en-usThe <i>Kidney Transplantation: Long-Term Management Challenges</i> series is a comprehensive set of review articles covering the most relevant aspects related to the care of kidney transplant recipients. With more than 20,000 kidney transplants performed yearly in the United States, and with excellent short-term outcomes, the focus is now directed toward the management of the long-term challenges these patients pose to the clinician. The series begins with a review of current noninvasive immune monitoring techniques to assess allograft status, along with an overview of contemporary immunosuppressive strategies. The series continues with reviews of clinical conditions frequently observed in this population, such as bone and mineral disease, cardiovascular disease, malignancies, infections, and recurrent glomerular diseases. The care of the pediatric transplant recipient and the very important topics of pregnancy, fertility, and contraception are also covered in detail. Finally, the series culminates with an article addressing the care of the patient with a failing allograft, with dedicated focus on promptly preparing the patient for a new transplant.<p></p><p></p> <p> The review articles are written by a team of experienced professionals in the field, and they are detailed, comprehensive, and clinically oriented. This series will be a valuable resource for physicians in training, general nephrologists, and transplant health care providers.</p> <p> For ease of reference, all of the articles have been combined into <a href="https://cjasn.asnjournals.org/sites/default/files/ASN/PDFs/Kidney%20Transplantation%20Series.pdf">a complete PDF.</a> </p>Mon, 15 Apr 2024 08:06:50 GMThttp://cct.highwire.org/feeds/asn/KidneyTransplantation.rssCancer is an important outcome after kidney transplantation because it is the second leading cause of death in most Western countries. The excess risk of cancer after transplantation is approximately two to three times higher than the age- and sex-matched general population, driven largely by viral- and immune-related cancers. Once cancer develops, outcomes are generally poor, particularly for those with melanoma, renal cell carcinoma, and post-transplant lymphoproliferative disease. More importantly, effective screening and treatment strategies are limited in this high-risk population. In this review, we begin with a patient’s journey that maps the experience of living with a kidney transplant and understand the patient’s knowledge, education, and experience of cancer in the context of transplantation. The epidemiology and burden of cancer in recipients of kidney transplants, along with the up-to-date screening and treatment strategies, are discussed. We also focus on the current understanding of optimal care for recipients of kidney transplants who are living with cancer from the patients’ perspectives.10.2215/CJN.14570920Mon, 29 Mar 2021 10:58:19 GMT-07:00De Novo Malignancies after Kidney TransplantationCancer is an important outcome after kidney transplantation because it is the second leading cause of death in most Western countries. The excess risk of cancer after transplantation is approximately two to three times higher than the age- and sex-matched general population, driven largely by viral- and immune-related cancers. Once cancer develops, outcomes are generally poor, particularly for those with melanoma, renal cell carcinoma, and post-transplant lymphoproliferative disease. More importantly, effective screening and treatment strategies are limited in this high-risk population. In this review, we begin with a patient’s journey that maps the experience of living with a kidney transplant and understand the patient’s knowledge, education, and experience of cancer in the context of transplantation. The epidemiology and burden of cancer in recipients of kidney transplants, along with the up-to-date screening and treatment strategies, are discussed. We also focus on the current understanding of optimal care for recipients of kidney transplants who are living with cancer from the patients’ perspectives.Al-Adra, DavidAl-Qaoud, TalalFowler, KevinWong, Germaine2021-03-29T10:58:19-07:00doi:10.2215/CJN.14570920hwp:resource-id:clinjasn;17/3/434American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycancer, kidney transplantation, Kidney Transplantation SeriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20222022-03-01March 202210.2215/CJN.145709201555-90411555-905X2021-03-29T10:58:19-07:002022-03Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges173434443Patients who receive a kidney transplant commonly experience failure of their allograft. Transplant failure often comes with complex management decisions, such as when and how to wean immunosuppression and start the transition to a second transplant or to dialysis. These decisions are made in the context of important concerns about competing risks, including sensitization and infection. Unfortunately, the management of the failed allograft is, at present, guided by relatively poor-quality data and, as a result, practice patterns are variable and suboptimal given that patients with failed allografts experience excess morbidity and mortality compared with their transplant-naive counterparts. In this review, we summarize the management strategies through the often-precarious transition from transplant to dialysis, highlighting the paucity of data and the critical gaps in our knowledge that are necessary to inform the optimal care of the patient with a failing kidney transplant.10.2215/CJN.14620920Wed, 10 Mar 2021 08:40:38 GMT-08:00Managing Patients with Failing Kidney AllograftPatients who receive a kidney transplant commonly experience failure of their allograft. Transplant failure often comes with complex management decisions, such as when and how to wean immunosuppression and start the transition to a second transplant or to dialysis. These decisions are made in the context of important concerns about competing risks, including sensitization and infection. Unfortunately, the management of the failed allograft is, at present, guided by relatively poor-quality data and, as a result, practice patterns are variable and suboptimal given that patients with failed allografts experience excess morbidity and mortality compared with their transplant-naive counterparts. In this review, we summarize the management strategies through the often-precarious transition from transplant to dialysis, highlighting the paucity of data and the critical gaps in our knowledge that are necessary to inform the optimal care of the patient with a failing kidney transplant.Davis, ScottMohan, Sumit2021-03-10T08:40:38-08:00doi:10.2215/CJN.14620920hwp:resource-id:clinjasn;17/3/444American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, chronic graft deterioration, transplant nephrectomy, transplant outcomes, allografts, Kidney Transplantation SeriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20222022-03-01March 202210.2215/CJN.146209201555-90411555-905X2021-03-10T08:40:38-08:002022-03Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges173444451Infections remain a common complication of solid-organ transplantation. Most infections in the first month after transplant are typically health care–associated infections, whereas late infections, beyond 6–12 months, are community-acquired infections. Opportunistic infections most frequently present in the first 12 months post-transplant and can be modulated on prior exposures and use of prophylaxis. In this review, we summarize the current epidemiology of postkidney transplant infections with a focus on key viral (BK polyomavirus, cytomegalovirus, Epstein-Barr virus, and norovirus), bacterial (urinary tract infections and Clostridioides difficile colitis), and fungal infections. Current guidelines for safe living post-transplant are also summarized. Literature supporting prophylaxis and vaccination is also provided.10.2215/CJN.15971020Tue, 20 Apr 2021 11:01:50 GMT-07:00Long-Term Infectious Complications of Kidney TransplantationInfections remain a common complication of solid-organ transplantation. Most infections in the first month after transplant are typically health care–associated infections, whereas late infections, beyond 6–12 months, are community-acquired infections. Opportunistic infections most frequently present in the first 12 months post-transplant and can be modulated on prior exposures and use of prophylaxis. In this review, we summarize the current epidemiology of postkidney transplant infections with a focus on key viral (BK polyomavirus, cytomegalovirus, Epstein-Barr virus, and norovirus), bacterial (urinary tract infections and Clostridioides difficile colitis), and fungal infections. Current guidelines for safe living post-transplant are also summarized. Literature supporting prophylaxis and vaccination is also provided.Agrawal, AkanshaIson, Michael G.Danziger-Isakov, Lara2021-04-20T11:01:50-07:00doi:10.2215/CJN.15971020hwp:resource-id:clinjasn;17/2/286American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycytomegalovirus, polyomavirus, norovirus, urinary tract infection, histoplasmosis, blastomycosis, coccidioidomycosis, vaccination, kidney transplantation, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20222022-02-01February 202210.2215/CJN.159710201555-90411555-905X2021-04-20T11:01:50-07:002022-02Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges172286295Pediatric kidney transplant recipients are distinguished from adult recipients by the need for many decades of graft function, the potential effect of CKD on neurodevelopment, and the changing immune environment of a developing human. The entire life of an individual who receives a transplant as a child is colored by their status as a transplant recipient. Not only must these young recipients negotiate all of the usual challenges of emerging adulthood (transition from school to work, romantic relationships, achieving independence from parents), but they must learn to manage a life-threatening medical condition independently. Regardless of the age at transplantation, graft failure rates are higher during adolescence and young adulthood than at any other age. All pediatric transplant recipients must pass through this high-risk period. Factors contributing to the high graft failure rates in this period include poor adherence to treatment, potentially exacerbated by the transfer of care from pediatric- to adult-oriented care providers, and perhaps an increased potency of the immune response. We describe the characteristics of pediatric kidney transplant recipients, particularly those factors that may influence their care throughout their lives. We also discuss the risks associated with the transition from pediatric- to adult-oriented care and provide some suggestions to optimize the transition to adult-oriented transplant care and long-term outcomes.10.2215/CJN.16891020Wed, 12 May 2021 07:36:09 GMT-07:00Long-Term Care of the Pediatric Kidney Transplant RecipientPediatric kidney transplant recipients are distinguished from adult recipients by the need for many decades of graft function, the potential effect of CKD on neurodevelopment, and the changing immune environment of a developing human. The entire life of an individual who receives a transplant as a child is colored by their status as a transplant recipient. Not only must these young recipients negotiate all of the usual challenges of emerging adulthood (transition from school to work, romantic relationships, achieving independence from parents), but they must learn to manage a life-threatening medical condition independently. Regardless of the age at transplantation, graft failure rates are higher during adolescence and young adulthood than at any other age. All pediatric transplant recipients must pass through this high-risk period. Factors contributing to the high graft failure rates in this period include poor adherence to treatment, potentially exacerbated by the transfer of care from pediatric- to adult-oriented care providers, and perhaps an increased potency of the immune response. We describe the characteristics of pediatric kidney transplant recipients, particularly those factors that may influence their care throughout their lives. We also discuss the risks associated with the transition from pediatric- to adult-oriented care and provide some suggestions to optimize the transition to adult-oriented transplant care and long-term outcomes.Fernandez, Hilda E.Foster, Bethany J.2021-05-12T07:36:09-07:00doi:10.2215/CJN.16891020hwp:resource-id:clinjasn;17/2/296American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypediatric kidney transplantation, transition of care, adherence, risk factors, long-term care, children, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20222022-02-01February 202210.2215/CJN.168910201555-90411555-905X2021-05-12T07:36:09-07:002022-02Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges172296304Placed in a historical context, this overview focuses on post-transpant pregnancy, fatherhood, and contraception in women and men. The critical importance of early reproductive counseling because of improved sexual function and the early return of ovulation and menses post-transplant is emphasized. We explain the decision making regarding contraception choices. The available data on the safety of immunosuppressive drugs in pregnancy, and for men desiring fatherhood, are detailed. The risk of maternal ingestion of mycophenolate products on the in utero fetus is considered and contrasted with the lack of concern for their use by men fathering children. Pregnancy risks to the allograft, baby, and mother are discussed. An infant’s exposure to specific immunosuppressant medications through breastfeeding is reviewed. The ethics and realities of post-transplant parenthood are explored.10.2215/CJN.14100820Wed, 17 Mar 2021 12:46:02 GMT-07:00Post-Transplant Pregnancy and ContraceptionPlaced in a historical context, this overview focuses on post-transpant pregnancy, fatherhood, and contraception in women and men. The critical importance of early reproductive counseling because of improved sexual function and the early return of ovulation and menses post-transplant is emphasized. We explain the decision making regarding contraception choices. The available data on the safety of immunosuppressive drugs in pregnancy, and for men desiring fatherhood, are detailed. The risk of maternal ingestion of mycophenolate products on the in utero fetus is considered and contrasted with the lack of concern for their use by men fathering children. Pregnancy risks to the allograft, baby, and mother are discussed. An infant’s exposure to specific immunosuppressant medications through breastfeeding is reviewed. The ethics and realities of post-transplant parenthood are explored.Klein, Christina L.Josephson, Michelle A.2021-03-17T12:46:02-07:00doi:10.2215/CJN.14100820hwp:resource-id:clinjasn;17/1/114American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypregnancy, contraception, post-transplant, Kidney Transplantation SeriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20222022-01-01January 202210.2215/CJN.141008201555-90411555-905X2021-03-17T12:46:02-07:002022-01Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges171114120After kidney transplantation, mineral and bone disorders are associated with higher risk of fractures and consequent morbidity and mortality. Disorders of calcium and phosphorus, vitamin D deficiency, and hyperparathyroidism are also common. The epidemiology of bone disease has evolved over the past several decades due to changes in immunosuppressive regimens, mainly glucocorticoid minimization or avoidance. The assessment of bone disease in kidney transplant recipients relies on risk factor recognition and bone mineral density assessment. Several drugs have been trialed for the treatment of post-transplant mineral and bone disorders. This review will focus on the epidemiology, effect, and treatment of metabolic and skeletal derangements in the transplant recipient.10.2215/CJN.03410321Mon, 14 Jun 2021 11:46:48 GMT-07:00Bone and Mineral Disease in Kidney Transplant RecipientsAfter kidney transplantation, mineral and bone disorders are associated with higher risk of fractures and consequent morbidity and mortality. Disorders of calcium and phosphorus, vitamin D deficiency, and hyperparathyroidism are also common. The epidemiology of bone disease has evolved over the past several decades due to changes in immunosuppressive regimens, mainly glucocorticoid minimization or avoidance. The assessment of bone disease in kidney transplant recipients relies on risk factor recognition and bone mineral density assessment. Several drugs have been trialed for the treatment of post-transplant mineral and bone disorders. This review will focus on the epidemiology, effect, and treatment of metabolic and skeletal derangements in the transplant recipient.Khairallah, PascaleNickolas, Thomas L.2021-06-14T11:46:48-07:00doi:10.2215/CJN.03410321hwp:resource-id:clinjasn;17/1/121American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation series, mineral metabolismKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20222022-01-01January 202210.2215/CJN.034103211555-90411555-905X2021-06-14T11:46:48-07:002022-01Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges171121130Cardiovascular disease remains a leading cause of death and morbidity in kidney transplant recipients and a common reason for post-transplant hospitalization. Several traditional and nontraditional cardiovascular risk factors exist, and many of them present pretransplant and worsened, in part, due to the addition of immunosuppression post-transplant. We discuss optimal strategies for identification and treatment of these risk factors, including the emerging role of sodium-glucose cotransporter 2 inhibitors in post-transplant diabetes and cardiovascular disease. We present common types of cardiovascular disease observed after kidney transplant, including coronary artery disease, heart failure, pulmonary hypertension, arrhythmia, and valvular disease. We also discuss screening, treatment, and prevention of post-transplant cardiac disease. We highlight areas of future research, including the need for goals and best medications for risk factors, the role of biomarkers, and the role of screening and intervention.10.2215/CJN.00520121Thu, 23 Sep 2021 06:53:28 GMT-07:00Post-Transplant Cardiovascular DiseaseCardiovascular disease remains a leading cause of death and morbidity in kidney transplant recipients and a common reason for post-transplant hospitalization. Several traditional and nontraditional cardiovascular risk factors exist, and many of them present pretransplant and worsened, in part, due to the addition of immunosuppression post-transplant. We discuss optimal strategies for identification and treatment of these risk factors, including the emerging role of sodium-glucose cotransporter 2 inhibitors in post-transplant diabetes and cardiovascular disease. We present common types of cardiovascular disease observed after kidney transplant, including coronary artery disease, heart failure, pulmonary hypertension, arrhythmia, and valvular disease. We also discuss screening, treatment, and prevention of post-transplant cardiac disease. We highlight areas of future research, including the need for goals and best medications for risk factors, the role of biomarkers, and the role of screening and intervention.Birdwell, Kelly A.Park, Meyeon2021-09-23T06:53:28-07:00doi:10.2215/CJN.00520121hwp:resource-id:clinjasn;16/12/1878American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation series, cardiovascular disease, kidney transplantation, diabetes, immunosuppression, obesity, heart failure, coronary artery disease, hypertensionKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-12-01December 202110.2215/CJN.005201211555-90411555-905X2021-09-23T06:53:28-07:002021-12Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges161218781889Despite the reduction in the incidence of acute rejection, a major risk factor for graft loss, there has been only modest improvement in long-term graft survival. Most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or calcineurin inhibitor nephrotoxicity. Distinct immunologic and nonimmunologic factors conspire to lead to a common pathway of allograft fibrosis. It remains plausible that mitigating nonimmunologic damage using strategies proven effective in native kidney disease may yield benefit in kidney transplantation. In this review, we will focus on nonimmunologic aspects of kidney transplant care that may prove to be valuable adjuncts to a well-managed immunosuppression regimen. Topics to be addressed include the roles of hypertension and agents used to treat it, lipid lowering, sodium and water intake, elevated uric acid, metabolic acidosis, and the use of sodium-glucose cotransporter 2 inhibitors on long-term kidney transplant health.10.2215/CJN.15070920Tue, 23 Mar 2021 07:48:28 GMT-07:00Thinking Outside the Box: Novel Kidney Protective Strategies in Kidney TransplantationDespite the reduction in the incidence of acute rejection, a major risk factor for graft loss, there has been only modest improvement in long-term graft survival. Most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or calcineurin inhibitor nephrotoxicity. Distinct immunologic and nonimmunologic factors conspire to lead to a common pathway of allograft fibrosis. It remains plausible that mitigating nonimmunologic damage using strategies proven effective in native kidney disease may yield benefit in kidney transplantation. In this review, we will focus on nonimmunologic aspects of kidney transplant care that may prove to be valuable adjuncts to a well-managed immunosuppression regimen. Topics to be addressed include the roles of hypertension and agents used to treat it, lipid lowering, sodium and water intake, elevated uric acid, metabolic acidosis, and the use of sodium-glucose cotransporter 2 inhibitors on long-term kidney transplant health.Ibrahim, Hassan N.Murad, Dina N.Knoll, Greg A.2021-03-23T07:48:28-07:00doi:10.2215/CJN.15070920hwp:resource-id:clinjasn;16/12/1890American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, hypertension, outcomesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-12-01December 202110.2215/CJN.150709201555-90411555-905X2021-03-23T07:48:28-07:002021-12Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges161218901897Recurrent glomerular disease after kidney transplant remains an important cause of allograft failure. Many of the different entities post-transplant still suffer from incomplete knowledge on pathophysiology, and therefore lack targeted and effective therapies. In this review, we focus on specific clinical dilemmas encountered by physicians in managing recurrent glomerular disease by highlighting new insights into the understanding and treatment of post-transplant focal segmental glomerulosclerosis, membranous nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, amyloid light-chain (AL) amyloidosis, and IgA nephropathy.10.2215/CJN.00280121Fri, 22 Oct 2021 06:42:10 GMT-07:00Recurrent Glomerular Disease after Kidney TransplantationRecurrent glomerular disease after kidney transplant remains an important cause of allograft failure. Many of the different entities post-transplant still suffer from incomplete knowledge on pathophysiology, and therefore lack targeted and effective therapies. In this review, we focus on specific clinical dilemmas encountered by physicians in managing recurrent glomerular disease by highlighting new insights into the understanding and treatment of post-transplant focal segmental glomerulosclerosis, membranous nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, amyloid light-chain (AL) amyloidosis, and IgA nephropathy.Uffing, AudreyHullekes, FrankRiella, Leonardo V.Hogan, Jonathan J.2021-10-22T06:42:10-07:00doi:10.2215/CJN.00280121hwp:resource-id:clinjasn;16/11/1730American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerulonephritis, kidney transplantation, glomerular disease, allograft failure, recurrent glomerular disease, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-11-01November 202110.2215/CJN.002801211555-90411555-905X2021-10-22T06:42:10-07:002021-11Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges161117301742With the incremental improvements in long-term kidney transplant survival, there is renewed focus on what causes failure of the transplanted allograft. Over the past decade, our understanding of the injuries that lead to loss of graft function over time has evolved. Chronic allograft injury includes both immune-mediated and nonimmune-mediated injuries, which may involve the organ donor, the recipient, or both. The targets of injury include the kidney tubular epithelium, the endothelium, and the glomerulus. As a response to injury, there are the expected tissue remodeling and repair processes. However, if inflammation persists, which is not uncommon in the transplant setting, the resulting maladaptive response is matrix deposition and/or fibrosis. This ultimately leads to declining graft function and, finally, failure. With our advancing knowledge of the multiple etiologies and mechanisms, enhanced by more recent cohort studies in humans, there is an opportunity to identify those at greater risk to initiate new strategies to ameliorate the process. Although the most recent studies focus on immune-mediated injuries, there is a critical need to identify both markers of injury and mechanisms of injury. In this review, we highlight the findings of recent studies, highlight the potential therapeutic targets, and identify the continued unmet need for understanding the mechanisms of late graft failure.10.2215/CJN.15590920Mon, 05 Apr 2021 07:48:23 GMT-07:00Chronic Allograft InjuryWith the incremental improvements in long-term kidney transplant survival, there is renewed focus on what causes failure of the transplanted allograft. Over the past decade, our understanding of the injuries that lead to loss of graft function over time has evolved. Chronic allograft injury includes both immune-mediated and nonimmune-mediated injuries, which may involve the organ donor, the recipient, or both. The targets of injury include the kidney tubular epithelium, the endothelium, and the glomerulus. As a response to injury, there are the expected tissue remodeling and repair processes. However, if inflammation persists, which is not uncommon in the transplant setting, the resulting maladaptive response is matrix deposition and/or fibrosis. This ultimately leads to declining graft function and, finally, failure. With our advancing knowledge of the multiple etiologies and mechanisms, enhanced by more recent cohort studies in humans, there is an opportunity to identify those at greater risk to initiate new strategies to ameliorate the process. Although the most recent studies focus on immune-mediated injuries, there is a critical need to identify both markers of injury and mechanisms of injury. In this review, we highlight the findings of recent studies, highlight the potential therapeutic targets, and identify the continued unmet need for understanding the mechanisms of late graft failure.Langewisch, EricMannon, Roslyn B.2021-04-05T07:48:23-07:00doi:10.2215/CJN.15590920hwp:resource-id:clinjasn;16/11/1723American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, renal fibrosis, renal injury, chronic allograft failure, allografts, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-11-01November 202110.2215/CJN.155909201555-90411555-905X2021-04-05T07:48:23-07:002021-11Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges161117231729Immune monitoring of kidney allograft recipients and personalized therapeutics may help reach the aspirational goal of “one transplant for life.” The invasive kidney biopsy procedure, the diagnostic tool of choice, has become safer and the biopsy classification more refined. Nevertheless, biopsy-associated complications, interobserver variability in biopsy specimen scoring, and costs continue to be significant concerns. The dynamics of the immune repertoire make frequent assessments of allograft status necessary, but repeat biopsies of the kidney are neither practical nor safe. To address the existing challenges, we developed urinary cell mRNA profiling and investigated the diagnostic, prognostic, and predictive accuracy of absolute levels of a hypothesis-based panel of mRNAs encoding immunoregulatory proteins. Enabled by our refinements of the PCR assay and by investigating mechanistic hypotheses, our single-center studies identified urinary cell mRNAs associated with T cell–mediated rejection, antibody-mediated rejection, interstitial fibrosis and tubular atrophy, and BK virus nephropathy. In the multicenter National Institutes of Health Clinical Trials in Organ Transplantation-04, we discovered and validated a urinary cell three-gene signature of T-cell CD3 ε chain mRNA, interferon gamma inducible protein 10 (IP-10) mRNA, and 18s ribosomal RNA that is diagnostic of subclinical acute cellular rejection and acute cellular rejection and prognostic of acute cellular rejection and graft function. The trajectory of the signature score remained flat and below the diagnostic threshold for acute cellular rejection in the patients with no rejection biopsy specimens, whereas a sharp rise was observed during the weeks before the biopsy specimen that showed acute cellular rejection. Our RNA sequencing and bioinformatics identified kidney allograft biopsy specimen gene signatures of acute rejection to be enriched in urinary cells matched to acute rejection biopsy specimens. The urinary cellular landscape was more diverse and more enriched for immune cell types compared with kidney allograft biopsy specimens. Urinary cell mRNA profile–guided clinical trials are needed to evaluate their value compared with current standard of care.10.2215/CJN.14010820Tue, 27 Apr 2021 08:22:12 GMT-07:00Urinary Cell mRNA Profiles Predictive of Human Kidney Allograft StatusImmune monitoring of kidney allograft recipients and personalized therapeutics may help reach the aspirational goal of “one transplant for life.” The invasive kidney biopsy procedure, the diagnostic tool of choice, has become safer and the biopsy classification more refined. Nevertheless, biopsy-associated complications, interobserver variability in biopsy specimen scoring, and costs continue to be significant concerns. The dynamics of the immune repertoire make frequent assessments of allograft status necessary, but repeat biopsies of the kidney are neither practical nor safe. To address the existing challenges, we developed urinary cell mRNA profiling and investigated the diagnostic, prognostic, and predictive accuracy of absolute levels of a hypothesis-based panel of mRNAs encoding immunoregulatory proteins. Enabled by our refinements of the PCR assay and by investigating mechanistic hypotheses, our single-center studies identified urinary cell mRNAs associated with T cell–mediated rejection, antibody-mediated rejection, interstitial fibrosis and tubular atrophy, and BK virus nephropathy. In the multicenter National Institutes of Health Clinical Trials in Organ Transplantation-04, we discovered and validated a urinary cell three-gene signature of T-cell CD3 ε chain mRNA, interferon gamma inducible protein 10 (IP-10) mRNA, and 18s ribosomal RNA that is diagnostic of subclinical acute cellular rejection and acute cellular rejection and prognostic of acute cellular rejection and graft function. The trajectory of the signature score remained flat and below the diagnostic threshold for acute cellular rejection in the patients with no rejection biopsy specimens, whereas a sharp rise was observed during the weeks before the biopsy specimen that showed acute cellular rejection. Our RNA sequencing and bioinformatics identified kidney allograft biopsy specimen gene signatures of acute rejection to be enriched in urinary cells matched to acute rejection biopsy specimens. The urinary cellular landscape was more diverse and more enriched for immune cell types compared with kidney allograft biopsy specimens. Urinary cell mRNA profile–guided clinical trials are needed to evaluate their value compared with current standard of care.Lubetzky, Michelle L.Salinas, ThaliaSchwartz, Joseph E.Suthanthiran, Manikkam2021-04-27T08:22:12-07:00doi:10.2215/CJN.14010820hwp:resource-id:clinjasn;16/10/1565American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyurinary cell mRNA, kidney transplantation, acute allograft rejection, gene expression, kidney biopsy, mRNA, allografts, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-10-01October 202110.2215/CJN.140108201555-90411555-905X2021-04-27T08:22:12-07:002021-10Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges161015651577Improved long-term kidney allograft survival is largely related to better outcomes at 12 months, in association with declining acute rejection rates and more efficacious immunosuppression. Finding the right balance between under- and overimmunosuppression or rejection versus immunosuppression toxicity remains one of transplant’s holy grails. In the absence of precise measures of immunosuppression burden, transplant clinicians rely on nonspecific, noninvasive tests and kidney allograft biopsy generally performed for cause. This review appraises recent advances of conventional monitoring strategies and critically examines the plethora of emerging tests utilizing tissue, urine, and blood samples to improve upon the diagnostic precision of allograft surveillance.10.2215/CJN.14840920Fri, 06 Aug 2021 09:21:35 GMT-07:00Beyond the Biopsy: Monitoring Immune Status in Kidney RecipientsImproved long-term kidney allograft survival is largely related to better outcomes at 12 months, in association with declining acute rejection rates and more efficacious immunosuppression. Finding the right balance between under- and overimmunosuppression or rejection versus immunosuppression toxicity remains one of transplant’s holy grails. In the absence of precise measures of immunosuppression burden, transplant clinicians rely on nonspecific, noninvasive tests and kidney allograft biopsy generally performed for cause. This review appraises recent advances of conventional monitoring strategies and critically examines the plethora of emerging tests utilizing tissue, urine, and blood samples to improve upon the diagnostic precision of allograft surveillance.Bloom, Roy D.Augustine, Joshua J.2021-08-06T09:21:35-07:00doi:10.2215/CJN.14840920hwp:resource-id:clinjasn;16/9/1413American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, transplant outcomes, molecular genetics, immunosuppression, biopsy, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-09-01September 202110.2215/CJN.148409201555-90411555-905X2021-08-06T09:21:35-07:002021-09Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges1691413142210.2215/CJN.13440820Wed, 10 Mar 2021 09:39:07 GMT-08:00Introduction to Kidney Transplantation: Long-Term Management ChallengesSawinski, DeirdrePoggio, Emilio D.2021-03-10T09:39:07-08:00doi:10.2215/CJN.13440820hwp:resource-id:clinjasn;16/8/1262American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, Kidney Transplantation SeriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesother20212021-08-01August 202110.2215/CJN.134408201555-90411555-905X2021-03-10T09:39:07-08:002021-08Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges16812621263The long-term management of maintenance immunosuppression in kidney transplant recipients remains complex. The vast majority of patients are treated with the calcineurin inhibitor tacrolimus as the primary agent in combination with mycophenolate, with or without corticosteroids. A tacrolimus trough target 5–8 ng/ml seems to be optimal for rejection prophylaxis, but long-term tacrolimus-related side effects and nephrotoxicity support the ongoing evaluation of noncalcineurin inhibitor–based regimens. Current alternatives include belatacept or mammalian target of rapamycin inhibitors. For the former, superior kidney function at 7 years post-transplant compared with cyclosporin generated initial enthusiasm, but utilization has been hampered by high initial rejection rates. Mammalian target of rapamycin inhibitors have yielded mixed results as well, with improved kidney function tempered by higher risk of rejection, proteinuria, and adverse effects leading to higher discontinuation rates. Mammalian target of rapamycin inhibitors may play a role in the secondary prevention of squamous cell skin cancer as conversion from a calcineurin inhibitor to an mammalian target of rapamycin inhibitor resulted in a reduction of new lesion development. Early withdrawal of corticosteroids remains an attractive strategy but also is associated with a higher risk of rejection despite no difference in 5-year patient or graft survival. A major barrier to long-term graft survival is chronic alloimmunity, and regardless of agent used, managing the toxicities of immunosuppression against the risk of chronic antibody-mediated rejection remains a fragile balance.10.2215/CJN.15040920Wed, 14 Apr 2021 06:10:56 GMT-07:00Long-Term Immunosuppression ManagementThe long-term management of maintenance immunosuppression in kidney transplant recipients remains complex. The vast majority of patients are treated with the calcineurin inhibitor tacrolimus as the primary agent in combination with mycophenolate, with or without corticosteroids. A tacrolimus trough target 5–8 ng/ml seems to be optimal for rejection prophylaxis, but long-term tacrolimus-related side effects and nephrotoxicity support the ongoing evaluation of noncalcineurin inhibitor–based regimens. Current alternatives include belatacept or mammalian target of rapamycin inhibitors. For the former, superior kidney function at 7 years post-transplant compared with cyclosporin generated initial enthusiasm, but utilization has been hampered by high initial rejection rates. Mammalian target of rapamycin inhibitors have yielded mixed results as well, with improved kidney function tempered by higher risk of rejection, proteinuria, and adverse effects leading to higher discontinuation rates. Mammalian target of rapamycin inhibitors may play a role in the secondary prevention of squamous cell skin cancer as conversion from a calcineurin inhibitor to an mammalian target of rapamycin inhibitor resulted in a reduction of new lesion development. Early withdrawal of corticosteroids remains an attractive strategy but also is associated with a higher risk of rejection despite no difference in 5-year patient or graft survival. A major barrier to long-term graft survival is chronic alloimmunity, and regardless of agent used, managing the toxicities of immunosuppression against the risk of chronic antibody-mediated rejection remains a fragile balance.Wojciechowski, DavidWiseman, Alexander2021-04-14T06:10:56-07:00doi:10.2215/CJN.15040920hwp:resource-id:clinjasn;16/8/1264American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyimmunosuppression, immune tolerance, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-08-01August 202110.2215/CJN.150409201555-90411555-905X2021-04-14T06:10:56-07:002021-08Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges16812641271