Rationale & Objective Haemodialysis is a resource intensive treatment associated with high environmental impact. This study aimed to quantify the environmental burden of haemodialysis procurement and waste and identify key contributors to emissions, energy use and water consumption. Study Design Life cycle assessment study. Setting & Participants Data were collected from the Nephrology Dialysis and Kidney Transplant Unit at the University Hospital Policlinico of Modena, Italy. The analysis reflects one patient year of haemodialysis treatment. Exposure(s) or Predictor(s) Procurement and lifecycle of haemodialysis consumables and equipment. Outcome(s) Greenhouse gas emissions (kg CO2-eq), primary energy demand (MJ) and water use (m3). Analytical Approach A life cycle assessment was conducted in accordance with ISO 14040/14044 standards using OpenLCA software and the Ecoinvent database. Ten key haemodialysis products were analysed across all lifecycle stages from raw material extraction to disposal. Results The dialyser and bicarbonate cartridge were the largest contributors, together accounting for approximately 70% of total carbon emissions. Additional impacts arose from saline solution, blood tubing and dialysate bags. Plastic production, transport, and waste incineration were key drivers of environmental burden. Electricity use from haemodialysis machine operation also contributed substantially to total energy demand. Limitations This study was based on data from a single centre and relied on life cycle databases that may not fully capture variability in manufacturing and disposal processes. Some consumables and clinical variations were not included. Conclusions Haemodialysis procurement is a major source of environmental impact, largely driven by a small number of high-impact consumables. Targeted strategies including product redesign, reduction of single-use materials, and improved waste management may reduce the environmental footprint of dialysis care.
Chronic kidney disease (CKD) is a major public health problem associated with cardiovascular disease, kidney failure, and mortality. With population aging and rising prevalence of diabetes and hypertension, scalable risk-prediction methods are needed to address the growing CKD burden. We conducted a scoping review assessing machine learning (ML) models published between 2014–2025 predicting incidence and progression of CKD. We identified 28 ML studies predicting CKD incidence (n=6) and progression (n=22). Common algorithms included extreme gradient boosting, random forests, decision trees, logistic regression, and elastic net, with reported area under the curve (AUC) values ranging from 0.75-0.96. Most studies originated from high-income countries and relied on internal validation, while only two performed external validation and advanced toward clinical use. Key limitations included small samples, imbalanced data, limited explainability, and clinical integration challenges. Overall, ML shows strong potential for CKD risk-stratification and prediction, but broader validation and prospective evaluation are needed.
Rationale & Objective:Risk factors for adverse outcomes after first transplant have been established, but less is known about predictors of risk at the time of retransplant, including the impact of first transplant characteristics. Therefore, in this study, we aimed to examine how first transplant factors may affect subsequent transplant. Study Design:Retrospective cohort study. Setting & Participants:We analyzed data from adult patients in the United States (Scientific Registry of Transplant Recipients) who underwent second kidney transplant (2000-2017). Exposure:First transplant characteristics (age, human leukocyte antigen match, panel-reactive antibody [PRA], first transplant graft survival time, and time from failure of first transplant). Outcome:Death-censored graft loss (DCGL) after repeat transplant. Analytical Approach:Multivariable Cox proportional hazard models. Results:This study included 23,688 patients who underwent repeat transplant. DCGL risk was increased for patients with higher PRA at first transplant (adjusted HR [aHR], 1.16; 95% CI, 1.00-1.34 for PRA >80% vs <20%) and decreased for recipients aged 18-30 years at first transplant (aHR, 0.87; 95% CI 0.76-0.99 vs <18 years). Compared with preemptive retransplant, patients requiring a short duration of dialysis after the first transplant failed (<1 month) had the highest risk of DCGL (aHR, 2.36; 95% CI, 2.06-2.71). First transplant survival time was also associated with risk of DCGL (aHR, 0.56 [95% CI, 0.48-0.65] for <1 month; aHR, 0.90 [95% CI, 0.80-1.02] for 1-3 years; aHR, 0.70 [95% CI, 0.62-0.78] for 3-7 years; aHR, 0.50 [95% CI, 0.44-0.57] for >7 years [relative to survival time 1 month-1 year]). Human leukocyte antigen mismatch at first transplant was not significantly associated with DCGL at retransplant. Limitations:Potential for selection bias; patients who died before retransplant or became ineligible for repeat transplant were excluded. Conclusions:First transplant PRA >80%, age 18-30 years, time between a first transplant failing and retransplant, and first transplant survival duration are significantly associated with DCGL at kidney retransplantation.
Rationale & Objective:Symptom burden is distressing for patients living with kidney failure, but there is limited information about the combination of symptoms and individual symptoms that most strongly predict health care use in this group. We classified and summarized patients' symptom burden levels and changes over time and estimated associations with hospitalizations among patients receiving incident hemodialysis. Study Design:Longitudinal, observational. Setting & Participants:Individuals initiating dialysis in the United States. Exposure:Kidney Disease Quality of Life-36 (KDQOL-36) measure. Outcome:First hospitalization after dialysis initiation. Analytical Approach:Latent transition analysis was used to identify symptom burden classes using the KDQOL-36. Cox regression models were used to assess whether individual KDQOL-36 symptoms and symptom burden groups were associated with hospitalization risk after dialysis initiation, independent of demographics and comorbid conditions. Results:1,818 participants were Black (29%), were aged >65 years (59%), were women (42%), had diabetes (49%), and had hypertension (74%). Latent transition analysis identified the following 3 symptom burden groups: (1) low (low severity of all symptoms and kidney disease impacts), (2) moderate (high physical health impact and overall burden of kidney disease), and (3) high (high levels of all symptoms and kidney disease impact). After adjusting for patient characteristics, all KDQOL-36 scales except the Effects of Kidney Disease scale were associated with a higher hazard of hospitalization. Using the symptom burden groups, a high symptom burden was associated with a 20% increase in the hazard of hospitalization. A 1-category worsening in pain interference and in fatigue was associated with a 12% and an 8% increased hazard of hospitalization, respectively. Limitations:Findings may not generalize outside the United States. Conclusions:Pain interference and fatigue, as well as an overall symptom burden, are useful prognostic indicators in patients receiving in-center hemodialysis. Symptom burden should remain a treatment target in hemodialysis.
Rationale & Objective Uremic pruritus affects up to 50% of patients with kidney failure and negatively impacts quality of life. Itch often persists and remains insufficiently controlled despite standard of care treatments. We evaluated the effects of nabilone, a synthetic cannabinoid, in patients with kidney failure receiving dialysis and symptoms of chronic itch. Study Design Placebo controlled randomized crossover trial. Setting & Participants Adults >25 years old receiving maintenance hemodialysis at least 2x weekly or peritoneal dialysis daily with at least moderate itch. Interventions Participants were randomly allocated to a first treatment period of either oral nabilone (0.5mg daily for 1 week then twice a day for 3 weeks) or an identical placebo regimen. After a 2-week washout period, participants received whichever regimen they did not receive in the first treatment period. Outcomes The primary outcome was the difference in worst visual analog score (0 to 100mm) for itch over the last 24 hours in each treatment period. Results Of 14 participants randomized, all were on hemodialysis The worst visual analog score for the nabilone compared to the placebo was 4.88mm (95% CI -3.61 to 13.38, p=0.28), indicating worse itch with nabilone. The study was not able to detect any differences in nabilone from placebo in other measures of itch, sleep, quality of life or adverse events but was short in duration study and had a limited sample. Limitations Underpowered for secondary outcomes and to detect carryover effects, conservative nabilone dosing. Conclusions We were unable to detect if nabilone had any effects on uremic pruritus compared to placebo. Plain-Language Summary Uremic pruritus, also known as chronic itch that is associated with kidney disease, affects up to half of patients on dialysis and is associated with worse quality of life. Unfortunately, few effective and well-tolerated treatments exist for this troublesome symptom. Nabilone, a synthetic form of tetrahydrocannbinol (THC), is a potential new treatment for uremic pruritus, given the possible role of cannabinoid receptors in chronic itch. In this small crossover trial in which adults receiving maintenance dialysis each received nabilone and placebo in a random order for 4 weeks, we did not detect any differences in itch severity, sleep or quality of life between the two treatments but nabilone was well-tolerated without any significant side effects.
Rationale & Objective:Anemia is a major complication in chronic kidney disease. Although iron replacement therapies are commonly used, concerns about iron overload exist, for which data are limited, particularly in patients undergoing peritoneal dialysis (PD). This study investigated the impact of persistent iron overload and ferritin trends on clinical outcomes. Study Design:Single-center retrospective study. Setting & Participants:A single dialysis unit; 586 new adult patients undergoing PD between 2011 and 2020; a subgroup of 345 patients was analyzed using their persistent or reversal of high iron status. Predictors:Change in iron status in 12 months after start of PD, classified into 5 groups. Outcomes:Patient survival, technique survival, peritonitis-free survival, and number and length of hospitalization. Analytical Approach:Cox regression models for survival analysis; linear regression after log transformation for hospitalization. Results:The 3-year patient survival rates for groups of patients with a decrease or increase in serum ferritin levels of ≤ 250 ng/mL, a decrease in serum ferritin levels of > 250-750 ng/mL, a decrease in serum ferritin levels of > 750 ng/mL, an increase in serum ferritin levels of > 250-750 ng/mL, and an increase in serum ferritin levels of > 750 ng/mL were 84.0%, 77.3%, 79.2%, 81.1%, and 67.3%, respectively (P = 0.007), although the association became insignificant after adjusting for confounding factors. Notably, 70.0% of a subgroup had persistent iron overload after the first year of PD. There were no significant differences in survival rates among the control, persistent iron overload, and reversal groups. Limitations:Single-center retrospective study. Conclusions:A rise in serum ferritin levels of > 750 ng/mL was not associated with patient survival in a multivariable analysis. For patients with iron overload at the initiation of PD, the reversal of iron overload was not associated with any improvement in clinical outcomes.
Rationale & Objective:Inflammation is associated with adverse kidney, cardiovascular, and mortality outcomes. Investigation of the metabolic milieu as it relates to inflammation may provide important insights into these disease processes. Study Design:Prospective cohort. Setting & Participants:African American Study of Kidney Disease and Hypertension (AASK), Atherosclerosis Risk in Communities (ARIC) study, and Boston Kidney Biopsy Cohort (BKBC) participants with available metabolomics and inflammatory protein data. Predictors:Baseline blood levels of 718 metabolites. Outcomes:Baseline and longitudinal changes in blood levels of tumor necrosis factor receptors 1 and 2 (TNFR1, TNFR2), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukins 6, 8, and 10 (IL-6, IL-8, IL-10), uromodulin (UMOD), and epidermal growth factor (EGF). Analytical Approach:Multivariable linear regression and linear mixed-effects models. Results:Among 491 AASK participants (mean age 54 years; 37% women; mean glomerular filtration rate, 45 mL/min/1.73 m2), 367 cross-sectional associations between metabolites and inflammatory proteins were significant after correction for multiple comparisons. The direction of association was mostly positive for TNFR1 (97%), TNFR2 (97%), IL-8 (77%), and IL-10 (100%); negative for UMOD (80%) and EGF (97%); and variable for TNF-⍺, IFN-γ, and IL-6. Pathways were distinct for several inflammatory proteins (eg, tryptophan metabolism for TNFR2). Forty-five associations between metabolites and longitudinal change in inflammatory proteins were identified. Notable metabolites included tigylcarnitine and N 2,N 5-diacetylornithine, which were associated with 2-year increases in TNFR1 and/or TNFR2, and 1,5-anhydroglucitol, where lower levels were associated with decreases in UMOD. In ARIC (n = 3,773) and BKBC (n = 413), replication of cross-sectional associations was excellent for TNFR1 (ARIC 83%; BKBC 85%) and TNFR2 (ARIC 64%; BKBC 79%) but poor for IL-8 (ARIC 3%; BKBC 3%). Limitations:Metabolite data limited to baseline visit; potential for residual confounding. Conclusions:Using an untargeted approach, multiple metabolites were cross-sectionally and longitudinally associated with inflammatory proteins in persons with chronic kidney disease.
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe hypersensitivity reaction caused by certain medications, including allopurinol, antibiotics, and antiepileptic drugs. It is characterized by a widespread rash, fever, lymphadenopathy, eosinophilia, and multiorgan dysfunction, including hepatic and renal impairment. DRESS syndrome differs from typical drug eruptions in that clinical symptoms may continue or worsen even after the causative medication has been discontinued. We report the case of a 75-year-old Japanese woman who developed DRESS syndrome after taking carbamazepine. She subsequently experienced severe acute kidney injury. Despite drug discontinuation, renal function progressively deteriorated over 2 months. Renal biopsy revealed granulomatous interstitial nephritis characterized by granulomatous lesions confined to the perivascular areas of the arcuate and interlobular arteries. Additionally, lymphangiogenesis was observed. Administration of prednisolone 0.8 mg/kg/d resulted in partial improvement in renal function; however, chronic kidney disease persisted. This patient showed perivascular granulomatous interstitial nephritis, a rare histological finding in DRESS syndrome. This finding shows that granuloma formation may involve crosstalk between persistent interstitial inflammation and lymphangiogenesis. Therefore, delayed treatment initiation may negatively affect renal outcomes, underscoring the essence of the prompt recognition and treatment of DRESS syndrome.
Rationale & Objective Infectious diseases have been associated with pediatric idiopathic nephrotic syndrome (NS). The effect of pandemic-related changes in infection exposure on NS epidemiology remains unclear. Study Design Retrospective cohort study. Setting & Participants Data from children aged 6 months to 15 years from 11 hospitals in Japan, extracted from the Pediatric Medical Information Collection System. Two periods were compared: prepandemic (April 2019-March 2020) and first pandemic year (April 2020-March 2021). Analytical Approach Event counts (new-onset NS, relapse, respiratory tract infections, acetaminophen prescriptions, coronavirus disease 2019 diagnoses) were modeled using a negative binomial generalized linear mixed model with hospital-specific random intercepts. Sensitivity analyses used zero-inflated Poisson, Poisson mixed models, and quasi-Poisson. Results There were 218 new-onset NS cases (127 prepandemic, 91 during the pandemic). The pandemic period was associated with a decrease in incidence, and estimates were similar across distributional sensitivity analyses, whereas extended time-window analyses attenuated statistical significance. The relapse rate among 366 patients in remission was 0.094 per person-year before the pandemic and 0.056 per person-year during the pandemic; the period effect was not statistically significant. Respiratory tract infections decreased by approximately half, and acetaminophen prescriptions declined. The number of coronavirus disease 2019 diagnoses increased sharply. Limitations Observational design limits causal inference. Findings may not generalize beyond Japanese populations. Conclusions Reduced respiratory infection exposure during the pandemic may be associated with lower new-onset NS incidence. Preventive measures against respiratory infections may help reduce NS occurrence. Plain-Language Summary Idiopathic nephrotic syndrome is a childhood kidney disease that causes edema and protein loss in the urine. Some relapses occur after common colds. During the coronavirus disease 2019 pandemic, masking and distancing reduced many respiratory infections, offering a chance to study how infection exposure relates to this disease. We used electronic medical records from pediatric hospitals in Japan to compare new diagnoses and relapses in the year before the pandemic with those in the first pandemic year, and we also tracked respiratory infection visits and use of fever medicine. New diagnoses were lower during the pandemic year, whereas relapses showed a smaller, uncertain change. Preventing respiratory infections may help reduce some cases and improve care for vulnerable children.
Rationale & Objective Monogenic kidney diseases contribute substantially to chronic kidney disease (CKD), yet genomic testing remains underutilized in nephrology due to access, regulatory, and sociocultural barriers. We evaluated the diagnostic yield, clinical impact, and feasibility of a nephrologist-led genomic testing model for kidney diseases. Study Design Prospective, multicenter clinical implementation pilot. Setting & Participants Four tertiary hospitals in Singapore involving adult and pediatric nephrology services. Patients with suspected genetic glomerular disease or CKD of unknown etiology were enrolled. Predictors Age at onset, sex, family history, extrarenal manifestations, pre-test clinical diagnosis, and microscopic hematuria. Outcomes Primary outcomes were diagnostic yield and clinical impact. Secondary outcomes included genotype-phenotype spectrum and identifying predictors of a genetic diagnosis. Analytical Approach Targeted gene panels or whole exome sequencing were performed. Pre- and post-test counseling was provided by trained genetic nephrologists, with variant review by a multidisciplinary genomic board. Logistic regression identified predictors of a monogenic diagnosis. Results Among 216 probands, the overall diagnostic yield was 22%; Alport syndrome accounted for 77% of diagnosed cases. Genetic findings led to management changes in 81% of diagnosed individuals and in 37% of those with negative results. Cascade testing identified previously undiagnosed or misdiagnosed family members. Predictors of a monogenic diagnosis included younger age at onset, female sex, positive family history, extrarenal features, pre-test clinical diagnosis of Alport syndrome, and clinical suspicion of a genetic cause. Microscopic hematuria was strongly associated with Alport syndrome. Limitations Predominantly Chinese cohort enriched for glomerular phenotypes. Targeted sequencing may miss deep intronic, copy number, or structural variants. Long-term clinical outcomes are not yet available. Conclusions A nephrologist-led genomic care model supported by a multidisciplinary variant interpretation team is feasible with considerable diagnostic yield and clinical impact. Our findings provide a framework for implementing genomic care within nephrology practice in similar healthcare systems.
Introduction Genetic focal segmental glomerulosclerosis (FSGS) caused by a mutation in the coenzyme Q (COQ) is a rare podocytopathy that is associated with poor response to immunosuppression. Finerenone is a non-steroidal mineralocorticoid antagonist that reduces oxidative stress, glomerular inflammation and fibrosis, features seen in COQ coenzyme deficiency. We report the first case of its use in COQ8B–related FSGS. Case Presentation A 35-year-old woman was evaluated for persistent post-partum proteinuria and underwent a kidney biopsy that showed features of focal segmental glomerulosclerosis. She has a strong family history of early-onset kidney failure. She had no response to corticosteroids, Tacrolimus and Empgagliflozin. Genetic testing revealed homozygous COQ8B mutation. CoQ10 supplement was not tolerated. Finerenone was initiated in May 2024 with significant improvement in albuminuria from 6,460 mg/g to 1,430 mg/g after 12 months and a slowing of eGFR decline rate from −9.55 ml/min/1.73m2/year to −6.77 ml/min/1.73m2/year. There was only mild transient hyperkalaemia. It was stopped after 12 months due to hypotension, and by six months the proteinuria increased to 4,860 mg/g and creatinine from 1.56 mg/dL to 2.22 mg/dL. Conclusion This case suggests a potential role for finerenone as adjunctive therapy in genetic FSGS.
Rationale & Objective Patients with arteriovenous fistulas (AVFs) facing recurrent interventions endure high procedural burdens and costs. We evaluated a novel single-needle distal return (SNDR) technique in refractory AVF cases to assess its impact on dialysis adequacy, reintervention rates, and economic outcomes. Study Design Single-center retrospective self-controlled study. Setting & Participants Twenty-five maintenance hemodialysis patients at a tertiary Chinese center (2021-2025) with AVF failure due to complete outflow occlusion (n=6), venous hypertension (n=8), procedural fatigue (n=5), or inadequate cannulation length (n=6). Findings Over a median follow-up of 24 months, SNDR significantly improved dialysis adequacy (median single-pool Kt/V: 1.08 vs 1.46, P<0.001) and ultrafiltration achievement ratio (72% vs 98%, P<0.001). The annualized reintervention rate decreased by 90% (3.7 to 0.36 events/year, P<0.001), access-related costs fell by 88% (¥135,000 to ¥16,000/year, P<0.001), and temporary catheter use was eliminated in 88% of patients. Safety outcomes improved: dialysis machine alarms decreased from 28 to 3 per 100 sessions (P<0.001) and hematoma rates from 8.0% to 1.5% of sessions (P<0.001). Venous pressure remained within safe ranges (124 vs 118 mmHg, P=0.15). Limitations Single-center retrospective design and modest sample size limit generalizability. Conclusions The SNDR technique not only sustained but improved dialysis efficacy while substantially reducing reinterventions, costs, and complications in complex AVF failure. This approach represents a transformative salvage strategy that substantially reduces costs before resorting to catheter-dependent options.
Rationale & Objective Interest in nephrology fellowship training remains lower than in many other internal medicine subspecialties. Although prior studies have identified resident-defined factors influencing career choice, it is unclear whether nephrology program leadership accurately recognizes these influences. We evaluated leadership perceptions of factors shaping residents’ interest in nephrology and assessed concordance with previously reported resident priorities. Study Design National cross-sectional survey. Setting & Participants Program directors (PDs) and associate program directors (APDs) at ACGME-accredited programs in the United States (July-December 2025). Exposure(s) Leadership perceptions of factors influencing residents’ specialty choice, including financial compensation, work–life balance, prestige, stress, clinical exposure, and timing of subspecialty decision-making. Outcomes Perceived deterrents and facilitators to pursuing nephrology and alignment with previously published resident-reported priorities. Analytical Approach Descriptive statistics summarizing categorical and Likert-scale survey responses. Results Sixty-two PDs and APDs responded, representing 50 programs across 25 states. Most perceived nephrology as intellectually stimulating (97%) but challenging (100%), with a medically complex patient population (79%). Leadership identified low financial compensation (75%) and work–life balance (63%) as leading deterrents, consistent with resident-reported barriers. Discordance emerged in two domains: only 22% of respondents believed subspecialty decisions are made during medical school, despite prior resident data suggesting earlier interest formation; and leadership did not view nephrology’s broad scope as a recruitment barrier, whereas residents may favor subspecialties with clearer role differentiation. Limitations Modest response rate of 32% raises the possibility of nonresponse bias. Findings reflect self-reported perceptions and were not contemporaneously linked to resident responses. The survey instrument was not formally validated. Conclusions Program leadership recognizes key economic and lifestyle deterrents. However, misalignment regarding timing of career decisions and specialty identity suggests missed recruitment opportunities. Earlier medical school engagement and clearer delineation of nephrology career pathways represent actionable strategies.
Rationale & Objective Anemia in pediatric chronic kidney disease (CKD) is common which adds to morbidity, reduced quality of life and increased cardiovascular risk. Conventional oral iron is limited by poor absorption, poor adherence and high hepcidin level. Liposomal iron(iron pyrophosphate encapsulated within phospholipid membrane) has enhanced iron bioavailability. This study evaluates whether liposomal iron is superior to conventional oral iron in pediatric CKD-associated anemia. Study Design A single-center, open-label, randomized controlled trial. Setting & Participants Conducted at PGIMER, Chandigarh(February–September 2024) with 68 CKD stage 3–5 participants, ≤14 years and not on hemodialysis. Exposure Participants randomized into conventional oral iron(Group-1) or liposomal iron(Group-2) were assessed at enrolment and after 12 weeks for hemoglobin and iron profile (serum iron, total iron-binding capacity[TIBC], ferritin, and transferrin saturation[TSAT]). Outcomes Primary outcome was mean change in hemoglobin from baseline to 12 weeks. Secondary outcomes included changes in iron profile, hepcidin, and adverse events. Analytical Approach Intention-to-treat analysis with appropriate parametric or nonparametric test for intergroup and intragroup comparison(p<0.05 significant). Results Baseline hemoglobin level were comparable(9.3±1.2 g/dL in Group-1 vs. 9.1±1.4 g/dL in Group-2,p=0.88). After 12 weeks, hemoglobin increased by 1.2 g/dL in Group-2 versus 0.6 g/dL in Group-1, though not statistically significant(p=0.28). Serum iron significantly increased in Group-2(55.7±18.2 to 70.7±19.9 mcg/dL,p=0.03). Further, TSAT improved significantly in Group 2(22.6±15.6% to 30.2±12.6%, p=0.05). Ferritin, TIBC and hepcidin levels showed no significant changes. Adverse event incidence was lower in Group-2(19.4%) as compared to Group-1(43.7%) Limitations Single-centre design, open label study and short follow up. Conclusions In anemic CKD children not on hemodialysis, liposomal iron is not better than conventional iron in improving hemoglobin level. However, serum iron and TSAT improved significantly with liposomal iron accompanied by fewer adverse events. Longer follow up studies are required to recognize the efficacy of liposomal iron in this cohort.
