Green nephrology, also often called sustainable nephrology, has become a field of interest in our discipline in recent years. Although several reviews have been published, comparatively few original articles have appeared, witnessing interest but also lack of original data. Greater awareness of the effect nephrology has on the planet, including, but not limited to its carbon footprint, is needed to promote education and research on these issues. Increasing awareness entails increasing knowledge at various levels, and it is for this reason that we are presenting this review focusing on educational activities that have been and could further be undertaken to spread knowledge of these topics. We start from a description of the various approaches to green nephrology: technical, mainly focused on dialysis, clinical, encompassing medical and nonmedical treatments in all CKD phases, and comprehensive, embedding kidney care in the society. We further summarize what is known and the fundamental needs and problems we presently face in reducing dialysis carbon-print, optimizing the pathways of care, avoiding futility in clinical work and research, and implementing lifestyle interventions and education. We further acknowledge the lack of data on lifecycle of items and procedures, including commonly used drugs, and identify research needs at various levels. We finally discuss some examples of educational programs on green nephrology that are already available at various levels, from medical schools (an educational game), to medical meetings (healthy eating and reduction of plastic and paper waste), and daily clinical practice, in which teaching passes also through examples (personalizing dialysis and adapting schedules to each patient). Finally, we identify some barriers that educational approaches may offer ways to overcome, to promote effective, targeted interventions that will make us advance on the road to reduce nephrology's carbon footprint.

Background: Isolated tubulitis, borderline changes and isolated arteritis suspicious for histologic T-cell-mediated rejection (hTCMR) remain findings of uncertain significance. Although the Molecular Microscope Diagnostics System (MMDx) has not been trained on those lesions, it was suggested that MMDx might reclassify a subgroup to molecular TCMR (mTCMR). Methods: In this single-center cohort of 326 consecutive, unselected kidney allograft biopsies assessed by histology and MMDx, we analyzed 249 cases with isolated tubulitis (i0, t1–3, v0; n = 101), borderline changes (according to Banff 2022, v0; n = 9), isolated arteritis (no borderline, v1; n = 37), no inflammation (i0, t0, v0; n = 67) and a positive control cohort (hTCMR, n = 27; mixed histologic rejection, n = 8; both according to Banff 2022; total n = 35). The first three groups were summarized as TCMR-suspicion (n = 147). Subcategorization included the presence and absence of microvascular inflammation (MVI); g+ptc ptc ≥2. Molecular rejection rates and differentiation were investigated. Results: Molecular rejection rates were 37/147 cases (25.2%; 32 with MVI) in TCMR-suspicion, 6/67 (9%; 4 with MVI) in no inflammation and 30/35 (85.7%; 19 with MVI) in the positive control cohort. Molecular antibody-mediated rejection (mAMR) was present in 39/73 (53.4%) of cases. The presence of donor-specific antibodies at the time of the biopsy was high (127/249, 51%). Only 3 mAMR/TCMR and 0 pure mTCMR cases were detected in TCMR-suspicion and no inflammation, compared with 12 mAMR/TCMR and 10 mTCMR cases in the positive control cohort (P < .001). Even though the TCMR-specific molecular (Classifier) score differentiated between TCMR-suspicion and no inflammation (P = 0.005), rejection phenotype scores (R2 and R3) did not (P = .157 and .121). Conclusions: MMDx did not identify pure mTCMR among isolated tubulitis, borderline changes or isolated arteritis, likely due to low sensitivity for TCMR lesions. However, it identified mAMR or mAMR/TCMR, especially in cases with MVI. Subthreshold findings remain to be further studied.

Background: Letermovir (LTV) might be an alternative treatment to nephrotoxic foscarnet (FOS) in Ganciclovir (GCV) resistant cytomegalovirus (CMV) infection. However, its efficacy in controlling active CMV viremia is unclear, as it is only approved for CMV prophylaxis in hematopoietic stem‐cell transplantation.Methods: This case series describes 14 kidney transplant recipients (KTR) with moderate‐level GCV resistant CMV infection, treated by different step‐down strategies after initial FOS therapy: (1) Observation without antiviral follow‐up or switch to valganciclovir (VGCV) (pre‐LTV era), and (2) Switch to LTV±VGCV (LTV era).Results: One patient died under FOS. Thirteen patients were followed under step‐down regimens. All but two patients had ongoing CMV viremia when stopping FOS. In pre‐LTV era, 5/9 (56%) experienced a CMV breakthrough > 10 000 IU/ml calling for another course of FOS, as compared to 1/4 (25%) in the LTV era. Addition of VGCV to LTV at low‐level viral breakthrough, addressing a possible developing resistance against LTV, prevented viral surge in two patients. In the pre‐LTV era, CMV‐related death or graft loss occurred in three of nine (33%), compared to no death or graft loss in the LTV era.Conclusion: A step‐down strategy combining LTV+VGCV, might allow to safely stop FOS at ongoing low‐level viremia.

The health-care system and particularly renal replacement therapy has a significant carbon footprint adding to global warming and extreme weather conditions. Improving sustainability has become the focus of national and international working groups. Many reviews underline the need for improvement of sustainability in nephrology, in particular dialysis, and provide recommendations on how to reduce waste, energy, and water consumption. However, how to implement these recommendations, and where to start, is not always clear. This paper summarizes discussions within the ‘working group on sustainable nephrology’ of the Swiss Society of Nephrology. We do not provide a detailed review of the topic but instead present a practical 10-point action plan to help health-care workers in nephrology make a start and improve the carbon footprint of their dialysis centres. We emphasize the importance of ongoing research, cooperation, and dialogue, and welcome additional ideas from the wider renal community.

Biopsy-based transcript diagnostics may identify molecular antibody-mediated rejection (AMR) when microvascular inflammation (MVI) is absent. In this single-center cohort, biopsy-based transcript diagnostics were validated in 326 kidney allograft biopsies. 71 histological AMR and 35 T-cell mediated rejection (TCMR) cases were identified as molecular AMR and TCMR in 55% and 63%, respectively. Among 121 cases without MVI (g+ptc=0), 45 donor-specific antibody (DSA)-positive (37%) and 76 DSA-negative cases (63%) were analyzed. 21/121 (17%) cases showed borderline changes or TCMR, while BK nephropathy was excluded. None of the 45 DSA-positive patients showed molecular AMR. Among 76 DSA-negative patients, two had mixed molecular AMR/TCMR. The all AMR phenotype score (sum of R4-R6) exhibited median values of 0.13 and 0.12 for DSA-positive and DSA-negative patients, respectively (p=0.84). 6/45 (13%) DSA-positive and 8/76 (11%) DSA-negative patients showed an all AMR phenotype score >0.30 (p=0.77). Patients with a higher all AMR phenotype score showed 33% more histological TCMR (p=0.005). The median all AMR phenotype scores of glomerular basement membrane double contours (cg)=0 and cg>0 biopsies were 0.12 and 0.10, respectively (p=0.35). Biopsy-based transcript diagnostics did not identify molecular AMR in cases without MVI. Follow-up biopsies and outcome data should evaluate the clinical relevance of sub-threshold molecular alterations.

Some kidney allograft biopsies with microvascular inflammation (MVI) - a hallmark of antibody-mediated rejection (AMR) - lack evidence of anti-human leukocyte antigen (HLA) donor-specific antibodies (DSA). In these cases, alternative mechanisms of allograft injury may play a role, such as non-HLA angiotensin II type 1 receptor (AT1R) or endothelin type A receptor (ETAR) autoantibodies. In this single-center study, 196 biopsies were evaluated by histology and biopsy-based transcript diagnostics. Anti-HLA antibodies, AT1R-, and ETAR-Ab serology were determined at the time of biopsy. Of 61 histological AMR, 29 (48%) were identified as molecular AMR (mAMR); of 24 MVI, DSA negative, C4d negative biopsies, 11 (46%) biopsies were mAMR. Additionally, 6 (16%) of 37 probable AMR biopsies were mAMR. The AT1R-/ETAR-Ab concentration did not differ among histological categories or across different levels of molecular scores. However, biopsies with mAMR had higher concentrations of AT1R-Ab (p=0.09) and ETAR-Ab (p=0.02) compared to biopsies with no molecular rejection. The presence of non-HLA autoantibodies did not affect the outcome. Biopsies with MVI at/above threshold showed higher hazard (HR 2.09, 95% CI [0.90 to 4.86], p=0.09) of composite endpoint (allograft failure or eGFR <15ml/min). Non-HLA autoantibodies reflect molecular AMR injury, but their clinical utility is likely limited.