Pathogenetic Aspects of the Development of Acute Kidney Injury in Covid 19: Own Observation Data

Introduction: The coronavirus infections ( disease) (COVID-19) pandemic 2019 caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) began in December 2019 and has affected millions of lives worldwide, even though many aspects of the disease are still unknown.Current data shows that many hospitalized patients with COVID-19 suffer from kidney damage manifesting as proteinuria, hematuria, or acute kidney injury (AKI). AKI is especially common among severely and critically ill patients with COVID-19 and may be a predictor of mortality.The pathophysiology of AKI associated with COVID-19 may be due to non-specific mechanisms, but also to mechanisms specific to COVID. Evaluation of morphological changes in the kidneys and their mechanisms could help determine their spectrum and immediate or long-term effects. The aim of our study was to compare the initial clinical and laboratory data of patients with COVID 19 who developed AKI and to analyze the morphological changes in the kidneys that underwent autopsy when patients died of COVID 19 with AKI. Method(s): We conducted a preliminary retrospective analysis of cured patients with COVID 19 and AKI during the pandemic period of July 2021 - December 2021. We analyzed the clinical and laboratory parameters of 2 groups of patients: thise who survived and thise who died of AKI caused by COVID 19. We also studied he main frequently detected morphological changes in the renal biopsy: the subject ground was a dead group. Statistical processing of the obtained data was performed using the STATA program. The two groups were compared, and the statistical significance of the scores of the two groups was calculated using the Mann Whitney analysis and the chi-quadrant Results: According to the results of analyzes of clinical and laboratory parameters, it can be summarized that in the group of the dead in 80% of patients, the volume of lung damage is more than the deceased than the survivors. There is a deep lymphopenia and thrombinemia in the group of the dead. The level of azotemia also prevails in the group of the deceasedAccording to our studies, out of 10 lethal cases, 90% of the histology of samples taken from the kidneys of those who died from COVID 19 revealed the following changes: edema and plethora of renal glomeruli, atrophy and sclerosis from 10-50% of the glomeruli. In the tubules, total necrosis of the epithelium. In the stroma, vascular thrombosis, focal sclerosis with lymphoid infiltration, small focal hemorrhages [Formula presented] Conclusion(s): Acute kidney injury remains a fairly common and serious manifestation of the severe course of COVID 19. Regardless of the type of development of the mechanism, it is often associated with high mortality. Our results of the study can serve as a subject for further research. No conflict of interestCopyright © 2023

Efficient selective adsorption of cytokine IL-6 and other middle-macromolecular toxins in the serum of uremia patients with specially designed porous hollow carbon spheres

[Display omitted] • Porous hollow carbon spheres (HCSs) with adjustable size and pore width distribution were synthesized. • The clearance rate of HCSs to interleukin 6 (IL-6) in PBS buffer solution was up to 99.8%. • HCSs had a high adsorption rate and removal efficiency for PTH, β 2 -MG, IL-6 and TNF-α in the serum of uremic patients. • The selective adsorption of middle-macromolecular toxins or cytokines was achieved by regulating the pore structure of HCSs. Abnormally elevated middle-macromolecular toxins such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF- α) in human blood are fatal precipitating factors for patients suffered from immune-related diseases, especially for uremia and COVID-19 critical patients, while the effective clearance of them has always been problematic in clinic. In this work, porous hollow carbon spheres (HCSs) with different size and pore structure has been successfully prepared. The removal efficiency for IL-6 in PBS solution is about 99.8 %, even in the serum of uremic patients, HCSs could remove 94.75 % and 98.33 % of parathyroid hormone (PTH) and β 2 -microglobulin (β 2 -MG) efficiently within 5–10 min, and particularly, the adsorption of IL-6 and TNF- α is 17.6 and 11.4 times higher over that of the existing commercial hemoperfusion adsorbents. The adsorption balance can be achieved in 60 min, which would greatly shorten the current clinical treatment duration. Moreover, HCSs with different pore structure exhibit distinct adsorption selectivity for IL-6 and TNF- α, which is of special significance for modifying the middle-macromolecular cytokine level in the complicated human blood environment. [ FROM AUTHOR]

Not all shortness of breath and throat pain is COVID

Case Report: A previously, healthy 18-year-old female presents to a Pediatric Emergency Medicine Department with shortness of breath, fever, and worsening throat and abdominal pain for 3 days. She had a sick contact, a teacher that tested positive for COVID-19 2 weeks prior to presentation. She denies runny/stuffy nose, cough, loss of taste/smell, or rashes/lesions. She denies any significant past medical history including allergies, as well as any history of smoking or any illicit drug use. Upon arrival to the ED, the patient was noted to be tachycardic, hypotensive and febrile. There were no desaturations. Initial physical examination revealed a generally uncomfortable female that was alert and oriented, with noted tenderness over the right anterior neck region, diffuse cervical lymphadenopathy, and painful neck range of motion. Her pharynx was noted to be erythematous without exudates or any unilateral tonsillar swelling. In the ED patient received IV fluid resuscitation and was started on norepinephrine drip, broad spectrum antibiotics. Initial lab workup revealed an anion gap metabolic acidosis, likely secondary to uremia or lactic acidosis from poor perfusion in setting of sepsis and hypovolemia. BUN and creatinine were elevated, likely due to an acute kidney injury (AKI) secondary to hypovolemia. The patient was also found to have an elevated LDH, fibrinogen, and mild elevation of AST. D-Dimer was elevated at 29 000. Covid PCR, Rapid Strep, and respiratory PCR panel were negative. Her chest X-ray (CXR) was negative and ECG showed sinus tachycardia. Given the patient's history of throat and neck pain with shortness of breath, in the setting of a septic picture, a CT scan of neck, chest, abdomen was ordered prior to transferring the patient to the PICU. CT scan of the chest revealed small patches of consolidation with ground glass opacities in the right lung apex, as well as an nearly occlusive, acute thrombosis of the anterior right facial vein. The patient's initial blood cultures grew gram negative bacilli which later were revealed to be Fusobacterium necrophorum. These findings are consistent with Lemierre's syndrome. The patient was treated in the PICU on vasopressors, heparin anticoagulation, and antibiotics for 6 days and discharged with a course of Augmentin. Lemierre's syndrome is an infectious thrombophlebitis of the internal jugular vein. First described by Andre Lemierre in 1936, it begins as a bacterial pharyngitis, generally developing into a peritonsillar abscess or other deep space neck infection with progressive erosion into the internal jugular vein. Diagnostic criteria for Lemierre's syndrome includes radiographically evidence of thrombophlebitis of the internal vein and positive blood cultures. CT and MRI can help make the diagnosis, but are not always required. Treatment is prompt intravenous antibiotics with beta-lactamase penicillins, metronidazole, clindamycin, and third generation cephalosporins. [Figure presented] Copyright © 2023 Southern Society for Clinical Investigation.

Efficient selective adsorption of cytokine IL-6 and other middle-macromolecular toxins in the serum of uremia patients with specially designed porous hollow carbon spheres

Abnormally elevated middle-macromolecular toxins such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF- α) in human blood are fatal precipitating factors for patients suffered from immune-related diseases, especially for uremia and COVID-19 critical patients, while the effective clearance of them has always been problematic in clinic. In this work, porous hollow carbon spheres (HCSs) with different size and pore structure has been successfully prepared. The removal efficiency for IL-6 in PBS solution is about 99.8%, even in the serum of uremic patients, HCSs could remove 94.75% and 98.33% of parathyroid hormone (PTH) and β2-microglobulin (β2-MG) efficiently within 5-10 min, and particularly, the adsorption of IL-6 and TNF- α is 17.6 and 11.4 times higher over that of the existing commercial hemoperfusion adsorbents. The adsorption balance can be achieved in 60 min, which would greatly shorten the current clinical treatment duration. Moreover, HCSs with different pore structure exhibit distinct adsorption selectivity for IL-6 and TNF- α, which is of special significance for modifying the middle-macromolecular cytokine level in the complicated human blood environment.

ACUTE INTERSTITIAL NEPHRITIS AS A PRIMARY PRESENTATION OF CANDIDA INFECTIVE ENDOCARDITIS

Introduction: Acute Interstitial Nephritis (AIN) is an important cause of Acute Kidney Injury (AKI), and infections are the second most common etiology, after the drugs. However, AIN following fungal infections is rare. We describe two cases of AIN, which on the investigation turn out to be candidemia following fungal infective endocarditis. Methods: CASE 1: A 65-year-old man with hypertension and diabetes without diabetic or hypertensive retinopathy and prior normal renal function, presented to us with vague abdominal pain with steadily creeping creatinine to 2mg/dl within 2 weeks, and urine showed no albuminuria and sediments. There was no history of any specific drug intake. His hematological and other parameters were normal. Blood and urine cultures were sterile. He underwent a renal biopsy which revealed acute interstitial nephritis (Figure 1). He was started on prednisolone at 1mg/kg/day for 1-week following which he had a rapidly worsening azotemia requiring hemodialysis. Steroids were stopped. Repeat blood cultures were sent which grew candida albicans resistant to flucytosine. Re-evaluation of the fundus revealed macular infarct in the right eye with vitreoretinitis in the left eye suggestive of endophthalmitis. PET CT showed increased FDG uptake in both kidneys suggestive of pyelonephritis. Trans-esophageal echocardiography (TEE) showed aortic valve vegetations. He was treated with antifungals for 3 months. He was dialysis-dependent for 2 weeks. He gradually regained normal renal function 3 weeks after starting anti-fungal agents. CASE 2: A 57-years-old man with diabetic, hypertensive, and no diabetic retinopathy had severe covid pneumonia in June 2021 requiring oxygen and tocilizumab 80 mg for 4 days, recovered with normal renal function. He presented to us 1 month later with unexplained non-oliguric severe AKI requiring dialysis, with bland urine sediments. Renal biopsy showed lymphocytic infiltrates in the interstitium suggestive of AIN (Figure 2). Blood cultures were sterile, but serum beta-D-glucan was elevated at 333 pg/ml. He was Initiated on 1mg/kg of prednisolone, on the presumption of drug-induced AIN. Simultaneously workup for systemic infection revealed mitral anterior leaflet endocarditis. He was initiated on anti-fungal therapy on the advice of an infectious disease specialist and the steroid was stopped. He continued to be dialysis-dependent after 6 weeks, despite anti-fungal agents. Results: [Formula presented] Conclusions: AIN contributes a significant proportion of cases in unexplained AKI. Prompt evaluation with a renal biopsy is warranted. Acute interstitial nephritis particularly due to candidemia can be oligosymptomatic as seen in our two cases. Since steroids have a significant role in treating early AIN, a dedicated search for underlying silent endocarditis and candidemia is advisable before initiating steroid therapy. Ophthalmic fundus evaluation, TEE, and repeat blood culture may be necessary to identify hidden candidemia. We recommend an evaluation to exclude fungal endocarditis in patients with AIN who present with minimal or no symptoms and no definitive cause for AIN is present. No conflict of interest

COVID-19: A Rare Cause of Hemolytic Uremic Syndrome.

Hemolytic uremic syndrome (HUS) is a multisystemic condition characterized by a triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. HUS can be classified as atypical or typical, depending upon its association with the Shiga toxin-producing Escherichia coli (STEC). Approximately 90-95% of cases are classified as typical, while only 5-10% of cases are atypical. The pathogenesis of atypical HUS (aHUS) occurs when the complement cascade is activated and causes membrane attack complex (MAC) deposition in the renal tubular epithelium. Various infectious triggers have been associated with aHUS. A new and compelling correlation to this rare and potentially deadly diagnosis of aHUS is COVID-19 infection or vaccination. We present a case of COVID-19-induced exacerbation of a patient with a known history of aHUS. In addition, we performed a literature review of previously reported COVID-19-induced aHUS cases and identified the potential pathogenesis of the disease state.

Leptospirosis: A Consideration When Acute Liver Failure Accompanies Acute Kidney Injury (AKI)

A 48 y.o. male maintenance worker in a rat-infested building with history of tobacco and marijuana smoking, atrial fibrillation on no medications was admitted in July 2021 for fever, headache and body aches for 5 days and new onset of hemoptysis. Initial labs notable for BUN 36 mg/dl, Cr 1.4 mg/dl urine protein 100 mg/dl RBCs 5-10/hpf, platelets 46,000. total bilirubin 3.8 mg/dl direct bilirubin 3.0 SARS-CoV-PCR negative and CXR revealed patchy bilateral infiltrates. He was intubated on day 2 and had ventricular fibrillation and cardiac arrest on day 3 with rapid return of purposeful movement. He had worsening anemia and thrombocytopenia, positive ANA and dsDNA, leading to use of steroids and plasmapheresis on Day 6 when peak bun/cr was 91/3.1 with urine protein/cr ratio 0.7, urine microscopy 2 rbc/hpf, urine Na 20 meq/l, urine osm 775 mosm/kg and cpk 400 U/l. These tests were negative or normal: Anti-GBM, ANCA, repeat ANA, repeat dsDNA, C3, C4, HIV, RF, hepatitis C RNA, cryoglobulins, ASO titer, ADAMTS13, Pneumocystis PCR, Sputum AFB, blood, AFB and fungal cultures, viral and fungal testing, hanta virus antibodies. Leptospira antibodies IgM by Dot Blot were positive and Leptospirosis diagnosis confirmed by NYC Department of Health (DOH) after obtaining confirmatory microscopic agglutination testing from the CDC. Urine and blood Leptospira DNA PCR not detected. He remained intubated with FiO2 requirement at 100% prior to his death on hospital day 16. Initially pulmonary renal syndrome considered but he was later found to have pre-renal azotemia. The elevated bilirubin led to testing for leptospirosis, his final diagnosis. In September 2021 the NYC DOH reported 14 cases of leptospirosis (increased from 5 cases in 2020), 13 of which had acute renal and hepatic failure, with 2 having severe lung involvement (1). This case is the only one in this group who died. The leptospirosis case fatality rate for severe diffuse alveolar hemorrhage exceeds 50%. Early appropriate antibiotic treatment prior to lab confirmation has been recommended by the CDC and may decrease severity of disease.

Clinical course and mortality predictors of COVID-19 in hemodialysis patients, single center experience

Aim: Patients diagnosed with Coronavirus disease 2019 (COVID-19) with underlying health problems or comorbidities tend to progress rapidly and severely. Suppressed immune systems due to uremia in hemodialysis patients and comorbidities such as hypertension (HT), diabetes mellitus (DM) and coronary artery disease (CAD) pose a risk for the severe course of the disease. In this study, we aimed to examine the clinical and laboratory findings and risk factors affecting prognosis in hemodialysis patients followed up with a diagnosis of COVID-19. Material and Method: 58 adult hemodialysis patients diagnosed with COVID-19 with clinical, laboratory and radiological findings between 01.08.2020 and 15.11.2020 were retrospectively evaluated.

Epidemiology of acute kidney injury (AKI) within patients hospitalized in the emergency department of Mahdia

Introduction: Acute renal failure (AKI) is a real global public health which is a diagnostic and therapeutic issue in emergency departments. Better knowledge of the epidemiological characteristics will help improve the prevention and management of this disease. Methods: Prospective descriptive study carried out in the emergency department of the Taher Sfar CHU in Mahdia between March 1 and August 31, 2021. Patients older than 18 years with acute renal impairment were included. Chronic renal insufficiency with hemodialysis stage was excluded as well as renal insufficiency having kept stable creatinine figures. The main objective of this work was to study the epidemiological profile of AKI within patients hospitalized in the emergency department. Results: Our study englobed 103 patients: 53 men and 50 women, with a sex ratio of 1.06. The average age was 66 years. 94% of the patients included had a medical history of: diabetes 58.7% and HTA 54.4%, chronic renal failure was reported in 33%. Thus, most of the cases were under disease-modifying treatment: 64% under diuretics. The COVID attack affected 42% of hospitalized patients. Sepsis was the most common cause of AKI in the emergency room 38.8% of patients, followed by functional AKI(33,9%), 4 patients presented with obstructive AKI requiring placement of a JJ catheter. Patients were classified according to the KDIGO classification: stage I (n = 58) stage II (n = 8) stage (n = 37). Urgent hemodialysis was indicated in the presence of uremic syndrome (14.6%) in 23% of cases, otherwise vascular filling was indicated in 60 patients (58.3%). 64 patients were hospitalized in our emergency room (65%), 15 patients died (14.6%). Full recovery was observed in 18.4% of patients, 29.1% of patients partially recovered while 13.6% were dependent on long-term dialysis. Conclusions: Acute kidney injury is one of the most common serious complications for all hospital admissions. The early diagnosis as well as the management of AKI creates a challenge for the emergency physician.

Impact of CO VID -19 on the vascular access practice of hemodialysis patients in Tianjin, northern China

Background: The coronavirus disease 2019 (COVID-19) struck China from late 2019 before its rapid spread across the country. Tianjin, as one of the largest cites in the north of China, reported a number of confirmed COVID-19 cases shortly after its outbreak in Wuhan province. After the pandemic was brought under control in May, strict control measures were put in place as routine to prevent cross-infection, which contributed to the change in vascular access practice. Therefore, a retrospective study was conducted to evaluate the impact of COVID-19 on vascular access in non-hot-spot region, north China. Methods: In this multicenter cross-sectional study, vascular access data was collected from the hemodialysis patients treated at 52 hospitals in Tianjin from 1 January to 14 Decmeber 2020. The practice of vascular access was estimated during the outbreak of Covid-19 since late 2019. Results: Among the 6885 hemodialysis patients included, 4719 arteriovenous fistulas were identified as the main type of vascular access, accounting for 68.54%. While 2114 patients (30.7%) had tunneled cuffed catheter. The proportion of arteriovenous graft reached as low as 1%. Overall, 1819 vascular access sites were placed in the patients newly diagnosed with uremia, of whom 990 (54.5%) underwent catheter insertion, 811 (44.6%) underwent AVF creation, and only 18 AVGs were created. In addition, the proportion of vascular access sites performed in general hospitals was 88.6%. During the period, tempt catheter insertion was carried out for 1371 (75%) incident hemodialysis patients. Due to stenosis of AVF, percutaneous transluminal angioplasty was conducted for 83 patients. However, no patient got diagnosed with Covid-19. Conclusions: Catheter was the primary vascular access type during the pandemic and the rate of catheter use for incident patients was high. Most of vascular access creation was carried out in general hospitals while the numbers of AVG and PTA were relatively low.

Uremia-Associated Immunological Aging and Severity of COVID-19 Infection.

One year after the start of the COVID-19 pandemic it has become clear that some groups of individuals are at particular high risk of a complicated course of infection resulting in high morbidity and mortality. Two specific risk factors are most prominent, old age and the presence of co-morbidity. Recent studies have shown that patients with compromised renal function, especially those treated with renal replacement therapy or having received a kidney transplant are at a much higher risk for severe COVID infection and increased mortality. This may be in part due to the increased prevalence of co-morbid conditions in these patients but specific alterations in their immune system, reflecting premature immunological aging, may be equally important. In this review the different aspects, in particular thymus function and memory T cell expansion, of uremia-associated immunological aging are reviewed with respect to COVID 19 infection. In essence, the decreased generation of naïve T cells may be instrumental in suboptimal anti-viral immune responses while the relatively uncontrolled expansion of effector T cells may facilitate the feared phase of the COVID-19 infection with excessive and live-threatening inflammation of the lung parenchyma.

Clinical outcomes of dialysis patients with COVID-19 in the initial phase of the COVID-19 outbreak in Wuhan, China.

PURPOSE: Since the end of 2019, dialysis patients have been at risk of coronavirus disease 2019 (COVID-19) as well as other potential complications. Hence, we sought to describe the clinical characteristics of dialysis patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We reviewed clinical outcomes, which consisted of clinical data extracted from the medical records of 695 registered dialysis patients at the Dialysis Center of Central Hospital of Wuhan from January 13th, 2020, to February 29th, 2020, and performed statistical analysis. According to the results, there were 447, 227 and 21 hemodialysis (HD), peritoneal dialysis (PD) and combined HD and PD (HD&PD) cases, respectively. RESULTS: During the outbreak of COVID-19, 36 dialysis patients were infected by SARS-CoV-2. Among those 36 patients, 32 (7.2%) were on HD, and 4 (1.8%) were on PD. When comparing SARS-CoV-2 infection between HD and PD, the relative risk was 4.07 (RR = 4.07, 95% CI 1.46-11.35). We noted a median age of 66 years during the observation period, and the number of male patients was 23 (63.9%). There were 15 fatal cases tested positive for SARS-CoV-2 (13 cases on HD and 2 cases on PD). By comparing mortality in the same period of 2018, 2019 and 2020, the all-cause mortality of hemodialysis patients was significantly higher in 2020 (4.89%) than in either 2018 (2.55%) or 2019 (1.97%). There was no significant difference in mortality from all causes excluding COVID-19, during the same period among the 3-year period. However, during the COVID-19 outbreak, the mortality from all causes excluding COVID-19 was 2.73%, which was slightly higher than that from COVID-19 (2.16%). CONCLUSIONS: Although COVID-19 seriously threatens the health of people with uremia, deaths from all causes excluding COVID-19 during the epidemic cannot be ignored.