Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) updates the KDIGO 2012 guideline and has been developed with patient partners, clinicians, and researchers around the world, using robust methodology. This update, based on a substantially broader base of evidence than has previously been available, reflects an exciting time in nephrology. New therapies and strategies have been tested in large and diverse populations that help to inform care; however, this guideline is not intended for people receiving dialysis nor those who have a kidney transplant. The document is sensitive to international considerations, CKD across the lifespan, and discusses special considerations in implementation. The scope includes chapters dedicated to the evaluation and risk assessment of people with CKD, management to delay CKD progression and its complications, medication management and drug stewardship in CKD, and optimal models of CKD care. Treatment approaches and actionable guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations which followed the "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE) approach. The limitations of the evidence are discussed. The guideline also provides practice points, which serve to direct clinical care or activities for which a systematic review was not conducted, and it includes useful infographics and describes an important research agenda for the future. It targets a broad audience of people with CKD and their healthcare, while being mindful of implications for policy and payment.

Fracture Risk Among Living Kidney Donors 25 Years After Donation.

Importance: Living kidney donors may have an increased risk of fractures due to reductions in kidney mass, lower concentrations of serum 1,25-dihydroxyvitamin D, and secondary increases in serum parathyroid hormone. Objective: To compare the overall and site-specific risk of fractures among living kidney donors with strictly matched controls from the general population who would have been eligible to donate a kidney but did not do so. Design, Setting, and Participants: This survey study was conducted between December 1, 2021, and July 31, 2023. A total of 5065 living kidney donors from 3 large transplant centers in Minnesota were invited to complete a survey about their bone health and history of fractures, and 16 156 population-based nondonor controls without a history of comorbidities that would have precluded kidney donation were identified from the Rochester Epidemiology Project and completed the same survey. A total of 2132 living kidney donors and 2014 nondonor controls responded to the survey. Statistical analyses were performed from May to August 2023. Exposure: Living kidney donation. Main Outcomes and Measures: The rates of overall and site-specific fractures were compared between living kidney donors and controls using standardized incidence ratios (SIRs). Results: At the time of survey, the 2132 living kidney donors had a mean (SD) age of 67.1 (8.9) years and included 1245 women (58.4%), and the 2014 controls had a mean (SD) age of 68.6 (7.9) years and included 1140 women (56.6%). The mean (SD) time between donation or index date and survey date was 24.2 (10.4) years for donors and 27.6 (10.7) years for controls. The overall rate of fractures among living kidney donors was significantly lower than among controls (SIR, 0.89; 95% CI, 0.81-0.97). However, there were significantly more vertebral fractures among living kidney donors than among controls (SIR, 1.42; 95% CI, 1.05-1.83). Conclusions and Relevance: This survey study found a reduced rate of overall fractures but an excess of vertebral fractures among living kidney donors compared with controls after a mean follow-up of 25 years. Treatment of excess vertebral fractures with dietary supplements such as vitamin D3 may reduce the numbers of vertebral fractures and patient morbidity.

OPTN/SRTR 2021 Annual Data Report: Heart.

The past 5 years have posed challenges to the field of heart transplantation. The 2018 heart allocation policy revision was accompanied by anticipated practice adjustments and increased use of short-term circulatory support, changes that may ultimately serve to advance the field. The COVID-19 pandemic also had an impact on heart transplantation. While the number of heart transplants in the United States continued to increase, the number of new candidates decreased slightly during the pandemic. There were slightly more deaths following removal from the waiting list for reasons other than transplant during 2020, and a decline in transplants among candidates listed as status 1, 2, or 3 compared with the other statuses. Heart transplant rates decreased among pediatric candidates, most notably among those younger than 1 year. Despite this, pretransplant mortality has declined for both pediatric and adult candidates, particularly candidates younger than 1 year. Transplant rates have increased in adults. The prevalence of ventricular assist device use has increased among pediatric heart transplant recipients, while the prevalence of short-term mechanical circulatory support, particularly intra-aortic balloon pump and extracorporeal membrane oxygenation, has increased among adult recipients.

OPTN/SRTR 2021 Annual Data Report: Liver.

In 2021, liver transplant volume continued to grow, with a record 9,234 transplants performed in the United States, 8,665 (93.8%) from deceased donors and 569 (6.2%) from living donors. There were 8,733 (94.6%) adult and 501 (5.4%) pediatric liver transplant recipients. An increase in the number of deceased donor livers corresponded to an increase in the overall transplant rate and shorter waiting times, although still 10.0% of livers that were recovered were not transplanted. Alcohol-associated liver disease was the leading indication for both waitlist registration and liver transplant in adults, outpacing nonalcoholic steatohepatitis, while biliary atresia remained the leading indication for children. Related to allocation policy changes implemented in 2019, the proportion of liver transplants performed for hepatocellular carcinoma has decreased. Among adult candidates listed for liver transplant in 2020, 37.7% received a deceased donor liver transplant within 3 months, 43.8% within 6 months, and 53.3% within 1 year. Pretransplant mortality improved for children following implementation of acuity circle-based distribution. Short-term graft and patient survival outcomes up to 1 year worsened for adult deceased and living donor liver transplant recipients, which is a reversal of previous trends and coincided with the onset of the COVID-19 pandemic in early 2020. Longer-term outcomes among adult deceased donor liver transplant recipients were unaffected, with overall posttransplant mortality rates of 13.3% at 3 years, 18.6% at 5 years, and 35.9% at 10 years. Pretransplant mortality improved for children following implementation of acuity circle-based distribution and prioritization of pediatric donors to pediatric recipients in 2020. Pediatric living donor recipients had superior graft and patient survival outcomes compared with deceased donor recipients at all time points.

Challenges in the management of the kidney allograft: from decline to failure: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

In March 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a virtual Controversies Conference to address the important but rarely examined phase during which the kidney transplant is failing or has failed. In addition to discussing the definition of a failing allograft, 4 broad areas were considered in the context of a declining functioning graft: prognosis and kidney failure trajectory; immunosuppression strategies; management of medical and psychological complications, and patient factors; and choice of kidney replacement therapy or supportive care following graft loss. Identifying and paying special attention to individuals with failing allografts was felt to be important in order to prepare patients psychologically, manage immunosuppression, address complications, prepare for dialysis and/or retransplantation, and transition to supportive care. Accurate prognostication tools, although not yet widely available, were embraced as necessary to define allograft survival trajectories and the likelihood of allograft failure. The decision of whether to withdraw or continue immunosuppression after allograft failure was deemed to be based most appropriately on risk-benefit analysis and likelihood of retransplantation within a few months. Psychological preparation and support was identified as a critical factor in patient adjustment to graft failure, as was early communication. Several models of care were noted that enabled a medically supportive transition back to dialysis or retransplantation. Emphasis was placed on the importance of dialysis-access readiness before initiation of dialysis, in order to avoid use of central venous catheters. The centrality of the patient to all management decisions and discussions was deemed to be paramount. Patient "activation," which can be defined as engaged agency, was seen as the most effective way to achieve success. Unresolved controversies, gaps in knowledge, and areas for research were also stressed in the conference deliberations.

Stakeholders' perspectives on transplant metrics: the 2022 Scientific Registry of Transplant Recipients' consensus conference.

In July 2022, the Scientific Registry of Transplant Recipients (SRTR) hosted an innovative, multistakeholder consensus conference to identify information and metrics desired by stakeholders in the transplantation system, including patients, living donors, caregivers, deceased donor family members, transplant professionals, organ procurement organization professionals, payers, and regulators. Crucially, patients, caregivers, living donors, and deceased donor family members were included in all aspects of this conference, including serving on the planning committee, participating in preconference focus groups and learning sessions, speaking at the conference, moderating conference sessions and breakout groups, and shaping the conclusions. Patients constituted 24% of the meeting participants. In this report, we document the proceedings and enumerate 160 recommendations, 10 of which have been highly prioritized. SRTR will use the recommendations to develop new presentations of information and metrics requested by stakeholders to support informed decision-making.

Factors enabling transplant program participation in the Scientific Registry of Transplant Recipients (SRTR) Living Donor Collective: A national survey.

BACKGROUND: The Scientific Registry of Transplant Recipients (SRTR) Living Donor Collective (LDC), the first effort to create a lifetime registry for living donor candidates in the United States, requires transplant programs to register donor candidates while the SRTR conducts follow-up. METHODS: To better understand facilitators and barriers to program participation, we conducted a brief electronic survey of U.S. transplant program staff from October 26, 2021 to December 17, 2021. RESULTS: We received 132 responses, with at least one response from 87 living donor programs (46 kidney programs, 33 kidney and liver programs, and eight liver programs alone). We found 86% of program representatives strongly agreed or agreed that funding adequate to cover the cost of data collection would facilitate LDC participation, 92% agreed or strongly agreed with importance of electronic data submission options, and 74% reported that elimination of requirements to submit duplicative pre-operative information to the Organ Procurement and Transplantation Network (OPTN) would be helpful. Other potentially enabling factors include reduction in duration of OPTN postdonation follow-up requirements, ease-of-use, protection from data use for regulation, adequate data security, and equity in data access. CONCLUSION: This survey identifies potential targets to strengthen participation in the effort to create a national living donor registry in the United States. Collaboration and investment to overcome barriers to LDC participation among transplant programs are vital to generate long-term data on living donation for donor candidates, donors, and patients in need of transplant.

The need for integrated clinical and administrative data models for risk adjustment in assessment of the cost transplant care.

INTRODUCTION: Value-based purchasing requires accurate techniques to appropriately measure both outcomes and cost with robust adjustment for differences in severity of illness. Traditional methods to adjust cost estimates have exclusively used administrative data derived from billing claims to identify comorbidity and complications. Transplantation uniquely has accurate national clinical registry data that can be used to supplement administrative data. METHODS: Administrative claims from the Vizient, Inc, Clinical Data Base (CDB) were linked with clinical records from the Scientific Registry for Transplant Recipients for 76 liver and 109 kidney transplant programs. Using either or both datasets, we fitted a regression model to the total direct cost of care for 16,649 kidney and 6058 liver transplants. RESULTS: The proportion of variation explained by these risk-adjustment models increased significantly when combined administrative and clinical data were used for kidney (administrative only R2 = .069, clinical only R2 = .047, combined R2 = .14, p < .0001) and liver (administrative only R2 = .28, clinical only R2 = .25, combined R2 = .33, p < .0001). CONCLUSION: Incorporating accurate clinical data into risk-adjustment methodologies can improve risk adjustment methodologies; however, as majority of variation in cost remains unexplained by these risk-adjustment models further work is needed to accuracy assess transplant value.

Deceased Donor Procurement Biopsy Practices, Interpretation, and Histology-Based Decision-Making: A Survey of US Kidney Transplant Centers.

Introduction: The utility of kidney procurement biopsies is controversial. Understanding the current landscape of how clinicians obtain and use biopsies in organ evaluation may help inform consensus-building efforts. Methods: An electronic survey was distributed to clinicians at US kidney transplant programs (April 22, 2021-June 30, 2021) to evaluate donor biopsy indications, frequency, processing and interpretation, and impact of findings on practices. Results: Responses from staff involved in organ acceptance (73% surgeons, 20% nephrologists, 6% coordinators) at 95 transplant centers were analyzed, representing 40% of US transplant centers and 50% of recent deceased donor kidney transplant volume. More than a third of centers (35%) reported obtaining procurement biopsies on most-to-all kidneys. Most clinicians decided when to biopsy jointly with the Organ Procurement Organization (OPO) (82%) based on formal criteria for the decision (72%), although 41% reported having requested a biopsy outside of the criteria. Most respondents used a semiquantitative scoring system for interpretation (57%). Many respondents reported rarely or never having access to renal specialty pathologists (37%) or to telepathology (59%). Most respondents reported that a favorable biopsy result would encourage them to accept a "marginal" donor kidney (72%); nearly half (46%) indicated that an unfavorable biopsy result would lead to decline of a standard criteria kidney. Conclusion: Procurement biopsies are commonly used in organ acceptance decisions despite inconsistent access to experienced renal pathologists and heterogeneous approaches to criteria, scoring, and interpretation. Ongoing study and consensus building are needed to direct procurement biopsy practice toward increasing organ utilization and reducing allocation inefficiency.

Transplant program evaluations in the middle of the COVID-19 pandemic.

Potential regional variations in effects of COVID-19 on federally mandated, program-specific evaluations by the Scientific Registry of Transplant Recipients (SRTR) have been controversial. SRTR January 2022 program evaluations ended transplant follow-up on March 12, 2020, and excluded transplants performed from March 13, 2020 to June 12, 2020 (the "carve-out"). This study examined the carve-out's impact, and the effect of additionally censoring COVID-19 deaths, on first-year posttransplant outcomes for transplants from July 2018 through December 2020. Program-specific hazard ratios (HRs) for graft failure and death estimated under two alternative scenarios were compared with published HRs: (1) the carve-out was removed; (2) the carve-out was retained, but deaths due to COVID-19 were additionally censored. The HRs estimated by censoring COVID-19 deaths were highly correlated with those estimated with the carve-out alone (r2  = .96). Removal of the carve-out resulted in greater variation in HRs while remaining highly correlated (r2  = .82); however, little geographic impact of the carve-out was observed. The carve-out increased average HR in the Northwest by 0.049; carve-out plus censoring reduced average HR in the Midwest by 0.009. Other regions of the country were not significantly affected. Thus, the current COVID-19 carve-out does not appear to impart substantial bias based on the region of the country.

Cancer risk in living kidney donors.

Living kidney donors are screened for transmissible diseases including cancer. Outcomes following donation are excellent, but concern exists regarding development of chronic kidney disease, and cancer risk is unknown. We used linked transplant and cancer registry data to identify incident cancers among 84,357 kidney donors in the United States (1995-2017). We compared risk with the general population using standardized incidence ratios (SIRs). For selected cancers, we used Poisson regression to compare donors with 47,451 Adventist Health Study 2 (AHS-2) participants, who typically have healthy lifestyles. During follow-up, 2843 cancers were diagnosed in donors, representing an overall deficit (SIR 0.79, 95%CI 0.76-0.82). None of 46 specified cancer sites occurred in excess relative to the general population, and 15 showed significant deficits (SIR < 1.00). Compared with AHS-2 participants, donors had similar incidence of liver cancer, melanoma, breast cancer, and non-Hodgkin lymphoma but, starting 7 years after donation, elevated incidence of colorectal cancer (adjusted incidence rate ratio 2.07, 95%CI 1.54-2.79) and kidney cancer (2.97, 1.58-5.58, accounting for the presence of a single kidney in donors). Elevated kidney cancer incidence may reflect adverse processes in donors' remaining kidney. Nonetheless, cancer risk is lower than in the general population, suggesting that enhanced screening is unnecessary.

Toward continuous improvement of Scientific Registry of Transplant Recipients performance reporting: Advances following 2012 consensus conference and future consensus building for 2022 consensus conference.

The Scientific Registry of Transplant Recipients (SRTR) held a consensus conference in 2012 that examined methods used by SRTR for constructing performance metrics and made recommendations on how to improve program-specific reports. That consensus conference provided 25 recommendations categorized as follows: statistical methods, risk adjustment, and outcomes and data. During the subsequent decade, SRTR has implemented most of these recommendations; these are described in this article along with plans for another consensus conference in 2022. With the present article, SRTR aims to create transparency in the field of transplant metrics and guide discussion in the planning of the next consensus conference in 2022. The new conference will revisit the previous topics and have a broader focus to improve the metrics and information that SRTR provides. Readers can provide feedback on topics to be discussed at the next consensus conference as early as possible, by emailing srtr@srtr.org with the subject line "Task 5 Public Comment."

Risk Prediction for Delayed Allograft Function: Analysis of the Deterioration of Kidney Allograft Function (DeKAF) Study Data.

BACKGROUND: Delayed graft function (DGF) of a kidney transplant results in increased cost and complexity of management. For clinical care or a DGF trial, it would be ideal to accurately predict individual DGF risk and provide preemptive treatment. A calculator developed by Irish et al has been useful for predicting population but not individual risk. METHODS: We analyzed the Irish calculator (IC) in the DeKAF prospective cohort (incidence of DGF = 20.4%) and investigated potential improvements. RESULTS: We found that the predictive performance of the calculator in those meeting Irish inclusion criteria was comparable with that reported by Irish et al. For cohorts excluded by Irish: (a) in pump-perfused kidneys, the IC overestimated DGF risk; (b) in simultaneous pancreas kidney transplants, the DGF risk was exceptionally low. For all 3 cohorts, there was considerable overlap in IC scores between those with and those without DGF. Using a modified definition of DGF-excluding those with single dialysis in the first 24 h posttransplant-we found that the calculator had similar performance as with the traditional DGF definition. Studying whether DGF prediction could be improved, we found that recipient cardiovascular disease was strongly associated with DGF even after accounting for IC-predicted risk. CONCLUSIONS: The IC can be a useful population guide for predicting DGF in the population for which it was intended but has limited scope in expanded populations (SPK, pump) and for individual risk prediction. DGF risk prediction can be improved by inclusion of recipient cardiovascular disease.

Incidence, Clinical Correlates, and Outcomes of Pulmonary Hypertension After Kidney Transplantation: Analysis of Linked US Registry and Medicare Billing Claims.

BACKGROUND: The incidence, risks, and outcomes associated with pulmonary hypertension (P-HTN) in the kidney transplant (KTx) population are not well described. METHODS: We linked US transplant registry data with Medicare claims (2006-2016) to investigate P-HTN diagnoses among Medicare-insured KTx recipients (N = 35 512) using billing claims. Cox regression was applied to identify independent correlates and outcomes of P-HTN (adjusted hazard ratio [aHR] 95%LCLaHR95%UCL) and to examine P-HTN diagnoses as time-dependent mortality predictors. RESULTS: Overall, 8.2% of recipients had a diagnostic code for P-HTN within 2 y preceding transplant. By 3 y posttransplant, P-HTN was diagnosed in 10.310.6%11.0 of the study cohort. After adjustment, posttransplant P-HTN was more likely in KTx recipients who were older (age ≥60 versus 18-30 y a HR, 1.912.403.01) or female (aHR, 1.151.241.34), who had pretransplant P-HTN (aHR, 4.384.795.24), coronary artery disease (aHR, 1.051.151.27), valvular heart disease (aHR, 1.221.321.43), peripheral vascular disease (aHR, 1.051.181.33), chronic pulmonary disease (aHR, 1.201.311.43), obstructive sleep apnea (aHR, 1.151.281.43), longer dialysis duration, pretransplant hemodialysis (aHR, 1.171.371.59), or who underwent transplant in the more recent era (2012-2016 versus 2006-2011: aHR, 1.291.391.51). Posttransplant P-HTN was associated with >2.5-fold increased risk of mortality (aHR, 2.572.843.14) and all-cause graft failure (aHR, 2.422.642.88) within 3 y posttransplant. Outcome associations of newly diagnosed posttransplant P-HTN were similar. CONCLUSIONS: Posttransplant P-HTN is diagnosed in 1 in 10 KTx recipients and is associated with an increased risk of death and graft failure. Future research is needed to refine diagnostic, classification, and management strategies to improve outcomes in KTx recipients who develop P-HTN.

The Effect of Acuity Circles on Deceased Donor Transplant and Offer Rates Across Model for End-Stage Liver Disease Scores and Exception Statuses.

Acuity circles (AC), the new liver allocation system, was implemented on February 4, 2020. Difference-in-differences analyses estimated the effect of AC on adjusted deceased donor transplant and offer rates across Pediatric End-Stage Liver Disease (PELD) and Model for End-Stage Liver Disease (MELD) categories and types of exception statuses. The offer rates were the number of first offers, top 5 offers, and top 10 offers on the match run per person-year. Each analysis adjusted for candidate characteristics and only used active candidate time on the waiting list. The before-AC period was February 4, 2019, to February 3, 2020, and the after-AC period was February 4, 2020, to February 3, 2021. Candidates with PELD/MELD scores 29 to 32 and PELD/MELD scores 33 to 36 had higher transplant rates than candidates with PELD/MELD scores 15 to 28 after AC compared with before AC (transplant rate ratios: PELD/MELD scores 29-32, 2.34 3.324.71 ; PELD/MELD scores 33-36, 1.70 2.513.71 ). Candidates with PELD/MELD scores 29 or higher had higher offer rates than candidates with PELD/MELD scores 15 to 28, and candidates with PELD/MELD scores 29 to 32 had the largest difference (offer rate ratios [ORR]: first offers, 2.77 3.955.63 ; top 5 offers, 3.90 4.394.95 ; top 10 offers, 4.85 5.305.80 ). Candidates with exceptions had lower offer rates than candidates without exceptions for offers in the top 5 (ORR: hepatocellular carcinoma [HCC], 0.68 0.770.88 ; non-HCC, 0.73 0.810.89 ) and top 10 (ORR: HCC, 0.59 0.650.71 ; non-HCC, 0.69 0.750.81 ). Recipients with PELD/MELD scores 15 to 28 and an HCC exception received a larger proportion of donation after circulatory death (DCD) donors after AC than before AC, although the differences in the liver donor risk index were comparatively small. Thus, candidates with PELD/MELD scores 29 to 34 and no exceptions had better access to transplant after AC, and donor quality did not notably change beyond the proportion of DCD donors.

Cost, healthcare utilization, and outcomes of antibody-mediated rejection in kidney transplant recipients in the US.

BACKGROUND: Antibody-mediated rejection (AMR) is one of the leading causes of graft loss in kidney transplant recipients but little is known about the associated cost and healthcare burden of AMR. METHODS: We developed an algorithm to detect AMR using the 2006-2011 Centers for Medicare & Medicaid Services (CMS) using ICD-10 and billing codes as there is no specific ICD-10 or procedure code for AMR. We then compared healthcare utilization, cost, and risk of graft failure or death in AMR. patients versus matched controls. RESULTS: The algorithm had a 39.4% true-positive rate (69/175) and a 4.1% false-positive rate (110/2,655). We identified 5,679/101,554 (5.6%) with AMR, who had a nearly 3-fold higher risk of graft failure (hazard ratio [HR], 2.75, 95% confidence interval [CI], 2.50 to 3.03; p < .0001) and death (HR, 2.59; 95% CI, 2.35 to 2.86; p < .0001) at 2 years, nearly 5 times the hospitalizations in the 60 d before AMR diagnosis, and increased nephrology and emergency department visits. Mean AMR attributable healthcare costs were 4 times higher than matched controls, at $13,066 more per patient in the 60 d before AMR diagnosis and $35,740 per patient per year higher in the 2 years after AMR diagnosis. CONCLUSIONS: US kidney transplant recipients with AMR have substantially greater healthcare utilization and higher costs and risk of graft loss and mortality.