Before patients with kidney failure can undergo kidney transplantation, their suitability is assessed through a transplantation work-up. Variation in the transplantation work-up could contribute to inefficiency and inequality in accessing the transplant waiting list and kidney transplantation. We conducted a scoping review on the evaluation of kidney transplant candidates prior to waitlisting, investigating: (i) content of the transplantation work-up; (ii) contraindications to waitlisting; and (iii) organization of the transplantation work-up. A systematic search was conducted in Ovid Medline and Ovid EMBASE in collaboration with a medical information specialist. Studies investigating practice patterns since 2013 related to the evaluation of adults receiving their first kidney graft from a deceased donor were included. Results from 20 studies showed substantial variation in the evaluation of kidney transplant candidates. The content of the transplantation work-up differed between studied centers, yet common domains included screening for infections, heart disease, peripheral artery disease, and malignancy. Commonly reported contraindications to waitlisting were obesity and age-related factors. However, strict cut-off for BMI and age were used less. The organization of the transplantation work-up differed across studied centers with regard to referral and waitlisting decisions, screening and prioritization, and the setting of the transplantation work-up. Literature on the evaluation of kidney transplant candidates is limited, but our findings suggest substantial variation in pre-waitlisting practices among centers. This may contribute to differences in kidney transplantation access and outcomes between countries. Further research on pre-transplantation practices, specifically regarding the standardization of the transplantation work-up, is needed. 10.1093/ckj/sfae377 Video Abstract Watch the video abstract of this contribution sfae377Media1 6367180609112

Abstract Background and Aims Before patients with end stage kidney disease can undergo kidney transplantation, their suitability is assessed through a transplantation work-up. Several international guidelines have outlined the most important factors in determining patient suitability for kidney transplantation, but there is little agreement among them and it is unclear whether their recommendations have been adopted into clinical practice. Variation in the evaluation of kidney transplant recipient candidates could contribute to inefficiency and inequality in accessing the transplant waiting list and kidney transplantation. Therefore, the standardization of pre-waitlisting practice patterns is desirable and in line with recommendations from Europe [1] and the US [2]. An overview of publications on pre-waitlisting practices for kidney transplantation is needed to increase the transparency of kidney transplant recipient candidacy evaluation and is a first step towards the standardization of pre-waitlisting procedures. To date, such an overview has not been performed. Therefore, our aim was to conduct a scoping review on the evaluation of kidney transplant recipient candidates prior to waitlisting, investigating: (a) the content of the transplantation work-up; (b) contraindications to waitlisting; and (c) the organization of the transplantation work-up. Method A systematic search was conducted in Ovid Medline and Ovid EMBASE in collaboration with a medical information specialist. Studies reporting practice patterns on the evaluation of adults receiving their first kidney graft from a deceased donor were included. Studies were excluded if they only reported: on pediatric patients; from the perspective of the patients; practice patterns following waitlisting; COVID-19-related changes to practice patterns; and results from novelty screening methods used to evaluate kidney transplant recipient candidates without evidence that these methods were also used in clinical practice. Results Results from 40 studies were summarized, of which a majority were conducted in Europe (n = 11) and the US (n = 21). The content of the transplantation work-up varied widely between studied centers. Results show that the presence of a written transplantation work-up was common in the US, UK, and Norway, while in other countries, the presence of a written transplantation work-up protocol was not reported. Common domains within the transplantation work-up included screening for infections, heart disease, peripheral artery disease, and malignancy. A wide range of contraindications to waitlisting were reported. The criteria for contraindications related to obesity and age/frailty varied between studied centers and appear to have changed over time. In general, the organization of the transplantation work-up (e.g. the referral process, the transplant care team, and the use of multidisciplinary meetings) was comparable across studied centers, but differences were observed in the way the transplantation work-up was carried out. Conclusion This is the first review summarizing practice patterns related to the evaluation of kidney transplant recipient candidates prior to waitlisting. Results showed substantial variation in the evaluation of kidney transplant recipient candidates and pre-waitlisting practice patterns globally. These findings contribute to increasing the transparency of pre-waitlisting practice patterns, as was endorse by EU and US recommendations. In turn, this may aid in standardizing criteria used to evaluate kidney transplant recipient candidates prior to waitlisting, which could improve kidney transplantation access and outcomes.

Whole-genome sequencing (WGS) now allows identification of multiple variants in non-coding regions. The large number of variants identified by WGS however complicates their interpretation. Through identification of the first deep intronic variant in NPHS2, which encodes podocin, a protein implicated in autosomal recessive steroid resistant nephrotic syndrome (SRNS), we compare herein three different tools including a newly developed targeted NGS-based RNA-sequencing to explore the splicing effect of intronic variations. WGS identified two different variants in NPHS2 eventually involved in the disease. Through RT-PCR, exon-trapping Minigene assay and targeted RNA sequencing, we were able to identify the splicing defect in NPHS2 mRNA from patient kidney tissue. Only targeted RNA-seq simultaneously analyzed the effect of multiple variants and offered the opportunity to quantify consequences on splicing. Identifying deep intronic variants and their role in disease is of utmost importance. Alternative splicing can be predicted by in silico tools but always requires confirmation through functional testing with RNA analysis from the implicated tissue remaining the gold standard. When several variants with potential effects on splicing are identified by WGS, a targeted RNA sequencing panel could be of great value.

Abstract Background Since patient survival after kidney transplantation is significantly improved with a shorter time on dialysis, it is recommended to start the transplant workup in a timely fashion. Methods This retrospective study analyses the chronology of actions taken during the care for patients with chronic kidney disease (CKD) stage 5 who were waitlisted for a first kidney transplant at the Antwerp University Hospital between 2016 and 2019. We aimed to identify risk factors for a delayed start of the transplant workup (i.e. after dialysis initiation) and factors that prolong its duration. Results Of the 161 patients included, only 43% started the transplant workup before starting dialysis. We identified the number of hospitalization days {odds ratio [OR] 0.79 [95% confidence interval (CI) 0.69–0.89]; P < 0.001}, language barriers [OR 0.20 (95% CI 0.06–0.61); P = 0.005] and a shorter nephrology follow-up before CKD stage 5 [OR 0.99 (95% CI 1.0–0.98); P = 0.034] as factors having a significant negative impact on the probability of starting the transplant screening before dialysis. The workup took a median of 8.6 months (interquartile range 5–14) to complete. The number of hospitalization days significantly prolonged its duration. Conclusion The transplant workup was often started too late and the time needed to complete it was surprisingly long. By starting the transplant workup in a timely fashion and reducing the time spent on the screening examinations, we should be able to register patients on the waiting list before or at least at the start of dialysis. We believe that such an internal audit could be of value for every transplant centre.

Cocaine is often sold in a mixture with levamisole to increase the profit margin and potentiate the euphoric effect. Apart from an overdose, cocaine can induce a wide range of clinical symptoms. We present a case of cocaine/levamisole-induced pauci-immune glomerulonephritis. A 22-year-old patient was sent to the hospital after a laboratory result showed an unexpected acute kidney injury, with an estimated glomerular filtration rate of 34 mL/min/1.73 m(2). The medical history included cocaine abuse. Renal biopsy showed a pauci-immune necrotizing glomerulonephritis. Antineutrophil cytoplasmic antibodies were positive with a perinuclear staining pattern and target specificity for leucocyte myeloperoxidase (antimyeloperoxidase). Despite treatment, the kidney function did not show significant improvement. The forensic implication of this case is that even if the toxicological values are not high enough to suggest a lethal intoxication, an idiosyncratic reaction on cocaine and/or levamisole has to be taken into account.