Performance of estimated glomerular filtration rate equations in Black living kidney donor candidates.

INTRODUCTION: New estimated glomerular filtration rate (eGFR) equations using serum creatinine and/or cystatin C have been derived to eliminate adjustment by perceived Black ancestry. We sought to analyze the performance of newer eGFR equations among Black living kidney donor candidates. METHODS: Black candidates (n = 64) who had measured iothalamate GFR between January 2015 and October 2021 were included, and eGFR was calculated using race adjusted (eGFRcr2009 and eGFRcr-cys2012) and race unadjusted (eGFRcys2012, eGFRcr2021, and eGFRcr-cys2021) CKD-EPI equations. Bias and accuracy were calculated. RESULTS: The eGFRcr2021 equation had a negative bias of 9 mL/min/1.73 m2 , while other equations showed a modest positive bias. Accuracy within 10% and 30% was greatest using the eGFRcr-cys2021 equation. With the eGFRcr2021 equation, 9.4% of donors with an mGFR > 80 mL/min/1.73 m2 were misclassified as having an eGFR < 80 mL/min/1.73 m2 . eGFR was also compared among 18 kidney donors at 6-24 months post-donation. Post-donation, the percentage of donors with an eGFR < 60 mL/min/1.73 m2 was 44% using the eGFRcr2021 equation compared to 11% using the eGFRcr-cys2021 equation. CONCLUSION: The CKD-EPICr2021 equation appears to underestimate true GFR in Black living donor candidates. Alternatively, compared to CKD-EPICr2021, the CKD-EPICr-CysC2021 equation appears to perform with less bias and improved accuracy.

Prospective observational study to validate a next-generation sequencing blood RNA signature to predict early kidney transplant rejection.

The objective of this study was to validate the performance of Tutivia, a peripheral blood gene expression signature, in predicting early acute rejection (AR) post-kidney transplant. Recipients of living or deceased donor kidney transplants were enrolled in a nonrandomized, prospective, global, and observational study (NCT04727788). The main outcome was validation of the area under the curve (AUC) of Tutivia vs serum creatinine at biopsy alone, or Tutivia + serum creatinine at biopsy. Of the 151 kidney transplant recipients, the mean cohort age was 53 years old, and 64% were male. There were 71% (107/151) surveillance/protocol biopsies and 29% (44/151) for-cause biopsies, with a 31% (47/151) overall rejection rate. Tutivia (AUC 0.69 [95% CI: 0.59-0.77]) and AUC of Tutivia + creatinine at biopsy (0.68 [95% CI: 0.59-0.77]) were greater than the AUC of creatinine at biopsy alone (0.51.4 [95% CI: 0.43-0.60]). Applying a model cut-off of 50 (scale 0-100) generated a high- and low-risk category for AR with a negative predictive value of 0.79 (95% CI: 0.71-0.86), a positive predictive value of 0.60 (95% CI: 0.45-0.74), and an odds ratio of 5.74 (95% CI: 2.63-12.54). Tutivia represents a validated noninvasive approach for clinicians to accurately predict early AR, beyond the current standard of care.

The Number and Size of Individual Kidney Medullary Pyramids is Associated with Clinical Characteristics, Kidney Biopsy Findings, and CKD Outcomes among Kidney Donors.

SIGNIFICANCE STATEMENT: Segmentation of multiple structures in cross-sectional imaging is time-consuming and impractical to perform manually, especially if the end goal is clinical implementation. In this study, we developed, validated, and demonstrated the capability of a deep learning algorithm to segment individual medullary pyramids in a rapid, accurate, and reproducible manner. The results demonstrate that cortex volume, medullary volume, number of pyramids, and mean pyramid volume is associated with patient clinical characteristics and microstructural findings and provide insights into the mechanisms that may lead to CKD. BACKGROUND: The kidney is a lobulated organ, but little is known regarding the clinical importance of the number and size of individual kidney lobes. METHODS: After applying a previously validated algorithm to segment the cortex and medulla, a deep-learning algorithm was developed and validated to segment and count individual medullary pyramids on contrast-enhanced computed tomography images of living kidney donors before donation. The association of cortex volume, medullary volume, number of pyramids, and mean pyramid volume with concurrent clinical characteristics (kidney function and CKD risk factors), kidney biopsy morphology (nephron number, glomerular volume, and nephrosclerosis), and short- and long-term GFR <60 or <45 ml/min per 1.73 m 2 was assessed. RESULTS: Among 2876 living kidney donors, 1132 had short-term follow-up at a median of 3.8 months and 638 had long-term follow-up at a median of 10.0 years. Larger cortex volume was associated with younger age, male sex, larger body size, higher GFR, albuminuria, more nephrons, larger glomeruli, less nephrosclerosis, and lower risk of low GFR at follow-up. Larger pyramids were associated with older age, female sex, larger body size, higher GFR, more nephrons, larger glomerular volume, more nephrosclerosis, and higher risk of low GFR at follow-up. More pyramids were associated with younger age, male sex, greater height, no hypertension, higher GFR, lower uric acid, more nephrons, less nephrosclerosis, and a lower risk of low GFR at follow-up. CONCLUSIONS: Cortex volume and medullary pyramid volume and count reflect underlying variation in nephron number and nephron size as well as merging of pyramids because of age-related nephrosclerosis, with loss of detectable cortical columns separating pyramids.

Age-Based Versus Young-Adult Thresholds for Nephrosclerosis on Kidney Biopsy and Prognostic Implications for CKD.

SIGNIFICANCE STATEMENT: Nephrosclerosis (glomerulosclerosis, interstitial fibrosis, and tubular atrophy) is the defining pathology of both kidney aging and CKD. Optimal thresholds for nephrosclerosis that identify persons with a progressive disease are unknown. This study determined a young-age threshold (18-29 years) and age-based 95th percentile thresholds for nephrosclerosis on the basis of morphometry of kidney biopsy sections from normotensive living kidney donors. These thresholds were 7.1-fold to 36-fold higher in older (70 years or older) versus younger (aged 18-29 years) normotensive donors. Age-based thresholds, but not young-age threshold, were prognostic for determining risk of progressive CKD among patients who underwent a radical nephrectomy or a for-cause native kidney biopsy, suggesting that age-based thresholds are more useful than a single young-age threshold for identifying CKD on biopsy. BACKGROUND: Nephrosclerosis, defined by globally sclerotic glomeruli (GSG) and interstitial fibrosis and tubular atrophy (IFTA), is a pathology of both kidney aging and CKD. A comparison of risk of progressive CKD using aged-based thresholds for nephrosclerosis versus a single young-adult threshold is needed. METHODS: We conducted morphometric analyses of kidney biopsy images for %GSG, %IFTA, and IFTA foci density among 3020 living kidney donors, 1363 patients with kidney tumor, and 314 patients with native kidney disease. Using normotensive donors, we defined young-age thresholds (18-29 years) and age-based (roughly by decade) 95th percentile thresholds. We compared age-adjusted risk of progressive CKD (kidney failure or 40% decline in eGFR) between nephrosclerosis that was "normal compared with young," "normal for age but abnormal compared with young," and "abnormal for age" in patients with tumor and patients with kidney disease. RESULTS: The 95th percentiles in the youngest group (18-29 years) to the oldest group (70 years or older) ranged from 1.7% to 16% for %GSG, 0.18% to 6.5% for %IFTA, and 8.2 to 59.3 per cm 2 for IFTA foci density. Risk of progressive CKD did not differ between persons with nephrosclerosis "normal compared with young" versus "normal for age but abnormal compared with young." Risk of progressive CKD was significantly higher with %GSG, %IFTA, or IFTA foci density that was abnormal versus normal for age in both cohorts. CONCLUSIONS: Given that increased risk of progressive CKD occurs only when nephrosclerosis is abnormal for age, age-based thresholds for nephrosclerosis seem to be better than a single young-age threshold for identifying clinically relevant CKD.

An Improved Method for Estimating Nephron Number and the Association of Resulting Nephron Number Estimates with Chronic Kidney Disease Outcomes.

SIGNIFICANCE STATEMENT: Nephron number currently can be estimated only from glomerular density on a kidney biopsy combined with cortical volume from kidney imaging. Because of measurement biases, refinement of this approach and validation across different patient populations have been needed. The prognostic importance of nephron number also has been unclear. The authors present an improved method of estimating nephron number that corrects for several biases, resulting in a 27% higher nephron number estimate for donor kidneys compared with a prior method. After accounting for comorbidities, the new nephron number estimate does not differ between kidney donors and kidney patients with tumor and shows consistent associations with clinical characteristics across these two populations. The findings also indicate that low nephron number predicts CKD independent of biopsy and clinical characteristics in both populations. BACKGROUND: Nephron number can be estimated from glomerular density and cortical volume. However, because of measurement biases, this approach needs refinement, comparison between disparate populations, and evaluation as a predictor of CKD outcomes. METHODS: We studied 3020 living kidney donors and 1354 patients who underwent radical nephrectomy for tumor. We determined cortex volume of the retained kidney from presurgical imaging and glomerular density by morphometric analysis of needle core biopsy of the donated kidney and wedge sections of the removed kidney. Glomerular density was corrected for missing glomerular tufts, absence of the kidney capsule, and then tissue shrinkage on the basis of analysis of 30 autopsy kidneys. We used logistic regression (in donors) and Cox proportional hazard models (in patients with tumor) to assess the risk of CKD outcomes associated with nephron number. RESULTS: Donors had 1.17 million nephrons per kidney; patients with tumor had 0.99 million nephrons per kidney. A lower nephron number was associated with older age, female sex, shorter height, hypertension, family history of ESKD, lower GFR, and proteinuria. After adjusting for these characteristics, nephron number did not differ between donors and patients with tumor. Low nephron number (defined by <5th or <10th percentile by age and sex in a healthy subset) in both populations predicted future risk of CKD outcomes independent of biopsy and clinical characteristics. CONCLUSIONS: Compared with an older method for estimating nephron number, a new method that addresses several sources of bias results in nephron number estimates that are 27% higher in donors and 1% higher in patients with tumor and shows consistency between two populations. Low nephron number independently predicts CKD in both populations.

Using Kane's framework to build an assessment tool for undergraduate medical student's clinical competency with point of care ultrasound.

INTRODUCTION: Point-of-care ultrasonography (POCUS) is a portable imaging technology used in clinical settings. There is a need for valid tools to assess clinical competency in POCUS in medical students. The primary aim of this study was to use Kane's framework to evaluate an interpretation-use argument (IUA) for an undergraduate POCUS assessment tool. METHODS: Participants from Memorial University of Newfoundland, the University of Calgary, and the University of Ottawa were recruited between 2014 and 2018. A total of 86 participants and seven expert raters were recruited. The participants performed abdominal, sub-xiphoid cardiac, and aorta POCUS scans on a volunteer patient after watching an instruction video. The participant-generated POCUS images were assessed by the raters using a checklist and a global rating scale. Kane's framework was used to determine validity evidence for the scoring inference. Fleiss' kappa was used to measure agreement between seven raters on five questions that reflected clinical competence. The descriptive comments collected from the raters were systematically coded and analyzed. RESULTS: The overall agreement between the seven raters on five questions on clinical competency ranged from fair to moderate (κ = 0.32 to 0.55). The themes from the qualitative data were poor image generation and interpretation (22%), items not applicable (20%), poor audio and video quality (20%), poor probe handling (10%), and participant did not verbalize findings (14%). CONCLUSION: The POCUS assessment tool requires further modification and testing prior before it can be used for reliable undergraduate POCUS assessment.

Characteristics of Potential and Actual Living Kidney Donors: A Single-center Experience.

BACKGROUND: There are limited data and no national capture of barriers associated with initiating and completing the donation process for potential living kidney donors (LKDs). METHODS: We performed a retrospective analysis of 3001 intake forms completed by prospective LKDs from 2016 to 2019 at a single transplant center. We analyzed data from all potential donors who completed the intake until they became ineligible or withdrew or donation was complete. We used univariate and multivariate models to evaluate independent factors associated with donation at various stages in the donation process. RESULTS: The donation process was deconstructed into 5 steps: intake form, immunologic compatibility testing, clinic evaluation, selection committee review, and donation. The highest percentage of potential donors dropped out after completing the intake form, primarily because of not responding to the follow-up phone call (22.6%). Of 455 potential LKDs that completed immunologic compatibility testing, 36% were ABO or crossmatch incompatible. One-hundred eighty-eight (7.5%) of all LKD applicants reached donation, the majority of whom were White (91.0%) and female (63.8%). CONCLUSIONS: A minority of LKD applicants make it to donation. Our ability to track all potential LKDs from the initial touch point to the transplant center will help us develop interventions to address barriers to a successful donation.

Self-reported marijuana use and its effects on overall approval in potential living kidney donors.

BACKGROUND: Past and present substance use is an important part of the psychosocial evaluation of potential living kidney donors (LKDs). Increasing state legalizations and social acceptance of marijuana (MJ) use can create challenges for transplant centers. METHODS: We investigated the frequency of reporting MJ use, and its effect on the LKD evaluation. A retrospective chart review was performed on all living donor candidates from December 2016 to December 2019 for reports of MJ use, both on an electronic intake form and during clinical evaluation with a licensed social worker (SW). Active MJ use was defined as current use or use within 1 year of evaluation. Baseline characteristics between MJ users and non-users were compared at each step of donor evaluation. We explored variables associated with MJ use including additional consults and testing during the donor evaluation. Overall approval and donation rates for living donors with active MJ use were compared to non-users. Additionally, 1-year donor follow-up was compared between the two groups. Results of 1818 living donor candidates who completed the intake form, 132 admitted to active MJ use. Compared to non-users, MJ users were more likely to be younger, male, single, renting a home, and with a lower level of education. Thirty three out of 338 candidates who completed a social work evaluation reported MJ use. Compared to non-users, MJ users were more frequently classified as moderate or high risk on SW evaluation, and often required a toxicology screen or psychiatry visit for clearance to donate. Altogether 24.2% of MJ users versus 9.5% of non-users discontinued their evaluation (p < .01). Altogether 42.4% of MJ users versus 56.1% of non-users donated their kidney (p = .13). For those who donated, MJ users were less likely than non-users to follow up at 1 year (57.1% vs. 83.0, p-value .02). CONCLUSION: MJ users were often asked to complete additional steps in their evaluation before an approval decision was made, which may have led to the higher rate of donor drop out observed in this group. Further research is needed to assess the effects of MJ use on living donor candidacy, as well as any effects of MJ use on long-term donor outcomes.

Donor-Derived Renal Cell Carcinoma in a Kidney Allograft: A Case Report.

Renal cell carcinoma (RCC) in the kidney allograft is a relatively rare complication most commonly seen approximately a decade or more after transplant. We report a case of diffuse multifocal RCC within 6 months of transplant. The initial signal leading to an abnormality in the graft was an elevated routine cell-free DNA. Initial imaging findings appeared consistent with post-transplant lymphoproliferative disorder; however, biopsy would ultimately yield RCC. The patient's diffuse disease necessitated radical nephrectomy. Tumor DNA fingerprinting was employed in this case to show the tumor originated from donor tissue rather than host, indicating primary rather than metastatic disease. Early RCC is a rare complication. Most cases are detected at an early stage, likely as a result of increased surveillance with ultrasound imaging. A donor's social history including significant tobacco use should be considered when evaluating the risk of malignancy transmission in the allograft. Clinicians should be aware of multifocal RCC as a potential differential diagnosis for diffuse nodular infiltrates in the allograft.

Automated Segmentation of Kidney Cortex and Medulla in CT Images: A Multisite Evaluation Study.

BACKGROUND: In kidney transplantation, a contrast CT scan is obtained in the donor candidate to detect subclinical pathology in the kidney. Recent work from the Aging Kidney Anatomy study has characterized kidney, cortex, and medulla volumes using a manual image-processing tool. However, this technique is time consuming and impractical for clinical care, and thus, these measurements are not obtained during donor evaluations. This study proposes a fully automated segmentation approach for measuring kidney, cortex, and medulla volumes. METHODS: A total of 1930 contrast-enhanced CT exams with reference standard manual segmentations from one institution were used to develop the algorithm. A convolutional neural network model was trained (n=1238) and validated (n=306), and then evaluated in a hold-out test set of reference standard segmentations (n=386). After the initial evaluation, the algorithm was further tested on datasets originating from two external sites (n=1226). RESULTS: The automated model was found to perform on par with manual segmentation, with errors similar to interobserver variability with manual segmentation. Compared with the reference standard, the automated approach achieved a Dice similarity metric of 0.94 (right cortex), 0.90 (right medulla), 0.94 (left cortex), and 0.90 (left medulla) in the test set. Similar performance was observed when the algorithm was applied on the two external datasets. CONCLUSIONS: A fully automated approach for measuring cortex and medullary volumes in CT images of the kidneys has been established. This method may prove useful for a wide range of clinical applications.

The Effect of Reactive Balance Training on Falls in Daily Life: An Updated Systematic Review and Meta-Analysis.

OBJECTIVE: Reactive balance training (RBT) is an emerging approach to reducing falls risk in people with balance impairments. The purpose of this study was to determine the effect of RBT on falls in daily life among individuals at increased risk of falls and to document associated adverse events. METHODS: Databases searched were Ovid MEDLINE (1946 to March 2022), Embase Classic and Embase (1947 to March 2022), Cochrane Central Register of Controlled Trials (2014 to March 2022), and Physiotherapy Evidence Database (PEDro; searched on 22 March 2022). Randomized controlled trials of RBT were included. The literature search was limited to the English language. Records were screened by 2 investigators separately. Outcome measures were number of participants who reported falls after training, number of falls reported after training, and the nature, frequency, and severity of adverse events. Authors of included studies were contacted to obtain additional information. RESULTS: Twenty-nine trials were included, of which 17 reported falls and 21 monitored adverse events. Participants assigned to RBT groups were less likely to fall compared with control groups (fall risk ratio = 0.76; 95% CI = 0.63-0.92; I2 = 32%) and reported fewer falls than control groups (rate ratio = 0.61; 95% CI = 0.45-0.83; I2 = 81%). Prevalence of adverse events was higher in RBT (29%) compared with control groups (20%). CONCLUSION: RBT reduced the likelihood of falls in daily life for older adults and people with balance impairments. More adverse events were reported in RBT than control groups. IMPACT: Balance training that evokes balance reactions can reduce falls among people at increased risk of falls. Older adults and individuals with balance problems were less likely to fall in daily life after participating in RBT compared with traditional balance training. LAY SUMMARY: If you are an older adult and/or have balance problems, your physical therapist may prescribe reactive balance training rather than traditional balance training in order to reduce your likelihood of falling in daily life.

The prevalence and patterns of use of point-of-care ultrasound in Newfoundland and Labrador.

INTRODUCTION: Point-of-care ultrasound (POCUS) is used for diagnostic and procedural guidance by physicians in Newfoundland and Labrador (NL). POCUS use is largely limited to urban locations and the training is variable amongst physicians. The primary aim of this study was to determine the prevalence of POCUS devices in NL and the secondary aim was to characterise the patterns of POCUS use amongst physicians in NL. METHODS: This is a mixed-methods cross-sectional study. We determined the prevalence of POCUS devices from purchase records and the patterns of POCUS use through theme-based interviews. The interviews were transcribed, coded and analysed using standardised qualitative methods. RESULTS: Ten physicians (3 females, 5 rural) participated in the interviews. The overall prevalence of POCUS devices in NL was 12.5/100,000 population. Participants in urban areas had more access to POCUS training and devices. Participants used POCUS on a daily or weekly basis to rule in or out life-threatening conditions and improve access to specialist care. The benefits of POCUS included expedited investigations, decreased radiation and increased patient satisfaction. The barriers to using POCUS were lack of training, time, devices, image archiving software, difficulty generating and interpreting images and patient body habitus. CONCLUSION: This is the first study to our knowledge to report the prevalence of POCUS devices in Canada. Physicians who practise in rural NL have limited access to POCUS devices and have identified barriers to POCUS training. Connecting physicians in rural areas with POCUS experts through a province-wide POCUS network may address these barriers and improve healthcare access.

Résumé Introduction: L'échographie ciblée est utilisée par les médecins de Terre-Neuve-et-Labrador (T.-N.-L.) pour guider le diagnostic et certaines interventions. L'échographie ciblée est grandement limitée aux régions urbaines et la formation des médecins sur son utilisation est variable. Cette étude visait en premier lieu à déterminer la prévalence des appareils d'échographie ciblée à T.-N.-L. et en deuxième lieu, à caractériser les habitudes d'utilisation de l'échographie ciblée chez les médecins de T.-N.-L. Méthodes: Il s'agit d'une étude transversale à méthodes mixtes. Nous avons déterminé la prévalence des appareils d'échographie ciblée à partir de registres d'achat, et les habitudes d'utilisation de l'échographie ciblée à partir d'entrevues thématiques. Dix médecins (3 de sexe féminin, 5 de régions rurales) ont participé aux entrevues. Les entrevues ont été transcrites, codées et analysées à l'aide de méthodes qualitatives standardisées. Résultats: La prévalence générale des appareils d'échographie ciblée à T.-N.-L. était de 12.5/100 000 populations. Les participants des régions urbaines avaient un meilleur accès à la formation sur l'échographie ciblée et aux appareils. Les participants utilisaient l'échographie ciblée tous les jours ou toutes les semaines pour inclure ou éliminer les affections potentiellement mortelles et améliorer l'accès aux spécialistes. Les bienfaits de l'échographie ciblée étaient l'accélération des examens, la réduction des rayonnements et une meilleure satisfaction des patients. Les obstacles à l'échographie ciblée étaient l'absence de formation, de temps, d'appareils et de logiciel d'archivage des images, la difficulté à générer et à interpréter les images, et les caractéristiques physionomiques du patient. Conclusion: À notre connaissance, il s'agit de la première étude à avoir rapporté la prévalence des appareils d'échographie ciblée au Canada. Les médecins qui pratiquent dans les régions rurales de T.-N.-L. ont un accès limité aux appareils d'échographie ciblée et ont identifié des obstacles à la formation sur l'échographie ciblée. Pour faire tomber ces obstacles et améliorer l'accès aux soins de santé, il serait utile de relier les médecins des régions rurales à des spécialistes d'échographie ciblée dans un réseau provincial d'échographie ciblée. Mots-clés: Échographie, examen ciblé, services de santé ruraux, formation médicale continue, cadre de compétences.

Beyond the Biopsy: Monitoring Immune Status in Kidney Recipients.

Improved 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.

Rural family physician perspectives on communication with urban specialists: a qualitative study.

OBJECTIVE: Communication is a key competency for medical education and comprehensive patient care. In rural environments, communication between rural family physicians and urban specialists is an essential pathway for clinical decision making. The aim of this study was to explore rural physicians' perspectives on communication with urban specialists during consultations and referrals. SETTING: Newfoundland and Labrador, Canada. PARTICIPANTS: This qualitative study involved semistructured, one-on-one interviews with rural family physicians (n=11) with varied career stages, geographical regions, and community sizes. RESULTS: Four themes specific to communication in rural practice were identified. The themes included: (1) understanding the contexts of rural care; (2) geographical isolation and patient transfer; and (3) respectful discourse; and (4) overcoming communication challenges in referrals and consultations. CONCLUSIONS: Communication between rural family physicians and urban specialists is a critical task in providing care for rural patients. Rural physicians see value in conveying unique aspects of rural clinical practice during communication with urban specialists, including context and the complexities of patient transfers.

Fitness Shifts the Balance of BDNF and IL-6 from Inflammation to Repair among People with Progressive Multiple Sclerosis.

Physical sedentarism is linked to elevated levels of circulating cytokines, whereas exercise upregulates growth-promoting proteins such as brain-derived neurotrophic factor (BDNF). The shift towards a 'repair' phenotype could protect against neurodegeneration, especially in diseases such as multiple sclerosis (MS). We investigated whether having higher fitness or participating in an acute bout of maximal exercise would shift the balance of BDNF and interleukin-6 (IL-6) in serum samples of people with progressive MS (n = 14), compared to matched controls (n = 8). Participants performed a maximal graded exercise test on a recumbent stepper, and blood samples were collected at rest and after the test. We assessed walking speed, fatigue, and maximal oxygen consumption (V·O2max). People with MS achieved about 50% lower V·O2max (p = 0.003) than controls. At rest, there were no differences in BDNF between MS and controls; however, IL-6 was significantly higher in MS. Higher V·O2max was associated with a shift in BDNF/IL-6 ratio from inflammation to repair (R = 0.7, p = 0.001) when considering both groups together. In the MS group, greater ability to upregulate BDNF was associated with faster walking speed and lower vitality. We present evidence that higher fitness indicates a shift in the balance of blood biomarkers towards a repair phenotype in progressive MS.

Renal function outcomes and kidney biopsy features of living kidney donors with hypertension.

BACKGROUND: The medium- to long-term outcomes of living kidney donors with hypertension compared to normotensive donors are not well understood, especially with the recent changes in hypertension guidelines. METHODS: We studied a cohort of 950 living kidney donors using different definitions of hypertension based on either ≥140/90 or ≥130/80 mmHg thresholds and based on either office or ambulatory blood pressure readings. Microstructural features on kidney biopsy at the time of donation were compared using different definitions of hypertension. RESULTS: After adjusting for years of follow-up, age, sex, and baseline eGFR, hypertension (by any definition) did not significantly predict an eGFR < 45 ml/min/1.73 m2 at a median follow-up of 10 years postdonation, though there was a borderline association with ambulatory blood pressure ≥ 130/80 mmHg predicting a 40% decline in eGFR (OR = 1.53, 1.00-2.36; p = .051). Proteinuria was predicted by office blood pressure ≥ 140/90 mmHg and by nondipper profile on nocturnal ambulatory blood pressure measurements. At the time of donation, larger glomeruli and arterial hyalinosis on biopsy were associated with hypertension defined by either ≥140/90 or ≥130/80 mmHg (by office or ambulatory measurements). Nocturnal nondipper status was associated with larger glomeruli size but not arteriolar hyalinosis when compared to dippers. CONCLUSIONS: In programs that accept donors with controlled hypertension, various definitions of hypertension are associated with histological findings in the donated kidney, but none predict a clinically significant decline in kidney function 10 years after donation. These data support allowing healthy individuals with controlled hypertension to donate a kidney. However, donors with office hypertension (≥140/90 mmHg) and nondippers (regardless of hypertension status) are at greater long-term risk for proteinuria, and particularly for these donors, longer follow-up is warranted.

Failure to Advance Access to Kidney Transplantation over Two Decades in the United States.

BACKGROUND: Extensive research and policies have been developed to improve access to kidney transplantation among patients with ESKD. Despite this, wide variation in transplant referral rates exists between dialysis facilities. METHODS: To evaluate the longitudinal pattern of access to kidney transplantation over the past two decades, we conducted a retrospective cohort study of adult patients with ESKD initiating ESKD or placed on a transplant waiting list from 1997 to 2016 in the United States Renal Data System. We used cumulative incidence models accounting for competing risks and multivariable Cox models to evaluate time to waiting list placement or transplantation (WLT) from ESKD onset. RESULTS: Among the study population of 1,309,998 adult patients, cumulative 4-year WLT was 29.7%, which was unchanged over five eras. Preemptive WLT (prior to dialysis) increased by era (5.2% in 1997-2000 to 9.8% in 2013-2016), as did 4-year WLT incidence among patients aged 60-70 (13.4% in 1997-2000 to 19.8% in 2013-2016). Four-year WLT incidence diminished among patients aged 18-39 (55.8%-48.8%). Incidence of WLT was substantially lower among patients in lower-income communities, with no improvement over time. Likelihood of WLT after dialysis significantly declined over time (adjusted hazard ratio, 0.80; 95% confidence interval, 0.79 to 0.82) in 2013-2016 relative to 1997-2000. CONCLUSIONS: Despite wide recognition, policy reforms, and extensive research, rates of WLT following ESKD onset did not seem to improve in more than two decades and were consistently reduced among vulnerable populations. Improving access to transplantation may require more substantial interventions.

Effects of body mass index on kidney transplant outcomes are significantly modified by patient characteristics.

Body mass index (BMI) is a known risk factor associated with kidney transplant outcomes and is incorporated for determining transplant candidate eligibility. However, BMI is a coarse health measure and risks associated with BMI may vary by patient characteristics. We evaluated 296 807 adult (age > 17) solitary kidney transplant recipients from the Scientific Registry of Transplant Recipients (2000-2019). We examined effects of BMI using survival models and tested interactions with recipient characteristics. Overall, BMI demonstrated a "J-Shaped" risk profile with elevated risks for overall graft loss with low BMI and obesity. However, multivariable models indicated interactions between BMI with recipient age, diagnosis, gender, and race/ethnicity. Low BMI was relatively higher risk for older recipients (>60 years), people with type I diabetes, and males and demonstrated no additional risk among younger (18-39) and Hispanic recipients. High BMI was associated with elevated risk for Caucasians and attenuated risk among African Americans and people with type II diabetes. Effects of BMI had variable risks for mortality vs graft loss by recipient characteristics in competing risks models. The association of BMI with posttransplant outcomes is highly variable among kidney transplant recipients. Results are important considerations for personalized care and risk stratification. Findings suggest that transplant contraindications should not be based on absolute BMI thresholds but modified based on patient characteristics.