American Board of Internal Medicine Nephrology Procedure Requirements for Initial Certification: Time for a Change and Pursuing Consensus in the Nephrology Community.

In 1988, the American Board of Internal Medicine (ABIM) defined essential procedural skills in nephrology, and candidates for ABIM certification were required to present evidence of possessing the skills necessary for placement of temporary dialysis vascular access, hemodialysis, peritoneal dialysis, and percutaneous renal biopsy. In 1996, continuous renal replacement therapy was added to the list of nephrology requirements. These procedure requirements have not been modified since 1996 while the practice of nephrology has changed dramatically. In March 2021, the ABIM Nephrology Board embarked on a policy journey to revise the procedure requirements for nephrology certification. With the guidance of nephrology diplomates, training program directors, professional and patient organizations, and other stakeholders, the ABIM Nephrology Board revised the procedure requirements to reflect current practice and national priorities. The approved changes include the Opportunity to Train standard for placement of temporary dialysis catheters, percutaneous kidney biopsies, and home hemodialysis, which better reflects the current state of training in most training programs, and the new requirements for home dialysis therapies training will align with the national priority to address the underuse of home dialysis therapies. This perspective details the ABIM process for considering changes to the certification procedure requirements and how ABIM collaborated with the larger nephrology community in considering revisions and additions to these requirements.

A randomized, placebo-controlled, dose-escalation phase I/II multicenter trial of low-dose cidofovir for BK polyomavirus nephropathy.

BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) is an important cause of allograft dysfunction and failure in kidney transplant recipients (KTRs) and there are no proven effective treatments. Case reports and in vitro data support the potential activity of cidofovir against BK polyomavirus (BKPyV). METHODS: We report the results of a phase I/II, double-blind, placebo-controlled randomized dose-escalation trial of cidofovir in KTRs with biopsy-confirmed BKPyVAN and estimated glomerular filtration rate ≥30 mL/min. Intravenous cidofovir (0.25 mg/kg/dose or 0.5 mg/kg/dose) or placebo was administered on days 0, 7, 21, and 35, with final follow-up through day 49. RESULTS: The trial was prematurely discontinued due to slow accrual after 22 KTRs had completed the study. Cidofovir was safe and tolerated at the doses and duration studied. The proportion of subjects with any adverse event (AE) was similar between groups (9/14 [64%] in the combined cidofovir dose groups and 6/8 [75%] in the placebo group); 84% of AEs were mild. BKPyV DNAemia reduction by day 49 was similar between groups (>1 log10 reduction in (2/9 [22.2%] of 0.25 mg/kg group, 1/5 [20%] of 0.5 mg/kg group, and 2/8 [25%] of placebo group). CONCLUSIONS: These preliminary results indicate that low-dose cidofovir was safe and tolerated but had no significant BKPyV-specific antiviral effect in KTRs with BKPyVAN.

Kidney transplant candidacy evaluation and waitlisting practices in the United States and their association with access to transplantation.

There are limited data on the degree of variability in practices surrounding prioritization of referrals for transplant evaluation and criteria for transplant candidacy and their association with transplantation rates. We surveyed transplant programs across the United States between January 2020 and May 2020 to determine current pre-transplantation practices. We examined the relation between these reported practices and the outcomes of waitlisted patients at responding programs between January 2015 and March 2021 using Scientific Registry of Transplant Recipients data. We used adjusted Cox models with random effects to accommodate clustering by program. Primary outcomes included living or deceased donor transplantation. Of 172 surveyed programs, 90 participated. Substantial variations were noted in when the candidacy evaluation began (13% reported when eGFR was <30 mL/min/1.73 m2 and 17% reported no set policy) and the approach to pre-transplantation cardiac workup (multi-modality [58%], stress echocardiogram [20%]). Using adjusted models, a program policy of using other measures of body habitus to determine transplant candidacy rather than requiring patients to meet a body mass index (BMI) threshold of ≤35 kg/m2 (reference group) for candidacy was associated with a higher hazard of living donor transplantation (HR 1.83 [95% CI 1.10-3.03]). Pre-transplant practices vary substantially across the United States, and select practices were associated with transplantation rates.

Racial Disparities in Eligibility for Preemptive Waitlisting for Kidney Transplantation and Modification of eGFR Thresholds to Equalize Waitlist Time.

BACKGROUND: Patients may accrue wait time for kidney transplantation when their eGFR is ≤20 ml/min. However, Black patients have faster progression of their kidney disease compared with White patients, which may lead to disparities in accruable time on the kidney transplant waitlist before dialysis initiation. METHODS: We compared differences in accruable wait time and transplant preparation by CKD-EPI estimating equations in Chronic Renal Insufficiency Cohort participants, on the basis of estimates of kidney function by creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys). We used Weibull accelerated failure time models to determine the association between race (non-Hispanic Black or non-Hispanic White) and time to ESKD from an eGFR of ≤20 ml/min per 1.73 m2. We then estimated how much higher the eGFR threshold for waitlisting would be required to achieve equity in accruable preemptive wait time for the two groups. RESULTS: By eGFRcr, 444 CRIC participants were eligible for waitlist registration, but the potential time between eGFR ≤20 ml/min per 1.73 m2 and ESKD was 32% shorter for Blacks versus Whites. By eGFRcys, 435 participants were eligible, and Blacks had 35% shorter potential wait time compared with Whites. By the eGFRcr-cys equation, 461 participants were eligible, and Blacks had a 31% shorter potential wait time than Whites. We estimated that registering Blacks on the waitlist as early as an eGFR of 24-25 ml/min per 1.73 m2 might improve racial equity in accruable wait time before ESKD onset. CONCLUSIONS: Policies allowing for waitlist registration at higher GFR levels for Black patients compared with White patients could theoretically attenuate disparities in accruable wait time and improve racial equity in transplant access.

Association between Longer Travel Distance for Transplant Care and Access to Kidney Transplantation and Graft Survival in the United States.

BACKGROUND: Transplant candidates may gain an advantage by traveling to receive care at a transplant center that may have more favorable characteristics than their local center. Factors associated with longer travel distance for transplant care and whether the excess travel distance (ETD) is associated with access to transplantation or with graft failure are unknown. METHODS: This study of adults in the United States wait-listed for kidney transplantation in 1995-2015 used ETD, defined as distance a patient traveled beyond the nearest transplant center for initial waiting list registration. We used linear regression to examine patient and center characteristics associated with ETD and Fine-Gray models to examine the association between ETD (modeled as a spline) and time to deceased or living donor transplantation or graft failure. RESULTS: Of 373,365 patients, 11% had an ETD≥50 miles. Traveling excess distance was more likely among patients who were of non-Black race or those whose nearest transplant center had lower annual living donor transplant volume. At an ETD of 50 miles, we observed a lower likelihood of deceased donor transplantation (subhazard ratio [SHR], 0.85; 95% confidence interval [95% CI], 0.84 to 0.87) but higher likelihood of living donor transplantation (SHR, 1.14; 95% CI, 1.12 to 1.16) compared with those who received care at their nearest center. ETD was weakly associated with higher risk of graft failure. CONCLUSIONS: Patients who travel excess distances for transplant care have better access to living donor but not deceased donor transplantation and slightly higher risk of graft failure. Traveling excess distances is not clearly associated with better outcomes, especially if living donors are unavailable.

Management of Kidney Transplant Recipients by General Nephrologists: Core Curriculum 2019.

Kidney transplantation is associated with improvement in quality of life and mortality as compared to remaining on dialysis. It is therefore the optimal treatment for kidney failure for most patients. While transplantation nephrologists typically care for the patient in the first 6 months posttransplantation, general nephrologists and internists often care for kidney transplant recipients after this period. Medical management of the kidney transplant recipient can be challenging, and primary care physicians and nephrologists may be unfamiliar with the medical nuances of caring for these patients. This includes drug interactions, which are common and can result in drug toxicities, rejection, and graft injury. Infections and malignancies related to long-term immunosuppression may pose diagnostic and treatment challenges. In this article, we review the mechanisms of immunosuppression, types of rejection, complications of recurrent disease, common infectious diseases, and the nonrenal complications commonly encountered in the kidney transplant recipient.

Barriers and Facilitators to Exercise in Older Adults Awaiting Kidney Transplantation and Their Care Partners.

Rationale & Objective: Despite guidelines calling to improve physical activity in older adults, and evidence suggesting that prekidney transplant physical function is highly associated with posttransplant outcomes, only a small percentage of older patients treated with dialysis are engaged in structured exercise. We sought to elucidate barriers and facilitators of exercise among older adults treated with dialysis awaiting transplant and their care partners. Study Design: Individual, in-depth, cognitive interviews were conducted separately for patients and care partners through secure web-conferencing. Setting & Participants: Twenty-three patients (≥50 years of age, treated with dialysis from the University of San Francisco kidney transplantation clinic, with a short physical performance battery of ≤10) and their care partners. Analytical Approach: All audio interviews were transcribed verbatim. Three investigators independently coded data and performed qualitative thematic content. The interview guide was updated iteratively based on the Capability Opportunity Motivation Behavior model. Results: Patients' median age was 60 years (57 ± 63.5) and care partners' median ages was 57 years (49.5 ± 65.5). Thirty-nine percent of patients and 78% of care partners were female, 39% of patients and 30% of care partners self-identified as African American, and 47% of dyads were spouse or partner relationships. Major themes for barriers to pretransplant exercise included lack of understanding of an appropriate regimen, physical impairments, dialysis schedules, and safety concerns. Major facilitators included having individualized or structured exercise programs, increasing social support for patients and care partners, and motivation to regain independence or functionality or to promote successful transplantation. Limitations: Participants geographically limited to Northern California. Conclusions: Although patients and care partners report numerous barriers to pretransplant exercise and activity, they also reported many facilitators. An individualized, structured, home-based exercise program could circumvent many of the reported barriers and allow older patients to improve pretransplant physical function.

Although exercise can improve the fitness of older adults treated with dialysis for kidney transplantation and reduce posttransplant complications, many such individuals do not exercise. We sought to elicit perspectives on barriers and facilitators to prekidney transplant exercises from older adults treated with dialysis and their care partners. We found that although patients and care partners had unique perspectives, they shared many barriers (such as physical and/or cognitive impairment, difficulty scheduling around dialysis, lack of guidance on exercise, and reduced exercise motivation related to dialysis) and several facilitators (such as desire to regain functionality and participate in life and motivation for successful transplantation). A shared interest among patients and care partners in joint participation in structured and home-based exercise may represent a tool to overcome barriers to pretransplant exercise.

Inadequacy of cardiovascular risk factor management in chronic kidney transplantation - evidence from the FAVORIT study.

BACKGROUND: Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD). Our objective is to describe the prevalence of CVD risk factors applying standard criteria and use of CVD risk factor-lowering medications in contemporary KTRs. METHODS: The Folic Acid for Vascular Outcome Reduction in Transplantation study enrolled and collected medication data on 4107 KTRs with elevated homocysteine and stable graft function an average of five yr post-transplant. RESULTS: CVD risk factors were common (hypertension or use of blood pressure (BP) lowering medication in 92%, borderline or elevated low-density lipoprotein (LDL) or use of lipid-lowering agent in 66%, history of diabetes mellitus in 41%, and obesity in 38%); prevalent CVD was reported in 20% of study participants. National Kidney Foundation BP guidelines (BP <130/80 mmHg) were not met by 69% of participants. Uncontrolled hypertension (BP of 140/90 mmHg or higher) was present in 44% of those taking antihypertension medication; 18% of participants had borderline or elevated LDL, of which 60% were untreated, and 31% of the participants with prevalent CVD were not using an antiplatelet agent. CONCLUSION: There is opportunity to improve treatment and control of traditional CVD risk factors in kidney transplant recipients.

Comparison of 2021 CKD-EPI Equations for Estimating Racial Differences in Preemptive Waitlisting for Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Wait time for kidney transplantation can accrue when GFR is ≤20 ml/min. We examined whether using the race-free 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to guide preemptive waitlisting could attenuate racial differences in accruable preemptive wait time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our retrospective cohort study included Black or White Chronic Renal Insufficiency Cohort (CRIC) participants who were theoretically eligible for waitlist registration. We used Weibull accelerated failure time models to determine the association between race (Black or White) and time to kidney failure from the qualifying visit when the eGFR by creatinine or creatinine-cystatin C 2021 CKD-EPI equations fell to ≤20 ml/min per 1.73 m2. We then tested for differences in the time ratios from models using the 2021 creatinine- or creatinine-cystatin C-based CKD-EPI equation through a bootstrapping approach. RESULTS: By the creatinine equation, 472 CRIC participants were theoretically eligible for waitlist registration, and potential preemptive wait time was similar for Black versus White participants (time ratio, 1.05; 95% confidence interval, 0.81 to 1.35). The median wait time by the creatinine equation that could be accrued for Black participants was 23 versus 22 months in White participants. By the creatinine-cystatin C equation, 441 CRIC participants were eligible, and potential wait time was 20% shorter (95% confidence interval, 0.62 to 1.02) for Black than White participants. The median wait time that could be accrued for Black participants was 21 versus 26 months for White participants when using the creatinine-cystatin C equation. Using bootstrapping, the ratio of the time ratio of the models using the creatinine versus creatinine-cystatin C equation was statistically significantly different (ratio of the time ratios = 1.31 with 95% confidence interval, 1.06 to 1.62). CONCLUSIONS: Use of the 2021 creatinine-based CKD-EPI equation to determine preemptive waitlist eligibility reduced racial differences in preemptive wait time accrual more than use of the creatinine-cystatin C 2021 CKD-EPI equation within a theoretical context.

Management of Hospitalized Kidney Transplant Recipients for Hospitalists and Internists.

The number of kidney transplant recipients has grown incrementally over the years. These patients have a high comorbidity index and require special attention to immunosuppression management. In addition, this population has an increased risk for cardiovascular events, electrolyte abnormalities, allograft dysfunction, and infectious complications. It is vital for hospitalists and internists to understand the risks and nuances in the care of this increasingly prevalent, but also high-risk, population.

Solid-Phase C1q/C3d Fixing Readouts Correlate with High Median Fluorescence Intensity (MFI) De Novo Donor-Specific HLA Antibodies and C4d⁺ Antibody-Mediated Rejection in Kidney Transplant Recipients.

BACKGROUND Solid-phase assays to investigate the complement-activating capacity of HLA antibodies have been utilized to optimize organ allocation and improve transplant outcomes. The clinical utility of C1q/C3d-binding characteristics of de novo donor-specific anti-HLA antibodies (dnDSA) associated with C4d-positive antibody-mediated rejection (C4d⁺ AMR) in kidney transplants (KTx) has not been defined. MATERIAL AND METHODS Sera from 120 KTx recipients that had dnDSA concurrent with protocol/cause biopsy (median 3.8 years after transplantation) were screened for C1q and C3d-binding dnDSA. The difference in the incidence of C4d⁺ AMR between recipients with and without C1q/C3d-binding dnDSA was assessed. RESULTS Over 86% of dnDSAs were class II antibodies. The immunodominant dnDSAs characterized by the highest median fluorescence intensity (MFI) in most recipients were HLA-DQ antibodies (67%). Most recipients (62%, n=74) had either C1q⁺ (56%), C3d⁺ (48%), or both C1q⁺C3d⁺ (41.2%) dnDSA, while the remaining 38% were negative for both C1q and C3d. Of those with C1q⁺/C3d⁺ dnDSA, 87% had high-MFI IgG (MFI=14144±5363 and 13932±5278, respectively), while 65% of C1q⁻C3d⁻ dnDSA had low-MFI IgG (MFI=5970±3347). The incidence of C4d+ AMR was significantly higher in recipients with C1q⁺ (66%), C3d+ (74%), and C1q⁺C3d⁺ (72%) dnDSA than in those with C1q⁻C3d⁻ dnDSA (30%) recipients. Recipients with C3d⁺/C1q⁺ dnDSA had higher C4d⁺ scores on biopsy. CONCLUSIONS C1q⁺/C3d⁺ dnDSA were associated with C4d⁺ AMR and high-IgG MFI. Our data call into question the predictive utility of C1q/C3d-binding assays in identifying KTx recipients at risk of allograft failure. In conclusion, IgG MFI is sufficient for clinical management, and the C1q/C3d-assays with added cost do not provide any additional information.

KDOQI US commentary on the 2009 KDIGO clinical practice guideline for the care of kidney transplant recipients.

In response to recently published KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for the care of kidney transplant recipients (KTRs), the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) organized a working group of transplant nephrologists and surgeons to review these guidelines and comment on their relevance and applicability for US KTRs. The following commentaries on the KDIGO guidelines represent the consensus of our work group. The KDIGO transplant guidelines concentrated on aspects of transplant care most important to this population in the posttransplant period, such as immunosuppression, infection, malignancy, and cardiovascular care. Our KDOQI work group concurred with many of the KDIGO recommendations except in some important areas related to immunosuppression, in which decisions in the United States are largely made by transplant centers and are dependent in part on the specific patient population served. Most, but not all, KDIGO guidelines are relevant to US patients. However, implementation of many may remain a major challenge because of issues of limitation in resources needed to assist in the tasks of educating, counseling, and implementing and maintaining lifestyle changes. Although very few of the guidelines are based on evidence that is strong enough to justify their being used as the basis of policy or performance measures, they offer an excellent road map to navigate the complex care of KTRs.

Efficacy of levofloxacin in the treatment of BK viremia: a multicenter, double-blinded, randomized, placebo-controlled trial.

BACKGROUND AND OBJECTIVES: BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. RESULTS: At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. CONCLUSIONS: A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression.

Women and kidney transplantation.

Kidney transplant is the best kidney replacement treatment for end-stage kidney disease. The first step in moving toward kidney transplantation is referral to a transplant center for transplant evaluation. Education of dialysis staff and health-care providers may help increase referrals for evaluation. Patient education has been shown to enhance patient completion of the evaluation process. Patients have difficulty asking others to donate a kidney, but this process can be improved with home and community education. Living donors are more likely to be women than men, especially spousal donors. Deceased donors are more likely to be males younger than 35 years of age. There is a slight decrease in the rate of transplantation of women as compared with men, although not statistically significant. Pretransplant development of anti-human leukocyte antigen antibodies is more common amongst women and can be a barrier to successful transplantation and may prolong the waiting time for transplant. The long-term management of cardiovascular risk factors, osteoporosis, and age-appropriate cancer screening need to be addressed with posttransplant recipients. Women have an overall increased patient and graft survival as compared with men after transplant.

The kidney transplant recipient with hepatitis C infection: pre- and posttransplantation treatment.

Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in dialysis patients and kidney transplant recipients. Evaluation of patients with chronic HCV infection is warranted to determine stage of disease and the need for HCV therapy. Although combination therapy with interferon (IFN) plus ribavirin is the standard of care for chronic HCV infection, IFN monotherapy is recommended in dialysis patients because ribavirin is contraindicated in the presence of renal failure. The goals of pretransplantation HCV therapy are to decrease the risk for progression of HCV-associated liver disease, stabilize renal function in patients with HCV-related glomerulopathy, and prevent development of HCV-associated renal disease after transplantation. Posttransplantation HCV therapy is generally not recommended because of concerns regarding risk for precipitating acute rejection; however, antiviral therapy may be indicated to treat HCV-related glomerulopathy or prevent progression of chronic hepatitis C in patients with more advanced stages of fibrosis. When treatment is required, restored renal function allows use of combination therapy with IFN and ribavirin. Limitations of current HCV therapy include lack of tolerability and suboptimal response rates. New antiviral agents that can be used in dialysis patients (e.g., ribavirin alternatives) and in the posttransplantation setting (e.g., IFN alternatives) are needed to improve outcomes in these populations.