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Background The aim of this study was to provide an overview of age, sex and primary renal disease (PRD) distribution among first kidney transplant recipients across Europe. Method The European Renal Association (ERA) Registry database was used to obtain data on patients aged 20 years or older receiving their first kidney transplant between 2010 and 2019 from 12 European countries. The numbers and percentages of recipients in each age, sex and PRD group were calculated by country, donor type and year. Results In total, 99 543 adults received a first kidney transplant. Overall, 23% of the recipients were 65 years or older, 36% were female, and 21% had glomerulonephritis and 15% diabetes mellitus as PRD. Compared with deceased donor kidney transplant recipients, living donor kidney transplant recipients were less often 65 years or older (13% versus 26%), more often had glomerulonephritis (25% versus 20%) and less often diabetes mellitus (8% versus 17%) as PRD. We found large international differences, which were most prominent for age and PRD and less prominent for sex. Over time, the largest change in recipient characteristics was observed for the percentage of recipients aged 65 years or older, increasing from 18% in 2010 to 28% in 2019 for all countries combined with a similar trend in most countries. Conclusion We observed large differences for age and PRD distribution between recipients of living and deceased donor kidneys and between European countries. Over time, the percentage of older first kidney transplant recipients increased. [ABSTRACT FROM AUTHOR]

Background We investigated 10-year trends in deceased donor kidney quality expressed as the kidney donor risk index (KDRI) and subsequent effects on survival outcomes in a European transplant population. Methods Time trends in the crude and standardized KDRI between 2005 and 2015 by recipient age, sex, diabetic status and country were examined in 24 177 adult kidney transplant recipients in seven European countries. We determined 5-year patient and graft survival probabilities and the risk of death and graft loss by transplant cohort (Cohort 1: 2005–06, Cohort 2: 2007–08, Cohort 3: 2009–10) and KDRI quintile. Results The median crude KDRI increased by 1.3% annually, from 1.31 [interquartile range (IQR) 1.08–1.63] in 2005 to 1.47 (IQR 1.16–1.90) in 2015. This increase, i.e. lower kidney quality, was driven predominantly by increases in donor age, hypertension and donation after circulatory death. With time, the gap between the median standardized KDRI in the youngest (18–44 years) and oldest (>65 years) recipients widened. There was no difference in the median standardized KDRI by recipient sex. The median standardized KDRI was highest in Austria, the Netherlands and the Basque Country (Spain). Within each transplant cohort, the 5-year patient and graft survival probability were higher for the lowest KDRIs. There was no difference in the patient and graft survival outcomes across transplant cohorts, however, over time the survival probabilities for the highest KDRIs improved. Conclusions The overall quality of deceased donor kidneys transplanted between 2005 and 2015 has decreased and varies between age groups and countries. Overall patient and graft outcomes remain unchanged. [ABSTRACT FROM AUTHOR]

Background (Val)ganciclovir resistance mutations in CMV UL97 (UL97-GCV-R) complicate anti-CMV therapy in recipients of solid organ and hematopoietic stem cell transplants, but comprehensive data on prevalence, emergence, and outcome are scarce. Methods Using next-generation sequencing (NGS; Illumina MiSeq platform), we analyzed UL97-GCV-R in patients with available plasma samples and refractory CMV replication/DNAemia (n = 87) containing viral loads ≥910 IU/mL. Twenty-one patients with CMV DNAemia resolving under antiviral therapy were analyzed as controls. Detected mutations were considered induced and of potential clinical significance if they increased by ≥10% compared with the first detected frequency or if they had a maximum frequency ≥25%. Results Nineteen of 87 (21.8%) with refractory CMV replication had ≥1 UL97-GCV-R detected by NGS, in comparison to 0/21 of the controls (P  = .02). One-third of the recipients had 2 or more induced UL97-GCV-R mutations. The most frequently induced mutations affected codons 595 (42% [8/19]), 594 (32% [6/19]), and 603 (32% [6/19]). C592G was present in all episodes of both cases and controls at frequencies <15%, but never induced. UL97-GCV-R tended to be more frequent in donor/recipient CMV immunoglobulin G mismatch or following failure to complete primary prophylaxis, and many developed invasive CMV disease. Conclusions UL97-GCV-R is common among transplant patients with refractory CMV replication. Early testing by NGS allows for identification of major mutations at codons 595, 594, and 603 and excludes a major role of C592G in ganciclovir resistance. Large prospective studies on UL97-GCV-R are warranted. [ABSTRACT FROM AUTHOR]

Background Renal transplant recipients (RTRs) have increased risk of human papillomavirus (HPV)–related cancers, including anal cancer. We investigated the prevalence of anal high-grade intraepithelial lesions (HSILs) in RTRs compared with immunocompetent controls and risk factors for anal HSIL in RTRs. Methods We included 247 RTRs and 248 controls in this cross-sectional study. We obtained anal samples for HPV testing with INNO-LiPA and performed high-resolution anoscopy on all participants. The participants completed a questionnaire on lifestyle and sexual habits. We used logistic regression to estimate odds ratios (ORs) of histologically confirmed anal HSIL in RTRs vs controls and risk factors for anal HSIL in RTRs, stratified by sex and anal high-risk (hr) HPV status, adjusting for age, smoking, lifetime sexual partners, and receptive anal sex. Results RTRs had higher anal HSIL prevalence than controls, both among men (6.5% vs 0.8%; adjusted OR [aOR], 11.21 [95% confidence interval {CI}, 1.46–291.17]) and women (15.4% vs 4.0%; aOR, 6.41 [95% CI, 2.14–24.10]). Among those with anal hrHPV, RTRs had higher anal HSIL prevalence than controls (33.8% vs 9.5%; aOR, 6.06 [95% CI, 2.16–20.27]). Having had receptive anal sex (aOR, 6.23 [95% CI, 2.23–19.08]) or genital warts (aOR, 4.21 [95% CI, 1.53–11.48]) were risk factors for anal HSIL in RTRs. All HSIL cases occurred in individuals with anal hrHPV. Conclusions RTRs had increased risk of anal HSIL compared with immunocompetent controls, with particularly high prevalence in female RTRs. Receptive anal sex, previous genital warts, and anal hrHPV infection were risk factors for anal HSIL in RTRs. Screening for anal HSIL in RTRs should be considered. Clinical Trials Registration NCT03018927. [ABSTRACT FROM AUTHOR]

Background While there are many cross-sectional studies of glomerulonephritis (GN) incidence, changes in incidence over time, particularly in the 21st century have received less attention. Similarly, little is known about temporal changes in GN prognosis. The presence in Denmark of comprehensive registries for renal biopsy results, end-stage renal disease (ESRD), comorbidity and mortality permit these questions to be addressed. Methods Data for all renal biopsies in Denmark between 1985 and 2014 were extracted from the Danish Renal Biopsy Registry and Patobank registries. The date of first dialysis or transplantation was extracted from the Danish Nephrology Registry for those patients developing ESRD. Dates of death and presence of chronic comorbid conditions at date of biopsy were extracted from the National Patient Registry. The incidence of GN, adjusted to the 2013 European standard population, was calculated. ESRD incidence and mortality were calculated, both in absolute terms and after correction for age, comorbidity and presence of renal tubulointerstitial fibrosis. Results The incidence rose from 33.3 patients per million (ppm)/year in 1985–94 to 46.5 ppm in 2005–14. The increase could in part be related to changes in renal biopsy policy. Large increases in Anti-neutropil cytoplasmic antibody (ANCA) vasculitis (ANCAV) (3.1–7.7 ppm/year) and focal segmental glomerulosclerosis (FSGS) (1.5–5.7 ppm/year) incidence were noted. The biopsy-proven prevalence of GN in 2014 was 748 ppm of which 155 ppm were being treated with dialysis or transplantation. Adjusted ESRD incidence fell by 25% during the study period, mortality by 62% and combined ESRD/mortality by 46%. The fall in ESRD incidence was limited to minimal change GN, FSGS, membranous GN and lupus nephritis, while reductions in mortality, and the combination of ESRD and/or death, were seen for nearly all GN diagnoses. Conclusions This study suggests that the incidence of GN has generally increased between 1985 and 2014, but some of the increase may be related to changes in renal biopsy policy. Major increases in FSGS and ANCAV incidence have occurred. The prognosis of GN, both as regards ESRD and mortality, has improved. [ABSTRACT FROM AUTHOR]

Background Nephropathy is common in Fabry disease (FD). Prior studies of renal function during enzyme replacement therapy (ERT) have primarily used estimated glomerular filtration rate (eGFR). We studied the attrition of renal function in FD by measured GFR (mGFR) and urine protein excretion, and explored the influence of age. Methods This was a long-term observational study of a nationwide, family-screened cohort of FD patients. All Danish genetically verified FD patients on ERT, without end-stage renal disease at baseline and with three or more mGFR values were included. Results In all, 52 patients with consecutive mGFR values (n  = 841) over median 7 years (range 1–13) were evaluated. Blood pressure remained normal and urine protein excretion was unchanged. Plasma globotriaosylceramide (Gb-3) levels normalized while plasma lyso-Gb-3 remained abnormal in 34% of patients. Baseline mGFR was 90 ± 3 mL/min/1.73 m2 and rate of renal function loss 0.9 ± 0.2 mL/min/1.73 m2/year. Baseline eGFR was 97 ± 5 mL/min/1.73 m2 and rate of renal function loss 0.8 ± 0.3 mL/min/1.73 m2/year. mGFR was age- adjusted to renal healthy non-FD subjects, giving a standard deviation score of −0.8 ± 0.2 with an annual slope of −0.03 ± 0.01 (P = 0.099), without differences between genders. Age grouping of age-adjusted data showed exaggerated renal function loss with age. Urine albumin–creatinine ratio (UACR) >300 mg/g was associated with faster renal function loss, independent of baseline mGFR, age and gender. Conclusions ERT-treated FD patients did not have a faster attrition of renal function than renal healthy non-FD subjects (background population). The rate of renal function loss with age was independent of gender and predicted by high UACR. We suggest cautious interpretation of non-age-adjusted FD renal data. [ABSTRACT FROM AUTHOR]

Background Rates and risk factors for cytomegalovirus (CMV) prophylaxis breakthrough and discontinuation were investigated, given uncertainty regarding optimal dosing for CMV primary (val)ganciclovir prophylaxis after solid organ transplantation (SOT). Methods Recipients transplanted from 2012 to 2016 and initiated on primary prophylaxis were followed until 90 days post-transplantation. A (val)ganciclovir prophylaxis score for each patient per day was calculated during the follow-up time (FUT; score of 100 corresponding to manufacturers' recommended dose for a given estimated glomerular filtration rate [eGFR]). Cox models were used to estimate hazard ratios (HRs), adjusted for relevant risk factors. Results Of 585 SOTs (311 kidney, 117 liver, 106 lung, 51 heart) included, 38/585 (6.5%) experienced prophylaxis breakthrough and 35/585 (6.0%) discontinued prophylaxis for other reasons. CMV IgG donor+/receipient- mismatch (adjusted HR [aHR], 5.37; 95% confidence interval [CI], 2.63 to 10.98; P < 0.001) and increasing % FUT with a prophylaxis score <90 (aHR, 1.16; 95% CI, 1.04 to 1.29; P =.01 per 10% longer FUT w/ score <90) were associated with an increased risk of breakthrough. Lung recipients were at a significantly increased risk of premature prophylaxis discontinuation (aHR, 20.2 vs kidney; 95% CI, 3.34 to 121.9; P =.001), mainly due to liver or myelotoxicity. Conclusions Recipients of eGFR-adjusted prophylaxis doses below those recommended by manufacturers were at an increased risk of prophylaxis breakthrough, emphasizing the importance of accurate dose adjustment according to the latest eGFR and the need for novel, less toxic agents. [ABSTRACT FROM AUTHOR]

Background Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficiency of α-galactosidase A (α-Gal A) causes intracellular accumulations of globotriaosylceramide (GL-3) and related glycosphingolipids in all organs, including the kidney, often leading to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes and tubular epithelial cells. We have previously shown that α-Gal A is delivered to these cells by different pathways involving different receptors. This study investigated the long-term changes in albuminuria, estimated glomerular filtration rate (eGFR) and urinary markers of both glomerular and tubular dysfunction in women with Fabry disease treated with ERT. Methods A retrospective, single centre, cohort study evaluated the long-term association between ERT, albuminuria and eGFR in 13 women with Fabry disease and mild renal involvement. In particular, we analysed the changes in the proteinuric profile, including the glomerular marker IgG, the tubular markers α1-microglobulin and retinol-binding protein (RBP), and the shared tubular and glomerular markers albumin and transferrin. Results ERT was associated with a significant reduction in albuminuria and a relatively stable eGFR. The decrease in albuminuria was paralleled by a decrease in both glomerular and tubular urine protein markers. Conclusions The data indicate that long-term ERT is associated with a reduction in albuminuria and glomerular and tubular urinary protein markers in women with Fabry disease and mild renal manifestations. [ABSTRACT FROM PUBLISHER]