Nephrology in the 21st Century: Native Kidney Diseases and Impact of Artificial Intelligence, and Advances in Renal Transplantation

Dear Colleagues,

The application of Artificial intelligence (AI) is transforming the field of nephrology in the domains of native kidney diseases and kidney transplantation. AI applications in nephrology are varied and offer substantial potential for improving patient care through predictive analytics, diagnostic support, and treatment optimization. AI has already started helping predictive analysis for variable kidney conditions, improving diagnostic accuracy, and optimizing treatment outcomes. The impact and role of AI may be summarized in the following areas of nephrology: Forecasting the progression of chronic kidney disease (CKD) by identifying modifiable risk factors; Accurately predicting the progression of diabetic kidney disease; Prediction of hospitalization and mortality rates in patients with end-stage renal disease (ESRD); As a diagnostic tool, helping the detection of renal tumors on imaging studies and analyzing kidney structures in histopathological slides; Current research is focusing on using AI to enhance digital pathology’s diagnostic accuracy for glomerular diseases. Lastly, AI has applications in optimizing management of dialysis by monitoring electrolytes and urea to determine optimal sessions times to meet target solute removal.

Advances in the domain of renal transplantation, highlight other aspects of the nephrology of the 21rst century. With advancements in surgical techniques and immunosuppressive drugs, living donor kidney transplantation has become more common. This allows for the faster availability of a compatible organ and reduces the risk of organ shortage. For highly sensitized patients who have developed antibodies against a wide range of donor HLA types, desensitization strategies are being used to make them eligible for transplantation. These include techniques such as plasmapheresis, intravenous immunoglobulin, and rituximab infusion to reduce the antibody levels in the patient's blood before transplantation. Kidney Paired Donation (KPD) and Swap Programs allow for the exchange of donors between pairs of patients who are not a good match but have compatible living donors. Swap programs extend this concept to involve multiple pairs, facilitating more transplants overall. The development of new and more effective immunosuppressant drugs is essential for minimizing the risk of rejection while maintaining a strong immune system to prevent infections. Some examples include belatacept, everolimus, and sirolimus. The new advances in Machine Perfusion Technology techniques can help maintain the function and integrity of donor organs during transport and preservation, reducing the risk of ischemic injury and improving graft survival rates. Continued advancements in artificial kidney technology could provide a long-term solution for patients requiring dialysis, potentially eliminating the need for transplantation altogether or serving as a bridge to transplantation. Researchers are developing techniques for growing functional organs using stem cells derived from the patient's own body. This could potentially eliminate the need for donor matching and reduce rejection rates in the future.

However, the most promising and wonderful advance in kidney transplantation with advances, following progress in gene editing technologies, might be the creation and use of xenograft organ. Researchers have made significant progress in pig-to-primate xenotransplantation by engineering pigs with human-like genes that can help prevent immune rejection. This has shown promising results, but more work is needed before it can be applied to humans. The recent experiment was performed by the University of Alabama using genetically engineered pigs with ten genetic modifications (10-GE pigs). This modification includes targeted insertion of two human anticoagulant genes (hTBM and hEPCR), two human complement inhibitor genes (hDAF and hCD46), and two immunomodulatory genes (hCD47 and hHO1), as well as the deletion (knockout) of three pig carbohydrate antigens (GGTA1, Neu5Gc and B4GALNT2) and the pig growth hormone receptor gene. Another benefit of the medication of these 10-GE pigs is that they do not express red blood cell antigens and are therefore universal donors with respect to blood type. Even though this experiment was performed on a very limited number of deceased humans, none had hyperacute rejection! Interestingly one case developed thrombotic microangiopathy in the xenograft without any appreciable c4d or detectable antibody formation, raising the possibility that TMA is not mediated by complement or antibody in the xenografts and is instead the result of some other unknown mechanism or molecular incompatibility!

This Special Issue aims to gather and showcase the latest advancements and knowledge in the field of renal transplantation research. We welcome the submission of both original research articles and comprehensive review papers.

Dr. Marjan Afrouzian
Guest Editor

Dr. Lukman Cheraghvandi
Dr. Jenna Reisler
Guest Editor Assistants

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• Artificial Intelligence (AI)
• nephrology
• native kidney diseases
• renal transplantation