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Background There is scarce information on biopsy-verified kidney disease in childhood and its progression to chronic kidney disease stage 5 (CKD 5). This study aims to review biopsy findings in children, and to investigate risk of kidney replacement therapy (KRT). Methods We conducted a retrospective long-term follow-up study of children included in the Norwegian Kidney Biopsy Registry (NKBR) and in the Norwegian Renal Registry (NRR) from 1988 to 2021. Results In total, 575 children with a median (interquartile range, IQR) age of 10.7 (6.1 to 14.1) years were included, and median follow-up time (IQR) after kidney biopsy was 14.3 (range 8.9 to 21.6) years. The most common biopsy diagnoses were minimal change disease (MCD; n = 92), IgA vasculitis nephritis (IgAVN; n = 76), IgA nephropathy (n = 63), and focal and segmental glomerulosclerosis (FSGS; n = 47). In total, 118 (20.5%) of the biopsied children reached CKD 5, median (IQR) time to KRT 2.3 years (7 months to 8.4 years). Most frequently, nephronophthisis (NPHP; n = 16), FSGS (n = 30), IgA nephropathy (n = 9), and membranoproliferative glomerulonephritis (MPGN; n = 9) led to KRT. Conclusions The risk of KRT after a kidney biopsy diagnosis is highly dependent on the diagnosis. None of the children with MCD commenced KRT, while 63.8% with FSGS and 100% with NPHP reached KRT. Combining data from kidney biopsy registries with registries on KRT allows for detailed information concerning the risk for later CKD 5 after biopsy-verified kidney disease in childhood. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Ann Christin Gjerstad [sup.1] , Rannveig Skrunes [sup.2] [sup.3] , Camilla Tøndel [sup.4] [sup.5] , Anders Åsberg [sup.6] [sup.7] [sup.8] , Sabine Leh [sup.3] [sup.9] , Claus Klingenberg [sup.10] [...]

Background Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death. Methods We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence and survival. Results The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. Immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidences, of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had 5-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death [adjusted hazard ratio 1.8 (95% confidence interval 1.6–1.9)] compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%). Conclusion The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach. [ABSTRACT FROM AUTHOR]

This article summarizes the lessons learned from the COCKTAIL study: an open, three‐armed, single‐center study including patients with obesity scheduled for treatment with Roux‐en‐Y gastric bypass (RYGB) or nonsurgical calorie restriction, and a normal‐ to overweight control group. The clinical implications of the results from multiple peer‐reviewed articles describing the effects of RYGB, severe caloric restriction, weight loss, and type 2 diabetes on the in vivo activity and protein expression of drug‐metabolizing enzymes (cytochrome P450 (CYP) 1A2, 2C9, 2C19, and 3A) and transporters (DMETs; organic anion‐transporting polypeptide (OATP) 1B1 and P‐glycoprotein (P‐gp)) are discussed in the perspective of three clinically relevant questions: (1) How should clinicians get the dose right in patients after RYGB? (2) Will drug disposition in patients with obesity be normalized after successful weight loss? (3) Are dose adjustments needed according to obesity and diabetes status? Overall, RYGB seems to have a lower impact on drug disposition than previously assumed, but clinicians should pay close attention to drugs with a narrow therapeutic range or where a high maximum drug concentration may be problematic. Whether obesity‐related alterations of DMETs normalize with substantial weight loss depends on the DMET in question. Obesity and diabetes downregulate the in vivo activity of CYP2C19 and CYP3A (only obesity) but whether substrate drugs should be dose adjusted is also dependent on other factors that influence clearance, that is, liver blood flow and protein binding. Finally, we recommend frequent and individualized follow‐up due to high inter‐ and intraindividual variability in these patients, particularly following RYGB. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV) infection remains a challenge following kidney transplantation (KTx). Currently, CMV-IgG serostatus at transplantation is used to individualize CMV preventive strategies. We assessed the clinical utility of CMV-IGRA for predicting CMV infection following KTx. Methods: We performed a nationwide prospective cohort study from August 2016 until December 2022. Data from all adult KTx recipients in Norway, n=1,546 (R+; n=1,157, D+/R-; n=260, D-/R-; 129), were included with a total of 3,556 CMV-IGRA analyses (1,375 at KTx, 1,188 at eight weeks, 993 one-year after KTx) and 35,782 CMV DNAemia analyses. Results: In R+ recipients CMV-IGRA status, measured at any of the time-points, could not identify any differential risk of later CMV infection. D+/R- recipients remaining CMV-IGRA negative 1-year after transplantation (regardless of positive CMV DNAemia and/or CMV IgG status at that time) had increased risk of developing later CMV infection compared to D+/R- recipients who had become CMV-IGRA positive (14% vs. 2%, p=0.01). Conclusion: Knowledge of pre-transplant CMV-IGRA status did not provide additional information to CMV-IgG serostatus that could improve current post-transplant CMV treatment algorithms. However, D+/R- recipients with a persisting negative CMV-IGRA one-year after transplantation remained at increased risk of experiencing later CMV infection. Therefore we advocate post-transplant CMV-IGRA monitoring in these patients. [ABSTRACT FROM AUTHOR]

Background The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper is a summary of the ERA Registry Annual Report 2021, including a comparison across treatment modalities. Methods Data was collected from 54 national and regional registries from 36 countries, of which 35 registries from 18 countries contributed individual patient data and 19 registries from 19 countries contributed aggregated data. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities and expected remaining lifetimes were calculated. Result In 2021, 533.2 million people in the general population were covered by the ERA Registry. The incidence of KRT was 145 per million population (pmp). In incident patients, 55% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes (22%). The prevalence of KRT was 1040 pmp. In prevalent patients, 47% were 65 years or older, 62% were male, and the most common PRDs were diabetes and glomerulonephritis/sclerosis (both 16%). On 31 December 2021, 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. The kidney transplantation rate in 2021 was 37 pmp, a majority coming from deceased donors (66%). For patients initiating KRT between 2012–2016, 5-year survival probability was 52%. Compared to the general population, life expectancy was 65% and 68% shorter for males and females receiving dialysis, and 40% and 43% shorter for males and females living with a functioning graft. [ABSTRACT FROM AUTHOR]

Aims: Finger‐prick sampling has emerged as an attractive tool for therapeutic drug monitoring and associated diagnostics. We aimed to validate the clinical performance of using two volumetric devices (Capitainer® qDBS and Mitra®) for monitoring tacrolimus, creatinine and haemoglobin in kidney transplant (KTx) recipients. Secondarily, we evaluated potential differences between finger‐prick sampling performed by healthcare professionals vs. self‐sampling, and differences between the two devices. Methods: We compared finger‐prick and venous sampling in three settings: microsampling performed by healthcare personnel, self‐sampling under supervision, unsupervised self‐sampling. The finger‐prick samples were analysed with adapted methods and results compared to routine method analysis of the venous blood samples. Results: Twenty‐five KTx recipients completed the main study and 12 KTx recipients completed a post hoc validation study. For tacrolimus measurements and predicted area under the curve, the proportions within ±20% difference were 79%–96% for Capitainer and 77%–95% for Mitra. For creatinine and haemoglobin, the proportions within ±15% were 92%–100% and 93%–100% for Capitainer and 79%–96% and 67%–92% for Mitra, respectively. Comparing sampling situations, the success rate was consistent for Capitainer (92%–96%), whereas Mitra showed 72%–88% and 52%–72% success rates with samples collected by healthcare personnel and the patients themselves. Conclusions: Capitainer and Mitra are technically feasible for measuring tacrolimus, creatinine and haemoglobin. In the context of self‐sampling, Capitainer maintained consistent sampling success and analytical quality. Implementing volumetric finger‐prick self‐sampling for the monitoring of tacrolimus, creatinine and haemoglobin may simplify and improve the follow‐up of KTx recipients. [ABSTRACT FROM AUTHOR]

Background: Reliable methods to detect and reduce medication nonadherence in solid organ‐transplanted (SOT) adolescents are warranted. We aimed to evaluate the feasibility of combining a medication‐manager application (TusenTac®‐app) with home‐sampling of tacrolimus (Tac) in young SOT recipients. Methods: Kidney and combined SOT recipients between 14 and 25 years were included. During an 8‐week intervention period, the participants were instructed to use the transplant‐specific, age‐adapted TusenTac®‐app daily and to perform weekly at‐home Tac trough finger‐prick microsampling. Microsample Tac concentrations were controlled against timed venous samples twice. Medication implementation and persistence adherence were measured with BAASIS© questionnaires, TusenTac®‐registrations, Tac trough concentration coefficient of variation (CV%) and self‐reporting by interview. For comparison, venous Tac trough CV% were obtained from the year before and after the short‐term intervention. Results: Twenty‐two recipients were included, two withdrawals, leaving 20; median age 17.9 (14.5–24.8) years, 12 females (60%). The participants registered their dosage intake 88% (1502/1703) of the expected times, and 90% (106/118) of the microsamples were obtained correctly. At inclusion, 11 recipients (55%) were nonadherent assessed with BAASIS© questionnaire, four of these (36%) turned adherent during the intervention period. At the end, 70% reported improved timing‐adherence at the interview. There was no significant change in TacCV% from the year before to the year after the short‐term intervention. Home‐sampling was reliable and measured Tac concentrations accurately. Conclusions: Home‐monitoring, combining Tac finger‐prick microsampling and a medication‐manager app, is feasible in adolescent SOT recipients with 70% perceived improvement in medication timing‐adherence. There were no significant long‐term changes in TacCV% confirming the need for continuous use and individualized interventions. [ABSTRACT FROM AUTHOR]