Ramy Magdy Hanna

Background: The KBindER (K⁺ Binders in Emergency Room and hospitalized patients) clinical trial is the first head-to-head evaluation of oral potassium binders (cation-exchange resins) for acute hyperkalemia therapy. Methods: Emergency room and hospitalized patients with a blood potassium level ≥ 5.5 mEq/L are randomized to one of four study groups: potassium binder drug (sodium polystyrene sulfonate, patiromer, or sodium zirconium cyclosilicate) or nonspecific laxative (polyethylene glycol). Exclusion criteria include recent bowel surgery, ileus, diabetic ketoacidosis, or anticipated dialysis treatment within 4 h of treatment drug. Primary endpoints include change in potassium level at 2 and 4 h after treatment drug. Length of hospital stay, next-morning potassium level, gastrointestinal side effects and palatability will also be analyzed. We are aiming for a final cohort of 80 patients with complete data endpoints (20 per group) for comparative statistics including multivariate adjustment for kidney function, diabetes mellitus, congestive heart failure, metabolic acidosis, renin-angiotensin-aldosterone system inhibitor prescription, and treatment with other agents to lower potassium (insulin, albuterol, loop diuretics). Discussion: The findings from our study will inform decision-making guidelines on the role of oral potassium binders in the treatment of acute hyperkalemia. Trial registration: ClinicalTrials.gov Identifier: NCT04585542. Registered 14 October 2020.

A 70‐year‐old female patient developed acute interstitial nephritis (AIN) after treatment with non‐steroidal anti‐inflammatory drugs (NSAIDs), proton pump inhibitors (PPI), and Bromhexine. Renal biopsy confirmed the diagnosis, and the patient was treated with oral prednisone. Careful attention to timing of acute kidney injury (AKI) is crucial to diagnosing AIN.

Calcium is a key ion involved in cardiac and skeletal muscle contractility, nerve function, and skeletal structure. Global calcium balance is affected by parathyroid hormone and vitamin D, and calcium is shuttled between the extracellular space and the bone matrix compartment dynamically. The kidney plays an important role in whole-body calcium balance. Abnormalities in the kidney transport proteins alter the renal excretion of calcium. Various hormonal and regulatory pathways have evolved that regulate the renal handling of calcium to maintain the serum calcium within defined limits despite dynamic changes in dietary calcium intake. Dysregulation of renal calcium transport can occur pharmacologically, hormonally, and via genetic mutations in key proteins in various nephron segments resulting in several disease processes. This review focuses on the regulation transport of calcium in the nephron. Genetic diseases affecting the renal handling of calcium that can potentially lead to changes in the serum calcium concentration are reviewed.

Background: Atypical Hemolytic Uremic Syndrome (aHUS) is a renal threatening multi-system disorder with significant hematologic findings of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. Early recognition and institution of late complement inhibitors can interrupt a cycle of progressive hemolysis and renal injury. Methods: We present an informative case of aHUS triggered by pregnancy termination. Diagnostic, laboratory, and treatment measures are reviewed. Results: Clinical evidence demonstrates immediate improvement in hemolysis, platelet consumption, and acute kidney injury following initiation of eculizumab. Conclusion: Pregnancy is a recognized trigger of aHUS and its proper management requires early recognition and institution of late complement blockade. Genetic testing can be sent for genetic counseling purposes, but initiation of treatment should neither await these results nor be discontinued when high-risk polymorphisms are absent.

Purpose of review: Nearly 20 years ago, vascular endothelial growth factor (VEGF)inhibitors (VEGFi) were adapted from systemic use from antiangiogenesis roles to intravitreal uses. Initially bevacizumab a murine immunoglobulin was injected ‘off label’ as a treatment for diabetic macular edema and age-related macular degeneration. Throughout the following decade aflibercept and finally ranibizumab were adapted and obtained Food and Drug Administration approval for intravitreal use. Initially systemic absorption was thought to be quite low after intravitreal injections and was quoted as being 200-fold lower than levels postulated to induce significant VEGF inhibition. Pharmacodynamic studies obtained in 2014 and again in 2017 revealed significant systemic absorption and detectable VEGF inhibition, this has since been confirmed in multiple subsequent studies. Recent findings: A few case reports of renal dysfunction and glomerular disease related to VEGFi were initially identified. Mixed findings on effects on blood pressure were noted in studies. More recently, 32 cases of de-novo glomerular disease and/or proteinuria exacerbation were identified. New studies have corroborated increased blood pressure, proteinuria exacerbation in patients with pre-existing nephrotic syndrome, and systemic VEGF depletion. Further, the most common lesion of systemic VEGFi nephrotoxicity, thrombotic microangiopathy, has recently been reported by our group. Summary: We will review the pharmacokinetic, translational, and epidemiological data that year upon year establish the finite-yet real risk of intravitreal VEGFi.

Cetyl Alcohol is a rare cause of acidosis if ingested in large quantities. Hyponatremia with overlapping anion gap and osmolal gap‐positive metabolic acidosis may appear to have iso‐osmolar serum. This is a case of an unusual toxic exposure.

Thrombotic microangiopathies (TMAs) involve multiple organ systems due to the presence of microangiopathic hemolysis. One such condition, atypical hemolytic uremic syndrome (aHUS), is a complement-mediated process that is part of a spectrum of disorders that have underlying complement dysfunction of the alternative pathway due to overactivity or decreased self-nonself discrimination by innate immunity. Complement-amplifying conditions such as pregnancy may unmask a diagnosis of aHUS. We present an important case of a pregnant 23-year-old Hispanic female who presented in mid-gestation (21 weeks) with an initial diagnosis of systemic lupus erythematosus (SLE) complicated by aHUS. She met clinical criteria for aHUS on presentation and was found to have a pathogenic CFHR1–3 homozygous deletion. She has been treated with intravenous and oral steroids, cyclophosphamide, subsequently also with plasma exchange, and finally with eculizumab with partial improvement in renal function. This case adds to the emerging literature showing that SLE and aHUS (or complement-mediated TMA) can be successfully treated with C5 blockade.

Intravitreal vascular endothelial growth factor (VEGF) receptor blockade is used for a variety of retinal pathologies. These include age-related macular degeneration (AMD), diabetic macular edema (DME) and central retinal vein obstruction. Reports of absorption of intravitreal agents into systemic circulation have increased in number and confirmation of depletion of VEGF has been confirmed. Increasingly there are studies and case reports showing worsening hypertension, proteinuria, renal dysfunction and glomerular disease. The pathognomonic findings of systemic VEGF blockade, thrombotic microangiopathies (TMAs), are also being increasingly reported. One lesion that occurs in conjunction with TMAs that has been described is collapsing focal segmental glomerulosclerosis (cFSGS). cFSGS has been postulated to occur due to TMA-induced chronic glomerular hypoxia. In this updated review we discuss the mechanistic, pharmacological, epidemiological and clinical evidence of intravitreal VEGF toxicity. We review cases of biopsy-proven toxicity presented by our group and other investigators. We also present the third reported case of cFSGS in the setting of intravitreal VEGF blockade with a chronic TMA component that was crucially found on biopsy. This patient is a 74-year-old nondiabetic male receiving aflibercept for AMD. Of the two prior cases of cFSGS in the setting of VEGF blockade, one had AMD and the other had DME. This case solidifies the finding of cFSGS and its association with chronic TMA as a lesion that may be frequently encountered in patients receiving intravitreal VEGF inhibitors.