completeness of data items collected by the UK Renal Registry (UKRR) that are required to audit the care of patients with diabetes on RRT. METHODS: The UKRR receives data on all patients receiving RRT in the UK. Patients with diabetes, diabetes type, and method of renal diagnosis were identified from primary renal disease (PRD) codes and comorbidity data for patients commencing RRT at one of the 57 renal centres in England and Wales between 2010 and 2016. The completeness of demographic and clinical data (blood pressure, cholesterol, glycated haemoglobin [HbA1c], and smoking status) was assessed for the first year of RRT. RESULTS: Ninety-three per cent of all patients on RRT irrespective of diagnosis had a PRD code, but only 28/57 renal centres had comorbidity data completeness ≥70%; 34.9% of patients with diabetic nephropathy (DN) had type 1 diabetes, but this varied between centres (9.2-100%). Overall, 4.2% of DN diagnoses were by biopsy. Data completeness in the first year of RRT for cardiovascular risk factors ranged between 50.0 and 80.0%, with HbA1c data completeness being 63.0%. Of 57 centres, 20 had HbA1c data for ≥70% of patients in the first year of RRT. CONCLUSIONS: There is persistent variation between renal centres in the completeness of data collected on patients with diabetes on RRT, impacting on the ability to undertake robust audit. Data linkages and expanded data permissions could see registry data play a key role in ongoing audit and research into patients with diabetes and CKD, provided adequate data can be collected.

Causes of renal allograft failure in the UK: trends in UK Renal Registry and National Health Service Blood and Transplant data from 2000 to 2013.

Background: Improvement in long-term renal allograft survival is impeded by incomplete or erroneous coding of causes of allograft loss. This study reports 13-year trends in causes of graft failure across the UK. Methods: National Health Service Blood and Transplant (NHSBT) and UK Renal Registry data were linked to describe UK kidney patients transplanted in 2000-13. NHSBT graft failure categories were used, with 'other' recoded when free text was available. Adjusted analyses examined the influence of age, ethnicity and donor type on causes of graft failure. Results: In 22 730 recipients, 5389 (23.7%) grafts failed within a median follow-up of 5 years. The two most frequent causes were death with a functioning graft (40.8%) and alloimmune pathology (25.0%). Graft survival was higher in recipients who were younger (mean 47.3 versus 50.7 years), received a pre-emptive transplant (20.2% versus 10.4%), spent less time on dialysis (median 1.6 versus 2.4 years) and received a living donor transplant (36.3% versus 22.2%), with no differences by sex, ethnicity or human leucocyte antigen mismatch. Allograft failure within 2 years of transplantation fell from 12.5% (2000-4) to 9.8% (2009-13). Surgical- and alloimmune-related failures decreased over time while death with a functioning graft became more common. Age, ethnicity and donor type were factors in recurrent primary disease and alloimmune pathology. Conclusions: Since 2000 there have been reductions in surgical and alloimmune graft failures in the UK. However, graft failure codes need to be revised if they are to remain useful and effective in epidemiological and quality improvement trials.

Genotypic diversity and differentiation among populations of two benthic freshwater diatoms as revealed by microsatellites.

Given their large population sizes and presumed high dispersal capacity, protists are expected to exhibit homogeneous population structure over large spatial scales. On the other hand, the fragmented and short-lived nature of the lentic freshwater habitats that many protists inhabit promotes strong population differentiation. We used microsatellites in two benthic freshwater diatoms, Eunotia bilunaris 'robust' and Sellaphora capitata, sampled from within a pond and connected ponds, through isolated ponds from the same region to western Europe to determine the spatial scale at which differentiation appears. Because periods of low genotypic diversity contribute to population differentiation, we also assessed genotypic diversity. While genotypic diversity was very high to maximal in most samples of both species, some had a markedly lower diversity, with up to half (Eunotia) and over 90% (Sellaphora) of the strains having the same multilocus genotype. Population differentiation showed an isolation-by-distance pattern with very low standardized FST values between samples from the same or connected ponds but high values between isolated ponds, even when situated in the same region. Partial rbcL sequences in Eunotia were consistent with this pattern as isolated ponds in the same region could differ widely in haplotype composition. Populations identified by Structure corresponded to the source ponds, confirming that 'pond' is the main factor structuring these populations. We conclude that freshwater benthic diatom populations are highly fragmented on a regional scale, reflecting either less dispersal than is often assumed or reduced establishment success of immigrants, so that dispersal does not translate into gene flow.

Barcoding diatoms: exploring alternatives to COI-5P.

Diatoms are a diverse lineage with species that can be difficult to identify or cryptic, but DNA barcoding, a molecular technique, can assist identification and facilitate studies of speciation and biogeography. The most common region used for DNA barcoding, COI-5P, can distinguish diatom species, but has not displayed universality (i.e., successful PCR amplification from diverse taxa). Therefore, we have assessed the following alternative markers: ∼1400bp of rbcL; 748bp at the 3' end of rbcL (rbcL-3P); LSU D2/D3 and UPA. Sellaphora isolates were used to determine each marker's ability to discriminate among closely related species and culture collection material was utilized to explore further marker universality. All of the alternative markers investigated have greater universality than COI-5P. Both full and partial (3P) rbcL regions had the power to discriminate between all species, but rbcL-3P can be sequenced more easily. LSU D2/D3 could distinguish between all but the most closely related species (96%), whereas UPA only distinguished 20% of species. Our observations suggest that rbcL-3P should be used as the primary marker for diatom barcoding, while LSU D2/D3 should be sequenced as a secondary marker to facilitate environmental surveys.

SCALY INCUNABULA, AUXOSPORE DEVELOPMENT, AND GIRDLE POLYMORPHISM IN SELLAPHORA MARVANII SP. NOV. (BACILLARIOPHYCEAE)(1).

Uniparental auxosporulation was observed in a monoclonal culture of a Sellaphora clone isolated from the epipelon of a fishpond in the Czech Republic. The cox1 sequence for the clone confirmed that it belonged to the Sellaphora pupula-bacillum species complex but showed significant differences from all previously characterized Sellaphora species, and it is therefore described as S. marvanii sp. nov. Protoplast, valve, and girdle structure resembled those of other Sellaphora species, but a novel finding for all diatoms was a change in girdle structure during the life cycle: the most advalvar girdle band (valvocopula) bore a single line of pores in enlarged postauxospore cells but was entirely plain in small cells and gametangia. The young auxospores were covered by incunabula containing large, delicate, ± circular scales, resembling those of centric diatom auxospores; similar scales have been reported in a few other raphid diatoms (Pseudo-nitzschia multiseries, Diploneis sp.) but contrast with the strip incunabula of some Nitzschia and Pinnularia and the helmet-like caps of Neidium. The scales persisted during auxospore expansion, mostly as two caps over the auxospore poles. The transverse perizonium comprised a very wide, closed primary band, flanked by numerous secondary bands whose open ends were strongly incurved toward the center. Initial valves were differentiated from their immediate descendants by the very strong external demarcation of the raphe sternum, irregular shape, and curved transapical profile.

Highly differentiated populations of the freshwater diatom Sellaphora capitata suggest limited dispersal and opportunities for allopatric speciation.

The diversities and distributions of diatoms are much more complex than was ever imagined. To understand the underlying mechanisms, research must focus on evolutionary processes occurring at a population level and employ sufficiently informative molecular markers. Using ten microsatellites and ITS rDNA sequence data, we investigated the genetic structure of populations of the benthic freshwater diatom Sellaphora capitata (until 2004 a cryptic entity within the S. pupula agg. species complex). This is the first time that microsatellites have been used to investigate the genetic structure of any freshwater or benthic microalga. Using an integrated approach (morphology, DNA barcoding and specificity of the microsatellite primers), we verified the identity of 70 S. capitata isolates obtained from lakes in the UK, Belgium and Australia. Standardized F'(ST) values were very high (>0.4) and in Bayesian analyses, isolates clustered according to their country of origin, with limited evidence of admixture. However, selected isolates from all countries were sexually compatible, a result consistent with limited ITS divergence. Considering the apparent absence of desiccation-resistant resting stages in most diatoms, we conclude that such levels of differentiation are likely to be a consequence of limited dispersal. With restricted dispersal, previously unacknowledged opportunities for allopatric speciation exist, which may help to explain the huge extant diversity of diatoms.

Ten microsatellite markers for the freshwater diatom Sellaphora capitata.

Ten polymorphic microsatellite markers were developed for the benthic freshwater diatom Sellaphora capitata and tested on 40 isolates from a Belgian pond. Genotyping was very successful (95%). The number of alleles per locus ranged from three to 12 (mean 6.6) and expected heterozygosities from 0.2 to 0.86 (mean 0.67). This is the first time that microsatellite markers have been developed for a freshwater or benthic diatom.

A MOLECULAR SYSTEMATIC APPROACH TO EXPLORE DIVERSITY WITHIN THE SELLAPHORA PUPULA SPECIES COMPLEX (BACILLARIOPHYTA)(1).

The common and cosmopolitan freshwater benthic diatom Sellaphora pupula (Kütz.) Mereschk. is a model system for studying the nature of species in microalgae; the biological significance of morphological variation in this species complex has been widely demonstrated. The aim of this study was to establish a two-gene phylogeny (18S rDNA and rbcL) for 23 Sellaphora taxa, including 19 S. pupula aggregate (agg.) demes or species, S. bacillum (Ehrenb.) D. G. Mann, and S. laevissima (Kütz.) D. G. Mann. A range of analyses on separate and combined data sets indicated that Sellaphora is a monophyletic group containing four major clades. Of the traditionally recognized species, S. bacillum and S. laevissima are natural groups, but S. pupula is paraphyletic or polyphyletic because S. bacillum groups with S. pupula"small lanceolate" and S. lanceolata. Thickened bars at the poles of valves within the core "pupula-bacillum" group may be a morphological synapomorphy; the fossil record suggests that this group is at least 12 million years old. Otherwise, there was no clear pattern in the distribution of different morphologies among the major clades; each clade was also heterogeneous with respect to mating system. More intensive and extensive sampling will doubtless uncover even greater diversity; the challenge lies in its interpretation. Our results demonstrate the limitations of paleoecological, ecological, and biogeographical research based on morphospecies.

An assessment of potential diatom "barcode" genes (cox1, rbcL, 18S and ITS rDNA) and their effectiveness in determining relationships in Sellaphora (Bacillariophyta).

Due to limited morphological differentiation, diatoms can be very difficult to identify and cryptic speciation is widespread. There is a need for a narrower species concept if contentious issues such as diatom biodiversities and biogeographies are to be resolved. We assessed the effectiveness of several genes (cox1, rbcL, 18S and ITS rDNA) to distinguish cryptic species within the model 'morphospecies', Sellaphora pupula agg. This is the first time that the suitability of cox1 as an identification tool for diatoms has been assessed. A range of cox1 primers was tested on Sellaphora and various outgroup taxa. Sequences were obtained for 34 isolates belonging to 22 Sellaphora taxa and three others (Pinnularia, Eunotia and Tabularia). Intraspecific divergences ranged from 0 to 5bp (=0.8%) and interspecific levels were at least 18bp (=c. 3%). Cox1 divergence was usually much greater than rbcL divergence and always much more variable than 18S rDNA. ITS rDNA sequences were more variable than cox1, but well-known problems concerning intragenomic variability caution against its use in identification. More information and less sequencing effort mean that cox1 can be a very useful aid in diatom identification. The usefulness of cox1 for determining phylogenetic relationships among Sellaphora species was also assessed and compared to rbcL. Tree topologies were very similar, although support values were generally lower for cox1.