Nephron[JOURNAL]
Sun
200 papers
Abnormal Right Ventricular to Pulmonary Artery Coupling in Patients with End-Stage Kidney Disease and Normalization after Renal Transplantation: An Observational Study.
Çetin Güvenç R, Güvenç TS, Karakaya ES … +6 more , Açık H, Korkmaz A, Salem AF, Şahin O, Ferhatoğlu F, Gürkan A
Nephron · 2026 · PMID 41166546 · Publisher ↗
INTRODUCTION: Pulmonary hypertension and right ventricular (RV) dysfunction are associated with an increase in mortality and worse prognosis in patients with end-stage kidney disease (ESKD), but pathophysiologic mechanis...
INTRODUCTION: Pulmonary hypertension and right ventricular (RV) dysfunction are associated with an increase in mortality and worse prognosis in patients with end-stage kidney disease (ESKD), but pathophysiologic mechanisms underlying the progression of RV dysfunction remain incompletely understood. The present study aimed to understand right ventricular to pulmonary artery (RV-PA) coupling, which is an early indicator of transition to RV dysfunction, to better characterize adaptive RV response to increased afterload in ESKD patients and changes in RV-PA coupling following renal transplantation. METHODS: One hundred eleven patients with ESKD, including 49 patients scheduled for renal transplantation, underwent a detailed echocardiographic examination and measurement of tricuspid annular plane excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio, and a repeat examination was performed 6 months after the baseline examination. RESULTS: Patients with ESKD had significantly lower TAPSE/PASP ratio at baseline (1.02 [0.71-1.63] vs. 1.29 [1.09-1.96], p < 0.001). In 40 patients that underwent transplantation, TAPSE/PASP ratio increased significantly from (0.97 [0.72-1.42] to 1.30 [1.01-1.82], p = 0.03), while in 27 patients remained on dialysis, there was a nonsignificant reduction in TAPSE/PASP ratio (1.21 [0.71-1.62] vs. 0.84 [0.61-1.38], p = 0.44). The change in TAPSE/PASP ratio correlated significantly with the change in pulmonary vascular resistance (OR: 0.61, 95% CI: 0.51-0.72, p < 0.001) and left ventricular mass index (OR: 0.97, 95% CI: 0.96-0.99, p = 0.001) after adjustment. CONCLUSIONS: Patients with ESKD had abnormal RV-PA coupling, as indicated by a reduced TAPSE/PASP ratio, which normalizes 6 months after renal transplantation.
Role of Mitophagy in Ischemia-Reperfusion Renal Injury: New Insights from Bioinformatics Analysis.
Zhou H, Huang Q, Huang A … +4 more , Feng J, Chen S, Li P, Zhu LJ
Nephron · 2026 · PMID 41166509 · Publisher ↗
INTRODUCTION: Mitophagy is central to acute kidney injury (AKI) pathogenesis. Elucidating its molecular interplay with AKI is crucial for novel therapeutics. METHODS: This study is based on transcriptome sequencing combi...
INTRODUCTION: Mitophagy is central to acute kidney injury (AKI) pathogenesis. Elucidating its molecular interplay with AKI is crucial for novel therapeutics. METHODS: This study is based on transcriptome sequencing combined with single-cell sequencing and applies bioinformatics analysis. Finally, it is verified by in vitro, in vivo, and clinical specimen experiments. RESULTS: In transcriptome analysis, combining protein-protein interaction mapping with machine intelligence algorithms, we screened out two mitophagy-related differentially expressed genes (MitoDEGs), solute carrier family 3 member 2 (SLC3A2) and thioredoxin (TXN). The immunological analysis revealed a notable rise in monocyte infiltration in the immune microenvironment of ischemia-reperfusion injury (IRI)-AKI. Spearman analysis indicated hub MitoDEGs were positively correlated with pro-inflammatory immune cell infiltration and negatively correlated with anti-inflammatory or regulatory immune cell infiltration. Based on the highest binding score, 506-26-3 CTD (gamma-linolenic acid) was determined to be the top promising therapeutic candidate. At the single-cell level, hub MitoDEGs were mainly expressed in proximal tubular. In cell experiments, mitophagy was inhibited after hypoxia-reoxygenation, SLC3A2 matched earlier results, while TXN was contrary to the previous analysis results. In the IRI-AKI rat experiments, the findings regarding hub MitoDEGs aligned with our prior analysis, revealing a decrease in the expression of genes associated with mitophagy. Consequently, we directed our attention to the expression levels of SLC3A2 in clinical cases of AKI, where we observed a notable increase. CONCLUSION: Our research indicates that SLC3A2 could be a crucial target for enhancing IRI-AKI through the modulation of the mitophagy pathway.
Transcriptomic Insights into Polyomavirus Nephropathy in Kidney Transplants: Evaluating the Utility of the Banff Human Organ Transplant Panel.
Hatanaka K, Iwasaki S, Tanaka S … +12 more , Tanabe T, Sasaki H, Harada H, Miura M, Nakazawa D, Ishii Y, Yamaguchi T, Katayama Y, Aoyama S, Tanaka S, Taniguchi K, Tsuji T
Nephron · 2025 · PMID 41129417 · Publisher ↗
BACKGROUND: Polyomavirus nephropathy (PyVN) is a significant complication following kidney transplantation, characterized by tubulointerstitial inflammation that mimics T-cell-mediated rejection (TCMR). The Banff Human O...
BACKGROUND: Polyomavirus nephropathy (PyVN) is a significant complication following kidney transplantation, characterized by tubulointerstitial inflammation that mimics T-cell-mediated rejection (TCMR). The Banff Human Organ Transplant (B-HOT) panel, a transcriptomic analysis tool comprising 770 genes, has been developed to facilitate the diagnosis of allograft rejection. However, its utility in distinguishing PyVN from TCMR remains unclear. OBJECTIVE: This study aimed to evaluate the biochemical characteristics of PyVN and TCMR using the B-HOT panel, investigate changes after PyVN treatment, and assess the panel's diagnostic utility. METHODS: Formalin-fixed paraffin-embedded tissue samples from 11 PyVN patients were analyzed both at diagnosis and follow-up using the B-HOT panel. Public datasets were compared to identify differentially expressed genes and activated pathways. Prognostic factors were explored based on viral clearance and renal function outcomes. RESULTS: BK VP1 gene expression was significantly elevated in PyVN cases, aiding diagnosis. While tissue homeostasis pathways were upregulated in PyVN compared to TCMR in the original data, no specific pathways were identified in public datasets. Successful viral clearance correlated with enhanced T-cell checkpoint signaling at diagnosis, suggesting its role in immune-mediated viral elimination. CONCLUSION: The B-HOT panel provides limited utility for diagnosing PyVN beyond viral gene quantification. However, T-cell checkpoint signaling may serve as a prognostic marker for viral clearance and renal function preservation in PyVN cases. Further studies are needed to refine molecular diagnostics for PyVN and improve transplant outcomes.
Erratum.
Nephron · 2025 · PMID 41115111 · Publisher ↗
In the article "Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1" [Nephron. 2024;148:587-600; https://doi.org/10.1159/000534788] by Bi et al....
In the article "Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1" [Nephron. 2024;148:587-600; https://doi.org/10.1159/000534788] by Bi et al., the funding grant (No. 82200836) from the Natural Science Foundation of China was mistakenly omitted from the funding statement of the published version.
Prospects for Artificial Intelligence-Based Pathological Diagnosis of Renal Transplant Biopsy.
Iwadoh K, Tonsho M
Nephron · 2025 · PMID 41108711 · Publisher ↗
BACKGROUND: Artificial intelligence, initiated in the 1950s, has matured after two setbacks into deep neural networks (DNNs) and large language models (LLMs). Key drivers of success were the adoption of nonlinear models...
BACKGROUND: Artificial intelligence, initiated in the 1950s, has matured after two setbacks into deep neural networks (DNNs) and large language models (LLMs). Key drivers of success were the adoption of nonlinear models and autonomous learning. DNNs function as discriminative models that hierarchically interpret features to classify images, while LLMs, as generative models trained on vast datasets, generate text based on contextual meaning. SUMMARY: Digital pathology (DP) employing DNNs and LLMs is advancing globally, yet Japan lags behind. To standardize diagnostic interpretation and reduce the workload of pathologists, integration of DP into renal transplant pathology (RTP) is essential. The CAMELYON16 challenge demonstrated that AI can achieve diagnostic accuracy comparable to or surpassing expert pathologists. In the USA, over ten DP systems have been approved by the FDA as class II medical devices for primary diagnosis. Moreover, US law assigns liability for AI-related misdiagnosis jointly to pathologists and institutions, promoting both accuracy and legal protection for pathologists. In 2019, the Banff Digital Pathology Working Group was established to build a pathology repository, share AI algorithms, and foster model standardization through competitions. With numerous AI systems emerging, DP platforms should evolve in parallel with biennial Banff classification updates. KEY MESSAGES: AI in RTP can enhance diagnostic objectivity and alleviate pathologists' workload. Linking Banff updates with AI retraining enables continuously updated, globally standardized DP. Advanced DP requires close collaboration between transplant pathologists, AI engineers, and cutting-edge graphics processing unit resources.
Association of Monocyte-Lymphocyte Ratio with Cardiovascular Events and All-Cause Mortality in Patients Undergoing Hemodialysis: A Prospective Cohort Study.
Mallisetty Y, Kabeil A, Bergeron CJ … +4 more , Han Z, Chiu CY, Kovesdy CP, Sumida K
Nephron · 2026 · PMID 41108709 · Publisher ↗
INTRODUCTION: Elevated monocyte to lymphocyte ratio (MLR) represents a pro-inflammatory immune microenvironment and has been associated with poor clinical outcomes such as cardiovascular disease. However, little is known...
INTRODUCTION: Elevated monocyte to lymphocyte ratio (MLR) represents a pro-inflammatory immune microenvironment and has been associated with poor clinical outcomes such as cardiovascular disease. However, little is known about its association with outcomes among patients on hemodialysis. METHODS: In a nationwide prospective cohort of 952 patients receiving maintenance hemodialysis from 2011-2013, we examined the association of baseline MLR with subsequent risk of cardiovascular events (cardiovascular-related hospitalization and cardiovascular death) and all-cause mortality, using multivariable Cox proportional-hazards models with adjustment for potential confounders. We also examined the mediation effect of inflammatory markers on the association between MLR and cardiovascular events and all-cause mortality, respectively. RESULTS: Overall, patients were 60.1 ± 13.4 years old; 53.3% were male; 39.7% were African American; and 56.9% were diabetic. The median dialysis vintage was 3.1 years. During a median follow-up of 2.1 years, 184 and 207 cases experienced cardiovascular events and all-cause death, respectively. A higher MLR was incrementally associated with higher risk of cardiovascular events and all-cause mortality. The multivariable-adjusted hazard ratios (95% confidence interval) of cardiovascular events and all-cause mortality for 0.1-unit increase in MLR were 1.22 (1.09-1.37) and 1.18 (1.07-1.30), respectively. There was a modest but significant mediation effect of plasma interleukin-6 (IL-6) on the association between MLR and cardiovascular events (28.2%) and all-cause mortality (24.1%). CONCLUSION: A higher MLR was independently associated with higher risk of cardiovascular events and all-cause mortality in patients on hemodialysis. Our findings suggest the potential of MLR as a simple, cost-effective prognostic biomarker and support IL-6-targeted therapeutic interventions to improve clinical outcomes in patients with ESKD.
Clinical Presentation, Genetic Testing, and Outcome of Congenital Nephrotic Syndrome in KwaZulu-Natal, South Africa.
Bhimma R, Winkler CA, Nandlal L … +3 more , David V, Cho S, Naicker T
Nephron · 2026 · PMID 41100440 · Full text
INTRODUCTION: The aetiology of congenital nephrotic syndrome (CNS) is heterogenous with genetic and more rarely infectious or maternal allo-immune disease causes. In resource-replete settings, 60-80% of CNS is attributab...
INTRODUCTION: The aetiology of congenital nephrotic syndrome (CNS) is heterogenous with genetic and more rarely infectious or maternal allo-immune disease causes. In resource-replete settings, 60-80% of CNS is attributable to monogenic causes, with other causes much more rarely diagnosed. The relative prevalence of these aetiologies and differences in clinical presentation are understudied in southern Africans. We describe the aetiology, clinical presentation, outcomes, and genetic testing results in black African infants with CNS. METHODS: We enrolled 36 children with CNS from a tertiary referral centre in KwaZulu-Natal, South Africa. Chart reviews were performed to identify aetiology, clinical features, and outcomes. Genetic testing for variants in NPHS1, NPHS2, WT1, LAMB2, and PLCE1 was performed for a subset of 9 children with CNS without infection. RESULTS: Of the 36 CNS cases, 15 (41.7%) children were diagnosed with infection-associated CNS: 11 (30.6%) with cytomegalovirus (CMV) and 4 (11.1%) with human immunodeficiency virus (HIV). Twenty-one (58.3%) of the cases had unknown aetiology after the exclusion of other non-genetic causes, nine of whom underwent genetic testing, yielding a genetic diagnosis for 3 (33.3%) of the 9: 2 (22.2%) children were homozygous for NPHS1 p.R460Q and one for NPHS2 p.V260E. There were no statistically significant differences in age of diagnosis, age at kidney failure, age of death or kidney function markers between the group of infants with CNS attributed to infection and those without infection (p > 0.05). Infants with monogenic CNS experienced, on average, an earlier diagnosis (mean age 28 days, SD 11) than those with infection-associated CNS (43 days, SD 19.11). CONCLUSION: South African black children are diagnosed with high rates of CNS attributed to untreated maternal CMV and HIV infections likely resulting from limited prenatal maternal care in this population. The diagnostic genetic yield was much less than expected, most likely due to the small number of patients tested compared to larger studies in Western settings, indicating a need for further investigation of the genetic landscape of CNS in African populations.
Tailored Complex Symptom Management Intervention for Adults with Advanced Kidney Disease and Their Informal Caregivers: Protocol for the COMFORT Research Program.
Finderup J, Agerskov H, Deele M … +4 more , Frandsen CE, Kristensen IV, Bonner A, Konradsen H
Nephron · 2026 · PMID 41078064 · Full text
<p>Introduction: To co-design and test the effectiveness of a tailored COmplex symptom Management intervention FOR adulTs with advanced kidney disease and their informal caregivers along with healthcare professionals who...
<p>Introduction: To co-design and test the effectiveness of a tailored COmplex symptom Management intervention FOR adulTs with advanced kidney disease and their informal caregivers along with healthcare professionals who deliver care and support to both patients and informal caregivers. Methods: Informed by Symptom Management Theory, COMFORT is a program of research involving multiple studies and structured around the United Kingdom Medical Research Council's framework for developing complex interventions. The program involves building capacity of nurse researchers across three studies: first development of an intervention using mixed methods, followed by co-design workshops and prototype testing; thereafter testing of the symptom intervention through a feasibility trial. Lastly, evaluation of the intervention's effectiveness and implementation using a type two hybrid randomised control trial design, focussing on both clinical outcomes and implementation fidelity. Conclusion: This research program is expected to demonstrate that the COMFORT intervention is superior to standard care in improving symptom burden among adults with advanced kidney disease and reduce caregiver burden among informal caregivers. The COMFORT Nursing Program addresses a critical gap in clinical practice by focusing on non-pharmacological interventions tailored to individual patient needs and symptom clusters. By integrating shared decision-making and self-management support, the program aims to empower patients and caregivers, enhances clinical practice, and contributes substantial evidence to the domain of symptom management in advanced kidney disease. The involvement of stakeholders throughout the research process ensures the relevance and applicability of the findings to real-world clinical settings. </p>.
<sc>L</sc>-Glutamine-Induced Acute Kidney Injury: A Clinical Observation.
Bhoelan S, Kürül S, Krol CG … +2 more , van Midden D, Bakker R
Nephron · 2026 · PMID 41021436 · Publisher ↗
INTRODUCTION: <sc>L</sc>-Glutamine is increasingly used as a dietary supplement and its use is, as is the case with other amino acids, considered safe. <sc>L</sc>-Glutamine is the most abundant amino acid in the human bo...
INTRODUCTION: <sc>L</sc>-Glutamine is increasingly used as a dietary supplement and its use is, as is the case with other amino acids, considered safe. <sc>L</sc>-Glutamine is the most abundant amino acid in the human body and is involved in many metabolic reactions. Within the kidney <sc>L</sc>-glutamine has an important role in the generation of ammonia and bicarbonate. CASE PRESENTATION: We report a case of acute kidney injury (AKI) as a result of tubular damage in a patient who used 18 grams of <sc>L</sc>-glutamine on a daily basis. Possible mechanisms are proposed of which increased single nephron ammonia production and toxicity seems most likely cause of AKI. CONCLUSION: We advise cautious use of <sc>L</sc>-glutamine supplements in elderly patient with an already compromised kidney function.
Association of Employment Status with Quality of Life in Patients across Chronic Kidney Disease G3-G5 Non-Dialysis and Kidney Replacement Therapies.
Rolon-Barbosa SN, Cueto-Manzano AM, Romero-Ornelas NG … +7 more , Chavez-Chavez HE, Díaz-Canchola LM, Avalos-Lopez M, Cerrillos-Gutiérrez JI, Zambrano-Melín JR, Rojas-Campos E, Martín-Del-Campo-Lopez F
Nephron · 2026 · PMID 41014582 · Publisher ↗
INTRODUCTION: Treatment conditions and progression of chronic kidney disease (CKD) are factors for work incapacity, related with physical limitations and social and emotional distress, affecting quality of life (QOL). ME...
INTRODUCTION: Treatment conditions and progression of chronic kidney disease (CKD) are factors for work incapacity, related with physical limitations and social and emotional distress, affecting quality of life (QOL). METHODS: In a cross-sectional study, 343 patients with CKD were included: chronic kidney disease non-dialysis (CKD G3-G5ND) (n = 98), hemodialysis (HD) (n = 95), peritoneal dialysis (PD) (n = 96), and kidney transplant (KT) (n = 54). A clinical and nutritional assessment was carried out using the Subjective Global Assessment instrument. QOL was assessed using the Kidney Disease Quality of Life Short Form instrument. RESULTS: Employed patients (44%) were younger (40 ± 14 vs. 51 ± 16 years, p < 0.0001), had >9 years of schooling (49 vs. 29%, p < 0.0001), lower diabetes frequency (21 vs. 47%, p < 0.0001), hypertension (71 vs. 87%, p < 0.0001), cardiovascular disease (5 vs. 16%, p = 0.002), and better nutritional status score (6 ± 1 vs. 5 ± 1, p < 0.0001) than unemployed. Employed patients with KT had better QOL than employed patients on CKD G3-G5ND, HD, and PD (76 ± 6, 68 ± 13, 68 ± 12, and 67 ± 7, respectively, p < 0.05). In multivariate analysis, employment predicted QOL in all kidney replacement therapies (KRTs): HD (B = 10.1, 95% CI: 5.5-14.6), PD (B = 4.5, 95% CI: 0.08-8.9) and KT (B = 13.3, 95% CI: 6.1-20.5). Nutritional status predicted QOL in all groups: CKD G3-G5ND (B = 3.6, 95% CI: 1.24-5.97), HD (B = 2.44, 95% CI: 0.4-4.4), PD (B = 3.73, 95% CI: 2.1-5.3), and KT (B = 4.4, 95% CI: 0.05-8.8). CONCLUSION: Only 44% of patients had employment. Employed patients had better QOL, were younger, more educated, had fewer comorbidities and better nutritional status than unemployed patients. Employment predicted QOL in all three KRTs but not in CKD G3-G5ND patients, and nutritional status was a predictor QOL in all groups.
Clinical Presentation, Treatment Patterns, Burden of Disease, and the Association of Proteinuria with Clinical Outcomes in C3 Glomerulopathy and Primary Immune Complex Membranoproliferative Glomerulonephritis: A Systematic Review.
Caravaca-Fontán F, Fakhouri F, Pickering MC … +6 more , Lionikaite V, Baird A, Horneff R, López-Lázaro L, Quintana-Gallardo L, Rich C
Nephron · 2026 · PMID 40971335 · Full text
INTRODUCTION: Knowledge gaps and controversies remain regarding the natural history and variability of C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). The objectives...
INTRODUCTION: Knowledge gaps and controversies remain regarding the natural history and variability of C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). The objectives were to provide an overview of these diseases for the following outcomes of interest: clinical presentation, treatment patterns, and disease burden, including the association between proteinuria and kidney outcomes. METHODS: This systematic literature review (SLR) included studies of adults and children with C3G or primary IC-MPGN investigating outcomes of interest. Embase and MEDLINE were searched from January 2012 to February 22, 2024, combining terms for C3G or IC-MPGN and outcomes of interest. Supplementary congress searches and reference list checking of relevant articles were conducted. Study details, outcomes of interest, and key findings were extracted, and data were narratively summarized. RESULTS: In total, 148 articles were included. No clear trend for differences between C3G and primary IC-MPGN were observed for clinical presentation. Treatments included immunosuppressive therapies and off-label anti-complement agents. Kidney failure occurred in up to 50% and 37% of patients with C3G and primary IC-MPGN, respectively, and kidney transplantation was required in up to 32% and 24% of patients, respectively. Mortality was reported in up to 21% of patients. No clear trend of complete remission across treatments was observed. In longitudinal studies, proteinuria was associated with increasing risk of kidney failure. No articles reported on patient quality of life or caregiver burden. Several articles reported an economic burden according to length of hospital stay. Possible limitations include that terms used for electronic searches limited which articles were identified, many studies were retrospective and small (<10 participants), and risk of bias was not performed. CONCLUSIONS: This SLR provides insights into C3G and primary IC-MPGN, emphasizing the need for new targeted and effective treatments. Proteinuria was identified to be an acceptable marker in assessing the efficacy of treatments on long-term kidney outcomes.
Regional Citrate Anticoagulation and Infectious Complications in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.
Gist KM, Iyer SPN, Humes HD … +14 more , Goldstein SL, Damian M, Cappoli A, Joseph C, Soranno DE, Starr M, Tolwani A, Chung KK, Mottes T, Zang H, Seo J, Ollberding NJ, Menon S, WE-ROCK Investigators
Nephron · 2026 · PMID 40952919 · Full text
INTRODUCTION: Recent studies have identified an association between regional citrate anticoagulation (RCA) and subsequent infectious complications during continuous renal replacement therapy (CRRT). We aimed to determine...
INTRODUCTION: Recent studies have identified an association between regional citrate anticoagulation (RCA) and subsequent infectious complications during continuous renal replacement therapy (CRRT). We aimed to determine if RCA was associated with infectious complications in children and young adults receiving CRRT. METHODS: A secondary analysis of the multinational Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry (34 centers, 9 countries), was performed, including patients from 2015 to 2018. Patients were excluded if they (1) died within 72 h of CRRT initiation, had minor trauma or were postsurgical (analysis 1), or (2) met an exclusion in analysis 1 or had sepsis prior to CRRT initiation or chronic immunosuppression (analysis 2). Multivariable mixed-effects logistic (analysis 1) and mixed-effects Cox regression (analysis 2) were used to determine the associations between anticoagulant type and culture-positive infection after CRRT initiation. RESULTS: A total of 874 patients were included in analysis 1 and 283 in analysis 2. Culture-positive infection occurred in 25% and 17% of each analysis. In analysis 1, culture-positive infection was higher in RCA (29%) vs. heparin (23%) and other (15%); p = 0.008. There was no association between RCA and infection in multivariable analysis. In analysis 2, there was no difference in the frequency of infection by anticoagulation type. A longer time to achieve the first negative fluid balance was associated with culture-positive infection. CONCLUSION: RCA was not associated with culture-positive infection after CRRT initiation in this study. The systemic effects of AKI and longer time to first negative fluid balance may be inciting factors for an infection and represent a potentially modifiable factor that warrants future studies in this high-risk population.
Clinicopathological Analysis of Immunologically High-Risk Kidney Transplantation Using High-Dose Intravenous Immunoglobulin as Desensitization Therapy.
Tanabe T, Sasaki H, Shiono Y … +10 more , Seito T, Ujihashi K, Takada Y, Higuchi H, Takamoto D, Minami K, Tanaka H, Harada H, Tsuji T, Hotta K
Nephron · 2025 · PMID 40934134 · Publisher ↗
INTRODUCTION: High-dose intravenous immunoglobulin (H-IVIg) has been used as a desensitization therapy for donor-specific anti-HLA antibody (DSA)-positive kidney transplant recipients in Japan since 2019. This study repo...
INTRODUCTION: High-dose intravenous immunoglobulin (H-IVIg) has been used as a desensitization therapy for donor-specific anti-HLA antibody (DSA)-positive kidney transplant recipients in Japan since 2019. This study reports the clinical and pathological outcomes of patients who received H-IVIg at Sapporo City General Hospital. METHODS: This study included 7 patients who underwent kidney transplantation at our hospital and received H-IVIg as pretransplant desensitization therapy. At our institution, H-IVIg is indicated for patients with a history of sensitization, such as prior blood transfusion, pregnancy, or organ transplantation, and who tested positive in a flow cytometry crossmatch (FCXM) before transplantation. The recipients (mean age: 55.2 ± 11 years) included one male and six females. The donors (mean age: 62.8 ± 8.8 years) included five males and two females. All were living donor transplants, with four cases involving spousal donation. We assessed the immunological status before and after desensitization and retrospectively analyzed kidney function, anti-donor antibody status, and pathological findings. RESULTS: Before desensitization, 6 patients were FCXM-T positive, and all were FCXM-B positive. After desensitization, 3 patients converted to FCXM-T negative; however, all remained FCXM-B positive. The Luminex single antigen test was positive in 4 patients before desensitization; one converted to negative, while one initially negative patient became positive. Consequently, 4 patients remained DSA positive at transplantation. Three patients experienced acute rejection within 1 month: one had antibody-mediated rejection (ABMR), and two had T-cell-mediated rejection. All patients responded to antirejection therapy, preserving their graft function. At 36 months of follow-up, all the patients survived with functional grafts. Pathological findings revealed early rejection in 3 patients, who later developed chronic ABMR. The remaining 4 patients did not experience rejection episodes. CONCLUSION: The H-IVIg regimen facilitates kidney transplantation in immunologically high-risk recipients. However, the risk of early postoperative rejection and the potential development of chronic ABMR necessitate careful posttransplant monitoring.
Person-Centred Healthcare: Time to Rethink Nephrology Healthcare.
Bonner A, Finderup J
Nephron · 2025 · PMID 40892684 · Publisher ↗
Abstract loading — click title to view on PubMed.
The Relationship of Dietary Inflammatory Index with Anemia in Diabetic Kidney Disease: A Cross-Sectional Study of the NHANES.
Guo L, Wang T
Nephron · 2026 · PMID 40875729 · Publisher ↗
INTRODUCTION: This study examined the relationship between the dietary inflammatory index (DII) and anemia in patients with diabetic kidney disease (DKD). METHODS: All the data were obtained from the National Health and...
INTRODUCTION: This study examined the relationship between the dietary inflammatory index (DII) and anemia in patients with diabetic kidney disease (DKD). METHODS: All the data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. The final analysis included 1918 DKD patients, with 500 experiencing anemia. Weighted multivariate logistic regression models were used to assess the association between DII and anemia, with results expressed as odds ratios. RESULTS: Elevated DII scores correlated with an increased incidence of anemia (OR = 1.13, 95% CI: 1.02-1.25). When analyzed as categorical variables, DII scores of 1.57-2.64 (OR = 1.77, 95% CI: 1.13-2.77) and >2.64 (OR = 1.78, 95% CI: 1.12-2.85) were linked to higher anemia risk. Subgroup analyses revealed consistent associations in individuals aged 65 and older (OR = 1.92, 95% CI: 1.16-3.17), those with serum iron levels <73 μg/dL (OR = 2.01, 95% CI: 1.11-3.62), and males (OR = 2.23, 95% CI: 1.21-4.11). Higher DII scores correlated with greater odds of moderate-severe anemia (OR = 1.22, 95% CI: 1.07-1.38). CONCLUSION: The results indicate that elevated DII scores are associated with an increased occurrence of anemia in DKD patients, emphasizing the importance of lowering pro-inflammatory food consumption as a potential strategy to prevent anemia in this group.
The Effectiveness of Lesion Detection for Immunoglobulin G4-Related Kidney Diseases by Diffusion-Weighted Imaging.
Amaike H, Kanda M, Yamazaki H … +9 more , Nakamura K, Ma L, Nagahata K, Nakamura H, Osanami A, Yama N, Hatakenaka M, Furuhashi M, Takahashi H
Nephron · 2026 · PMID 40815121 · Publisher ↗
OBJECTIVES: The aim of the study was to compare the efficacy of magnetic resonance imaging (MRI) with that of plain or contrast-enhanced computed tomography (CT) in the detection of renal parenchymal and pelvic lesions o...
OBJECTIVES: The aim of the study was to compare the efficacy of magnetic resonance imaging (MRI) with that of plain or contrast-enhanced computed tomography (CT) in the detection of renal parenchymal and pelvic lesions of immunoglobulin G4-related kidney disease (IgG4-RKD). METHODS: Patients with IgG4-RKD and controls, who performed plain, contrast-enhanced CT and MRI around the kidney region in our hospital, were enrolled. The diagnosis of IgG4-RKD was made by definite cases of IgG4-RKD diagnostic criteria in 2020. Five blinded observers independently assessed image datasets by confidence scores to assess diagnostic accuracy, sensitivity, specificity, areas under the receiver operating characteristic curve (AUROC), and Cronbach's alpha coefficient. RESULTS: A total of 31 patients were included in the study. Fourteen (45.2%) had IgG4-RKD. Five patients with IgG4-RKD had parenchymal lesions, 5 had renal pelvic lesions, and 4 had both. In the parenchymal lesions, there was no significant difference in diagnostic performance between contrast-enhanced CT and diffusion-weighted imaging (DWI)-b800. The AUROC and sensitivity were higher in DWI-b800 than in plain CT (p < 0.05). Cronbach's alpha coefficient was 0.44 for plain CT and over 0.80 for contrast-enhanced CT and DWI-b800. In the pelvic lesions, there were fewer differences in the performance among each sequence. Cronbach's alpha coefficient was over 0.80 for plain CT, contrast-enhanced CT, and DWI-b800. CONCLUSION: Plain MRI, especially in DWI-b800, can effectively detect renal parenchymal lesions in IgG4-RKD. In cases where the use of a contrast agent of CT is difficult, DWI-b800 can be an alternative for the screening of IgG4-RKD.
Clinicopathological Investigation of Medial Smooth Muscle Cell Atrophy in Small Arteries in Kidney Allografts.
Kounoue N, Oguchi H, Muramatsu M … +6 more , Mikami T, Itabashi Y, Kawamura T, Hamasaki Y, Yamaguchi Y, Sakai K
Nephron · 2025 · PMID 40763720 · Publisher ↗
INTRODUCTION: Atrophy of smooth muscle cells (SMCs) in the media of small arteries is occasionally observed, especially in long-term kidney allograft biopsies. The intima-media ratio is used as an index of arterioscleros...
INTRODUCTION: Atrophy of smooth muscle cells (SMCs) in the media of small arteries is occasionally observed, especially in long-term kidney allograft biopsies. The intima-media ratio is used as an index of arteriosclerosis in native kidneys, and medial SMC atrophy suggests severe arteriosclerosis. We aimed to investigate the clinicopathological significance of medial SMC atrophy in small arteries in biopsies from long-term kidney transplants. METHODS: Samples were obtained from kidney allograft biopsies carried out from January 2016 to December 2019, and biopsies obtained 10 years after transplantation were included in the study. The distal small arteries with the most atrophic SMCs in longitudinal sections in each biopsy specimen were selected (outer diameter <150 µm and ≥60 µm). The outer diameter and width of the media, intima, and lumen of each artery were measured. SMC atrophy was evaluated as the media-outer diameter ratio. RESULTS: Fifty biopsies were eligible. The mean media-outer diameter ratio was 0.27 ± 0.11. Donor age and allograft age were significantly inversely correlated with media-outer diameter ratio (rank correlation coefficient -0.3522, p = 0.0141 and -0.3700, p = 0.0096, respectively). After separation into two groups according to the media-outer diameter ratio, donor age and allograft age were both significantly higher and more focal segmental glomerular sclerosis (FSGS) lesions were observed in the low media-outer diameter ratio group. Multivariate analysis revealed that media-outer diameter ratio was significantly related to donor age, allograft age, and FSGS. CONCLUSIONS: Medial SMC atrophy appears to be related to donor age, allograft age, and FSGS in kidney allografts. Disruption of vascular contraction as a result of medial SMC atrophy in aging allografts may lead to the development of FSGS.
Association of Urine-to-Plasma Urea Ratio with Outcomes in Patients with Chronic Kidney Disease: A Retrospective Cohort Study.
Kumari U, Sumida K, Wall BM … +1 more , Kovesdy CP
Nephron · 2025 Aug · PMID 40763712 · Publisher ↗
BACKGROUND: Estimated glomerular filtration rate (eGFR) and proteinuria are the gold-standard markers for kidney function used traditionally to assess kidney outcomes. Increased evidence of tubule involvement in nearly a...
BACKGROUND: Estimated glomerular filtration rate (eGFR) and proteinuria are the gold-standard markers for kidney function used traditionally to assess kidney outcomes. Increased evidence of tubule involvement in nearly all causes of chronic kidney disease (CKD) warrants exploring the association between markers of tubular function with clinical outcomes in patients with CKD. METHODS: We conducted a single-center retrospective cohort study in 626 patients with eGFR <60 mL/min/1.73 m2. We examined the association between spot urine-to-plasma (U/P) urea and the incidence of kidney failure, all-cause death, and their composite outcome using the Kaplan-Meier method and multivariable-adjusted Cox proportional hazard models. RESULTS: Our cohort predominantly consisted of males (96%) with a mean ± standard deviation age of 67.4 ± 10.8 years and eGFR of 23.6 ± 10.5 mL/min/1.73 m2. There were 448 composite outcome events (event rate: 159/1,000 patient-years; 95% confidence interval [CI]: 145-175) over a median follow-up of 4.5 years. Lower U/P urea was associated with a higher risk of the composite outcome in unadjusted (hazard ratio and 95% CI for 1 log-unit lower U/P urea: 1.98 [1.73-2.26], p < 0.001) and after multivariable adjustment (1.67 [1.37-2.07], p < 001). Associations were similar for kidney failure and for all-cause death. CONCLUSION: Lower U/P urea, a marker of tubular dysfunction, is associated with a higher risk of adverse clinical outcomes in patients with moderate and advanced CKD, independent of eGFR and proteinuria.
Clinical Trials for Developing Treatment and Early Diagnostic Methods for Chronic Active Antibody-Mediated Rejection in Kidney Transplantation: A Review.
Hotta K
Nephron · 2025 · PMID 40763710 · Publisher ↗
BACKGROUND: Development of immunosuppressants has reduced the incidence of acute T-cell-mediated rejection (TCMR) and significantly improved the short-term outcome of kidney transplantation. However, in the long term, ma...
BACKGROUND: Development of immunosuppressants has reduced the incidence of acute T-cell-mediated rejection (TCMR) and significantly improved the short-term outcome of kidney transplantation. However, in the long term, many cases of transplanted kidney failure are due to chronic active antibody-mediated rejection (CAAMR) caused by donor-specific antibodies. Overcoming this is essential for improving long-term outcomes. The mechanism of CAAMR remains largely unknown and no effective treatment is currently available. SUMMARY: Various therapeutic approaches have been attempted for cases that have progressed to CAAMR. However, an effective treatment method has yet to be established. Therefore, efforts are underway to develop diagnostic methods for identifying patients at risk of developing CAAMR either before its occurrence or as early as possible. Recent reports have identified potential biomarkers in the urine and blood for the early diagnosis of CAAMR. In addition, the molecular analyses of kidney allograft biopsy tissues are being explored for early diagnostic methods. This review summarizes the current treatments for CAAMR and the trials aimed at developing early-stage diagnostic methods for detecting CAAMR. KEY MESSAGES: Various new diagnostic methods have successively attempted to replace histological examination in the diagnosis of kidney transplant rejection; most have focused on TCMR or acute antibody-mediated rejection. The development of early diagnostic methods for CAAMR is still in its infancy and future advancements are anticipated.
T-Cell Receptor CRαβCD4CD8 (Double-Negative) T Cells May Predict Pathological Kidney Findings in Patients with Suspected Lupus Nephritis.
Sekine A, Wada T, Sawa N … +6 more , Hasegawa E, Kono K, Oba Y, Ubara Y, Hoshino J, Ohashi K
Nephron · 2025 Aug · PMID 40763672 · Full text
INTRODUCTION: T-cell receptor αβ+CD4-CD8- (double-negative) T cells (DNT) exist as a small population of lymphocytes in the peripheral blood of healthy individuals, but have been reported to be increased in autoimmune ly...
INTRODUCTION: T-cell receptor αβ+CD4-CD8- (double-negative) T cells (DNT) exist as a small population of lymphocytes in the peripheral blood of healthy individuals, but have been reported to be increased in autoimmune lymphoproliferative syndrome (ALPS) and other collagen diseases, such as systemic lupus erythematosus (SLE), and to be involved in disease activity. However, there are no reports on their relationship with histological classification of lupus nephritis, influencing the management of SLE. METHODS: The study included 15 patients with SLE who underwent kidney biopsy for suspected lupus nephritis at Toranomon Hospital from June 2014 to March 2019 and also had their peripheral DNT cell levels measured. We defined high DNT as more than 1.5% DNT among peripheral blood lymphocytes, in accordance with the ALPS diagnostic criteria, and divided patients into a high and low DNT group. RESULTS: In the 15 cases analyzed, mild glomerular lesions tended to be more common in patients in the high DNT group than those in the low group (60% vs. 10%, respectively; p = 0.077, Fisher's exact test), as did moderate to severe leukocytic inflammation in the interstitium (100% vs. 20%, respectively; p = 0.004, Fisher's exact test). CONCLUSIONS: Elevated peripheral DNT cell levels may be associated with mild glomerular lesions but moderate to severe interstitial inflammation in SLE patients. A prospective clinical study with a larger patient cohort is warranted to validate this possibility and investigate its potential causality.
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