Bone and mineral disorders occur frequently in kidney transplant recipients and are associated with a high risk of fracture, morbidity, and mortality. There is a broad spectrum of often overlapping bone diseases seen after transplantation, including osteoporosis as well as persisting high-or low-turnover bone disease. The pathophysiology underlying bone disorders after transplantation results from a complex interplay of factors, including preexisting renal osteodystrophy and bone loss related to a variety of causes, such as immunosuppression and alterations in the parathyroid hormone-vitamin D-fibroblast growth factor 23 axis as well as changes in mineral metabolism. Management is complex, because noninvasive tools, such as imaging and bone biomarkers, do not have sufficient sensitivity and specificity to detect these abnormalities in bone structure and function, whereas bone biopsy is not a widely available diagnostic tool. In this review, we focus on recent data that highlight improvements in our understanding of the prevalence, pathophysiology, and diagnostic and therapeutic strategies of mineral and bone disorders in kidney transplant recipients.

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BackgroundAnti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) are recognized as a major barrier to patients’ access to organ transplantation and the major cause of graft failure. The capacity of circulating anti-HLA DSAs to activate complement has been suggested as a potential biomarker for optimizing graft allocation and improving the rate of successful transplantations.Methods and findingsTo address the clinical relevance of complement-activating anti-HLA DSAs across all solid organ transplant patients, we performed a meta-analysis of their association with transplant outcome through a systematic review, from inception to January 31, 2018. The primary outcome was allograft loss, and the secondary outcome was allograft rejection. A comprehensive search strategy was conducted through several databases (Medline, Embase, Cochrane, and Scopus).A total of 5,861 eligible citations were identified. A total of 37 studies were included in the meta-analysis. Studies reported on 7,936 patients, including kidney (n = 5,991), liver (n = 1,459), heart (n = 370), and lung recipients (n = 116). Solid organ transplant recipients with circulating complement-activating anti-HLA DSAs experienced an increased risk of allograft loss (pooled HR 3.09; 95% CI 2.55–3.74, P = 0.001; I2 = 29.3%), and allograft rejection (pooled HR 3.75; 95% CI: 2.05–6.87, P = 0.001; I2 = 69.8%) compared to patients without complement-activating anti-HLA DSAs. The association between circulating complement-activating anti-HLA DSAs and allograft failure was consistent across all subgroups and sensitivity analyses. Limitations of the study are the observational and retrospective design of almost all included studies, the higher proportion of kidney recipients compared to other solid organ transplant recipients, and the inclusion of fewer studies investigating allograft rejection.ConclusionsIn this study, we found that circulating complement-activating anti-HLA DSAs had a significant deleterious impact on solid organ transplant survival and risk of rejection. The detection of complement-activating anti-HLA DSAs may add value at an individual patient level for noninvasive biomarker-guided risk stratification.Trial registrationNational Clinical Trial protocol ID: NCT03438058.