April 2022 Edition
Kidney International continues to publish cutting-edge basic and clinical papers in Transplantation to inform the global community of contemporary issues in Transplantation. This eDigest provides a potpourri of such studies and reviews for the general nephrologist to help keep current in the field of Transplantation.
Recent investigations published in KI Reports on transplantation patients reveal ways in which co-morbidities, social deprivation and combination therapy can affect outcomes.
KIDNEY INTERNATIONAL ARTICLES
30 years of the International Banff Classification for Allograft Pathology: The Past, Present and Future of Kidney Transplant Diagnostics
Accurate pathological diagnosis of graft pathology is a key component of the success of kidney transplantation, and the Banff Classification of Allograft Pathology is the world gold standard for objective pathology, underpinning all modern clinical trials. Loupy, Mengel and Haas provide an elegant overview of how the Banff criteria have evolved over the past 30 years since their initial publication in Kidney International. This review documents the changes to the Banff criteria and their evolution to rapidly incorporate the latest changes in methodology and current concepts, with an emphasis on incorporation of the emerging field of transcriptomics into the latest Banff criteria.
Glomerular Endothelial Cell-podocyte Stresses and Crosstalk in Structurally Normal Kidney Transplants
Basic science insights into the kidney allograft continue to underscore our understanding of how the transplant may be set up for later glomerular dysfunction. In an elegant study by Menon et al from Michigan, the interaction between the Glomerular Endothelial Cells (GEC) and the podocyte in healthy kidney donors was studied. The GEC analysis using RNA-seq showed upregulation of endothelial stress after transplant. In the accompanying podocyte analysis, podocytes showed molecular evidence of hypertrophic stress. Taken together the transcriptomic analysis showed that even histologically normal transplanted kidneys have evidence of molecular stress signals that potentially prime the transplant kidney to develop glomerular hyperfiltration and dysfunction later in the transplant life.
Our current understanding of the fundamental nature of allorecognition and the cells mediating allograft dysfunction is reviewed by Jasper Callemeyn and colleagues. The important emerging roles of recipient Natural Killer (NK) cells, non HLA antibodies, memory B cells and the formation of tertiary lymphoid organs within the kidney allograft are reviewed in this cutting-edge review. The authors emphasize the important changing paradigm of the role of innate allorecognition and microvascular inflammation as determinants in allograft outcomes.
The Spatially Resolved Transcriptional Profile of Acute T Cell-mediated Rejection in a Kidney Allograft
Applying molecular techniques to paraffin section biopsies opens the door to detailed studies of the transcriptomic composition of the kidney transplant. Salem and the team from Mt Sinai use the GeoMX Digital Space Profiling platform to study separate glomerular and tubular regions of a patient with T cell-mediated rejection (TCMR). The key finding was a heterogenous expression of molecular species across differing compartments in the biopsy, giving rise to the suggestion of differing sections expressing molecular markers of different phases of acute cellular rejection. Application of these sorts of techniques to paraffin section kidney biopsies of many diseases will give insight into focal kidney pathological processes and greater understanding of the diseases we treat.
Clinical Outcomes from the Assessing Donor-derived Cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal Surveillance (ADMIRAL) Study
An early and non-invasive way to accurately predict and diagnose kidney allograft rejection has been the holy grail of transplantation nephrologists for years. KI published the clinical outcomes from the ADMIRAL study, which uses the detection of serum donor-derived cell-free DNA (dd-cfDNA) as a marker of graft injury post-transplant. The detection of dd-cfDNA is a novel technique that predicts the development of donor-specific antibody and 25% decline in eGFR – key parameters that clinicians need to best manage their patients. This study by Bu et al is the largest prospective cohort of kidney transplant patients studied with dd-cfDNA and points the way forward in 21st century transplant monitoring.
New approaches to study the health of the kidney allograft by non-invasive techniques also provide us with the means to understand the internal renal milieu and potentially intervene in a timely manner to prevent allograft dysfunction. Extracellular vesicles (EV), derived from the urine, provide a window into kidney donor quality and allograft rejection. In a timely review from Ashcroft et al, the formation of EV, their classification, isolation and characterisation are summarised, and their unique potential as novel therapeutic agents for prevention of ischaemia reperfusion injury and modulation of alloimmunity are discussed.
Diffusion-magnetic Resonance Imaging Predicts Decline of Kidney Function in Chronic Kidney Disease and in Patients with a Kidney Allograft
Imaging techniques, such as Diffusion-weighted Magnetic Resonance Imaging (MRI), allow the quantification of diffusion coefficient between renal cortex and medulla as an imaging surrogate of interstitial fibrosis. In a fascinating clinical investigation, Berchtold et al from Switzerland prospectively studied 154 transplant patients showing that this radiological change predicted decline in renal function independent of classical biomarkers of graft dysfunction (baseline function and proteinuria).
Findings from 4C-T Study Demonstrate an Increased Cardiovascular Burden in Girls with End Stage Kidney Disease and Kidney Transplantation
Pulse wave velocity (PWV) is another non-invasive technique, which assesses arterial stiffness using ultrasound. In this landmark clinical investigation, Sugianto et al analyzed a subset of patients participating in the 4C-T study (Cardiovascular Complications in Children with Chronic Kidney Disease – Transplantation). The key finding from 700 children (235 undergoing transplantation) in this study was the demonstration of faster progression of arterial stiffness in girls compared to boys, which persists after transplantation and may contribute to higher mortality seen in girls with kidney failure.
Results of the Prospective Multicenter SoLKiD Cohort Study Indicate Bio-psycho-social Outcome Risks to Kidney Donors 12 Months after Donation
In another pivotal paper on the impact of living kidney donation, Suwelack et al provide key insights into the psychological impact of donation from 20 German transplant centers. Key findings in this largest prospective study of the long term health impact of living kidney donation was the demonstration of impairment of kidney function and increased fatigue and stress in a number of donors. Studies such as these provide important information for physicians counselling patients about all of the consequences of living kidney donation.
KIDNEY INTERNATIONAL REPORTS ARTICLE
Social Deprivation is Associated with Lower Access to Pre-emptive Kidney Transplantation and More Urgent-start Dialysis in the Pediatric Population
A study in France on pediatric patients with ESRD found that patients with low socio-economic status were less likely to have access to pre-emptive transplantation and peritoneal dialysis, more urgent initiation of hemodialysis with a catheter, and be referred late to a nephrologist.
This study looked at kidney transplantation outcomes in a small group of transplant patients with multiple myeloma. Those who received bortezomib before or after transplantation had somewhat more favorable outcomes. However, the authors note that relapse and mortality are common in this population regardless of medication use.
A Randomized Controlled Trial on Safety of Steroid Avoidance in Immunologically Low-risk Kidney Transplant Recipients
This study from Sweden reported the safety and efficacy of complete steroid avoidance in immunologically low-risk kidney recipients without diabetes who received the standard-of-care maintenance regimen with tacrolimus/mycophenolate mofetil. Kidney function and adverse events were comparable in the steroid and non-steroid groups two years later. Steroid-free treatment was thus found to be safe and effective for two years following transplantation.