OBJECTIVE: Highaltitude hypoxia impairs frontal executive functions. This study examines whether serum creatinine mediates the relationship between altitude acclimatization (AAI) SpO₂/HCT ratio and frontal neural oscill...OBJECTIVE: Highaltitude hypoxia impairs frontal executive functions. This study examines whether serum creatinine mediates the relationship between altitude acclimatization (AAI) SpO₂/HCT ratio and frontal neural oscillations. METHODS: In 190 adults at 3,650 m (Lhasa), we measured SpO₂, hematocrit, serum creatinine, and restingstate frontal EEG. Power spectral density was calculated across multiple frequency bands (1-80 Hz) and Zstandardized. Mediation analysis with bootstrap tested the indirect effect of AAI on each band via creatinine. RESULTS: AAI significantly negatively predicted creatinine (p < 0.001). Creatinine significantly negatively predicted frontal ZPSD in theta (4-7 Hz), alpha (8-13 Hz), and beta (14-30 Hz) bands (all p < 0.01), but not in other bands. The indirect effect via creatinine was significant for theta (p = 0.011, partial mediation), alpha (p = 0.031, full mediation), and beta (p = 0.020, full mediation). CONCLUSIONS: The kidneybrain axis mediates hypoxic neurocognitive adaptation with frequencyspecific patterns. Creatinine dynamics reflect acclimatization efficacy, suggesting a target for preserving frontal executive function at high altitude.
BACKGROUND AND AIMS: The nephron index provides a non-invasive and theoretical estimate of the functional nephrons based on the assumption that serum fibroblast growth factor 23 (FGF23) concentrations correlate with phos...BACKGROUND AND AIMS: The nephron index provides a non-invasive and theoretical estimate of the functional nephrons based on the assumption that serum fibroblast growth factor 23 (FGF23) concentrations correlate with phosphate excretion per functional nephron. This study aimed to investigate the effects of exercise on the nephron index under different conditions. METHODS: Nine middle-aged adults performed exercise under three experimental conditions: moderate-intensity continuous exercise (MICE), high-intensity intermittent exercise (HIIE), and moderate-intensity intermittent exercise (MIIE). Blood and urine samples were collected before exercise, immediately after exercise and 60 minutes post-exercise. The nephron index was assessed using blood and urine phosphate and creatinine concentrations, serum FGF23 levels, and the estimated glomerular filtration rate. RESULTS: A significant time effect was observed for the log-transformed nephron index (p = 0.012, ηp² = 0.42). The log-transformed nephron index increased immediately after exercise (p = 0.059) and 60 minutes post-exercise (p = 0.008) across MICE, HIIE, and MIIE conditions. Additionally, urinary fractional excretion of phosphate (defined as the ratio of phosphate to creatinine clearance) significantly increased at 60 minutes post-exercise across all conditions (p = 0.038). These findings suggest that a single bout of exercise may result in acute beneficial effects on renal microcirculation. CONCLUSIONS: These results suggest that a single bout of exercise may influence nephron responsiveness in middle-aged individuals. However, as this is a preliminary study, further investigations are warranted to confirm the physiological relevance of the nephron index under dynamic conditions.
Matsumoto M, Yamamoto S, Shinkawa K
… +15 more, Matsubara T, Takeda J, Kitawaki T, Arai Y, Teramoto Y, Minamiguchi S, Kanetsuna Y, Joh K, Yamaguchi Y, Kang D, Honda K, Mii A, Shimizu A, Ubara Y, Yanagita M
Lysozyme-associated nephropathy (LyN) is an underrecognized cause of kidney dysfunction, commonly associated with chronic myelomonocytic leukemia (CMML). We present two cases of LyN with distinct clinical manifestations....Lysozyme-associated nephropathy (LyN) is an underrecognized cause of kidney dysfunction, commonly associated with chronic myelomonocytic leukemia (CMML). We present two cases of LyN with distinct clinical manifestations. In Case 1, an 80-year-old man with primary myelofibrosis developed progressive monocytosis, kidney dysfunction, proteinuria, and elevated serum and urinary lysozyme levels. Kidney biopsy revealed lysozyme-positive intracytoplasmic granules within proximal tubular cells, confirming the diagnosis of LyN. Notably, the progressive increase in the number of lysozyme- positive bone marrow cells may serve as an indicator of LyN activity. Treatment with hydroxycarbamide, a cytoreductive agent, and ruxolitinib, a Janus kinase inhibitor, successfully stabilized kidney function. In Case 2, a 63-year-old man with CMML developed acute kidney injury. Although the etiology of kidney dysfunction could not be determined during life, autopsy revealed diagnostic features of LyN. To further investigate LyN pathophysiology, we performed the first mass spectrometry-based proteomic analysis of proximal tubules in two cases. LyN samples showed marked lysozyme accumulation and upregulation of proteins involved in lysosomal system, lipid metabolism, cellular stress, and chronic inflammation. These findings suggest that chronic lysozyme overload disrupts intracellular homeostasis and contributes to kidney injury. LyN is underdiagnosed as unexplained tubular damage or chronic kidney disease, highlighting the need for awareness of the clinicopathological features.
BACKGROUND: Omicron variants of COVID-19 have driven global waves of infection. Hemodialysis patients are particularly vulnerable to severe outcomes. However, clinical data on the impact of Omicron infection in hemodialy...BACKGROUND: Omicron variants of COVID-19 have driven global waves of infection. Hemodialysis patients are particularly vulnerable to severe outcomes. However, clinical data on the impact of Omicron infection in hemodialysis patients remain limited. METHODS: We retrospectively collected clinical data on hemodialysis patients infected with the COVID-19 Omicron variant at Huashan Hospital between March 31 and May 3, 2022, a period marked by a rapid increase in COVID-19 cases. Patients were categorized into two groups based on chest CT: the non-COVID-19 pneumonia group and the COVID-19 pneumonia group. Additionally, 74 diabetic patients who did not receive hemodialysis and who contracted COVID-19 during the study period were analyzed as controls. RESULTS: A total of 150 hemodialysis patients were admitted to the hospital during this period, and 3 were excluded because of a lack of chest CT. At admission, 105 (71.4%) patients were diagnosed with COVID-19 pneumonia on the basis of chest CT. In contrast, 41.9% of non-hemodialysis diabetic patients exhibited manifestations of COVID-19 pneumonia. In dialysis patients, compared to the non-pneumonia group, the pneumonia group was older (65.7 ± 12.0 vs. 59.9 ± 16.3 years; p = 0.041) and had a higher prevalence of diabetes (39.0% vs. 11.9%; p = 0.003). The median time from the initial positive RT‒PCR result for SARS-CoV-2 to the first negative result was similar between the two groups. Serum levels of fibrinogen, NT-pro-BNP, and creatinine were independent factors associated with CT-defined COVID-19 pneumonia Conclusions: Hemodialysis patients had a higher prevalence of COVID-19 pneumonia. The fibrinogen level was an independent factor associated with CT-defined COVID-19 pneumonia.
BACKGROUND: Monoclonal Gammopathy of Renal Significance (MGRS) is a rare group of renal disorders caused by monoclonal immunoglobulins from non-malignant B-cell or plasma cell clones, with distinct amyloid (MGRS-A) and n...BACKGROUND: Monoclonal Gammopathy of Renal Significance (MGRS) is a rare group of renal disorders caused by monoclonal immunoglobulins from non-malignant B-cell or plasma cell clones, with distinct amyloid (MGRS-A) and non-amyloid (MGRS-NA) subtypes. METHODS: We explored real-world renal, haematologic, and survival outcomes in 17 MGRS patients (10 MGRS-A, 7 MGRS-NA) from a single tertiary centre. RESULTS: MGRS-NA patients presented with significantly worse baseline renal function (median eGFR 18.0 mL/min/1.73m² vs 49.0 mL/min/1.73m² in MGRS-A, p < 0.05) and progressed faster to dialysis (p < 0.01). Haematologic responses (≥VGPR) were achieved in 57.1% of MGRS-NA and 50% of MGRS-A patients, but these did not significantly correlate with renal improvement. Survival was similar between groups, with deaths in 28.6% of MGRS-NA and 20% of MGRS-A. Relapse occurred in 47.1% of patients, with median times of 51 months in MGRS-NA and 69 months in MGRS-A. Treatment, primarily Bortezomib-based chemotherapy, was associated with toxicities (94.1%), yet renal responses remained limited. CONCLUSION: The findings highlight the poor prognosis and rapid renal decline in MGRS-NA, emphasising the need for early diagnosis and integrated renal-haematologic service to improve outcomes in this rare population.
Kotenko O, Kozlovskaya N, Emirova K
… +16 more, Muzurov A, Moiseev S, Konakova I, Shavkin A, Makarova T, Gazizulina M, Vinogradov V, Ivanova E, Demyanova K, Korotchaeva Y, Proshina T, Melnikova Y, Рoladova L, Mazur Y, Markova O, Borozinets A
BACKGROUND: The objective of a multicentre, prospective, observational study of an eculizumab biosimilar (Elizaria®) was to analyse the efficacy and safety of long-term complement inhibitor therapy in patients with atypi...BACKGROUND: The objective of a multicentre, prospective, observational study of an eculizumab biosimilar (Elizaria®) was to analyse the efficacy and safety of long-term complement inhibitor therapy in patients with atypical haemolytic uraemic syndrome (aHUS). MATERIALS AND METHODS: The study included 50 patients aged 1 to 55 years, with 42% of them under the age of 18. The patients received the eculizumab biosimilar in routine clinical practice within 56 weeks; 19 patients (38%) had been treated with eculizumab prior to enrolment, whereas 31 patients (62%) were naive to complement inhibitors. RESULTS: By the end of the study, an increase in platelet count of 39.48±21.7×109/L and 33.61±24.06×109/L was reported in treatment-naive and treatment-experienced patients, respectively. By the end of the study, 96% of treatment-experienced patients and 100% of treatment-naive patients had normal platelet counts. The mean LDH activity did not change significantly, with levels of 253.84±122.22 U/L registered at screening and 245.24±93.52 U/L at the end of the study. In total, 39 patients (77.6%) at Week 21 and 40 patients (80%) at Week 52 had no thrombotic microangiopathy (TMA) events. During the study, the proportion of patients with a complete TMA response increased significantly, rising to 8% (P = 0.046). The proportion of patients with an eGFR improvement of 15 mL/min/1.73 m2 and more at Week 52 was 12%. During the safety assessment, 63 adverse events not related to the investigational medicinal product were reported. CONCLUSIONS: Long-term complement inhibitor therapy with the eculizumab biosimilar in patients with aHUS has demonstrated a stable effect, a favourable safety profile and low immunogenicity.
Background Progress in nephrology is still constrained by the limited ability of conventional experimental models to faithfully recapitulate the complex structure and function of the human kidney. Human pluripotent stem...Background Progress in nephrology is still constrained by the limited ability of conventional experimental models to faithfully recapitulate the complex structure and function of the human kidney. Human pluripotent stem cells (hPSCs)-derived kidney organoids provide a 3D in vitro experimental system that allows investigation of kidney development and disease-related mechanisms in a human cellular context, although still limited in their ability to reproduce the full structural and physiological complexity of the native kidney. Summary Kidney organoids have emerged as a powerful system to investigate both inherited and acquired kidney disorders. Genetic applications include cystic kidney diseases and ciliopathies, as well as inherited tubular and storage disorders, and glomerular genetic diseases. For acquired diseases and injuries, organoids support modeling of kidney damage (including exposure to pathogenetic factors, metabolic, diabetic, and profibrotic stress) and drug nephrotoxicity. These platforms enable research on mechanistic pathways through transcriptomic, proteomic, imaging, and functional readouts that can be applied at the level of specific nephron segments. Methodological advances, including improved differentiation protocols and organoid-on-chip systems, are enhancing maturation and physiological relevance. Nevertheless, kidney organoids remain immature, showing variable cellular composition and lacking a fully integrated vasculature and urinary outflow system, which currently limit their applicability as experimental models. Key Messages Kidney organoids provide a human-based platform for mechanistic and translational nephrology research. At present, they are primarily used for disease modeling and nephrotoxicity testing, while their broader applicability remains limited by current technical and biological challenges. Regenerative translation will depend on advances in maturation and integration of fully developed vascular and urinary system components.
BACKGROUND: Frailty and chronic kidney disease (CKD) are common, interrelated conditions in ageing populations, yet the association between kidney function and frailty remains incompletely characterized, particularly whe...BACKGROUND: Frailty and chronic kidney disease (CKD) are common, interrelated conditions in ageing populations, yet the association between kidney function and frailty remains incompletely characterized, particularly when estimated using different eGFR equations. METHODS: We analyzed 17,864 participants aged ≥45 years from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study (CHARLS). Frailty was defined primarily by the deficit-accumulation frailty index (FI), with the Fried physical frailty phenotype applied in a prespecified sensitivity analysis. Kidney function was estimated using the CKD-EPI creatinine (eGFRcr), cystatin C (eGFRcys), and combined creatinine-cystatin C (eGFRcr-cys) equations. Multivariable logistic regression, restricted cubic splines, and threshold effect models were used to assess linear and non-linear associations, with adjusted predicted probabilities derived to quantify absolute risk. RESULTS: Overall, 10.0% of participants were frail and 38.6% prefrail. Lower eGFR was independently associated with higher odds of frailty across all three equations, with the strongest and most consistent associations observed for eGFRcys (eGFRcys <30 vs ≥90 mL/min/1.73 m²: OR 4.39; 95% CI, 2.32-8.32; P for trend <0.001), corresponding to an adjusted absolute risk difference of 18.9 percentage points. eGFRcr-cys showed similar but attenuated associations, whereas eGFRcr was associated with frailty only at severely reduced levels (<30 mL/min/1.73 m²). Non-linear relationships were evident for eGFRcys and eGFRcr-cys, with inflection points at 58.78 and 51.65 mL/min/1.73 m², respectively. Sensitivity analyses using the Fried phenotype and a model excluding laboratory parameters yielded directionally consistent results. CONCLUSION: Cystatin C-based eGFR was more strongly and consistently associated with frailty than creatinine-based estimates in middle-aged and older Chinese adults, with associations emerging at earlier stages of kidney dysfunction. Incorporating eGFRcys into kidney function assessment in this population may aid the identification of individuals at increased risk of frailty, pending confirmation in longitudinal and interventional studies.
BACKGROUND: Kidney replacement therapies (KRT) such as dialysis have a significant environmental impact, yet clinician engagement with sustainable kidney care remains limited. Our objective was to develop a mobile phone...BACKGROUND: Kidney replacement therapies (KRT) such as dialysis have a significant environmental impact, yet clinician engagement with sustainable kidney care remains limited. Our objective was to develop a mobile phone application to raise awareness of clinicians about Green Nephrology. METHODS: We developed and piloted a web-based mobile application designed to raise awareness of "Green Nephrology" through short, interactive information modules. The app was introduced at the World Congress of Nephrology 2025. It presented users with real-world dilemmas and evidence-based facts about the environmental impact of kidney care choices. We discuss the possibilities of using such interactive modules for sensitizing doctors, nurses and technicians. RESULTS: Thirty-eight delegates used the app and reported it as intuitive, enjoyable, and thought-provoking. CONCLUSION: This feasibility pilot suggests that lightweight, gamified digital tools can effectively promote reflection and discussion on environmentally sustainable nephrology practices.
INTRODUCTION: Human fetal kidneys contain macrophages, innate immune cells postulated to enhance their development. Macrophages have also been implicated in the pathobiology of human kidney malformations and Wilms tumour...INTRODUCTION: Human fetal kidneys contain macrophages, innate immune cells postulated to enhance their development. Macrophages have also been implicated in the pathobiology of human kidney malformations and Wilms tumour. Human pluripotent stem cell (hPSC)-derived kidney organoids contain nephrons but lack macrophages. METHODS: We hypothesised that combining hPSC-derived macrophages with hPSC-derived kidney precursors would modify nephrogenesis. Macrophages were added in numbers of 1%, 5% or 20% relative to a constant number of nephrogenic cells. RESULTS: As assessed by CD68 immunostaining, no macrophages were detected in organoids derived from MAN13 hPSCs without added hPSC-derived macrophages. Composite organoids contained macrophages between tubules, mimicking native human fetal kidneys. Quantification of macrophages in histology sections positively correlated with numbers of macrophages added. Assessed by CD31/PECAM-1 and CD68 co-immunostaining, macrophages were scattered through organoids, with some near endothelia. Added macrophages, however, did not alter the extent of CD31/PECAM-1 immunostaining. Macrophages added at 5% were associated with increases in the percentage cross-sectional areas occupied by immunostaining for the glomerular markers synaptopodin and nephrin. Higher numbers (20%) of macrophages disrupted organoid growth. CONCLUSION: This preliminary study demonstrates that it is technically feasible to populate hPSC derived-nephron organoids with hPSC- derived maturing macrophages. The study also suggests that, depending on their quantity, added macrophages may have beneficial or harmful effects on nephron organoids. These insights support the proposition that macrophages play roles in normal and abnormal development of human kidneys. Further studies are needed to discover the molecular mechanisms of these effects and to replicate findings using other hPSC lines.
Vanholder R, Abdellatif D, Soares Dos Santos AC
… +8 more, Correa-Rotter R, Gopalakrishnan N, Wang B, Roumeliotis S, Balducci A, Haris Á, Yadla M, Hsiao LL
BACKGROUND: Kidney xenotransplantation has re-emerged as a viable therapeutic strategy to address the global shortage of donor organs, driven by substantial advances in porcine genetic engineering and immunomodulatory th...BACKGROUND: Kidney xenotransplantation has re-emerged as a viable therapeutic strategy to address the global shortage of donor organs, driven by substantial advances in porcine genetic engineering and immunomodulatory therapies. Clinical experiences in brain-dead decedents and, more recently, in living recipients have demonstrated that genetically modified pig kidneys can provide life-sustaining renal function in humans, marking a pivotal milestone in the field. SUMMARY: Elimination of major carbohydrate xenoantigens, particularly through GGTA1 deletion, has effectively abrogated hyperacute rejection, enabling short- to intermediate-term xenograft survival. However, emerging data reveal that xenotransplantation elicits a uniquely aggressive and persistent immune response involving both innate and adaptive immunity. Conventional immunosuppressive regimens used in kidney allotransplantation appear insufficient when reduced in intensity and require full-dose application combined with B-cell depletion and costimulation blockade to control pre-existing xenoreactive T-cells and de novo antibody formation. Complement activation remains a central pathogenic mechanism despite extensive donor genetic modification, with emerging evidence suggesting that sustained control of both terminal and proximal complement activation may be beneficial in selected settings. An additional, unexpected challenge is the development of early and often persistent nephrotic-range proteinuria, which may reflect species-specific glomerular barrier incompatibilities, immune-mediated injury or both, and may have important implications for graft survival by promoting urinary loss of biologic immunosuppressive agents. KEY MESSAGES: Hyperacute rejection in kidney xenotransplantation has been effectively overcome through targeted genetic modifications of donor pigs. However, xenotransplantation remains characterized by a sustained adaptive and innate immune response and ongoing complement activation, necessitating intensified and multimodal immunosuppression. An additional emerging challenge is early and sometimes persistent nephrotic-range proteinuria, which may compromise graft function and alter the pharmacokinetics of biologic immunosuppressive agents. Future progress will depend on integrated strategies combining genetic engineering, costimulation blockade, and appropriately targeted complement inhibition to achieve long-term xenograft survival.
Preterm birth disrupts kidney development, resulting in reduced nephron number and structural immaturity of glomeruli and podocytes that increases the risk of hypertension, proteinuria, and subsequently chronic kidney di...Preterm birth disrupts kidney development, resulting in reduced nephron number and structural immaturity of glomeruli and podocytes that increases the risk of hypertension, proteinuria, and subsequently chronic kidney disease (CKD) later in life. Since nephrogenesis ceases around 36 weeks of gestation, preterm infants cannot generate new nephrons after birth, making them vulnerable to long-term renal dysfunction. Unravelling the mechanisms behind this impaired development has been limited by the complexity of human nephrogenesis and the lack of physiologically relevant experimental models. Recent advances in human induced pluripotent stem cell-derived kidney organoids have made it possible to model nephrogenesis in vitro. These organoids replicate key processes such as nephron differentiation, ureteric bud branching, and kidney vascularization, allowing detailed study of kidney development and injury. Moreover, molecular interventions-including retinoic acid (RA), glial-cell-line-derived neurotrophic factor (GDNF), and insulin-like growth factor 1 (IGF1)-show the potential to enhance nephron formation and protect against kidney injury. Key Messages • Kidney organoids provide a powerful, human-relevant system to study nephrogenesis and CKD mechanisms. • Integration of the ureteric bud and enhanced vascularization significantly improves organoid maturity towards a more in vivo-like state. • Targeted molecular interventions such as RA, GDNF, and IGF1 offer potential strategies to enhance nephron endowment and mitigate CKD risk in preterm-born individuals, and may be studied using kidney organoids.
INTRODUCTION: Karyomegalic interstitial nephritis (KIN) is a rare entity characterized by enlarged, hyperchromatic, and pleomorphic tubular epithelial nuclei within the setting of chronic tubulointerstitial nephritis. Al...INTRODUCTION: Karyomegalic interstitial nephritis (KIN) is a rare entity characterized by enlarged, hyperchromatic, and pleomorphic tubular epithelial nuclei within the setting of chronic tubulointerstitial nephritis. Although classically associated with hereditary mutations in the FAN1 gene, acquired forms have been described, generally linked to the use of cytotoxic or immunomodulatory agents that presumably act as a "second hit." CASE PRESENTATION: We report the case of a 53-year-old male with a history of acute myeloid leukemia in complete remission after allogeneic stem cell transplantation, who developed acute kidney injury following prolonged treatment with ruxolitinib for graft-versus-host disease. Renal biopsy revealed characteristic features of KIN, while genetic testing was negative for FAN1 mutations. After ruxolitinib withdrawal, progressive improvement in renal function was observed. CONCLUSION: This represents the first reported case of KIN associated with JAK inhibitors. We propose that ruxolitinib may induce DNA repair defects in the absence of known genetic predisposition, highlighting the need to consider this entity in patients with unexplained chronic interstitial nephropathy under complex immunomodulatory therapies.
BACKGROUND: Imbalances in serum potassium levels increase morbidity, but data on their impact on outcomes in noncardiac surgery patients remain limited. OBJECTIVE: The aim of this surgery was to assess the association be...BACKGROUND: Imbalances in serum potassium levels increase morbidity, but data on their impact on outcomes in noncardiac surgery patients remain limited. OBJECTIVE: The aim of this surgery was to assess the association between preoperative potassium levels and postoperative outcomes in noncardiac surgery patients. METHODS: We conducted a retrospective study of patients who underwent noncardiac surgery at Cooper Hospital between 2010 and 2022. Clinical data were obtained from the NSQIP database, while preoperative potassium values were extracted from the electronic medical records. RESULTS: The sample consisted of 12,574 patients, comprising 39% males and 61% females. A total of 73% were white, and 18% were black. Elective procedures comprised 68.5% of cases. Preoperative potassium level was ≤3.5 mEq/L in 784 (6.2%) patients and > 5 mEq/L in 389 (3%). The hyperkalemic group was older on average and had a higher prevalence of ASA class 3 or higher. Hypokalemia was significantly associated with increased rates of postoperative mechanical ventilation (>48 h), deep vein thrombosis, sepsis, prolonged hospital stay, 30-day readmissions, and unplanned return to the operating room. Hyperkalemia was associated with higher incidences of cardiac arrhythmias, myocardial infarction, 30-day mortality, and readmissions. After multivariable regression, hypokalemia remained significantly associated with prolonged hospital length of stay and postoperative sepsis and hyperkalemia with mortality. CONCLUSION: Preoperative potassium abnormalities assessed within 48 h of noncardiac surgery identify patients at higher postoperative risk. Hypokalemia was associated with increased ventilator use, sepsis, and prolonged hospital stay, while hyperkalemia was associated with mortality and 30-day readmission. These results support incorporating potassium status into routine perioperative evaluation while avoiding assumptions about causality. Preoperative electrolyte optimization may improve surgical outcomes and should be prioritized.
BACKGROUND: The 2022 NYC Marathon was the hottest on record. At several hospitals near the race's finish, a larger volume of heat stress-related kidney injury was observed. We sought to examine the incidence of post-mara...BACKGROUND: The 2022 NYC Marathon was the hottest on record. At several hospitals near the race's finish, a larger volume of heat stress-related kidney injury was observed. We sought to examine the incidence of post-marathon rhabdomyolysis observed with respect to race day temperature and humidity. METHODS: All charts of patients who had a creatine phosphokinase (CPK) level >5,000 U/L on the date of the marathon and subsequent 4 days for the years 2017-2023 at four NYC hospitals were reviewed. Patients were included for analysis if marathon participation was indicated in the chart and no other causes of rhabdomyolysis were evident. Race day heat was measured as heat index to capture the effects of both temperature and humidity. RESULTS: In 2022, there were 24 runners with post-marathon rhabdomyolysis, compared to 15 total patients for the other 5 marathons combined. Cases of post-marathon rhabdomyolysis strongly correlated to race day heat index. In addition to record heat, the 2022 NYC Marathon had the largest change in heat as compared to the previous 14-day average. The 2022 cohort skewed male (20 male: 4 female), was on average 32.2 years of age, and presented within 2 days of the marathon. The average peak CPK was 21,426 IU/L (range 5,177 to 88,430 IU/L). All patients received intravenous fluids. Only 1 patient had a further rise in creatinine, reaching a peak of 8.69 mg/dL (from 5.81 on arrival) before starting hemodialysis. CONCLUSION: The 2022 NYC Marathon was the hottest on record, and was found to have the highest incidence of post-marathon rhabdomyolysis. Cases of rhabdomyolysis correlated with the race day heat index. Additionally, 2022 had the largest change in race day temperature, which may present an additional risk.
INTRODUCTION: Thrombotic microangiopathy (TMA) with associated nephrotic syndrome is a unique and rare condition that is infrequently described in pediatrics. CASE PRESENTATIONS: Four children with steroid-resistant neph...INTRODUCTION: Thrombotic microangiopathy (TMA) with associated nephrotic syndrome is a unique and rare condition that is infrequently described in pediatrics. CASE PRESENTATIONS: Four children with steroid-resistant nephrotic syndrome (SRNS), immune-mediated and of monogenic origin, presented with TMA during late stages of chronic kidney disease. All patients tested negative for Shiga toxin and had normal A Disintegrin-like and Metalloprotease with Thrombospondin type 1 repeats 13 (ADAMTS13) activity. Genetic and functional studies of complement dysregulation were negative. Three of the 4 patients treated with Eculizumab showed good hematologic response but no kidney function recovery. None of the three children who underwent kidney transplantation had recurrent TMA. CONCLUSIONS: TMA may develop in patients with SRNS, manifesting as an unexplained worsening of kidney function, new-onset hypertension, hemolytic anemia, and thrombocytopenia. Eculizumab was effective in improving hemolytic markers without kidney function recovery. TMA did not recur after kidney transplantation in this entity.
INTRODUCTION: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a form of monoclonal gammopathy of renal significance, characterized by kidney injury caused by monoclonal immunoglobulin...INTRODUCTION: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a form of monoclonal gammopathy of renal significance, characterized by kidney injury caused by monoclonal immunoglobulin deposition in the glomeruli. While detectable clones are only found in 20-30% of PGNMID, plasma cell- or B-cell-targeting therapies are suggested to be effective. Recent case reports suggested immune dysregulation, such as viral infections or vaccinations, could potentially trigger the onset or relapse of PGNMID. Here, we report a case of PGNMID without detectable clones, which relapsed after viral enteritis, presenting with severe acute kidney injury (AKI) and nephrotic syndrome. CASE PRESENTATION: A 60-year-old man, originally diagnosed with IgG3 lambda type PGNMID with nephrotic syndrome (urine protein/creatinine ratio (UPCR) of 5.3 g/gCr), was treated with non-clone-directed therapeutic regimens, including glucocorticoids. The patient initially achieved a partial response with a UPCR of 1-3 g/gCr and negative microhematuria. Approximately 2 years later, the patient presented with severe AKI (Cr 11.0 mg/dL) requiring dialysis, and nephrotic syndrome (UPCR 5.5 g/gCr, and serum albumin 2.4 g/dL) after having had viral enteritis. Second kidney biopsy confirmed a similar pattern of injury consistent with PGNMID with IgG3 lambda deposition, severe endocapillary inflammation, mesangial expansion, and remarkable narrowing of the glomerular capillary lumina. As it was refractory to glucocorticoid pulse therapy, clone-directed therapies with daratumumab and bortezomib were initiated. This intervention resulted in the cessation of dialysis and an improvement in urinary parameters. CONCLUSION: Clinicians should recognize that severe AKI may develop during the course of PGNMID, potentially triggered by infections. Furthermore, this case highlights the efficacy of clone-directed therapy with daratumumab and bortezomib in treating recurrent PGNMID without detectable clones.