We report the case of a 53-year-old man who presented with Fanconi syndrome as the initial clinical manifestation. Laboratory findings included hypokalemia, hypophosphatemia, mild metabolic acidosis, and renal glucosuria. Kidney biopsy revealed crystalline light-chain proximal tubulopathy (LCPT) with κ-restricted light-chain deposition in proximal tubular epithelial cells. Bone marrow examination demonstrated multiple myeloma with plasma cells containing Auer rod-like intracytoplasmic inclusions, an extremely rare morphological finding. The coexistence of crystalline κ-restricted LCPT and Auer rod-like inclusions in plasma cells is exceedingly rare and remains poorly characterized. This case underscores the diagnostic value of kidney biopsy in unexplained Fanconi syndrome and suggests that abnormal physicochemical properties of monoclonal κ light chains may contribute to intracellular crystal formation in both renal tubular epithelial cells and plasma cells.

Glycosuria, whether genetically induced or triggered by SGLT2 inhibitors, activates compensatory glucose-producing pathways that limit glucose lowering in type 2 diabetes. To define these pathways, we studied renal Glut2 knockout mice, which progressively lose Slc5a2 (encoding SGLT2) expression yet maintain normoglycemia despite marked urinary glucose loss. Metabolic profiling and isotope tracing revealed coordinated adaptations in mannose and glutamine metabolism during glycosuria. Skeletal muscle reduced glucose utilization and showed increased incorporation of mannose-derived carbon into oxidative metabolism while whole-body glycolysis declined, establishing a systemic glucose-sparing state. Disruption of glutamine transport or mannose utilization caused hypoglycemia in mice treated with an SGLT2 inhibitor, consistent with reliance on these substrates to maintain glucose homeostasis during glycosuria. Multiomic profiling revealed increased expression and chromatin accessibility of mannose and glutamine transport pathways. These findings identify a kidney-coordinated metabolic program associated with maintenance of systemic glucose homeostasis during glycosuria and may inform strategies to optimize the glucose-lowering efficacy of SGLT2 inhibitors.

The association between Cushing's syndrome (CS) and diabetes mellitus (DM) in cats is rarely reported. Complications related to hypercortisolism and persistent hyperglycemia may occur, which may complicate the control of both endocrinopathies. This report describes the case of a 10-year-old Persian cat diagnosed with CS and DM. The patient presented with polyuria, polydipsia, chronic dry seborrhea on the dorsal region and flanks, and lack of hair regrowth on the abdomen. Through the dexamethasone suppression test (0.1 mg/kg) and the presence of persistent hyperglycemia with elevated fructosamine levels and glycosuria, diagnoses of Cushing's syndrome and DM were established. Treatment was initiated with trilostane (2 mg/kg PO BID) for CS and insulin glargine (2 IU/animal SC BID) for DM, resulting in stabilization of blood glucose, cortisol concentrations, and the patient's clinical condition, although cutaneous fragility persisted for a prolonged period. Diagnostic investigation for hypercortisolism should be considered in cats with DM to allow earlier diagnosis, reduce underdiagnosis, and improve the availability of epidemiological and clinical data on this association. The diagnostic approach and clinical management described may aid veterinarians in recognizing this coexistence and anticipating therapeutic challenges, such as persistent cutaneous fragility despite cortisol control.

Heart failure with preserved ejection fraction (HFpEF) remains a major cause of cardiovascular morbidity and mortality, yet lacks effective disease-modifying therapies owing to pronounced biological heterogeneity. Emerging evidence indicates that HFpEF is not merely a disorder of diastolic dysfunction but a systemic immunometabolic condition characterized by mitochondrial energetic impairment, altered substrate utilization, and chronic low-grade inflammation. This review examines the potential role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in modulating mitochondrial-inflammatory coupling in HFpEF and proposes this axis as an emerging mechanistic framework that may contribute to their therapeutic effects. We review preclinical and clinical evidence suggesting that HFpEF is associated with coordinated immunometabolic reprogramming across cardiomyocytes, endothelial cells, and cardiac immune populations, which may contribute to mitochondrial-inflammatory uncoupling. We discuss evidence that SGLT2 inhibitors act beyond glycosuria to potentially improve myocardial energetic efficiency, enhance mitochondrial quality control, reduce oxidative stress, and attenuate maladaptive inflammatory signaling, including inflammasome activation. Collectively, these findings suggest that restoration of mitochondrial-inflammatory coupling may partly explain the clinical benefits of SGLT2 inhibitors in HFpEF, although direct mechanistic evidence in humans remains limited. Finally, we highlight emerging biomarkers and future therapeutic strategies targeting the mitochondrial-inflammatory axis to support the development of precision medicine approaches for HFpEF.

The introduction of the sodium-glucose cotransporter-2 inhibitors (SGLT2i) was a landmark moment in the treatment of diabetes. Their unique insulin independent mechanism of action, results in decreased reabsorption of glucose at the renal tubular level and increased glucosuria, which lowers blood glucose along with modest weight reduction due to caloric loss in the urine. Today, the SGLT2i are approved not only for their glycemic benefits, but also to reduce the risk of heart failure (HF) hospitalization and progression to chronic kidney disease (CKD) in patients with type 2 diabetes (T2DM) and CKD/HF. Notably, the SGLT2i are also approved for cardiorenal benefits in those without diabetes. However, SGLT2i are not approved for use in those with type 1 diabetes (T1DM) due to the increased risk for diabetic ketoacidosis (DKA) and euglycemic ketoacidosis. This review provides an overview of the various metabolic effects seen with the use of SGLT2i and dual SGLT1/2 inhibitors in patients with T1DM, including beneficial effects on glycemia despite a paradoxical increase in endogenous glucose production (EGP), changes in insulin sensitivity, hyperglucagonemia and changes in substrate oxidation. We also discuss mechanisms leading to increased ketogenesis and a higher risk of DKA in those with T1DM and potential measures to mitigate this risk, so that patients with T1DM can safely avail the robust glycemic and cardiorenal benefits of these agents.

Renal complications of sickle cell disease (SCD) often begin with tubular dysfunction (TD), yet this entity remains insufficiently recognized in African populations. Data from adults in Kinshasa are particularly scarce. We conducted a cross-sectional study between March 2023 and April 2024, enrolling 279 clinically stable adult SCD patients from 14 centers in Kinshasa. Tubulopathy was defined by the concomitant presence of three abnormalities: urinary α1-microglobulin-to-creatinine ratio (A1M/Cr) ≥20 mg/g, dipstick glucosuria ≥1+ with plasma glucose <126 mg/dL, and urine pH ≥5.5. Glomerular involvement was assessed by urinary albumin to creatinine ratio (UACR ≥30 mg/g). Measured GFR (mGFR) was obtained by iohexol clearance. Multivariable logistic regression was used to identify independent factors associated with tubulopathy. Tubulopathy was identified in 58 patients (20.8%). Compared with those without tubulopathy, affected patients had significantly higher median A1M/Cr (44.7 vs. 14.2 mg/g; p < 0.001) and UACR (22.1 vs. 10.7 mg/g; p = 0.007). They also displayed lower mean eGFR by CKD-EPIcrea+cys2021 (107.4 vs. 115.9 mL/min/1.73 m[2]; p = 0.031) and higher LDH levels (217.0 vs. 209.1 IU/L; p = 0.016). In multivariable analysis, independent predictors of tubulopathy included higher LDH (per 100 IU/L increase) (aOR 2.53, 95% CI 1.14-5.61), UACR ≥30 mg/g (aOR 1.94, 95% CI 1.18-5.18), while hydroxyurea use was independently associated with lower odds of tubulopathy (aOR 0.37, 95% CI 0.16-0.87). One in five stable adult SCD patients in Kinshasa presented with tubulopathy. This phenotype was associated with hemolysis, albuminuria, and lower eGFR, whereas hydroxyurea use was inversely associated with tubulopathy.

Biological sex is an important determinant of kidney disease susceptibility and outcomes. The epigenetic modifier KDM6A is an X chromosome-expressed lysine demethylase and molecular scaffold that escapes X chromosome inactivation. Here, we compared the effects of deletion of KDM6A from kidney tubule epithelial cells in female and male mice (KDM6A [TubKO]). Knockout of KDM6A from tubule cells aggravated kidney fibrosis caused by unilateral ureteral obstruction (UUO) in female mice, whereas male mice were unaffected by KDM6A absence. Unexpectedly, female (but not male) KDM6A [TubKO] mice developed spontaneous glucosuria that, when stressed by ligation of one ureter, presented as polyuria and a Fanconi renotubular syndrome-like picture affecting the unobstructed kidney. Absence of KDM6A from tubule epithelial cells of female mice caused mitochondrial circularization, tubule cell vacuolization with focal atrophy and lymphoid infiltration, and diminished sodium/glucose cotransporter 2 (SGLT2). Spatial transcriptomics and untargeted metabolomics revealed that knockout of KDM6A in female mice caused a shift in gene programs and metabolic pathways indicative of tubule cell metabolic dysfunction. In male mice, transcripts of the Y chromosome-expressed gametolog of Kdm6a , Uty were present in tubule epithelial cells at levels comparable to Kdm6a and they were upregulated with UUO. In summary, KDM6A is essential for normal tubule epithelial cell homeostasis in females but not in males. KDM6A and UTY are a dynamically regulated X-Y gene pair with at least partial compensatory overlap in function necessary for the preservation of kidney health and stress tolerance.

AimTo examine the feasibility and short-term outcomes of implementing a standardized nursing care plan based on NANDA International (NANDA-I) nursing diagnoses, Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC) in the emergency management of patients with type 1 and type 2 diabetes.DesignQuantitative pre-test/post-test pilot study.MethodsA convenience sample of 40 patients admitted to an emergency department for acute diabetic complications was enrolled. A structured nursing care plan grounded in NANDA-I, NIC, and NOC taxonomies was implemented during the emergency care episode. Nursing outcomes related to glycemia, glucosuria, and ketonuria were measured before and after the intervention using standardized five-point NOC indicators. Pre-post comparisons were analyzed using paired-sample t-tests.ResultsStatistically significant improvements were observed in all nursing-sensitive outcomes following the intervention. Mean glycemia scores increased from 2.05 ± 1.65 to 4.40 ± 0.74 (p < .001), glucosuria scores from 1.98 ± 1.67 to 4.50 ± 0.88 (p < .001), and ketonuria scores from 1.68 ± 1.33 to 4.63 ± 0.93 (p < .001). Post-intervention outcomes demonstrated reduced variability, indicating more consistent clinical stabilization within the emergency timeframe.Conclusion: The implementation of a standardized NANDA-I/NIC/NOC-based nursing care plan in an emergency department was feasible and was associated with significant short-term improvements in key metabolic indicators among patients with acute diabetic complications. However, given the absence of a control group, these findings should be interpreted as preliminary and require confirmation in controlled studies.Relevance to Clinical PracticeThis study supports the use of standardized nursing terminologies to structure nursing clinical judgment, guide targeted interventions, and evaluate nursing-sensitive outcomes in emergency settings. Adoption of NANDA-I, NIC, and NOC may enhance the visibility, consistency, and measurability of nursing contributions to acute diabetes care.

Sodium-glucose co-transporter-2 inhibitors are routinely withheld before surgery to reduce the risk of peri-operative metabolic complications. However, their pharmacodynamic effects may persist beyond the recommended discontinuation period. We report a 67-year-old man with type 2 diabetes who developed severe postoperative polyuria (6-7 l.day[-1]) with persistent glycosuria after partial hepatectomy despite discontinuation of canagliflozin 3 days before surgery. Marked transient hepatic dysfunction occurred immediately after surgery, while serum sodium remained within the normal range. Glycosuria and mild ketonuria were observed without overt ketoacidosis. Polyuria gradually resolved with supportive management including glucose-containing fluids and insulin infusion. This case suggests that postoperative hepatic dysfunction may prolong the pharmacological effects of sodium-glucose co-transporter-2 inhibitors and lead to clinically significant disturbances in fluid balance. Careful peri-operative monitoring is warranted in patients undergoing major hepatic surgery after treatment with these agents.