SGLT2 Inhibitor-Induced Euglycemic Diabetic Ketoacidosis: A Case Report.

Euglycemic diabetic ketoacidosis is a rare but serious adverse effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors. We present a case of a woman in her 40s with type 2 diabetes mellitus hospitalized for revascularization for moyamoya disease who developed empagliflozin-associated euglycemic diabetic ketoacidosis despite having stopped the medication before admission. Surgical stress, acute postoperative illness, and decreased carbohydrate intake are postulated to be contributing factors to the development of ketosis in this patient, while near-normal glucose levels initially suggested nondiabetic ketoacidosis physiology and led to delayed diagnosis and treatment. Patients with type 2 diabetes mellitus may develop diabetic ketoacidosis during states of relative insulinopenia, most frequently from inadequate medication or intercurrent illness. During periods of carbohydrate deficiency, volume depletion, and upregulation of counter-regulatory stress hormones, SGLT2 inhibitor therapy can promote lipolysis and ketogenesis while maintaining euglycemia. Clinical considerations to ensure safe SGLT2 inhibitor therapy include appropriate holding parameters, timely diagnosis of euglycemic diabetic ketoacidosis, and recognition that the pharmacologic effects of SGLT2 inhibitor treatment may persist beyond several half-lives of elimination.

Glomerular Pathology in Dent Disease and Its Association with Kidney Function.

BACKGROUND AND OBJECTIVES: Dent disease is a rare X-linked disorder characterized by low molecular weight proteinuria and often considered a renal tubular disease. However, glomerulosclerosis was recently reported in several patients. Thus, Dent disease renal histopathologic features were characterized and assessed, and their association with kidney function was assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Clinical renal pathology reports and slides (where available) were collected from 30 boys and men in eight countries who had undergone clinical renal biopsy between 1995 and 2014. RESULTS: Median (25th, 75th percentiles) age at biopsy was 7.5 (5, 19) years with an eGFR of 69 (44, 94) ml/min per 1.73 m2 and a 24-hour urine protein of 2000 (1325, 2936) mg. A repeat biopsy for steroid-resistant proteinuria was performed in 13% (four of 30) of the patients. Prominent histologic findings included focal global glomerulosclerosis in 83% (25 of 30; affecting 16%±19% glomeruli), mild segmental foot process effacement in 57% (13 of 23), focal interstitial fibrosis in 60% (18 of 30), interstitial lymphocytic infiltration in 53% (16 of 30), and tubular damage in 70% (21 of 30). Higher percentages of globally sclerotic glomeruli, foot process effacement, and interstitial inflammation were associated with lower eGFR at biopsy, whereas foot process effacement was associated with steeper annual eGFR decline. CONCLUSIONS: These associations suggest a potential role for glomerular pathology, specifically involving the podocyte, in disease progression, which deserves further study. Furthermore, Dent disease should be suspected in boys and men who have unexplained proteinuria with focal global glomerulosclerosis and segmental foot process effacement on renal biopsy.

Nephrological and obstetric complications of the antiphospholipid syndrome.

The antiphospholipid syndrome (APS) is a disorder of hypercoagulability, characterised by thromboembolic events, repeated miscarriages and thrombocytopenia in association with circulating antiphospholipid antibodies. These antibodies are directed against epitopes on either oxidised phospholipids complexed with a glycoprotein, beta 2-glycoprotein I, or against the glycoprotein itself. Renal manifestations of the APS are varied and depend on the type of renal pathology present. The renal vasculature may be affected by either a small vessel, thrombotic microangiopathy process or by large vessel thrombosis. In patients with end stage renal disease, the prevalence of antiphospholipid antibodies may increase with time on dialysis. Anticardiolipin antibodies have been associated with a high incidence of haemodialysis access clotting, a major source of morbidity and hospitalisation in end stage renal disease patients. In renal transplant recipients, antiphospholipid antibodies may be associated with a higher incidence of primary graft non-function, particularly in patients without a history of pretransplantation haemodialysis. Complications of the APS during pregnancy span all trimesters and include intrauterine growth retardation, placental abruption, pre-eclampsia, preterm labour and recurrent fetal loss. As these women have a high risk of recurrent fetal loss, multiple treatment modalities have been investigated, including aspirin, heparin, prednisone and intravenous immunoglobulin. Various treatment strategies for the APS have been developed and are based on a combination of anticoagulant therapy with either warfarin or heparin, along with antiplatelet therapy with aspirin. Experimental treatments involving immunomodulatory therapy with intravenous immunoglobulin, apheresis and novel antibody therapy are being investigated with hopes of successful clinical applications.