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Lithium (Li) carbonate has been established as a mood stabilizer and an efficacious treatment for bipolar disorder since its discovery by Dr. John Cade in 1948. Li interacts significantly with organ systems and endocrine pathways. One of the most challenging side effects of Li to manage is its effect on the parathyroid glands. Dysregulation of parathyroid signaling due to Li results in hypercalcemia due to increased vitamin D3 generation, increased calcium absorption from the gut, and bone resorption, occasionally resulting in concomitant hypercalciuria. However, hypercalciuria is not a definitive feature for hyperparathyroidism, and normal calcium excretion might be seen in these patients. Hypercalcemia may also result from volume contraction and decreased renal clearance, which are commonly seen in these patients. Anatomically the parathyroid abnormalities can present as single or multiglandular disease. We report 3 cases where the patients developed multiple side effects of Li therapy as well as hypercalcemia due to hyperparathyroidism. The literature is reviewed with regard to medical and surgical management of Li-associated hyperparathyroidism in the context of these 3 presented cases.

Certain diabetic and hypertensive patients started on intravitreal vascular endothelial growth factor inhibition for diabetic retinopathy may experience worsening of hypertension and proteinuria. The etiology of this is the newly recognized absorption of intravitreally injected vascular endothelial growth factor inhibitors, and the susceptibility of patients with pre-existing renal disease to exacerbations depends on the degree of systemic absorption. There are eighteen reported cases of worsening hypertension, woresening proteinuria, worsening renal function, thrombotic microangiopathy, and glomerular disease noted after initiation of intravitreal vascular endothelial growth factor blockade. This nineteenth case demonstrates worsening hypertension and proteinuria with the start of bevacizumab. Both blood pressure and proteinuria parameters showed overall improvement with switching to the less absorbed and lower potency agent ranibizumab. There was a slight rise in serum creatinine after bevacizumab therapy, which stabilized at a new baseline, and the serum creatinine remained stable on ranibizumab. There were no other nephrotoxic exposures that explained the mild rise in serum creatinine. Because of improvement in renal function and proteinuria, a renal biopsy was deferred for the time. This case re-demonstrates the risk of worsening proteinuria with vascular endothelial growth factor inhibitors when given intravitreally in some patients. The demonstration of improvement in blood pressure and proteinuria with the use of lower potency agents like ranibizumab is novel and an important concept confirming observations from pharmacokinetic studies. The switch to ranibizumab offers a therapeutic option when proteinuria worsens with intravitreal vascular endothelial growth factor blockade, and the patient requires ongoing intravitreal therapy for treatment of diabetic retinopathy.

Rationale & Objective Euvolemic hyponatremia often occurs due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Vasopressin 2 receptor antagonists may be used to treat SIADH. Several of the major trials used 15 mg of tolvaptan as the lowest effective dose in euvolemic and hypervolemic hyponatremia. However, a recent observational study suggested an elevated risk for serum sodium level overcorrection with 15 mg of tolvaptan in patients with SIADH. Study Design A retrospective chart review study comparing outcomes in patients with SIADH treated with 15 versus 7.5 mg of tolvaptan. Settings & Participants Patients with SIADH who were treated with a very low dose of tolvaptan (7.5 mg) at a single center compared with patients using a 15-mg dose from patient-level data from the observational study described previously. Predictors Tolvaptan dose of 7.5 versus 15 mg daily. Outcomes Appropriate response to tolvaptan, defined as an initial increase in serum sodium level > 3 mEq/L, and overcorrection of serum sodium level (>8 mEq/L per day, and >10 mEq/L per day in sensitivity analyses). Analytical Approach Descriptive study with additional outcomes compared using t tests and F-tests (Fischer's Exact χ2 Test). Results Among 18 patients receiving 7.5 mg of tolvaptan, the mean rate of correction was 5.6 ± 3.1 mEq/L per day and 2 (11.1%) patients corrected their serum sodium levels by >8 mEq/L per day, with 1 of these increasing by >12 mEq/L per day. Of those receiving tolvaptan 7.5 mg, 14 had efficacy, with increases ≥ 3 mEq/L; similar results were seen with the 15-mg dose (21 of 28). There was a statistically significant higher chance of overcorrection with the use of 15 versus 7.5 mg of tolvaptan (11 of 28 vs 2 of 18; P = 0.05; and 10 of 28 vs 1 of 18; P = 0.03, for >8 mEq/L per day and >10 mEq/L per day, respectively). Limitations Small sample size, retrospective, and nonrandomized. Conclusions Tolvaptan, 7.5 mg, daily corrects hyponatremia with similar efficacy and less risk for overcorrection in patients with SIADH versus 15 mg of tolvaptan., Graphical abstract

Transplant patients are at risk for hemodynamic injury and glomerular diseases such as focal segmental glomerulosclerosis (FSGS) and thrombotic microangiopathy (TMA). Calcineurin inhibitors (CNI) can cause various patterns of acute kidney injury (AKI) in transplant patients and their effects must be differentiated from kidney injury due to other agents. Transplant populations are also at risk for atypical infections and malignancies. These conditions and the agents that are used to treat them can then induce their own set of glomerular diseases. We report a patient with hepatitis C who had received an orthotopic liver transplant and then developed recurrent hepatocellular carcinoma, which was treated with the oral tyrosine kinase inhibitor (TKI) sorafenib. In a manner temporally related to the initiation of the TKI, progressive AKI and high-grade rising proteinuria were noted. A biopsy disclosed FSGS and concomitant TMA. Despite the discontinuation of the TKI and high-dose steroid treatment, the patient developed end-stage renal disease and was initiated on hemodialysis. After determining the TKI as the probable culprit, as opposed to CNIs, the patient successfully received a living related renal transplant. CNIs are used to maintain renal and hepatic allografts without the development of hematuria, significant proteinuria, or significant impairment of renal function. It is noted that the pathologic phenotype observed in this case is only the second reported case of concomitant TMA and FSGS in a sorafenib-treated patient.

Advanced mechanical circulatory support is increasingly being used with more sophisticated devices that can deliver pulsatile rather than continuous flow. These devices are more portable as well, allowing patients to await cardiac transplantation in an outpatient setting. It is known that patients with renal failure are at increased risk for developing worsening acute kidney injury during implantation of a ventricular assist device (VAD) or more advanced modalities like a total artificial heart (TAH). Dealing with patients who have an implanted TAH who develop renal failure has been a challenge with the majority of such patients having to await a combined cardiac and renal transplant prior to transition to outpatient care. Protocols do exist for VAD implanted patients to be transitioned to outpatient dialysis care, but there are no reported cases of TAH patients with end stage renal disease (ESRD) being successfully transitioned to outpatient dialysis care. In this report, we identify a patient with a TAH and ESRD transitioned successfully to outpatient hemodialysis and maintained for more than 2 years, though he did not survive to transplant. It is hoped that this report will raise awareness of this possibility, and assist in the development of protocols for similar patients to be successfully transitioned to outpatient dialysis care.

Hyponatremia is a complex process caused by dysregulation of total body sodium and total body water that can be seen in hypovolemic, euvolemic, and hypervolemic states. Rapid correction of hyponatremia can also lead to serious complications. The development of V2 antagonists, such as tolvaptan, has changed and simplified the management of dilutional hyponatremia by allowing the targeting of antidiuretic hormone (ADH) action and blocking its effect on the V2 receptor. This will decrease the synthesis and relocation of aquaporin 2 to the cortical collecting duct apical membrane. Tolvaptan is approved to be used in euvolemic and hypervolemic hyponatremia, specifically in the syndrome of inappropriate antidiuretic hormone secretion and heart failure. The SALT-1 and SALT-2 studies suggested a starting dose of 15 mg of tolvaptan based on pharmacokinetic data, and while this is an effective dose, multiple studies have shown that patients can overcorrect with this starting dose. At least 1 case of osmotic demyelination – the dreaded complication of overly rapid hyponatremia correction – has been observed with tolvaptan use. While strategies for rapid attenuation of this overcorrection exist, and are discussed, starting tolvaptan at a lower dose of 7.5 mg initially and up-titrating even within the first day is another strategy that can avoid overcorrection. This was noted to be especially important in cases of hyponatremia due to the syndrome of inappropriate ADH secretion. We note that this approach can more slowly correct the hyponatremia with less attendant neurological risks than the currently recommended minimum starting dose of tolvaptan.

Severe heart failure is increasingly being managed by cardiac transplantation, and in some cases mechanical support devices serve as destination therapies. Left ventricular assist devices (LVADs) were approved for destination therapy for end stage heart failure patients before the more advanced total artificial heart modality became available. One common complication of mechanical assist device placement is acute kidney injury. Historically, patients with mechanical support devices have had to have inpatient hemodialysis until combined heart kidney transplant. Though, some units have started accepting LVAD patients in outpatient dialysis clinics. The cost of in center hemodialysis remains high and home dialysis modalities are becoming increasingly popular. We report the first patient with an LVAD to undergo training and successful home hemodialysis while awaiting combined heart kidney transplantation.

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease induced by many triggers, all of which produce a common end phenotype of microangiopathic hemolysis and thrombotic microangiopathy. We herein describe a 63-year-old woman with ongoing protein-losing enteropathy and frequent transudates caused by hypoalbuminemia. The patient was treated with eculizumab with a full hematologic and partial renal response. Protein-losing enteropathy is an inflammatory condition that has been linked with increased complement activation, which can trigger aHUS in patients with loss of CD55 expression. The patient in the present case had an increased estimated glomerular filtration rate but stage IV to V chronic kidney disease. One year later, she remains off dialysis with a stable estimated glomerular filtration rate. We herein report an unusual trigger of complement activation that in turn triggered aHUS in this patient.

Cerebral venous sinus thrombosis (CVST) is a rare condition affecting mountaineers in high altitude areas. We present a case of a 45-year-old male who presented with head­ache, nausea, and visual impairment immediate­ly after the descent from K-2 mountain (8611 meters) in Pakistan. His neurological exam did not reveal any findings, CT scan brain was done which showed thrombosis in the superior sagit­tal sinus with associated wedge-shaped hemor­rhage in the frontal lobe. He was managed conservatively on anticoagulation and was discharged subsequently.

Vascular endothelial growth factor (VEGF) inhibitors have emerged as powerful tools to treat malignant neoplasms and ocular diseases by virtue of their ability to inhibit angiogenesis. Recent data indicate that intravitreal injections of VEGF inhibitors can lead to significant systemic absorption as well as a measurable reduction of plasma VEGF activity. There is increasing evidence showing that vitreal absorption of these drugs is associated with cases of accelerated hypertension, worsening proteinuria, glomerular disease, thrombotic microangiopathy, and possible chronic renal function decline. In this review, the 3 most commonly used anti-VEGF agents—bevacizumab, ranibizumab, and aflibercept—are discussed, highlighting their intravitreal absorption and associated effects on the kidney as a target organ system. We provide clinical suggestions for clinicians to both better manage patients receiving anti-VEGF agents intravitreally and detect any putative systemic renal effects of these agents. While acknowledging the risks of aberrant retinal angiogenesis, it is important for clinicians to be aware of the potential for adverse renal risks with use of these agents.

Renal artery dissections (RADs) are lesions that disrupt vessels that primarily occur in patients with a known history of hypertension and caused by stenosis or enlargement of the renal artery typically due to underlying connective tissue disorders. However, RADs may occur spontaneously from trauma and no previous history of hypertension. Here, we report a rare case of bilateral isolated spontaneous RADs that characteristically occurs in healthy males. A 52-year-old male presented with left lower quadrant abdominal pain and renal insufficiency. Two years prior, he had experienced a similar episode of pain on the contralateral side, which was due to an infarct of the right kidney. On this admission, a computed tomography angiogram confirmed a new infarct of the left kidney, with dissection of a branch of the renal artery supplying the upper lobe. Work-up for cardiovascular, hematologic, radiographic or connective tissue causes was negative. We postulate that both RADs were potentially associated with the rapid twisting and turning of the abdominal area on a daily basis required for his occupation as an air traffic controller. The patient was treated with a renin angiotensin system inhibitor. After one year, both RADs had significantly improved and his renal function increased by ~23%. Isolated RAD may be associated with consistent or long-term activities that require rapid twisting and turning of the abdominal area. If left untreated, this may result in malignant hypertension, bilateral dissections, or renal ischemia. To avoid misdiagnosis; we provide a comprehensive review of the typical presentation and necessary assessment and management.

Vascular endothelial growth factor (VEGF) receptor inhibition is a commonly used tool to prevent vascular proliferation in tumors and retinal diseases. The antiangiogenic effects of these drugs have made them potent adjunct therapies when given systemically for malignancies. They are also useful tools to ameliorate diminishing eyesight in retinopathy. Hypertension and proteinuria have been observed in systemic VEGF inhibitor therapy, with rarer presentations involving nephrotic-range proteinuria due to glomerulopathies. Pharmacokinetic studies have shown detectable blood levels of anti-VEGF inhibitors up to 30 days postintravitreal injection. Animal studies have also demonstrated binding of VEGF inhibitors in simian glomeruli 1 week after a single intravitreal injection. We report three patients who received intravitreal bevacizumab and/or aflibercept with worsening hypertension, proteinuria and renal injury. Data regarding emerging evidence of VEGF inhibitor nephrotoxicity after intravitreal injections are also presented. The clinical data and the existing literature are reviewed to support the hypothesis that intravitreal anti-VEGF agents may be unrecognized nephrotoxins. These agents are given to vulnerable patients with diabetes, hypertension and preexisting nephropathy and proteinuria. This case series is reported to spur further study of the systemic effects of intravitreal VEGF inhibitors.

Membranous nephropathy (MN), an autoimmune glomerulonephritis which can occur in primary and secondary forms, is one of the most common inflammatory glomerulopathies in elderly patients. The pathophysiology of the primary form is generally due to circulating immunoglobulin (IgG4) antibodies which often target phospholipase A2 receptors (anti-PLA2R) and Thrombospondin Type 1 Domain containing 7A (anti THSD7A). IgA nephropathy is one of the most common autoimmune glomerular diseases in the world and presents with a spectrum of disease ranging from asymptomatic mild hematuria and proteinuria to rapidly progressive crescentic glomerulonephritis. We present a rare case of concomitant IgA and primary MN in a single patient treated successfully with renin–angiotensin–aldosterone blockade, corticosteroids, and calcineurin inhibitors. The peak proteinuria was near 7.5–8 g protein/g creatinine by various measures. Serum creatinine remained normal, and anti-PLA2R was detectable and decreased with successful treatment. Clinicians should be aware of the possibility of two glomerular disorders in patients with glomerulonephritis and atypical presentations for any single disorder.

BACKGROUND National Early Warning Score has been studied well in indoor settings of developed countries but hasn’t been tested before in the Emergency Department of developing countries with fewer resources. Our objective was to determine whether the emergency department (ED) NEWS can be associated with Triage, admission, disposition, length of emergency/hospital stay, reappearance and mortality. METHODOLOGY A random sample of 1000 patients’ first encounter in the ED was extracted in the study period (between November 2018 and April 2019). Statistical analysis was done to analyze whether ED NEWS severity category can be associated with Triage, admission, disposition, length of emergency stay, length of hospital stay, reappearance in two weeks and mortality. RESULTS ED NEWS Score is associated with triage as shown by mean 2.68 (SD ± 0.6, p=0.01). Also, a high NEWS score also had impact on admission including 75 (66.4%) patients in severe and 55(74.3%) in moderate NEWS severity category respectively. NEWS score is also associated with Critical care admission and length of Emergency stay likely hood ratio of 26.0(p=0.038). Reappearance in emergency within next two weeks of discharge had no relation to NEWS severity. On the other hand both ED mortality and Hospital mortality were related to High NEWS. It correlates weakly with Length of Stay in emergency or with Length of Stay in Hospital. CONCLUSION NEWS Score can be used in the emergency department to identify and predict adverse outcome of patients presenting to ED. NEWS can be used as a triage tool when deciding whether and where patients should be admitted.

Aminoacylase 3 (AA3) mediates deacetylation of N-acetyl aromatic amino acids and mercapturic acids. Deacetylation of mercapturic acids of exo- and endobiotics are likely involved in their toxicity. AA3 is predominantly expressed in kidney, and to a lesser extent in liver, brain, and blood. AA3 has been recently reported to interact with the hepatitis C virus core protein (HCVCP) in the yeast two-hybrid system. Here we demonstrate that AA3 directly binds to HCVCP (Kd ∼10 μM) that may by implicated in HCV pathogenesis. AA3 also revealed a weak endopeptidase activity towards the N-terminus of HCVCP. Structured summary of protein interactions AA3 cleaves HCVCP by protease assay ( View interaction ). AA3 cleaves AA3 by protease assay ( View interaction ). AA3 binds to HCVCP by surface plasmon resonance (View Interaction: 1 , 2 , 3 , 4 , 5 )

Understanding the pathogenesis and treatment of hyponatremia is a challenge for medical students and experts alike. Although hyponatremia has a wide range of causes, the pathogenesis of hyponatremia is largely characterized by disorders of urinary dilution. In evaluating the renal mechanisms responsible for the pathophysiology of hyponatremia, an analysis of free water clearance (FWC) and electrolyte-free water clearance (EFWC) is often utilized to quantify the renal diluting defect in this disorder. In this article, the utility of free water clearance (FWC) and electrolyte-free water clearance (EFWC) in the diagnostic and therapeutic approach to hyponatremia is discussed.

The term Pseudoainhum is used in medical literature to elaborate the presence of constricting bands around the digits of hands and feet due to variety of etiologies. This phenomenon can lead to irreversible damage to the supplying neurovasculature and sequential autoamputation of the affected digits. The report herein, describes the rare presentation of pseudoainhum occurring concomitantly in acute psoriasis. Timely recognition of such rare disease entities by physicians is imperative to avoid unnecessary complications.