Key Points: CKD was undiagnosed in 56% of patients and linked to early mortality, kidney failure, and cardiovascular events despite milder disease. First-year mortality was two-fold higher among undiagnosed patients, emphasizing the short-term risks of missed diagnosis. Sodium-glucose cotransporter 2 inhibitors were associated with better cardiovascular and kidney outcomes, yet their uptake remained low. Background: CKD is a global public health challenge, yet underdiagnosis in routine care remains pervasive, leading to missed opportunities for early intervention. Evidence directly linking missed diagnosis to adverse outcomes in large, nationwide populations is limited. Methods: We conducted a nationwide, population-based cohort study including 640,217 adults meeting Kidney Disease Improving Global Outcomes (KDIGO) laboratory criteria for CKD (eGFR30 mg/g on at least two occasions ≥3 months apart) between 2000 and 2023. CKD underdiagnosis was defined as absence of a documented diagnosis in electronic medical records. The primary end point was a composite of all-cause mortality or KRT. Secondary end points included first-year mortality and time to all-cause mortality, KRT, and major cardiovascular events. Associations were assessed using multivariable Cox proportional hazards models, stratified by diabetes status, with additional propensity score–matched sensitivity analyses. Results: Of 640,217 patients who met laboratory criteria for CKD, 359,805 (56%) lacked a documented diagnosis. Undiagnosed patients were younger, more often female, and disproportionately from minoritized populations. Absence of a CKD diagnosis was associated with a markedly shorter time to death or KRT (hazard ratio, 1.10; 95% confidence intervals [CI], 1.09 to 1.11). First-year mortality was higher in undiagnosed versus diagnosed CKD (8.0% [95% CI, 7.9 to 8.1] versus 4.1% [95% CI, 4.0 to 4.2]), despite less advanced disease at baseline. Use of renoprotective and cardioprotective medications was significantly lower in undiagnosed patients. Sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy was independently associated with lower risks of death, kidney failure, and cardiovascular events, showing a consistent protective effect in both diabetic and nondiabetic subgroups. Findings were consistent across sensitivity analyses. Conclusions: In this real-world nationwide CKD cohort, underdiagnosis was common and associated with premature death, kidney failure, and cardiovascular morbidity. There was consistent association of SGLT2 inhibitors with better cardiovascular and kidney health outcomes.

Background/Objectives: Acute kidney injury is a frequent complication among patients hospitalized in internal medicine wards and is associated with adverse outcomes. While increased AKI burden has been reported during pandemics, data on AKI during other forms of acute healthcare system disruption, including armed conflict, are limited. We evaluated AKI incidence and outcomes during a period of wartime healthcare system disruption. Methods: We conducted a retrospective single-center cohort study comparing internal medicine hospitalizations during the initiation of the Israel–Gaza war with a corresponding pre-war period in 2022. AKI was identified based on changes in serum creatinine during hospitalization. Clinical characteristics, AKI etiology, hospitalization indication at admission, and in-hospital outcomes were compared between periods. Multivariable regression models assessed the association between year of hospitalization and outcomes, adjusting for sex, comorbidities, admission kidney function, vital signs, and hospitalization indication. Results: AKI occurred in 110 of 2228 hospitalizations in 2022 (4.9%) and in 95 of 1456 hospitalizations in 2023 (6.5%), representing a 32% relative increase during the wartime period (relative risk 1.32, 95% confidence interval 1.03–1.69). Baseline demographics, comorbidity burden, admission vital signs, and kidney function were similar between cohorts. During the wartime period, hospitalizations were less frequently infection-related, and AKI etiology shifted toward a higher proportion of pre-renal and unspecified causes. Patients hospitalized in 2023 more frequently required kidney replacement therapy and were more often discharged with ongoing dialysis or to nursing facilities. After multivariable adjustment, hospitalization during 2023 remained independently associated with less favorable AKI-related outcomes. Conclusions: Wartime healthcare system disruption was associated with higher AKI incidence and less favorable AKI-related outcomes among internal medicine hospitalizations, independent of measured patient-level risk factors. These findings suggest that kidney outcomes may be sensitive to system-level stress during healthcare emergencies and underscore the importance of maintaining AKI prevention, monitoring, and recovery pathways under such conditions.

Background/Objectives: Uremic middle molecules contribute to chronic inflammation and symptom burden in hemodialysis patients. The Theranova 500 medium-cutoff (MCO) dialyzer enhances clearance of larger uremic toxins and may offer clinical advantages. We hypothesized that Theranova 500 would improve dialysis adequacy (spKt/V), attenuate inflammation (CRP), and provide targeted improvement in symptom burden compared with the high-flux Revaclear 500. Methods: We conducted an open-label, prospective, quasi-randomized controlled trial including forty prevalent adult hemodialysis patients from two centers in Israel (Barzilai and Sheba Medical Centers). Patients were sequentially allocated 1:1 to Theranova 500 or Revaclear 500. Demographic, laboratory, and patient-reported outcomes (KDQOL-SF, Dialysis Symptom Index) were assessed at baseline and week 24. Within-group changes were analyzed using paired tests, and between-group differences using ANCOVA adjusted for baseline values. Safety monitoring included adverse events, dialyzer reactions, hospitalizations, and mortality. Results: Theranova 500 significantly increased mean spKt/V (1.24 ± 0.33 to 1.40 ± 0.36; p = 0.025), while Revaclear showed no significant change. CRP remained stable in the Theranova group but rose nearly threefold in the Revaclear group by week 24 (p < 0.001). Albumin, dry weight, anemia and mineral bone parameters remained stable in both groups. Total cholesterol increased modestly in the Theranova arm without nutritional compromise. Symptom-level analysis showed improvement in irritability, restless leg, dry skin, chest pain, and diarrhea with Theranova, whereas global KDQOL-SF domain scores improved similarly in both groups. No non-serious adverse events, hypersensitivity reactions, or dialyzer-related intolerance was observed. Hospitalizations (n = 8 per group) and mortality (two per group) were identical. Conclusions: Over 24 weeks, Theranova 500 MCO dialyzer improved dialysis adequacy and prevented the rise in inflammatory markers seen with Revaclear without compromising nutrition or safety. Targeted improvement in specific uremic symptoms suggests potential clinical benefit beyond small-molecule clearance. These findings support the safety and clinical utility of expanded hemodialysis and highlight the need for larger, fully randomized trials to validate these results.

Fibrillary glomerulonephritis (FGN) is an uncommon glomerular deposition disease characterized by randomly oriented, nonbranching fibrils that are usually Congo-red-negative and larger than amyloid fibrils on electron microscopy. The discovery of DNAJ homolog subfamily B member 9 (DNAJB9) has transformed FGN from a primarily ultrastructural diagnosis into a molecularly recognizable disease. However, the pathogenic significance of DNAJB9 remains unresolved: it may represent a highly specific biomarker, a putative autoantigen, a chaperone-associated scaffold, or a marker of disturbed protein quality control. We report two patients with positive glomerular DNAJB9 staining and markedly divergent clinical phenotypes. The first patient, a 58-year-old man, presented with severe acute kidney injury, nephritic urinary sediment, severe hypertension, crescentic immune-complex glomerulonephritis, and dialysis-requiring kidney failure. Electron microscopy and IgG subclass staining were unavailable; therefore, the findings were interpreted as probable rather than definitive DNAJB9-positive FGN. Diagnostic and causal interpretation was further complicated by concurrent Klebsiella pneumoniae urinary tract infection, mild bilateral hydronephrosis, acute tubulointerstitial injury, and severe hypertension. Kidney function did not recover despite glucocorticoids and cyclophosphamide, but the adverse outcome and treatment response cannot be attributed to FGN alone. The second patient, a 66-year-old woman, presented with chronic proteinuria, preserved kidney function, inactive urinary sediment, and lupus-like serologic findings. Electron microscopy demonstrated randomly arranged, nonbranching 13–19 nm fibrils, and DNAJB9 staining confirmed FGN. She was managed with angiotensin receptor blockade and dapagliflozin, with reduction of proteinuria to below 1 g/day. Together with previously published cohorts, these cases illustrate the diagnostic value of DNAJB9 staining and the potential clinicopathologic heterogeneity of FGN. However, Case 1 should be considered a clinically confounded, hypothesis-generating example and not definitive evidence that FGN alone caused the crescentic presentation, dialysis dependence, or lack of response to immunosuppression.

Individuals may be prone or resistant to the development of type 2 diabetes. The basis for susceptibility is in part genetic, but environmental factors are likely to come into play. The gut microbiome stands at the interface of genetics and the host microenvironment. Its role in mediating susceptibility to diabetes, however, has not been resolved. Here we investigated whether the gut microbial composition contributes to susceptibility to diabetes, as distinct from disease development. We hypothesized that distinct microbial signatures modulate sensitivity or resistance to a diabetogenic diet (DD) and that separate signatures are linked to disease development. To test this hypothesis, we studied the Cohen diabetic rat model, comprising a diabetes-sensitive strain (CDs/y) and a diabetes-resistant strain (CDr/y). When exposed to DD, diabetes develops in CDs/y but not in CDr/y rats; on a regular diet (RD), both strains remain metabolically normal. To establish the contribution of the gut microbiome to susceptibility, we studied the fecal microbial composition in young, metabolically healthy CDs/y and CDr/y rats, using 16S rRNA gene sequencing, measures of α- and β-diversity, and differential taxonomic abundance. We found distinct, strain-specific gut microbiota profiles that differentiated diabetes-sensitive from -resistant animals, indicating an association between microbial composition and susceptibility. To test causality, we co-housed sensitive and resistant animals to allow passive microbial cross-transfer and fed the animals with DD. Co-housing led to partial convergence of microbial communities and significantly attenuated the diabetic phenotype in CDs/y rats, supporting a contributory and causal role for the gut microbiome in modulating sensitivity to diabetes. The resistance phenotype, on the other hand, remained unchanged. To distinguish between the contribution of the gut microbiome to susceptibility to diabetes as opposed to the development of the disease, we studied the gut microbial profiles across strains after feeding with DD or RD and the development of diabetes in CDs/y but not in CDr/y. We found distinct taxonomic signatures that differentiated diabetic from non-diabetic animals. These findings demonstrate that the gut microbiome contributes to susceptibility to diabetes with separate pathways from those linked to the development of diabetes and may represent an important modifiable determinant of diabetes risk and a target for early intervention.

Background/Objectives: Acute kidney injury (AKI) is a clinically important complication among hospitalized urology patients. However, data from general urology inpatient populations remain limited. We aimed to assess AKI frequency in a monitored urology inpatient cohort, identify associated predictors, and develop an exploratory admission-based risk stratification model. Methods: We conducted a retrospective observational cohort study of adults admitted to a tertiary urology ward between June 2023 and May 2024 who had at least two serum creatinine measurements during hospitalization. AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria. Demographic, clinical, laboratory, and procedural data were analyzed. Multivariable logistic regression identified factors associated with AKI and was used to construct a reduced exploratory admission-based risk model. Results: Among 196 monitored patients, 67 (34.2%) developed AKI during hospitalization, and 82.1% had KDIGO Stage 1 AKI. Higher admission serum creatinine, hypertension, nephrolithiasis, and ureteral interventions were independently associated with AKI. AKI was also associated with longer hospitalization (6.4 ± 4.2 vs. 5.1 ± 3.2 days, p = 0.044). The reduced exploratory model identified low-, intermediate-, and high-risk groups with progressively increasing AKI incidence (7.7%, 32.3%, and 76%, respectively; AUC = 0.76). Conclusions: In this monitored cohort, AKI was frequent and associated with admission characteristics and prolonged hospitalization. These findings support targeted renal monitoring in higher-risk patients. The admission-based risk model is exploratory and requires validation in prospective multicenter cohorts before clinical implementation.