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BackgroundKidney transplantation is the best treatment option for patients with end-stage kidney disease (ESKD) with a superiority of graft survival after living kidney donation (LKD) compared to deceased donation. However, a large part of potential donors and recipients are ineligible for LKD. Here, we analyze the leading causes for disqualification of potential living donor-recipient pairs from the LKD program and the health-related consequences for ESKD patients excluded from the LKD program in a German transplant center.MethodsIn this single-center retrospective cohort study we evaluated all candidates (potential donors and recipients) presenting for assessment of LKD from 2012 to 2020 at our transplant center. Thereby we focused on candidates excluded from the LKD program. Main reasons for disqualification were categorized as medical (donor-related), psychosocial, immunological, recipient-related, and unknown.ResultsOverall, 601 donor-recipient pairs were referred to our transplant center for LKD assessment during the observation time. Out of those, 326 (54.2%) discontinued the program with 52 (8.7%) dropouts and 274 (45.6%) donor-recipient pairs being ineligible for LKD. Donor-related medical contraindications were the main reason for disqualification [139 out of 274 (50.7%) potential donors] followed by recipient-related contraindications [60 out of 274 (21.9%) of potential donor-recipient pairs]. Only 77 out of 257 (29.9%) potential recipients excluded from the LKD program received a kidney transplant afterward with a median waiting time of 2 (IQR: 1.0–4.0) years. Overall, 18 (7.0%) ESKD patients initially declined for LKD died in this period.ConclusionA large percentage of donor-recipient pairs are disqualified from the German LKD program, mostly due to medical reasons related to the donor and with partly severe consequences for the potential recipients. For these, alternative solutions that promptly enable kidney transplantation are essential for improving patient quality of life and survival.

Calcium oxalate (CaOx) crystal formation, aggregation and growth is a common cause of kidney stone disease and nephrocalcinosis-related chronic kidney disease (CKD). Genetically modified mouse strains are frequently used as an experimental tool in this context but observed phenotypes may also relate to the genetic background or intestinal microbiota. We hypothesized that the genetic background or intestinal microbiota of mice determine CaOx crystal deposition and thus the outcome of nephrocalcinosis. Indeed, Casp1-/-, Cybb-/- or Casp1-/-/Cybb-/- knockout mice on a 129/C57BL/6J (B6J) background that were fed an oxalate-rich diet for 14 days did neither encounter intrarenal CaOx crystal deposits nor nephrocalcinosis-related CKD. To test our assumption, we fed C57BL/6N (B6N), 129, B6J and Balb/c mice an oxalate-rich diet for 14 days. Only B6N mice displayed CaOx crystal deposits and developed CKD associated with tubular injury, inflammation and interstitial fibrosis. Intrarenal mRNA expression profiling of 64 known nephrocalcinosis-related genes revealed that healthy B6N mice had lower mRNA levels of uromodulin (Umod) compared to the other three strains. Feeding an oxalate-rich diet caused an increase in uromodulin protein expression and CaOx crystal deposition in the kidney as well as in urinary uromodulin excretion in B6N mice but not 129, B6J and Balb/c mice. However, backcrossing 129 mice on a B6N background resulted in a gradual increase in CaOx crystal deposits from F2 to F7, of which all B6N/129 mice from the 7th generation developed CaOx-related nephropathy similar to B6N mice. Co-housing experiments tested for a putative role of the intestinal microbiota but B6N co-housed with 129 mice or B6N/129 (3rd and 6th generation) mice did not affect nephrocalcinosis. In summary, genetic background but not the intestinal microbiome account for strain-specific crystal formation and, the levels of uromodulin secretion may contribute to this phenomenon. Our results imply that only littermate controls of the identical genetic background strain are appropriate when performing knockout mouse studies in this context, while co-housing is optional.

Kidney stone disease is caused by accumulation of oxalate crystals, which trigger tissue injury, inflammation and cell death. Mulay et al. show that crystals induce cell death in the kidney through necroptosis, and propose that this pathway may be a target for the treatment of crystal-induced disease.