COVID-19 Vaccine Seroresponse Based on The Timing of The Primary Series; Pre- versus Post-Renal Transplantation.

BACKGROUND: Coronavirus disease 2019 (COVID-19) poses a serious risk to patients with chronic kidney disease (CKD) and renal transplant. While COVID-19 vaccination is recommended before transplant, there are limited data comparing vaccine timing. Our aim is to evaluate serological responses to COVID-19 vaccines pre- and post-renal transplant and the durability of antibody levels. METHODS: We retrospectively evaluated the antibody response of adult renal transplant recipients who had received at least a primary series of the COVID-19 vaccine. The patients were divided into two groups based on the timing; pre- or post-transplant. Antibody titer levels were evaluated at least 4 weeks after vaccination for each group. Titer durability was assessed by calculating the median titer level of individuals. RESULTS: A total of 139 patients were identified between January 2019 and April 2022. Twenty-nine patients were excluded because of previous COVID-19 infection, and 15 patients were excluded each for insufficient vaccine doses and lack of titer data. Forty patients were included for the pre-transplant group and 40 for post-transplant. The number of pre-transplant patients who developed antibodies (39 patients, 97.5%) was significantly greater than the number of post-transplant patients (21 patients, 52.5%) with p < .01. The median post-vaccination titer levels were significantly greater in the pre-transplant group up to 5 months after vaccination (p < .05). The pre-transplant group's titers seemed sustained even after renal transplantation. CONCLUSION: Vaccinating renal transplant patients before transplant results in increased achievement of seroresponse, higher levels of antibody titers, and sustained titers following transplant. Larger and prospective studies are warranted to confirm the findings.

Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study.

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients. DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials). PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021. MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS: The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION: A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys. TRIAL REGISTRATION: ClinicalTrials.gov NCT05229939.

The Kidney in Heart Failure: The Role of Venous Congestion.

Heart failure can lead to renal impairment, an interaction now termed "cardiorenal syndrome." The prevalent physiological explanation for the renal impairment that accompanies heart failure centers around the forward failure hypothesis, which emphasizes the role of left ventricular dysfunction in causing edema, and the backward failure hypothesis, which singles out venous congestion as the dominant mechanism of edema and reduced glomerular filtration rate. In this review, we provide an appraisal on venous congestion, an extremely important contributor that has received little attention. We also summarize the pharmacology of loop diuretics, explain current understanding of diuretic resistance, and address controversies regarding decongestive treatments.

Kidney Disease after Heart and Lung Transplantation.

Chronic kidney disease (CKD) is not only common after lung and heart transplantation but also is associated with increased morbidity and mortality due to multiple pre-, peri- and post-transplant factors. While the exact incidence of CKD in this population is not well-defined, it seems to have gradually increased over the years as older recipients are more frequently considered. The increasing success of the procedure and expanding transplant candidate pool has allowed many with comorbid conditions to receive a transplant, which was considered prohibitive in the past. This review presents risk factors that have been linked to CKD as well as interventions that may help alleviate this serious problem. The impact of pretransplant renal function and the overexaggerated role of chronic nephrotoxicity of calcineurin inhibitors is discussed in detail. Until the exact pathophysiology of kidney disease is better understood, there is a dire need to expand the research agenda beyond observational studies.

Hypertension Management in Patients with Chronic Kidney Disease.

Hypertension and chronic kidney disease are closely linked. Patients with chronic kidney disease have hypertension almost universally and uncontrolled hypertension accelerates the decline in kidney function. The pathophysiology of hypertension in chronic kidney disease is complex, but is largely related to reduced nephron mass, sympathetic nervous system overactivation, involvement of the renin-angiotensin-aldosterone system, and generalized endothelial dysfunction. Consensus guidelines for blood pressure targets have adopted a blood pressure <120/80 mm Hg in native chronic kidney disease and <130/80 mm Hg in kidney transplant recipients. Guidelines also strongly advocate for renin-angiotensin-aldosterone system blockade as the first-line therapy.

Outcomes of kidney donors with sickle cell trait: A preliminary analysis.

Most transplant centers do not screen kidney donor candidates for sickle cell trait (SCT) and many decline candidates with SCT since it may associate with kidney disease. We compared 17 kidney donors with SCT to propensity score matched donor controls on mortality, reduced eGFR, proteinuria and kidney failure. The prevalence of SCT in African American (AA) donors was 11 per 1000 compared to 73 per 1000 in non-donor AA. Donors with SCT were younger; 33 versus 35 years in controls, nine were AA, six were White, and two were listed as other or unknown ethnicities. After a follow-up period of 18.2 ± 10.5 years, the proportions of donors with SCT and controls who were alive, developed hypertension or cardiovascular disease were similar. No donor with SCT developed an eGFR <30 mL/min/1.73 m2 or kidney failure. SCT was, however, associated with increased risk of proteinuria; RR 5.71 (95% CI 5.7 - 22.7), P = .01. This small and preliminary case series suggest that donors with SCT should perhaps be considered more often provided they were aware of the lack of evidence to support liberal acceptance and that these outcomes reported here likely represent a healthy cohort of donors with SCT.

Outcomes of Kidney Donors With Impaired Fasting Glucose.

BACKGROUND: Many kidney donor candidates with impaired fasting glucose (IFG) and all candidates with diabetes are currently excluded from kidney donation, fearing the development of an accelerated course of diabetic kidney disease in the remaining kidney. METHODS: We studied mortality, proteinuria, and end-stage kidney disease (ESKD) in 8280 donors who donated between 1963 and 2007 according to donation fasting plasma glucose (FPG): <100 mg/dL (n = 6204), 100-125 mg/dL (n = 1826), and ≥126 mg/dL (n = 250). RESULTS: Donors with IFG and those with FPG ≥126 mg/dL were older, less likely to be non-Hispanic White, had a higher body mass index, and were more likely to be related to their recipient. After 15.7 ± 10.5 y from donation to study close, 4.4% died, 29.4% developed hypertension, 13.8% developed proteinuria, and 41 (0.5%) developed ESKD. In both the logistic and Cox models, IFG was associated with a higher diabetes risk (adjusted hazard ratio [aHR], 1.65; 95% confidence interval [CI], 1.18-2.30) and hypertension (aHR, 1.35; 95% CI, 1.10-1.65; P = 0.003 for both), but not higher risk of proteinuria or ESKD. The multivariable risk of mortality in donors with ≥126 mg/dL was higher than the 2 other groups, but risks of proteinuria, cardiovascular disease, and reduced estimated glomerular filtration rate were similar to those with FPG <126 mg/dL. Three cases of ESKD developed in the 250 donors with FPG ≥126 mg/dL at 18.6 ± 10.3 y after donation (aHR, 5.36; 95% CI, 1.0-27.01; P = 0.04). CONCLUSIONS: Donors with IFG and the majority of donors with ≥126 mg/dL do well and perhaps should not be routinely excluded from donation.

Intermediate Renal Outcomes, Kidney Failure, and Mortality in Obese Kidney Donors.

BACKGROUND: Obesity is associated with the two archetypal kidney disease risk factors: hypertension and diabetes. Concerns that the effects of diabetes and hypertension in obese kidney donors might be magnified in their remaining kidney have led to the exclusion of many obese candidates from kidney donation. METHODS: We compared mortality, diabetes, hypertension, proteinuria, reduced eGFR and its trajectory, and the development of kidney failure in 8583 kidney donors, according to body mass index (BMI). The study included 6822 individuals with a BMI of <30 kg/m2, 1338 with a BMI of 30-34.9 kg/m2, and 423 with a BMI of ≥35 kg/m2. We used Cox regression models, adjusting for baseline covariates only, and models adjusting for postdonation diabetes, hypertension, and kidney failure as time-varying covariates. RESULTS: Obese donors were more likely than nonobese donors to develop diabetes, hypertension, and proteinuria. The increase in eGFR in obese versus nonobese donors was significantly higher in the first 10 years (3.5 ml/min per 1.73m2 per year versus 2.4 ml/min per 1.73m2 per year; P<0.001), but comparable thereafter. At a mean±SD follow-up of 19.3±10.3 years after donation, 31 (0.5%) nonobese and 12 (0.7%) obese donors developed ESKD. Of the 12 patients with ESKD in obese donors, 10 occurred in 1445 White donors who were related to the recipient (0.9%). Risk of death in obese donors was not significantly increased compared with nonobese donors. CONCLUSIONS: Obesity in kidney donors, as in nondonors, is associated with increased risk of developing diabetes and hypertension. The absolute risk of ESKD is small and the risk of death is comparable to that of nonobese donors.

Hypertension and renal outcomes in normotensive kidney donors with multiple renal arteries.

Having multiple renal arteries (MRA) has been linked to hypertension development. Whether kidney donors who are left with MRA in the nondonated kidney incur a higher risk of hypertension has not been studied. We compared the development of hypertension, reduced estimated glomerular filtration rate (eGFR), cardiovascular disease, and mortality in 2624 normotensive kidney donors with MRA in the nondonated kidney and to 2624 propensity score matched normotensive donor controls with a single renal artery. In total, 35% of donors had MRA. Donors with MRA were less likely to have undergone a left nephrectomy (51% vs. 83%). Postdonation hypertension was associated with age, male gender, non-White ethnicity, obesity, and family history of hypertension. Having MRA was not associated with risk of hypertension; aHR 0.92 (95% CI 0.82-1.03), P = 0.16. After 17 ± 11 years from donation, a similar proportion of donors with and without MRA developed cardiovascular disease, proteinuria and eGFR <30, <45 and <60 mL/min/1.73 m2 and the multivariable risks of developing these outcomes were similar in the two groups. Our study did not show increased risk for hypertension, reduced eGFR, proteinuria or cardiovascular disease in donors with MRA in the remaining kidney and without hypertension at donation.

Financial Hardship Among Nonelderly Adults With CKD in the United States.

RATIONALE & OBJECTIVE: The burden of financial hardship among individuals with chronic kidney disease (CKD) has not been extensively studied. Therefore, we describe the scope and determinants of financial hardship among a nationally representative sample of adults with CKD. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: Nonelderly adults with CKD from the 2014-2018 National Health Interview Survey. EXPOSURE: Sociodemographic and clinical characteristics. OUTCOME: Financial hardship based on medical bills and consequences of financial hardship (high financial distress, food insecurity, cost-related medication nonadherence, delayed/forgone care due to cost). Financial hardship was categorized into 3 levels: no financial hardship, financial hardship but able to pay bills, and unable to pay bills at all. Financial hardship was then modeled in 2 different ways: (1) any financial hardship (regardless of ability to pay) versus no financial hardship and (2) inability to pay bills versus no financial hardship and financial hardship but able to pay bills. ANALYTICAL APPROACH: Nationally representative estimates of financial hardship from medical bills were computed. Multivariable logistic regression models were used to examine the associations of sociodemographic and clinical factors with the outcomes of financial hardship based on medical bills. RESULTS: A total 1,425 individuals, representing approximately 2.1 million Americans, reported a diagnosis of CKD within the past year, of whom 46.9% (95% CI, 43.7%-50.2%) reported experiencing financial hardship from medical bills; 20.9% (95% CI, 18.5%-23.6%) reported inability to pay medical bills at all. Lack of insurance was the strongest determinant of financial hardship in this population (odds ratio, 4.06 [95% CI, 2.18-7.56]). LIMITATIONS: Self-reported nature of CKD diagnosis. CONCLUSIONS: Approximately half the nonelderly US population with CKD experiences financial hardship from medical bills that is associated strongly with lack of insurance. Evidence-based clinical and policy interventions are needed to address these hardships.

Outcomes of Hypertensive Kidney Donors Using Current and Past Hypertension Definitions.

INTRODUCTION: As many as 50% of U.S. transplant centers do not accept kidney donor candidates with hypertension, citing the link between hypertension, kidney disease, and cardiovascular disease (CVD). METHODS: We ascertained mortality, CVD, proteinuria, estimated glomerular filtration rate (eGFR) trajectory, reduced eGFR, and end-stage kidney disease (ESKD) in 904 hypertensive donors (blood pressure [BP] ≥140/90 mm Hg or receiving treatment) versus 7817 donors with BP <140/90 mm Hg. RESULTS: Hypertensive donors were older, 58.1% were <50 years of age, and they had a lower eGFR. The majority were white and related to their recipient. At the end of follow-up, 14.3 ± 10.1 years (range 4-48 years) from donation, hypertensive and nonhypertensive donors had a similar prevalence of cardiovascular disease and renal outcomes. The multivariable risk of mortality, CVD, and proteinuria were also comparable in normotensive and hypertensive donors. eGFR slope over time was similar in hypertensive and nonhypertensive donors, and in total 5 hypertensive and 39 normotensive donors developed ESKD 19.2 ± 10.3 years after donation (adjusted hazard ratio 1.14 [95% confidence interval 0.62-2.12], P = 0.67). Sensitivity analysis using the new definition of hypertension (≥130/80 mm Hg or requiring treatment) yielded similar results for renal outcomes, but hypertensive donors were more likely to develop CVD and diabetes. CONCLUSIONS: Kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD. Donors with current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD.

Thinking Outside the Box: Novel Kidney Protective Strategies in Kidney Transplantation.

Despite 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.

Long-term outcomes of kidney donors with fibromuscular dysplasia.

BACKGROUND: Fibromuscular dysplasia (FMD) is a non-atherosclerotic systemic arterial disease that is not infrequently discovered during kidney donor evaluation. Current guidelines do not provide recommendations regarding the use of kidneys from donors with FMD and there is a paucity of data on the outcomes of these donors. METHODS: The Renal and Lung Living Donor Evaluation (RELIVE) study addressed long-term outcomes of 8922 kidney donors who donated between 1963 and 2007. We compared the development of hypertension, cardiovascular disease (CVD), proteinuria and reduced estimated glomerular filtration rate (eGFR) in 113 kidney donors with FMD discovered during donor evaluation versus 452 propensity score matched donors without FMD. Outcomes modeling with logistic and Cox regression analysis and Kaplan-Meier statistics were performed. RESULTS: Donors with FMD were older (51 versus 39 years), were more likely to be women (80% versus 56%) and had a higher systolic blood pressure at donation (124.7 versus 121.3 mmHg) (P < 0.05 for all). After a mean ± standard deviation follow-up of 15.5 ± 8.9 years, a similar proportion of donors with and without FMD were alive, and developed hypertension (22.2% versus 19.8%), proteinuria (20.6% versus 13.7%) and CVD (13.3% versus 13.5%). No donor with FMD developed an eGFR <30 mL/min/1.73 m2 or end-stage kidney disease. The multivariable risk of mortality, CVD and renal outcomes in donors with FMD was not elevated. CONCLUSIONS: Kidney donors with FMD appear to do well, do not appear to incur increased risks of hypertension, proteinuria, CVD or reduced eGFR, and perhaps carefully selected candidates with FMD can safely donate as long as involvement of other vascular beds is ruled out.

Outcomes of kidney donors with pre- and post-donation kidney stones.

Roughly 25% of US transplant centers exclude donor candidates with kidney stones fearing future obstructive consequences and the possible association between stones and CKD. We compared the development of hypertension, proteinuria, and reduced eGFR in 227 kidney donors with kidney stones to 908 propensity score-matched donor controls without kidney stones using data from The Renal and Lung Donor Evaluation (RELIVE) Study which studied intermediate and long-term outcomes of 8922 donors who donated between 1963 and 2007. 200 donors had kidney stones prior to donation, 21 had post-donation stones, and 6 had pre- and post-donation stones. Donors with stones were older, more likely to be Caucasian, less likely to be related to the recipient and had a higher fasting glucose. After 16.5 ± 10.9 years (range 0-44 years) from donation to study close, no ESKD occurred in donors with stones. The multivariable risks of hypertension, proteinuria, and reduced GFR were similar in donors with and without kidney stones. We could not demonstrate an association between stones and adverse renal outcomes in kidney donors, and the occurrence of post-donation stones was distinctly rare. These data may provide a rationale for possibly a wider acceptance of donor candidates with low kidney stones burden.

Donor Age, Cold Ischemia Time, and Delayed Graft Function.

BACKGROUND AND OBJECTIVES: Increased donor age is one of the most important risk factors for delayed graft function (DGF), and previous studies suggest that the harmful effect of cold ischemia time is increased in kidneys from older donors. Our aim was to study the association of increased donor age and cold ischemia time with the risk of delayed graft function in a large cohort kidney transplants from the current era. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Scientific Registry of Transplant Recipients was used for this observational, retrospective registry analysis to identify all deceased donor kidney transplantations in the United States between 2010 and September 2018, who were on dialysis pretransplantation (n=90,810). The association of donor age and cold ischemia time with the risk of DGF was analyzed in multivariable models adjusted for recipient characteristics (age, race, sex, diabetes, calculated panel-reactive antibodies, pretransplant dialysis duration) and donor characteristics (cause of death, sex, race, body mass index, creatinine, donation after circulatory death status, history of hypertension, and HLA mismatch). RESULTS: Cold ischemia time and donor age were independently associated with the risk of DGF, but the risk of DGF was not statistically significantly lower in donor age categories between 50 and 64 years, compared with donors ≥65 years. The harmful association of cold ischemia time was not higher in kidneys from older donors in any age category, not even among donation after circulatory death donors. When donor risk was assessed with kidney donor profile index, although a statistically significant interaction with cold ischemia time was found, no practically meaningful increase in cold-ischemia susceptibility of kidneys with a high kidney donor profile index was found. CONCLUSIONS: We were unable to demonstrate an association between donor age and DGF. The association of longer cold ischemia time with the risk of DGF was not magnified in older or more marginal donors.

KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors.

Living kidney donation is widely practiced throughout the world. During the past 2 decades, various groups have provided guidance about the evaluation and care of living donors. However, during this time, our knowledge in the field has advanced substantially and many agreed on the need for a comprehensive, unifying document. KDIGO (Kidney Disease: Improving Global Outcomes) addressed this issue at an international level with the publication of its clinical practice guideline on the evaluation and care of living kidney donors. The KDIGO work group extensively reviewed the available literature and wrote a series of guideline recommendations using various degrees of evidence when available. As has become recent practice, NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) convened a work group to provide a commentary on the KDIGO guideline, with a focus on how these recommendations apply in the context of the United States. In the United States, the United Network for Organ Sharing (UNOS) guides and regulates the practice of living kidney donation. While the KDIGO guideline for the care of living kidney donors and UNOS policy are similar in most aspects of the care of living kidney donors, several important areas are not consistent or do not align with common practice by US transplantation programs in areas in which UNOS has not set specific policy. For the time being, and recognizing the value of the KDIGO guidelines, US transplantation programs should continue to follow UNOS policy.