Multifactorial Effects of Covid-19: A Review of Published Autopsy Reports

Introduction: SARS-CoV-2 is responsible for the current global pandemic. SARS-CoV-2 infection underlies the novel viral condition coronavirus disease 2019 (COVID-19). COVID-19 causes significant pulmonary sequelae contributing to serious morbidities. The pathogenesis of COVID-19 is complex with a multitude of factors leading to varying levels of injury numerous extrapulmonary organs. This review of 124 published articles documenting COVID- 19 autopsies included 1,142 patients. Method(s): A PubMed search was conducted for COVID-19 autopsy reports published before March 2021 utilizing the query COVID-19 Autopsy. There was no restriction regarding age, sex, or ethnicity of the patients. Duplicate cases were excluded. Findings were listed by organ system from articles that met selection criteria. Result(s): Pulmonary pathology (72% of articles;866/1142 patients): diffuse alveolar damage (563/866), alveolar edema (251/866), hyaline membrane formation (234/866), type II pneumocyte hyperplasia (165/866), alveolar hemorrhage (164/866), and lymphocytic infiltrate (87/866). Vascular pathology (41% of articles;771/1142 patients): vascular thrombi (439/771)-microvascular predominance (294/439)-and inflammatory cell infiltrates (116/771). Cardiac pathology (41% of articles;502/1142 patients): cardiac inflammation (186/502), fibrosis (131/502), cardiomegaly (100/502), hypertrophy (100/502), and dilation (35/502). Hepatic pathology (33% of articles;407/1142 patients): steatosis (106/402) and congestion (102/402). Renal pathology (30% of articles;427/1142 patients): renal arteries arteriosclerosis (111/427), sepsis-associated acute kidney injury (81/427) and acute tubular necrosis (77/427). Conclusion(s): This review revealed anticipated pulmonary pathology, along with significant extrapulmonary involvement secondary to COVID-19, indicating widespread viral tropism throughout the human body. These diverse effects require additional comprehensive longitudinal studies to characterize short-term and long-term COVID-19 sequelae and inform COVID-19 treatment.

Jahrestagung der Gesellschaft fur Padiatrische Nephrologie.

The proceedings contain 92 papers. The topics discussed include: cellular and humoral immune responses after SARS-CoV-2 vaccination in pediatric kidney recipients;adult outcomes of childhood-onset idiopathic nephrotic syndrome: findings from a health insurance database;the genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies;translational profiling of developing podocytes during glomerulogenesis;MAGED2 is required under hypoxia for cAMP signaling by inhibiting MDM2-dependent endocytosis of G-Alpha-S;high throughput investigation of the metabolic flux of intact cortical kidney tubules;peritoneal membrane junction and solute transporter expression and function in health, CKD and PD;and Function and interaction of coronavirus ion channel proteins.

Acute kidney injury in patient with severe SARS-CoV-2 infection.

Acute kidney injury (AKI) during SARS-CoV-2 infection is frequent and associated with mortality. Pathophysiology of AKI is multifactorial, and encompasses direct (viral invasion, endothelitis and thrombosis, renin-angiotensin-aldosteron system activation, cytokine elevation) and undirect mechanisms (hemodynamic instability, effect of mechanical ventilation, nephrotoxic medications). Acute tubular necrosis is the most frequent histological lesion identified, but glomerular disease can also be observed. To date, there is no specific treatment of SARS-CoV-2 induced AKI.Copyright © SRLF 2021.

Immunogenicity and Safety of Homologous Chadox1 Ncov-19 and Heterologous Prime-Boost of Coronavac and Chadox1 Ncov-19 among Kidney Transplant Recipients: An Observational Prospective Cohort Study

Introduction: Kidney transplant recipients (KTRs) are at risk for substantial morbidity and mortality during COVID-19 infection. Vaccination for this group of patients is reccommended. However, immunogenicity and safety data after COVID-19 vaccination among KTRs remains limited. Method(s): We conducted an observational prospective trial involving KTRs at Chiang Mai University hospital, Chiang Mai, Thailand. The participants were received homologous ChAdOx1 nCoV-19 (AZ-AZ), or the heterologous prime-boost of CoronaVac,followed by AZ (SV-AZ). The immunogenicity was assessed by measuring antibodies against the S1 receptor-binding domain (anti-RBD), and SARS-CoV-2 surrogate virus neutralization test (sVNT) at specific timepoints. The primary outcome was the seroconversion rate of sVNT at day 28 after complete vaccination. The secondary outcomes were the seroconversion rate of sVNT at day 28 after the first dose of vaccination, the level of sVNT and anti-RBD at specific timepoints, and the adverse events of each vaccine regimen. Result(s): A total of 18 KTRs were recruited. Among those, 13 (72.2%), and 5 (27.8%) patients were received AZ-AZ, and SV-AZ regimen, respectively. The seroconversion rate of sVNT at day 28 after the second dose were 23.1%, and 20.0% for AZ-AZ, and SV-AZ, respectively (P>0.99). The level of sVNT and the level of anti-RBD at day 28 after the first and at day 28 after the second dose were not different between groups (Figure 1). There were no serious adverse events reported in any vaccine groups. However, AZ-AZ showed sign of tubular dysfunction demonstrated by increasing of fractional excretion of magnesium after complete course of vaccination which correlated to the trend of urine albumin and urine protein creatinine ratio (r=0.720, P=0.013;and r=0.726, P=0.011, respectively). [Formula presented] [Formula presented] Figure 1 Percentage of neutralization inhibition (a) and level of anti-RBD antibody (b) at each visit of homologous ChAdOx1 nCoV-19 (AZ-AZ), and heterologous prime-boost of CoronaVac, followed by AZ (SV-AZ) regimen Conclusion(s): Immunogenicity after COVID-19 vaccination with either homologous or heterologous prime-boost regimen among KTRs was compromised. Homologous replication-defective viral vectors vaccine regimen seemed to affect renal tubular function, and further follow-up should be warranted. No conflict of interestCopyright © 2023

Spectrum of Indication Kidney Biopsies in Community Acquired Aki

Introduction: Community acquired acute kidney injury (CA-AKI) in low income settings is different from that in the high income settings. Infections, poisoning, toxic envenomations and pregnancy related AKI are common. Kidney biopsy is seldom performed in these patients unless atypical clinical course or features are present. We have established a prospective cohort of patients with CA-AKI at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh in India. We present the spectrum of kidney biopsies in patients who underwent kidney biopsy in this cohort. Method(s): The study is a single centre, prospective, observational cohort study of patients with CA-AKI at PGIMER. Patients aged >12 years and with a diagnosis of CA-AKI are eligible for enrolment. Patients with underlying CKD, urinary tract obstruction, COVID 19, malignancy or heart failure are excluded. Clinical and laboratory data are recorded at baseline. Follow up visits are scheduled at 1 and 4 months after hospital discharge. Kidney biopsies are done only in those patients who have atypical clinical course or features (e.g. persistent kidney dysfunction despite other clinical improvement, strong clinical suspicion of dominant glomerular involvement or interstitial nephritis etc.). We present the spectrum of histopathological diagnoses that were recorded in such patients till date. Result(s): Till now, 646 patients have been included in the cohort. The leading causes of CA-AKI are sepsis (52%), obstetric complications (14%), envenomation (8%), nephrotoxic drugs (6%) and poisons (3%) (figure 1). 18.4% patients had died after CA-AKI. At >=3 months after CA-AKI, 16.3% patients had not recovered completely with persistent eGFR <60 ml/min/1.73m2. 44 patients had undergone kidney biopsy in this cohort. Incomplete recovery, and clinical or diagnostic dilemmas were indications for doing kidney biopsy. The leading clinical diagnoses in this subgroup were sepsis (23%), nephrotoxic drugs (23%), envenomation (9%), obstetric causes (6.8%) and others (25%). Acute interstitial nephritis, acute tubular necrosis and acute cortical necrosis were most common histologic diagnoses (table 1). Combinations of various histologic features were not uncommon. Pigment casts were recorded in 13 patients. 4 patients had acute cortical necrosis, 2 being after post-partum AKI and one each due to acute gastroenteritis and unknown animal bite. Glomerular involvement were recorded in 8 patients (table 1). Thrombotic microangiopathy was present in 4 patients. In this subgroup of patients who underwent kidney biopsy, 3 (7%) had died and 8 (18%) had eGFR <60 ml/min/1.73m2 at >=3 months. Figure 1: Causes of CA-AKI in patients [Formula presented] Table 1: Histologic diagnoses in kidney biopsies in CA-AKI cohort. [Formula presented] Conclusion(s): Acute interstitial nephritis and acute tubular necrosis, alone or in combination with other findings, were the most common histologic diagnoses in indication kidney biopsies in CA-AKI. Adverse outcomes (mortality or progression to CKD) are common after CA-AKI. No conflict of interestCopyright © 2023

Quercetin potentially suppresses renal fibrosis in patients with COVID-19 under hypoxic state

Introduction: Renal fibrosis is a main outcome of acute kidney injury in COVID-19 survivors, which is emerging as a global public health concern. Lung damage in the COVID-19 patients leads to acute and chronic hypoxia, which results in inflammation, epithelial-mesenchymal transformation, and fibrosis in kidney. Quercetin is an abundant flavonoid in plant materials. Previous studies indicate that quercetin alleviates the decline of renal function, suppress epithelial to mesenchymal transformation in renal tubules, and reduce fibrosis. The study aimed to explore potential targets of quercetin on treating renal fibrosis in patients with COVID-19-induced hoxpia. Method(s): Gene/protein targets related to COVID-19, renal fibrosis, or quercetin were searched from ten databases, and Cytoscape 3.8.2 was then used to construct the protein-protein interaction network and to identify the core targets. The Metascape platform was used for bioconcentration analysis, while AutoDock Vina was used as the primary molecular docking tool. In vitro, the combination model of hypoxia- and transforming growth factor-beta (TGF-beta)- treated human proximal tubule epithelial cells (HK2 cells) was applied to determine the reno-protective effect of quercetin. Result(s): The network analysis showed that quercetin targeted on TGF-beta pathway in treating COVID-19 induced renal fibrosis. In the intersection PPI network, 115 targets were obtained, and gene enrichment analysis was conducted on 109 key nodes. Molecular docking analysis revealed that quercetin could spontaneously bind to eight targets on the TGF-beta pathway, and the binding energy of TGF-beta1 was 29.82 kJ/mol. The in vitro experiment further showed that quercetin significantly suppressed fibrosis in TGF-beta and hypoxia treated HK2 cells in a dose dependent manner by inhibiting TGF-beta/Smad3 pathway. Conclusion(s): Quercetin could attenuate renal fibrosis in patients with COVID-19 by suppressing TGF-beta/Smad3 pathway. No conflict of interestCopyright © 2023

SARS-CoV2 Infection and Acute Kidney Injury - A Rare Presentation

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) is one of the most devastating and lethal pandemics in human history. The disease initially affected adults much more than children, but now pediatric patients are being more commonly affected. Symptoms are often mild in pediatric age and characterized by the occurrence of fever and gastroenteritis. Respiratory involvement is generally benign in this age group and improves with symptomatic treatment. Kidneys can be a target of the disease and several factors have been incriminated. We report the case of a 5-year-old patient hospitalized for acute kidney injury following an asymptomatic SARS-CoV2 infection. We aim to focus practitioners' attention on a different aspect of renal involvement in this disease.Copyright © 2023, Pakistan Pediatric Journal. All rights reserved.

A renal transplant patient with COVID-19 presented with acute cellular rejection

A 27-year-old man underwent a deceased kidney transplant. Three days after transplantation, COVID-19 was diagnosed for our patient. Immunosuppressants were reduced and a renal biopsy was conducted, which showed acute T cell-mediated rejection. We intened to share a case to help clinicians to understand the risks that kidney transplant recipients face.Copyright © 2023 The Author(s);Published by Society of Diabetic Nephropathy Prevention.

Viral reactivation after hcv-positive renal allograft transplantation

Case Report: A 48y/o man with a history of ESRD secondary to FSGS was found to have hepatitis-C virus (HCV) reactivation after kidney transplantation (KT) with an HCV-positive allograft. The patient was HCV-negative before transplantation in July 2021. He was negative for hepatitis-B virus (HBV) core antibodies but had evidence of prior HBV vaccination and was negative for HIV 1/2. His induction therapy included thymoglobulin, and his maintenance immunosuppressive regimen included mycophenolate mofetil (MMF), tacrolimus, and prednisone. Aweek after KT, the patient tested positive for HCV genotype 1a, and he was started on sofosbuvir/velpatasvir in August 2021. Lab monitoring showed decreasing levels of HCV viral load (VL) until it was undetectable 2 months later. In January 2022, renal function remained stable, and urinalysis and hepatic function tests remained unremarkable. However, HCV viral load was positive in February 2022 and the HCV genotypewas 1a, as before. This result raised the possibility of reactivation of HCV from his allograft more than 6 months post KT. Additionally, despite negative BK polyoma VL initially, he was positive in January 2022 and discontinued his MMF. He was also positive for COVID-19 in January 2022 as well. Given his recurrence of HCV VL, he initiated sofosbuvir/velpatasvir/ voxilaprevir in April 2022 and completed therapy in July 2022, and maintained sustained viral response (SVR) as of October 2022. His BK VL was negative in May 2022. Recent guidelines on preventing HCV reactivation in allograft-positive KT recipients state that individuals should achieve SVR after 8-12 weeks of a course of direct-acting antiviral (DAA) therapy. The patient completed DAA therapy post-transplantation with a successful negative viral load 2 months later. However, he did not achieve SVR because his VL was again positive 3 months after completion of therapy. Reactivation of BKV, a DNA virus that establishes lifelong infection in renal tubular and uroepithelial cells, is common among KT recipients, but there is insufficient evidence to establish a causal association between BKV reactivation and HCV reactivation. There is no consensus on a chemotherapeutic maintenance regimen to prevent HCV reactivation. This case highlights the importance of close follow-up monitoring for HCV and BKV among KT recipients and the need to explore the relationship between BKV reactivation, HCV reactivation, and immunosuppression regimen. Copyright © 2023 Southern Society for Clinical Investigation.

Bilateral Cerebral Strokes and Adrenal Hemorrhage Associated with Mis-A

INTRODUCTION: Multisystem Inflammatory Syndrome in Adults (MIS-A) is an underrecognized post-infectious manifestation of COVID-19.We report a case of a 21-year-old male with MIS-A who presented with adrenal hemorrhages, acute kidney injury (AKI) and cerebral strokes leading to multiorgan system failure and death. DESCRIPTION: A 21-year-old, morbidly obese male presented at an outside hospital with COVID-19 and abdominal pain. His abdominal CT demonstrated bilateral adrenal hemorrhages, he was discharged home on hydrocortisone. A month later was readmitted with fever, diarrhea, thrombocytopenia and AKI. Laboratory work revealed creatinine 5.49mg/dL, ferritin 701ng/ml, BNP 3020 pg/ml and D-Dimer 17,650 ng/ml. He received hydrocortisone, intravenous immunoglobulin and enoxaparin. Fever subsided and renal function normalized. On day 7 he developed acute altered mental status and recurrent AKI. Head CTA showed multiple short stenotic segments in the anterior circulation, diminutive appearance of several intracranial arteries and basal ganglia hypodensities. Brain MRA demonstrated extensive bilateral acute/subacute strokes, no evidence of sinus thrombosis and markedly decreased caliber of internal carotid, left middle and anterior cerebral arteries without evidence of thrombus. He received aggressive neurocritical care management including decompressive craniectomy and pulse steroids for suspected vasculitis. Due to the severity of his neurological injury and poor neurologic prognosis family elected to withdraw support. His autopsy demonstrated hepatomegaly, acute tubular necrosis, bilateral adrenal hemorrhages and hypercellular bone marrow with myeloid predominance. Neuropathology showed severe segmental stenosis of the carotid arteries and bilateral vertebral arteries. DISCUSSION: Stroke is a potentially life-threatening complication of COVID-19 including large vessel occlusion and less frequently vasculitis-like phenotype with vessel wall enhancement. Despite initial improvement, our patient developed an acute extensive ischemic stroke leading to a devastating neurologic injury. The neuropathology findings suggest SARS-CoV-2 associated vasculitis. Stroke in the context of COVID-19 may have different pathogenetic mechanisms, clinical characteristics and complications that warrant further investigation.

Cholera in the Time of Covid

INTRODUCTION: Cholera is endemic to 50 countries with most US cases acquired during international travel. However, several cases have occurred from the ingestion of local oysters, crabs, and shrimp with resident Vibrio cholerae strains on the Gulf Coast. DESCRIPTION: A 52-year-old man with insulin dependent diabetes mellitus and well controlled HIV presented with hypovolemic shock. He reported 4 days of non-bloody diarrhea, poor oral intake, and oliguria. Before symptom onset, he ate crabs and tasted the water they were boiled in. He was prescribed azithromycin outpatient which mildly improved his diarrhea but presented to the hospital due to dizziness. He was initially hypotensive but this improved with 2 liters of normal saline without needing vasopressors. He had a blood glucose of 417 mg/dL, sodium bicarbonate of 13 mmol/L, anion gap of 29, creatinine of 10.5 mg/dL, calcium 8.3 mg/dL and corrected sodium of 124 mmol/L. Lactate and beta-hydroxybutyric acid levels were normal. Prior to admission, he took his insulin despite little oral intake. Given his glucose level and anion gap acidosis, he was placed on an insulin drip for concern of diabetic ketoacidosis (DKA). Stool PCR was positive for Vibrio cholerae and Salmonella enterica. Blood cultures were also positive for S. enterica. He received doxycycline for cholera and 14 days of ciprofloxacin for salmonella bacteremia. During his hospitalization, he got 14 liters of fluids with resolution of electrolyte abnormalities by discharge. DISCUSSION: In this patient, the anion gap acidosis was concerning for DKA but normal ketones made this diagnosis less likely. Cholera infection leads to "rice water" stool outputs up to 200cc/kg/hour in the first 2 days then ending after 4-6 days with profound electrolyte abnormalities. Due to rapid volume loss, patients present in hypovolemic shock with hyponatremia, hypocalcemia and hypoglycemia. Anion gap metabolic acidosis occurs due to acute tubular necrosis as in this patient. Stool culture is the gold standard for diagnosis. Treatment with doxycycline, ciprofloxacin or azithromycin decreases the duration of illness and reduces stool volume by 50%. Despite its rarity in the US, cholera should be considered and promptly treated in patients presenting with copious diarrhea, hypovolemia, and renal failure.

Multisystem Inflammatory Syndrome in Adults (Mis-a) after Covid-19 Infection

INTRODUCTION: Multisystem Inflammatory Syndrome was first described in children (MIS-C) after COVID-19 infection, it is characterized by gastrointestinal symptoms, shock, fevers, elevated inflammatory markers, and systolic dysfunction. A few similar presentations have also been reported in young adults designated as Multisystem Inflammatory Syndrome Adult type (MIS-A). Often, due to multi-organ involvement, extensive testing is undertaken with no yield of a clear etiological factor. We present a case of a 23-year-old male who was admitted into the Critical Care Unit for Encephalopathy with multi-organ dysfunction. DESCRIPTION: A 23-year-old male with a medical history of Williams-Campbell syndrome complicated by severe bronchiectasis and obstructive lung disease requiring 2 liters of oxygen at baseline, presented to the hospital with severe Encephalopathy, notably, he tested positive for COVID-19 one month before presentation with no increase in oxygen requirements until hospital presentation. Vitals were otherwise stable. Initial lab values were significant for an elevated AST of 6,620, ALT of 9,540, Creatinine of 4.71, Troponin-I of 3,913, CRP of 19.2, IL-6 of 22.1, and Ammonia of 171. Further investigative workup, including imaging, did not reveal a clear etiology for his presentation. An Echocardiogram however showed left ventricular dysfunction with an ejection fraction of 41%. Management included: broad-spectrum antibiotics which were discontinued after negative infectious workup, steroids for a suspected exacerbation of his lung condition, lactulose, and CRRT being initiated due to worsening renal function which was attributed to cardiac dysfunction leading to Acute Tubular Necrosis. MIS-A was eventually suspected as a diagnosis of exclusion considering the recent history of COVID-19 infection. Steroids were continued leading to gradual improvement of lab values. DISCUSSION: With COVID-19 continuing to make an impact, it is essential to be cognizant of various presentations and sequela. There have been multiple reports of different kinds of sequela, such is our case of MIS-A for which a long steroid taper is the mainstay of treatment. We want to raise awareness in the medical community of the possible consequences of COVID-19 infection such as MIS-A.

Anti-Glomerular Basement Membrane Disease Sans Kidney Involvement

Introduction: Anti-Glomerular Basement Membrane (anti-GBM) is an autoimmune disease involving glomerular and pulmonary capillaries diagnosed in 1 patient per million per year. Predominant lung involvement can be seen in 6% of patients most of which still demonstrate microscopic hematuria and biopsy with typical linear IgG immunofluorescence (99%). Case Description: We report a case of a 57-year-old man who presented with several weeks of dyspnea and myalgia, and was found to have acute kidney injury and multifocal tree-in-bud groundglass opacities throughout both lungs (Figure 1). His serum creatinine was elevated to 4.5 mg/dL from baseline of 0.8 mg/dL three months earlier but no proteinuria or hematuria. COVID19 was negative. Bronchoscopy showed blood throughout the tracheobronchial tree. Anti-GBM was elevated at 80 AU/mL. CRP was elevated at 17 mg/dL. Further work-up for other infectious or autoimmune causes was unremarkable. Kidney biopsy showed acute tubular necrosis (ATN), mixed interstitial inflammatory infiltrate, and one isolated fibrous cellular crescent. Immunofluorescence was negative. Due to the concern for progression of untreated anti-GBM disease, the patient was given high dose steroids, plasma exchange, and oral cyclophosphamide. His anti-GBM titer decreased to an undetectable level. Creatinine improved to 2.33 mg/dL. Discussion(s): This case brings to light a rare variant of anti-GBM with no detectable kidney involvement and presents a therapeutic dilemma. Two independent pathologists reviewed kidney biopsy and felt that crescent was a non-specific result of prior glomerular injury or pauci-immune focal glomerulonephritis. ANCA serologies were negative, and there were no other systemic manifestations. ATN was attributed to poor intake and Naproxen use. The patient received a typical anti-GBM treatment but more data are needed to support this approach in mild cases. (Figure Presented).

Cannabinoids May Be a Trigger or a Stop of Glomerular and Podocyte Injury From Parvovirus B-19 Infection

Introduction: Cannabinoids are widely distributed recreational substances and young patients with chronic epilepsy tend to use the substance even though harmful side effects such as acute tubular necrosis (ATN) and acute interstitial nephritis (AIN) have been reported. This is a rare case of glomerulopodocytopathy that might be triggered by Cannabinoids to raise awareness among clinicians and to emphasize on the need for patient education concerning the deleterious side effect of these substances. Case Description: A 21 years-old African American male was brought to the emergency room with seizure disorder and hypertension. Initial lab results showed a creatinine kinase of 233, serum creatinine of 1.13 mg/dL, it peaked at 7.6 in 72 hours. Upon nephrology consultation, obstructive nephropathy was ruled out. His renal ultrasound showed severe echogenicity. Urine microscopy showed granular cast with no WBC or RBC casts. His urine protein creatinine ratio was 1.3 gm. A physical examination showed mild lower extremity edema, he denies NSAIDs use. Serology was negative for ANA, Anti dsDNA, Anti Smith Ab, ANCA, COVID-19, HIV, HCV. Serology for Parvovirus B-19 (IgG) was positive while IgM was negative, APOL1 gene wasn't done due to lost follow up. 3 months earlier creatinine was 0.9 mg/dL, at time he was admitted for respiratory illness treated with steroid and antibiotics. Pathology revealed collapsing glomerulopathy in 4/22 glomeruli, no interstitial fibrosis and tubular atrophy and mild arterio- and arteriolosclerosis. His renal function responded well to pulsed steroids, He was maintained on 1 mg/kg daily prednisone taper, and his creatinine started trending down, while the edema resolved and the blood pressure normalized. The patient was discharged with nearly normal creatinine and a urine protein to creatinine ratio of 0.3. Discussion(s): Cannabinoids induced AKI with ATN or AIN are common. The renal injury related to delta-9-tetrahydrocannabinol (active ingredient in marijuana). The cannabinoid might trigger glomerulopathy and podocytopathy due to underlying viral illness could need further investigations, or it can be a protective substance for the glomerulus. Being vigilant with a high index of suspicions to any rapid progression of GN with a decline of renal functions, in order to take immediate actions with a diagnostic biopsy;prompting treatment to reverse salvaged renal functions.

Importance of Renal Biopsy in the Current COVID-19 Era: Acute Phosphate Nephropathy in a Patient With COVID-19 and New Systemic

Introduction: Lupus nephritis is a common manifestation of systemic lupus erythematosus. About 40-60% of patients with systemic lupus erythematosus will have renal involvement. We present a case of a young lady with SARS-CoV-2 pneumonia who additionally presented with alopecia, arthritis and acute renal injury. Initially, the consulting team presumed the diagnosis to be due to lupus nephritis. The patient was treated with IV methylprednisolone and oral prednisone. The renal biopsy revealed widespread calcium phosphate crystals within the tubular lumens, suggestive of acute phosphate nephropathy. Electron microscopy showed diffuse foot process effacement consistent with minimal change disease. Case Description: A 20-year-old lady with no past medical history presented with right-sided chest pain, myalgias, fever, and vomiting for 5-6 days. She had proteinuria and serum creatinine of 5 mg/dl. She was SARS-CoV-2 positive. She also had frontal alopecia and photosensitivity over the past five months, along with swelling/tenderness in her wrists and MCPs over the past year. The patient's mother had a diagnosis of lupus which was well controlled on Hydroxychloroquine. Further lab work revealed lymphopenia, positive for smith, coombs, cryoglobulins, RF, RNP, and SSA. Other pertinent work-up was negative. The patient was started on induction therapy for possible lupus nephritis of 1 g IV solumedrol daily for three days. The patient progressively became anuric, and creatinine peaked to 8 mg/dl. Dialysis was initiated. Her urine output improved after the third dialysis session, and dialysis was stopped. Her creatinine improved to 2.4 mg/dl. After the biopsy confirmed phosphate nephropathy, a focused history failed to reveal a cause. She denied sodium phosphate bowel preparations, consuming star fruit or ethylene glycol exposure. Discussion(s): This case shows the importance of biopsy even in a well-known condition such as lupus nephritis. The etiology of renal failure in SARS-CoV-2 is primarily acute tubular necrosis, with collapsing focal segmental glomerulosclerosis also reported. Calcium phosphate deposition is not a reported complication of COVID-19 or lupus nephritis. The tubuloreticular inclusions can be found with lupus nephritis and viral infection. The etiology of phosphate-induced nephropathy remains unclear.

ACUTE KIDNEY INJURY AS A PREDICTOR OF MORTALITY IN PATIENTS WITH COVID-19

SESSION TITLE: Late Breaking Posters in Critical Care SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Multiple mechanisms may cause acute kidney injury (AKI) after mechanical ventilation. Cross-talk between the lung and kidney precipitates other complications such as fluid overload, electrolyte derangements and pro-inflammatory cytokine production. In this study, we compared hospital mortality rates in unvaccinated COVID-19 patients with respiratory failure (requiring mechanical ventilation) who developed oliguric AKI. METHODS: Using an observational database, we analyzed 3183 unvaccinated hospitalized COVID-19 PCR-positive patients at Methodist Health System (Dallas, TX) from March 2020 to December 2020. The primary endpoint was all-cause in-hospital mortality in patients with respiratory failure requiring mechanical ventilation who developed AKI (as defined by the kidney disease improving global outcomes (KDIGO) guidelines). We also counted the rate of kidney replacement therapy and degree of kidney recovery among the survivors who developed AKI. Chi-square (X2), Fischer’s exact test, and odds ratio tests were used to analyze observed variables. RESULTS: Of the 3183 COVID-19 patients, 351 (11%) developed respiratory failure requiring invasive mechanical ventilation. Of those, 313 (89%) had previously normal kidney function (no documented CKD). Of the 313 intubated patients, 186 (59.4%) developed AKI and 127 (40.5%) patients did not. Thirty-five (18.9%) of the patients who developed AKI survived hospital admission, while 54 (42.5%) patients without AKI survived (OR = 3.306, 95% CI = 1.98-5.51, P<0.001). Ischemic acute tubular necrosis from septic shock was the most common cause of AKI. Hyperkalemia and metabolic acidosis were the most common indication for kidney replacement therapy, and continuous kidney replacement therapy was the most common modality used. The mean age for the AKI vs no AKI groups were 63.5 (SD 14.5) vs 62 (SD 14.49) years old. Mean BMI was comparable between both groups 32 (SD 9.7) vs 32 (SD 9.64), while the BUN level 26 (SD 26.75) vs 19 (SD 9.9) mg/dl and Cr 1.15 (SD 1.59) vs 0.08 (SD 0.27) mg/dl were higher in the AKI group. In the AKI group, kidney replacement therapy was prescribed in 73(39.2%) patients, of which only 33 (17.7%) recovered meaningful kidney function. CONCLUSIONS: As the world emerged from the COVID-19 pandemic, there are innumerable lessons still to be learned. In our study, we demonstrated that AKI in COVID-19 patients with respiratory failure is associated with a higher incidence of mortality compared to patients without AKI. CLINICAL IMPLICATIONS: The risk of new SARS-CoV-2 variants and the possibility of future pandemics makes the recognition of high-risk medical complications of COVID-19 crucial to improve outcomes in acutely ill patients. A true multi-disciplinary team and an incredible amount of resources is required to identify and treat such patients. This study reminds us that kidney replacement therapy is only a means of supportive treatment rather than a cure to COVID-19-related kidney pathology. DISCLOSURES: No relevant relationships by Victor Canela No relevant relationships by Manavjot Sidhu No relevant relationships by Lucas Wang

A HARD PILL TO SWALLOW

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Epiglottitis is an inflammation of the epiglottis which can be life-threatening in the absence of prompt intervention. Although primarily a pediatric condition, streptococcus pneumonia has been identified as a common pathogen in adults. SARS-CoV 2 has been known to affect a multitude of systems including the upper respiratory tract, but rarely the epiglottis. CASE PRESENTATION: A 66-year-old female with a past history of hypertension, and hypothyroidism presented with acute onset pharyngodynia and dysphagia with a feeling of throat closing up due to swelling and difficulty speaking. She had a recent COVID-19 diagnosis and was doing well except for mild fatigue. Upon presentation, she was hemodynamically stable. Physical exam revealed posterior pharyngeal edema without any exudate, mildly edematous uvula, and no stridor. Laboratory data was pristine except for elevated inflammatory markers. Rapid streptococcal test and MRSA swab were negative. Sputum culture showed usual respiratory flora and blood cultures were negative. A neck CT showed diffuse edema without any evidence of abscess. Laryngoscopy performed by the ENT surgeon revealed diffuse edema including epiglottitis. Emergent intubation revealed supra and epiglottis edema sparing the vocal cords. The patient was given Decadron and Benadryl to help with the edema along with clindamycin and subsequently transferred to ICU for further care. She was treated with Ceftriaxone for 7 days due to a chest X-ray finding of pneumonia. As for COVID 19 treatment, she received a course of Remdesivir and Decadron. Decadron was given at an increased interval to reduce edema around the epiglottis. Her ICU course was complicated with hypotension requiring intermittent vasopressor support, and acute kidney injury from ischemic acute tubular necrosis which slowly improved. Repeat CT chest showed bibasilar consolidations with peripheral ground-glass opacities. In view of hospital-acquired pneumonia, she was started on Ertapenem. Her clinical condition improved and she was successfully extubated. She was shifted to the floors from where she was discharged without any further complications. DISCUSSION: There are only two other reported cases of COVID 19 epiglottitis. The patient's advanced age and obesity were non-modifiable risk factors, but the COVID-19 infection played a role. The virus can lead to excessive upregulation of the host inflammatory response through repeat epithelial and endothelial damage leading to a cytokine storm, which may be responsible for this presentation. A great level of attention is to be maintained while attending to these patients given the multitude of systems that can be affected. CONCLUSIONS: COVID-19 is a potential cause of life-threatening acute epiglottitis. Early suspicion and direct visualization of the epiglottis is the key to success for early management. Reference #1: Emberey J, Velala SS, Marshall B, et al. Acute Epiglottitis Due to COVID-19 Infection. Eur J Case Rep Intern Med. 2021;8(3):002280. Published 2021 Mar 3. doi:10.12890/2021_002280 Reference #2: Smith C, Mobarakai O, Sahra S, Twito J, Mobarakai N. Case report: Epiglottitis in the setting of COVID-19. IDCases. 2021;24:e01116. doi: 10.1016/j.idcr.2021.e01116. Epub 2021 Apr 7. PMID: 33842206;PMCID: PMC8025537. DISCLOSURES: No relevant relationships by Arunava Saha

THE MONSTROSITY OF MAGNESIUM CITRATE

SESSION TITLE: Critical Gastrointestinal Case Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Magnesium citrate is an osmotic laxative which is occasionally used in the intensive care unit (ICU) for refractory constipation. We present a patient in whom a bowel regimen containing magnesium citrate resulted in severe hypermagnesemia with paralytic ileus, requiring renal replacement therapy. CASE PRESENTATION: 70-year-old male was admitted to the ICU for COVID-19 associated acute hypoxic respiratory failure and suffered multi-day, refractory constipation, treated with one dose of 17 grams of magnesium citrate. Vital signs were remarkable for bradycardia and hypotension. On examination, patient was lethargic and the abdomen was soft and non-distended, but there were decreased bowel sounds throughout. Subsequently, laboratory findings were notable for a magnesium level of 8.8 mg/dL and serum creatinine of 2.3 mg/dL (estimated glomerular filtration rate 28mL/min/1.73m2), all of which were previously normal at admission. Computerized Tomography of the abdomen was performed showing dilated cecum, ascending and transverse colon and moderate to large amount of intraluminal rectal stool and air. Patient was started on intravenous fluids, loop diuretics, and calcium gluconate, however, the patient required renal replacement therapy for magnesium clearance. Patient clinically improved with normalization of kidney function and magnesium levels as well as resolution of ileus. DISCUSSION: Magnesium homeostasis is regulated by gastrointestinal absorption and renal excretion, for which the kidney maintains magnesium equilibrium until creatinine clearance falls below 20 ml/min [1]. Elevated magnesium levels can decrease bowel motility by blocking myenteric neurons and interfere with excitation - contraction coupling of smooth muscle cells as well as serve as a reservoir for continuous magnesium absorption [2]. Our patient suffered acute kidney injury, likely from COVID-19 pneumonia and acute tubular necrosis from shock, placing him at increased risk for hypermagnesemia. One retrospective study identified that patients with COVID-19 are more prone to the development of hypermagnesemia, which is associated with renal failure and increased risk of mortality [3]. The magnesium load from magnesium citrate in our patient created for a seemingly out of proportion effect of hypermagnesemia-induced paralytic ileus and presumably a magnesium reservoir, refractory to conservative measures. CONCLUSIONS: The use of magnesium containing bowel regimens should be considered with caution due to the possibility of hypermagnesemia in at-risk patients, which may result in paralytic ileus and other sequelae. Hypermagnesemia reduces colonic peristalsis and interferes with magnesium equilibrium, prolonging its effects. There are rare case reports in the literature discussing this phenomenon, but should be further evaluated for specific patient susceptibility and effects on morbidity and mortality. Reference #1: Cascella, M. (2022, February 5). Hypermagnesemia. StatPearls [Internet]. Retrieved March 16, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK549811/ Reference #2: Bokhari, S., Siriki, R., Teran, F., & Batuman, V. (2018, September 8). Fatal Hypermagnesemia due to laxative use. The American Journal of the Medical Sciences. Retrieved March 16, 2022, from https://www.amjmedsci.org/article/S0002-9629(17)30467-6/fulltext Reference #3: Stevens, J. S., Moses, A. A., Nickolas, T. L., Husain, S. A., & Mohan, S. (2021, July 29). Increased mortality associated with hypermagnesemia in severe covid-19 illness. American Society of Nephrology. Retrieved March 16, 2022, from https://kidney360.asnjournals.org/content/2/7/1087 DISCLOSURES: No relevant relationships by Adnan Abbasi No relevant relationships by Sarah Upson

PRIMARY SJÖGREN'S SYNDROME with JUVENILE ONSET: REPORT of 15 CASES

Background: Primary Sjögren's syndrome (pSS) is a chronic and progressive multisystem autoimmune disease which rarely onset in children and adolescents. Diagnostic delay in large part of patients are common due to the non-specifc and variable symptoms and the slow progression of disease. Objectives: To analyse demographic data, specifc extraglandular, salivary and ocular manifestations, laboratory parameters and therapy of pSS with juvenile onset. Methods: Retrospective study of all patients (pts) with pSS in single center. Results: pSS was verifed in 15 pts (6.7% were boys), which amounted to 23.8% of all pts with SS in our pediatric rheumatologic department. The median age of pSS onset was 8.0 y.o. [IQR 7.0;10.2]. The median of disease duration at the time of pSS verifcation was 2.75 years [2.2;5.6]. All patients had systemic manifestations at onset: constitutional abnormalities-33.3%, nonerosive polyarthritis-64.3%, polyarthralgias-26.7%, lymphadenopathy-73.3%, cutaneous involvement-53.3% (2-xerosis, 2-annular erythema, 1-erythema nodo-sum, 2-Raynaud phenomenon, 2-nonspecifc spotty rashes, 1-hemorrhagic rash). At the time of diagnosis 7 pts (46.7%) had isolated involvement of salivary glands, 8 pts (53.3%)-combined with involvement of lacrimal glands. The decrease in salivary gland function was recorded in 80% of cases, hypolacrimia-in 46.7%, 1 patient had isolated hypolacrimia. Recurrent parotitis was present in 6 pts (40.0%). At time of diagnosis pulmonary involvement had 20.0% of pts, 1 patient had renal tubular acidosis. 8 pts (53.3%) had various hematological disorders: anemia-in 3 pts (20.0%), leukopenia-in 6 (40.0%). ANA Hep-2 were detected in 100% pts (in titer 1/640-4, 1/1280-7, 1/2560-3, 1/20480-1, with mixed patterns in all pts: speckled + homogeneous-9 pts, speckled + homogeneous+cytoplasmic-6 pts), anti-Ro-in 12 pts (80.0%), anti-La-in 8 pts (53.3%), RF+-in 9 pts (60.0%). 6 pts (40.0%) had polyclonal hypergammaglob-ulinemia, max 42%. 2 pts (13.3%) had concomitant autoimmune non-rheumatic disease;1-cutaneous psoriasis, 1-autoimmune thyroiditis. The treatment of each patient was justifed by the main individual manifestations: 93.3% received glucocorticoids, 26.7%-methotrexate, 33.3%-hydroxychloroquine, 6.7%-mycophenolate mofetil. Treatment with biologics (B) was received by 13 (93.3%) pts (7-rituximab (RTM), 6-abatacept (ABA)) with a good response in 10 pts, including improvement in the function of the salivary and lacrimal glands in 7 pts. 1 patient received 2B-RTM and ABA sequentially due to the development of MAS 7 days after 1st RTM infusion. B was discontinued in 3 pts: 1 due to development of hemorrhagic vasculitis 2 days after the 1st RTM infusion, 1-COVID-19 with lung involvement (CT 3-4) 2 weeks after the 1st RTM infusion, 1-inefficiency of ABA during 15 months. Conclusion: In our pediatric rheumatologic department pts with pSS made up less than a quarter of all pts with SS. The diagnosis was verifed delayed in all pts, which can be explained by a wide range of nonspecifc manifestations at the onset. However, the manifestations of SS that were present at the time of diagnosis were brought under control on the background of complex therapy, including the prescription of B, with a good efficacy and safety profile of therapy.

Impact of Genetic Testing in Nephrology: A Family's Experience with Dent Disease 2

Diagnosis of a genetic kidney disease can enhance treatment/management, allow patient/family counseling, and enable patient referral to specialists or clinical trials. Here we present a case study describing the use of a >380 gene panel associated with kidney diseases (The RenasightTM test, Natera, Inc.) to diagnose Dent disease 2 in a patient and their family members. A 41-year-old male was referred to Nephrology for evaluation of elevated SCr (4.6 mg/dL) and proteinuria. The patient’s medical history was unremarkable except for glaucoma in infancy. A renal biopsy identified glomerulomegaly. Genetic testing identified a likely pathogenic, hemizygous, frame-shift variant (c.311del;p.Cys104Phefs*2) in exon 5 of OCRL, an X-linked gene, which is associated with Dent disease 2. This genetic diagnosis prompted changes to the patient’s treatment plan, including patient counseling and preparation for renal replacement therapy (RRT). The patient’s 46-year-old brother was hospitalized due to COVID-19 symptoms with a SCr of 19.1 mg/dL. Due to limited medical history, it was unclear if he was presenting with acute kidney injury or chronic kidney disease. Although there was no evidence of nephrolithiasis or renal tubular acidosis typically associated with Dent disease 2, the family history prompted genetic testing that confirmed the presence of the familial variant in this patient. These genetic findings prevented delay in treatment, namely, initiation of RRT. Given the X-linked inheritance of Dent disease 2, the patients’ mother is an obligate carrier of the p.Cys104Phefs*2 variant in OCRL. Therefore, the third brother is an appropriate candidate for genetic testing due to his 50% chance of inheriting the familial variant. In this family, identification of an OCRL variant via broad panel renal genetic testing impacted patient counseling, management, and family testing. Notably, without genetic testing for the proband, his brother’s condition may have gone undiagnosed due to the atypical presentation, demonstrating the variability of OCRL-related conditions. Genetic testing can enable accurate disease diagnosis in individuals with an atypical presentation, syndromic kidney disease and/or a family history.