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Summary Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce osmotic diuresis by inhibiting the proximal renal tubular reabsorption of the filtered glucose load, which in turn can occasionally lead to severe dehydration and hypotension amidst other adverse effects. We present a case of a 49-year-old man with type 2 diabetes mellitus (T2D) on canagliflozin, a SGLT2i. The patient was brought to the emergency room following a motor vehicle accident. He was confused and had an altered mental status. His blood alcohol and urine toxicology screens were negative. Initial investigations revealed that he had severe hyponatremia with euglycemic ketoacidosis. The adverse condition was reversed with close monitoring and timely management, and the patient was eventually discharged. This is the first report to suggest hyponatremia as a potentially serious adverse effect following SGLT2i therapy. Its impact on the renal tubule handling of sodium and water is not yet well characterized. While further studies are warranted to understand better the pathophysiological mechanisms associated with SGLT2i-induced adverse effects, timely dose reduction or perhaps even its temporary discontinuation may be recommended to prevent complications. Learning points Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are usually well-tolerated, but some serious adverse effects have been documented. Our case report suggests hyponatremia as a potential, rare side effect of SGLT2i and makes physicians aware of the occurrence of such life-threatening but preventable complications. Timely and close monitoring of the patient, with temporary discontinuation of this drug, may be recommended towards effective management. Studies demonstrating a comprehensive understanding of SGLT2i-related electrolyte derangements are warranted.

Background Patients with sepsis are at risk for developing sepsis-induced cardiomyopathy (SIC). Previous studies offer inconsistent results regarding the association of SIC and mortality. This study sought to assess whether SIC is linked to mortality in patients with sepsis and to evaluate predictors of the development of SIC. Methods In this retrospective study, patients admitted to the medical intensive care unit with a diagnosis of sepsis in the absence of acute coronary syndrome were included. SIC was identified using transthoracic echocardiogram and was defined by a new-onset decline in left ventricular ejection fraction (LVEF) of up to 50% or a decline of at least 10% in LVEF relative to baseline in patients with a history of heart failure with reduced EF. Multivariable logistic regression analysis was performed using the R software program (R Foundation for Statistical Computing). Results Of the 359 patients in the final analysis, 19 (5.3%) had SIC, and eight (42.1%) of these 19 patients and 60 (17.6%) of the 340 patients in the non-SIC group died. SIC was associated with an increased risk for all-cause in-hospital mortality (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.15-18.69; P=0.03). Independent predictors for the development of SIC were albumin level (OR, 0.47; 95% CI, 0.23-0.93; P=0.03) and culture positivity (OR, 8.47; 95% CI, 2.24-55.61; P=0.006). Concomitant right ventricular hypokinesis was noted in 13 (68.4%) of the 19 SIC patients. Conclusion SIC was associated with an increased risk for all-cause in-hospital mortality. Low albumin level and culture positivity were independent predictors of SIC.

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors induce osmotic diuresis by inhibiting the proximal renal tubular reabsorption of the filtered glucose load. This can occasionally lead to severe dehydration, hypotension and in some cases, severe hyponatremia. The effects of SGLT2 inhibitors on sodium and water handling by the renal tubules is not well studied. Clinical Case: A 49-year-old male with history of type 2 diabetes mellitus on canagliflozin, an SGLT2 inhibitor, who was brought to the Emergency Room following a motor vehicle accident from acute onset of confusion and altered mental status. Initial trauma workup was negative. He was found to have severe hyponatremia to 118 mEq/ L (n 135–145 mEq/ L) and was also noted to be in euglycemic ketoacidosis with positive serum ketones (qualitative assessment) along with acute onset urinary retention. Urine toxicology was negative including negative blood alcohol level. Thyroid function was normal 1.080 mIU/ L (n 0.47- 6.90mIU/L). His total urine osmolar excretion was ~ 2400 mOsm in 12h (n 500–800 mOsm/kg of water/ 24 hours), confirming the diagnosis of his ongoing massive osmotic diuresis. On admission, his antidiuretic hormone (ADH) level was noted to be elevated to 9.1 pg/mL (n Conclusion: With more widespread use of this relatively new hypoglycemic medication with protective metabolic and cardiovascular benefits that include weight loss and reduction of BP in T2DM patients, it is equally important to understand the physiology of potentially life-threatening adverse effects associated with severe volume depletion by massive osmotic diuresis and electrolyte abnormalities that include hypernatremia (even hyponatremia), and the timely recognition of euglycemic ketoacidosis.

Diabetes Insipidus (DI) is either due to deficient secretion of arginine vasopressin (central) or to tubular unresponsiveness (nephrogenic). Drug induced DI is a well-known entity with an extensive list of medications. Polyuria is generally defined as urine output exceeding 3 liters per day in adults. It is crucial to identify the cause of diabetes insipidus and to implement therapy as early as possible to prevent the electrolyte disturbances and the associated mortality and morbidity. It is very rare to have an idiosyncratic effect after a short use of a medication, and physicians should be aware of such a complication to avoid volume depletion. The diagnosis of diabetes insipidus is very challenging because it relies on laboratory values, urine output, and the physical examination of the patient. A high clinical suspicion of diabetes insipidus should be enough to initiate treatment. The complications related to DI are mostly related to the electrolyte imbalance that can affect the normal physiology of different organ systems.

Immunotactoid gloemrulonephritis is a glomerular disease characterized by organized microtubular deposits of monoclonal immunoglobulin. These deposits are Congo red-negative, have hollow centers, measure > 30 nm, and are arranged in stacked or parallel arrays. Treatment of immunotactoid glomerulonephritis is not well-defined, with poor outcomes seen in native kidneys. In fewer than 10% of the cases, trials with steroids alone or cytotoxic agents with steroids or plasmapheresis with steroids has been associated with clinical remission of proteinuria. 50% of patients with renal impairment progress to end stage renal disease (ESRD) in two to four years. There are three case reports of recurrent ITG in renal allograft; one was treated with pulse steroids plus cyclophosphamide, pulse steroids in second case and use of rituximab in the third case. Recurrence of ITG has been described in the renal allograft but there is no literature on relapse of ITG in the native kidneys. Here, we have a case of ITG that relapsed in the native kidneys eight years after being in remission. Renal function improved with fludarabine both times and the patient had stable renal function at last follow-up.

Renal insufficiency is associated with high morbidity and mortality in multiple myeloma. One of the common causes for acute renal failure in multiple myeloma is cast nephropathy. It is important to reduce the levels of light chains to improve renal failure and also the overall outcome. Plasmapheresis has failed to show any significant improvement in renal failure due to cast nephropathy as demonstrated in a recent randomized control trial. Here, we present a case series of three patients who were treated with continuous venovenous hemofiltration as a modality to remove these free light chains. There was improvement in renal failure in these patients with decrease in the levels of free light chains. These patients remained off hemodialysis on follow-up and two of them were able to undergo hematopoietic stem cell transplantation.

Background. Alport's syndrome is an X-linked hereditary disorder affecting the glomerular basement membrane associated with ocular and hearing defects. In women, the disease is much less severe compared to that in men. However, women with Alport's syndrome can have an accelerated form of their disease during pregnancy with worsening of kidney function and can also develop preeclampsia. There are only four described cases of Alport's syndrome in pregnancy.Case Presentation. 20-year-old woman with a history of Alport's syndrome, which during pregnancy worsened resulting in hypertension, proteinuria, and acute kidney injury. Fortunately, there was complete resolution of the proteinuria and kidney injury with delivery, and the patient did not require any renal replacement therapy.Conclusion. One of the four reported cases had an accelerated form of the disease during pregnancy with rapid progression of kidney injury and end-stage renal disease. There are no definite guidelines to monitor these patients during pregnancy. Further studies are required to understand the exact pathophysiology of kidney damage that occurs in pregnant women with Alport's syndrome. This may give us some insight into the prognostic predictors, so that we can monitor these women more thoroughly and prevent adverse outcomes.

Hematopoietic stem cell transplantation (HSCT) has been one of the revolutionary discoveries in the world of science leading to cure of many of the hematological malignancies and for several nonmalignant conditions. It involves harvesting of stem cells from either the bone marrow most traditionally, peripheral blood or umbilical cord and then transplanting them into a recipient [1-3]. This could be either allogeneic i.e. from another donor or autologous i.e. from the patient himself [1,4]. The first successful series of autologous HSCT for lymphoma was reported in 1978 [5]. With a better understanding of immunological mechanisms and molecular sciences, it has now been possible to decrease the rates of rejection due to incompatibility thereby improving overall graft survival many fold. Today, more than 50.000 transplants are carried out annually worldwide and the numbers are increasing each year [6].

Ovarian vein thrombosis (OVT) is a rare condition occurring in 1/600 to 1/2000 pregnancies [Dunnihoo et al. 1991; Ortin et al. 2005] mainly in the postpartum setting. It is also known to be associated with other conditions such as malignancy, pelvic inflammatory disease, inflammatory bowel disease, sepsis and recent pelvic or abdominal surgery [Andre et al. 2004; Heavrin and Wrenn, 2008; Jacoby et al. 1990; Klima and Snyder, 2008; Marcovici and Goldberg, 2000; Salomon et al. 1999; Simons et al. 1993]. It is extremely rare to find OVT without identified etiology and, hence, idiopathic OVT is only described as case reports throughout the literature. Here, we report a unique case of idiopathic isolated OVT that presented with right flank pain and an abdominal mass. Although four similar cases of idiopathic isolated OVT have been reported in the literature [Heavrin and Wrenn, 2008; Murphy and Parsa, 2006; Stafford et al. 2010; Yildirim et al. 2005], none of these patients presented with an abdominal mass. The diagnosis of isolated OVT requires a high index of suspicion. If misdiagnosed, OVT can lead to potentially fatal complications such as sepsis and pulmonary embolism. [Benfayed et al. 2003; Kominiarek and Hibbard, 2006; Maldjian and Zurlow, 1997; Wysokinska et al. 2006]. A 53-year-old postmenopausal woman with a past medical history of hypertension presented to the medical clinic complaining of 1-week history of aching right flank pain that was not associated with fever, dysuria, hematuria, nausea, vomiting, diarrhea or vaginal discharge. The patient denied any other constitutional symptoms. She is a nonsmoker with no family history of hematologic disorders. On physical examination, she was afebrile, normotensive, without tachycardia. Pelvic exam revealed a nontender, normal size uterus and adnexa. However, a 3 cm tender mass was palpated in the right lower quadrant. Laboratory data revealed a white blood cell count of 4400-cells/mm3 and hemoglobin level 11.9 g/dl. Renal function and electrolytes were within normal limits. Computed tomography (CT) of the abdomen and pelvis with intravenous contrast showed right ovarian vein thrombus without extension to the inferior vena cava (IVC) (Figure 1). Figure 1. CT scan at presentation. Further work up for hypercoagulability was negative. Age- and sex-appropriate cancer screenings were all negative. Moreover, screening for ovarian pathology, with pelvic ultrasound and CA-125, was also normal. Shortly after the diagnosis of isolated OVT, the patient was placed on oral anticoagulation. It was elected not to administer antibiotics. Warfarin was continued for 5 months with the International Normalized Ratio (INR) maintained between 2 and 3. A follow-up CT scan of the abdomen and pelvis performed 5 months later showed persistence of the thrombus with no further extension beyond the ovarian vein (see Figure 2). Anticoagulation was discontinued at this point with close clinical follow up. Figure 2. CT scan after 5 months of anticoagulation therapy. Ovarian vein thrombosis was first described by Austin in 1956 [Austin, 1956]. It occurs in the right side in 70–90% of cases, and bilaterally in 11–14% [Baran and Frisch, 1987; Prieto-Nieto et al. 2004]. The most widely accepted hypothesis for the higher incidence on the right is that the right ovarian vein is longer than the left, and lacks competent valves. The typical presentation is the triad of pelvic pain, fever, and a right-sided abdominal mass [Dessole et al. 2003; Dunnihoo et al. 1991; Klima and Snyder, 2008; Prieto-Nieto et al. 2004]. Fever is present in 80% and right iliac fossa pain in 55% of the patients [Prieto-Nieto et al. 2004]. Given the nonspecific presenting symptoms, prompt diagnosis of OVT requires a high index of suspicion. The differential diagnosis includes most conditions that affect the abdominal lower quadrant such as acute appendicitis and inflammatory bowel diseases. Therefore, imaging studies are essential to establish the diagnosis of OVT. Magnetic resonance angiography (MRA) has the highest sensitivity and specificity that approaches 100%. CT scan with intravenous contrast enhancement has a sensitivity of 77.8% and specificity of 62.5%. Color Doppler ultrasound has the lowest sensitivity of 55.6% and a specificity of 41.5% among other imaging modalities [Kubik-Huch et al. 1999]. A delay in the diagnosis and treatment of OVT can lead to potentially life-threatening complications, such as thrombus extension into the IVC or ileofemoral vessels and eventually the evolution of pulmonary arterial embolization. The incidence of pulmonary embolism is approximately 25% in patients with untreated OVT and the mortality in these patients can reach about 4% [Benfayed et al. 2003; Dunnihoo et al. 1991; Kominiarek and Hibbard, 2006]. Other serious complications include septic thrombophlebitis and, rarely, infectious emboli [Dessole et al. 2003; Heavrin and Wrenn, 2008]. Ovarian vein thrombosis can resolve spontaneously but considering the potential catastrophic consequences, anticoagulation is usually recommended [Wysokinska et al. 2006]. There is no definite guideline regarding the duration of anticoagulation therapy. Wysokinska and colleagues studied the incidence and the recurrence of OVT compared with lower extremity deep venous thrombosis (DVT) [Wysokinska et al. 2006]. None of the 35 patients in the OVT group was idiopathic and the recurrence rate was comparable to patients diagnosed with lower extremity DVT (3 per 100 patient years of follow up). The average treatment with warfarin was 5.3 and 6.9 months for OVT and lower extremity DVT, respectively. Based on these findings, the authors suggested the application of lower extremity guidelines for the treatment of OVT. Antibiotics can also be administered for approximately 7 days especially in cases of postpartum OVT [Brown and Munsick, 1971; Dessole et al. 2003; Maldjian and Zurlow, 1997; Wysokinska et al. 2006]. In patients with hypercoagulable disorders, anticoagulation may need to be lifelong therapy [Wysokinska et al. 2006]. In rare cases of persistent OVTs, an IVC filter or surgical intervention to ligate the ovarian vein can be considered [Carr and Tefera, 2006; Clarke and Harlin, 1999]. Our patient was diagnosed with an idiopathic OVT since none of the above predisposing factors for OVT were found. The patient’s abdominal pain subsided few days after starting anticoagulation and she did not develop any worrisome signs such as fever, dyspnea, or chest pain. Five years later, the patient remains asymptomatic while off anticoagulation, without any further thrombotic conditions. To date, four cases of idiopathic OVT were described [Heavrin and Wrenn, 2008; Murphy and Parsa, 2006; Stafford et al. 2010; Yildirim et al. 2005]. None of these cases had abdominal or pelvic palpable masses at presentation. Therefore, our report describes a unique case of idiopathic OVT presenting with one symptom and one sign of the typical triad. The palpable mass in the right iliac fossa was only described in cases of OVT that occur in the postpartum period as well as in other inflammatory and hypercoagulable conditions. OVT is a rare condition with potential life-threatening complications. In female patients presenting with lower quadrant pain, with or without fever or palpable abdominal or pelvic mass, OVT should be considered in the differential diagnosis after ruling out other common conditions. MRA and CT scan with intravenous contrast are the most useful imaging modalities to diagnose this condition. Overlooking this diagnosis can lead to life-threatening conditions, such as pulmonary embolism, sepsis, and even death. Hence, prompt diagnosis of OVT requires a high index of suspicion in order to prevent these outcomes.