Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:The 2023 CONVINCE trial demonstrated improved survival with high-dose hemodiafiltration (HDF), prompting discussions about widespread adoption. However, this clinical advancement occurs amid growing awareness of healthcare's environmental impact, particularly dialysis treatments that consume extensive water and energy resources. This review examines the environmental implications of HDF adoption, synthesizing recent evidence on resource consumption and emerging sustainability solutions in the context of the climate crisis facing nephrology. RECENT FINDINGS/RESULTS:Life cycle assessments indicate HDF has a carbon footprint 30-40% higher than conventional hemodialysis, consuming an additional 10 300 L of water per patient annually. However, recent technological innovations show promise: expanded hemodialysis (HDx) using medium cut-off membranes reduces water usage by >20% and energy consumption by >30% compared to HDF while potentially achieving similar clinical outcomes. Water conservation technologies, including reverse osmosis, reject water reuse and reduced dialysate flow protocols, can decrease environmental impact by 30-50% without any difference in patient outcomes. SUMMARY/CONCLUSIONS:The adoption of HDF represents a critical test case for sustainable healthcare innovation. While the potential benefits should not be ignored, technology is not static and, if confirmed, additional sustainability work and comprehensive policy frameworks integrating environmental impact assessments into technology evaluation are urgently needed. The nephrology community must balance clinical excellence with planetary stewardship through technological innovation, resource optimization, and evidence-based environmental guidelines that benefit, not compromise, patient care.

PURPOSE OF REVIEW/OBJECTIVE:This review provides a comprehensive examination of the current inequities and ethical challenges in kidney transplantation and highlights some of the most urgent issues related to organ allocation and emerging technologies. RECENT FINDINGS/RESULTS:Several recent news and media reports have significantly undermined public trust in the organ transplantation and allocation process. This review discusses some of these controversies and proposes strategies to restore confidence in the system. With advancements in gene editing, xenotransplantation is becoming a tangible reality, bringing forth new ethical challenges explored in this paper. Likewise, as artificial intelligence continues to permeate medicine and moves closer to integration within transplantation, proactive preparation and ethical foresight are essential. SUMMARY/CONCLUSIONS:In conclusion, we aim to draw attention to pressing ethical dilemmas in kidney transplantation and suggest actionable steps to restore trust.

BACKGROUND:People on hemodialysis (HD) often report lower quality of life (QoL) compared to people not on HD. People with kidney disease have a high prevalence of health-related social needs (HRSN). The association of HRSN and QoL in people on HD remains understudied. Though some groups of patients treated with HD tend to have lower QoL, there exists minimal research investigating the mechanism by which this occurs. METHODS:We surveyed people receiving HD at five urban dialysis units using the Kidney Disease Quality of Life (KDQOL) and the Accountable Health Communities Health-Related Social Needs Screening Tool (AHC-HRSN) to assess their housing, food, transportation, utilities, and perceived safety. We calculated physical and mental component scores as well as sub scores measuring burden, symptoms, and effect of kidney disease. We analyzed scores using Python packages. We used the Shapiro-Wilk test to assess normality. For analysis we used the Wilcoxon Rank Sum test and univariate, multivariate, and LASSO regressions. RESULTS:A total of 324 patients participated in the study. HRSN was common with 56% of participants reporting at least one HRSN. Food insecurity (35%) and housing instability (24%) was most common. All QoL sub scores were significantly lower in patients who had at least one HRSN. In regression models, housing and transportation insecurity most frequently emerged as significant variables associated with lower QoL sub scores even after adjusting for patient demographics. Burden scores showed the largest effect sizes (housing instability β=-17.90, P<0.001, transportation problems β=-14.03, P=0.001). CONCLUSION/CONCLUSIONS:HRSN is significantly associated with lower QoL scores, with largest effect sizes seen with housing instability and transportation problems. Increased screening and intervention for HRSN may improve QoL among people on HD.

INTRODUCTION/UNASSIGNED:Membranous nephropathy (MN) is a common cause of nephrotic syndrome usually diagnosed using kidney biopsy. METHODS/UNASSIGNED:= 132). RESULTS/UNASSIGNED:In BKBC, 2 proteins, testican-2 and alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase (MGT5A), were associated with MN when compared with the reference diagnosis (normal or thin basement membrane [TBM] disease) as well as when compared with all other diagnoses among individuals who had undergone kidney biopsy for the indication of proteinuria or nephrotic syndrome. In NEPTUNE, plasma levels of both proteins, as well as glomerular expression of their cognate genes, were increased in MN compared with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). In receiver operating characteristic curve analyses, the addition of plasma testican-2 and MGT5A levels significantly improved discrimination of MN from other diagnoses in BKBC and NEPTUNE compared with models incorporating age, sex, race, estimated glomerular filtration rate (eGFR), and proteinuria. CONCLUSION/UNASSIGNED:Together, these findings motivate interest in testican-2 and MGT5A as markers and potential functional participants in MN. More work is required to understand the biological role of these proteins in the glomerular basement membrane in relation to immune complex deposition as well as to assess their performance as biomarkers alongside circulating autoantibodies in patients with MN.

BACKGROUND/UNASSIGNED:Kidney transplant recipients are at risk for adverse health outcomes. Digital health tools such as wearable accelerometers and continuous glucose monitors (CGMs) can provide detailed, noninvasive tracking of health behaviors and measures, such as physical activity, sleep, and glucose levels, that may offer insights into future health concerns, such as posttransplant diabetes mellitus, cognitive health, and transplant rejection. However, there is limited evidence on the feasibility and acceptability of these devices in kidney transplant candidates older than 50 y. METHODS/UNASSIGNED:This observational cross-sectional pilot study aimed to examine the feasibility of 2 digital health tools: an accelerometer and a continuous glucose monitor. Participants were eligible for the study if they were living donor kidney transplant candidates, aged 50 y or older, had no known cognitive impairments, and could provide informed consent. Participants were asked to wear a CGM and an accelerometer for up to 14 d before their kidney transplant surgery. Device feasibility was quantified by (1) the total time the devices were worn, and (2) the validated System Usability Scale survey administered after the devices were returned. RESULTS/UNASSIGNED:20 participants enrolled in the study (mean age 64 ± 9 y, 25% women, 40% with type 2 diabetes). The median number of days of accelerometer and CGM wear were 7 (interquartile range, 6-10) d and 7 (interquartile range, 7-10) d, respectively. Ninety percent of participants reported a favorable opinion of both devices. Participants wore the CGM 100% of the time and the accelerometer 90% of the time, indicating high adherence. CONCLUSIONS/UNASSIGNED:The use of digital devices was acceptable among kidney transplant candidates aged older than 50 y, paving the way for larger studies to identify early digital biomarkers of health outcomes in this high-risk population.

RATIONALE & OBJECTIVE/OBJECTIVE:Adults receiving maintenance hemodialysis (HD) frequently report pain, yet detailed descriptions of pain in this population are lacking. This study examines pain locations, characteristics, and associations with other symptoms in adults receiving HD. STUDY DESIGN/METHODS:Cross-sectional analysis. SETTING & PARTICIPANTS/METHODS:Adults with moderate to severe chronic pain receiving maintenance HD enrolled in the multicenter HOPE Consortium Trial from 2021 to 2023. EXPOSURES/METHODS:Sociodemographic, pain treatment, dialysis, medical comorbidity, and psychological and behavioral characteristics. Other patient-reported symptoms. OUTCOME/RESULTS:Pain interference and severity as assessed by the Brief Pain Inventory (BPI) Interference and Severity subscales (range 0-10). ANALYTICAL APPROACH/METHODS:Multivariable regression with LASSO to examine associations between participant characteristics and pain interference/severity, and Spearman's correlation to examine relationships between other symptoms and pain interference/severity at baseline. RESULTS:Among 643 participants, the median (IQR) BPI interference was 6.6 (5.1-7.9) and severity was 6.0 (4.5-7.5). 84% of participants reported pain >1 year and 75% had daily pain. 89% and 66% of participants endorsed musculoskeletal and neuropathic pain, respectively. Of 32 body regions, the median (IQR) number of painful regions was 8 (4-14). C ommon regions in females were lower back (72%), knees (64%), legs (60%), and upper back (59%). A similar pattern existed for males. In LASSO analyses, cardiovascular disease and depression were associated with significantly higher pain interference whereas White race (ref: Black race) and non-Hispanic ethnicity were associated with significantly lower pain interference. Similar findings were noted for pain severity. Pain catastrophizing and symptoms of fatigue, depression, and anxiety were moderately correlated with pain interference (r>0.4). LIMITATIONS/CONCLUSIONS:Neither relationship directionality nor causality can be inferred. CONCLUSIONS:Among adults treated with HD who have chronic pain, pain locations were numerous and diverse, with substantial musculoskeletal and neuropathic characteristics. Factors associated with pain interference were predominantly sociodemographic and psychological rather than those related to comorbid diseases and dialysis.

BACKGROUND/UNASSIGNED:To investigate the proteomic signatures of heart failure (HF) in diabetes. The underlying mechanisms of the elevated risk of HF in diabetes are unknown. METHODS/UNASSIGNED:In 10 189 ARIC study (Atherosclerosis Risk in Communities) participants free of HF (mean age 57±7 years, 56% women, 22% Black adults, 14% with diabetes), we conducted discovery and internal validation for the associations of 4955 plasma proteins with HF by diabetes status. We performed (1) Cox regression to identify proteins associated with HF by diabetes status, (2) external validation in the MESA study (Multi-Ethnic Study of Atherosclerosis, n=5233, 633 with diabetes), and (3) pathway analyses for identified proteins. RESULTS/UNASSIGNED:<0.05/19). Six of the internally validated proteins replicated in MESA (false discovery rate, q<0.05). Five proteins were specifically associated with HF in those with diabetes: 4 are novel (inactive tyrosine-protein kinase 7, chondroadherin, leucine-rich repeat, and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 and fibulin-5) and 1 is the previously known (cartilage intermediate layer protein 2). NPPB (N-terminal pro-BNP) was associated with HF in those with and without diabetes. Pathways over-represented among proteins associated with diabetes-related HF were lipid metabolism, inflammation, and brown adipose tissue (false discovery rate, q<0.05). CONCLUSIONS/UNASSIGNED:We identified 5 proteomic markers (4 novel) uniquely related to HF risk among individuals with diabetes and not among those without diabetes.

BACKGROUND:Biofluid proteomics can enhance our understanding of the neurodegenerative mechanisms underlying Alzheimer's disease and related dementias (ADRDs). Oligodendrocyte myelin glycoprotein (OMG) is a brain-specific protein implicated in myelination, but its potential mechanistic, biomarker, and therapeutic roles in ADRDs requires further elucidation. METHODS:After detecting an inverse association between its abundance in peripheral circulation and cortical amyloid deposition in two community-based cohorts, the current study characterized OMG's role in ADRDs with high-throughput proteomics from sixteen independent cohorts. Data included a variety of cross-sectional and longitudinal community-based and clinical cohorts from North America, Europe, and Asia, and incorporated complementary biofluids, biospecimens, and proteomic platforms. Statistical analyses were conducted separately in each cohort. RESULTS:We detected lower plasma OMG in individuals with cortical amyloid deposition, compromised brain structure, dementia, and multiple sclerosis, as well as in individuals who developed dementia over 7- to 20-year follow-up periods. OMG's CSF and brain proteomic signatures reflected broader neuroprotective mechanisms, especially axonal structural integrity, and two-sample Mendelian randomization causally implicated OMG as protective against multiple neurodegenerative diseases. CONCLUSIONS:Our findings implicate OMG as a mechanistic determinant of neurodegenerative resiliency among older adults, which is reliably captured by its abundance in peripheral circulation.

Globally, the prevalence of chronic kidney disease is estimated to be approximately 850 million cases, with approximately 4 million individuals needing kidney replacement therapy for kidney failure. By 2050, chronic kidney disease is projected to become the fifth leading underlying cause of death worldwide. Despite its numerous causes, chronic kidney disease can be screened for, diagnosed, and staged with simple laboratory tests. Individuals with chronic kidney disease are at increased risk of kidney failure and many other health implications. Risk of premature cardiovascular disease is particularly noteworthy, as most patients with chronic kidney disease develop a disability or die from cardiovascular disease before ever progressing to kidney failure. Since 2019, large randomised trials have identified several effective treatments that both slow progressive kidney function decline and reduce cardiovascular risk, greatly expanding available treatments for chronic kidney disease. The wide range of complications associated with chronic kidney disease means that patients encounter many different specialties. Active engagement in chronic kidney disease identification and timely initiation of cost-effective interventions by all clinicians could now substantially reduce the global burden of complications of chronic kidney disease and kidney failure.

BACKGROUND:Preeclampsia, a systemic hypertensive disorder of pregnancy, has been associated with the risk of kidney failure, an outcome that may take decades to develop. However, its association with early kidney disease, which could be targeted for intervention, remains underexplored. Here we quantified the risk of chronic kidney disease (CKD), defined by laboratory markers of kidney damage, in women who had a pregnancy complicated by preeclampsia versus a pregnancy without preeclampsia. METHODS:Population-based cohort study in Stockholm, Sweden, using inverse probability of treatment weights to minimize confounding. All nulliparous women who had at least one pregnancy ending in live or stillbirth between January 1, 2006, and December 31, 2020 were identified, excluding pre-existing hypertension, diabetes or CKD. Primary outcomes were (1) albuminuria defined by urine albumin to creatinine ratio >300mg/g; (2) estimated Glomerular Filtration Rate (eGFR)<60ml/min/1.73m2; and (3) composite of albuminuria>300mg/g and/or eGFR<60ml/min/1.73m2. RESULTS:The study included 171,693 pregnancies (170 192 women: mean [SD] age, 29[5] years), of whom 10,538 (6%) had at least one pregnancy complicated by preeclampsia. During median follow up of 7.0 years (IQR, 3.3-10.5), albuminuria >300mg/g occurred after 775 pregnancies (0.5%), eGFR <60ml/min/1.73m2 occurred after 248 pregnancies (0.1%), and the composite outcome occurred after 985 pregnancies (0.6%). Incidence rates per 1,000 person-years were higher after preeclampsia vs no preeclampsia for albuminuria>300mg/g (1.53 vs 0.57), eGFR<60ml/min/1.73m2 (0.52 vs 0.18), and the composite outcome (2.00 vs 0.73). Weighted hazard ratios were 2.53 (95% CI, 2.04-3.13) for albuminuria>300mg/g, 2.18 (95% CI, 1.49-3.19) for eGFR<60 mL/min/1.73 m2, and 2.43 (95% CI, 2.01-2.95) for the composite outcome. In the first postpartum year, 2080 (20%) and 1043 (10%) of women with preeclampsia had serum creatinine or urine albumin testing, respectively. CONCLUSIONS:Preeclampsia is associated with higher risk of laboratory signs of early kidney damage. There were low rates of postpartum kidney function monitoring.