The Predictive Value of Cystatin C for AKI in Patients with COVID-19.

Objective. To evaluate a potential of cystatin C blood concentration to predict acute kidney injury (AKI) in patients with severe and extremely severe pneumonia associated with a COVID-19. Materials and methods. An observational prospective study of 117 patients with severe and extremely severe pneumonia associated with a COVID-19 in an ICU setting was conducted in 2020-2022 (site: multifunctional Medical Center, 1586 Military Clinical Hospital of the Ministry of Defense of Russia, Moscow Region, Russia). Routine laboratory tests and instrumental examinations were performed according to generally accepted protocols. Cystatin C concentrations in blood (s-CysC) and urine (u-CysC) were measured by immunoturbidimetric method. Results. AKI was diagnosed in 21 (17.9%) patients, kidney dysfunction without AKI was found in 22 (18.8%) patients with severe and extremely severe pneumonia associated with COVID-19. s-CysC and u-CysC levels in the group of patients with AKI were statistically significantly higher compared to the levels in the group of patients without AKI. The levels of s-CysC obtained within Day 1 - T (-1), and Day 2 - T (-2) prior to AKI onset turned out to be the independent factors for AKI development in patients with severe and extremely severe pneumonia associated with COVID-19: OR 5.37, Wald chi-square 5.534 (CI: 1.324;21.788);P=0.019 and OR 3.225, Wald chi-square 4.121 (CI: 1.041;9.989);P=0.042, respectively. s-CysC T (-2) value is informative, and s- CysC T (-1) is a highly informative predictor of AKI development in severe and extremely severe pneumonia associated with COVID-19: ROC AUC 0.853 (95% CI, 0.74-0.966), P_0.001) with 90% sensitivity and 73% specificity at a cut-off of 1.67 mg/L, and ROC AUC 0.905 (95% CI, 0.837-0.973), P_0.001) with 90% sensitivity and 73% specificity at a cut-off of 1.69 mg/l, respectively. Serum CysC levels started increasing 3 days prior to AKI onset, outpacing the increase of SCr levels. The u-CysC levels were not predictive of AKI development. Impaired renal function probability was increasing with patients' age (P_0.0001). Conclusions. Serum CysC seems to be a statistically significant predictor of AKI. s-CysC levels started increasing 3 days prior to AKI onset, surpassing the increase of SCr levels in patients with severe and extremely severe pneumonia associated with COVID-19. Urine CysC did not achieve statistical significance as a predictor for AKI, although u-CysC concentrations were significantly higher on days 3, 2, 1 prior to AKI onset and on the day of AKI onset in the group of patients with AKI.Copyright © 2023, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

Incident New Onset Diabetes after Covid-19 Infection: A National Multicenter Cohort

Background: It is known that survivors of acute SARS-CoV-2 infection can experience a complex disease known as post-acute sequelae of COVID-19 (PASC). The clinical manifestations of acute COVID-19 have been well characterized however less is known about the risk of new onset diabetes mellitus (DM) in the post-acute phase of COVID-19. Method(s): An adult cohort with confirmed COVID-19 (by diagnosis or positive test) and without COVID-19 was sampled from a large national health research network between January 1st, 2020 and July 8th, 2022. We investigated the outcomes of a new diagnosis of DM (type I or II) occurring after COVID-19 through 12 months after infection. Risk estimates [incidence, relative risk (RR), attributable risk] were used to describe the probability of incident post-COVID diabetes. Hazard ratios and 95% confidence intervals were used to describe risk factors associated with new diabetes. Result(s): The 3-month probability of new diabetes was 2.48/1,000 among COVID+ and the relative risk (RR) of new diabetes was highest at 12 months [8.94 (8.54, 9.36)]. Vitamin D deficiency [HR: 1.52 (95% CI: 1.42, 1.63)] was associated with increased risk of T2DM and having vitamin D deficiency with either obesity (BMI > 30 kg/m2) or kidney dysfunction (GFR < 60) was associated with more than five times increased risk of T1DM. Conclusion(s): We observed a large proportion of excess diabetes starting at 3 months post COVID infection. Traditional risk factors for diabetes, omicron variant, and vitamin D deficiency are associated with increased risk of new diabetes outcome. PASC care should involve identification and management of diabetes. (Figure Presented).

Prognostic significance of early acute kidney injury in COVID-19 patients requiring mechanical ventilation: a single-center retrospective analysis.

Acute kidney injury (AKI) is associated with impaired outcomes in critically ill COVID-19 patients. However, the prognostic significance of early AKI is poorly described. We aimed to determine whether AKI on admission to the intensive care unit (ICU) and its development within the first 48 h predict the need for renal replacement therapy (RRT) and increased mortality. An analysis of 372 patients with COVID-19 pneumonia requiring mechanical ventilation without advanced chronic kidney disease from 2020 to 2021 was performed. The AKI stages on ICU admission and Day 2 were determined using adapted KDIGO criteria. The early development of renal function was assessed by the change in AKI score and the Day-2/Day-0 creatinine ratio. Data were compared between three consecutive COVID-19 waves and with data before the pandemic. Both ICU and 90-day mortality (79% and 93% vs. 35% and 44%) and the need for RRT increased markedly with advanced AKI stage on ICU admission. Similarly, an early increase in AKI stage and creatinine implied highly increased mortality. RRT was associated with very high ICU and 90-day mortality (72% and 85%), even surpassing that of patients on ECMO. No difference was found between consecutive COVID-19 waves, except for a lower mortality in the patients on RRT in the last omicron wave. Mortality and need for RRT were comparable in the COVID-19 and pre-COVID-19 patients, except that RRT did not increase ICU mortality in the pre-COVID-19 era. In conclusion, we confirmed the prognostic significance of both AKI on ICU admission and its early development in patients with severe COVID-19 pneumonia.

Medium term survival in patients over ninety years-old undergoing pacemaker implantation

Background: According to the Italian National Statistical Institute, the 12- month probability of survival in the general population between 90 and 94 years-old is 26%. Pacemaker (PM) implantation is often an urgent and necessary intervention, but in these patients the benefit in terms of quality and duration of life is unclear. Purpose(s): To analyze characteristics, outcome and factors associated with survival in patients who had turned 90 at the time of PM implant. Method(s): All the PM implants performed in patients >=90 from 1/1/2019 to 12/31/2020 were analyzed. Clinical parameters, device characteristics and follow-up data were extrapolated from the SuitEstensa Ebit reporting system;the exitus was verified by analyzing data from the Regional Health System. Result(s): During the study interval, among the 554 patients undergoing PM implantation in our Center, 69 (12%) were >=90 years-old (mean age 92+/-2 years, 46% male;complete/advanced AV block in 76%). Twenty-six (38%) patients had history of atrial fibrillation and 19 (28%) ischemic heart disease. A cardiological co-morbidity (excluding AF) was present in 23 patients (33%). Oncological, pneumological and neurological comorbidities were present in 12 (18%), 19 (28%) and 32 (46%) respectively. Renal impairment was present in 25 patients (36%). In 47 patients (68%) there were at least 2 co-morbidities. After implantation (single-chamber in 36, dualchamber in 25 and VDD single-lead dual-chamber in 8 patients) complications occurred in 3 patients (2 pneumothorax and 1 lead dislodgment). Remote monitoring was activated in 57 patients (83%). Within August 31st 2021 (mean follow-up 288+/-193 days) 24 patients died (35%, 219+/-241 days after implant). Five patients (19% of patients implanted in 2019) died within 12 months. No patients died for device malfunction. Three patients died because of COVID-19 pneumonia. Renal dysfunction (Hazard Ratio-HR 8.05, p=0.002) and the presence of 2 or more co-morbidities (HR 6.03;p=0.015) were associated with a higher risk of death at univariate analysis;other significant variables were diabetes (HR 2.34;p=0.038), left ventricular ejection fraction (LVEF) (HR 0.70 for 5% variation;p=0.005), walking impairment (HR 2.99, p=0.006), the presence of oncological (HR 2.21;p=0.003), pneumological (HR 2.55;p=0.024) and neurological (HR 1.90, p=0.007) comorbidities. At multivariable analysis the only significant parameter associated with survival was LVEF (0.76 for 5% difference;p=0.043) Conclusion(s): At our Center, patients >=90 years-old undergo PM implantation mainly for advanced AVB. The good survival in the medium term, even better than expected in the general population, does not justify a too conservative attitude especially, but exclusively, in patients with less comorbidities.

The association of angiotensin-converting enzyme inhibitors and angiotensin 2 receptor blockers with renal protection in patients with SARS-CoV-2

Background: Kidney dysfunction is a prevalent disease that leads to many complications over time, such as hypertension, heart disease, and death. ACEI/ARBs are known to be renoprotective. However, few studies describe the association between ACEI/ARB use and kidney dysfunction in patients with SARS-CoV-2 infection. Purpose(s): To explore the association between patients with SARS-CoV- 2 and kidney dysfunction in patients taking an ACEI/ARB. We hypothesize a negative association between patients with SARS-CoV-2 taking an ACEI/ARB and kidney dysfunction. Method(s): A retrospective query between March 2020 and April 2021 was performed in patients 18 years and older who tested positive for SARSCoV- 2 using a polymerase chain reaction test. Patients were divided into two groups: Kidney dysfunction and no kidney dysfunction. Kidney dysfunction was defined as any diagnosis of chronic kidney disease or acute kidney injury. Primary outcomes were all-cause mortality and hospitalization rate. Secondary outcomes included myocardial infarction (MI), hypotension, intubation, vasopressor use, ventricular tachycardia, and ventricular fibrillation. We used multivariate logistic regression to adjust for baseline characteristics. Result(s): We identified 996 patients with kidney dysfunction and 22,106 without kidney dysfunction who tested positive for SARS-CoV-2. The incidence was 258 (25.9%) for ACEI/ARB use in patients with kidney dysfunction. Adjusted odds ratio (OR) for patients with kidney dysfunction was 5.705 (95% Confidence Interval [CI]: 4.554-7.146;p<0.001) for hospitalization, 0.895 (95% CI: 0.707-1.135;p<0.361) for patients taking ACEI/ARB, and 0.529 (95% CI: 0.333-0.838;<0.007) for mortality in patients with kidney dysfunction who took ACEI/ARB. All secondary outcomes had significantly greater adjusted OR (p<0.001), except for MI (p<0.339), ventricular tachycardia (p<0.697), and ventricular fibrillation (p<0.060). Conclusion(s): To date, the benefits of ACEI/ARB in SARS-CoV-2 patients have been controversial. While ACEI/ARB is known to have renoprotective properties, we did not find a significant association between ACEI/ARB and kidney dysfunction in patients with SARS-CoV-2. However, we found the use of ACEI/ARB in patients with kidney dysfunction to be associated with lower mortality. Therefore, clinicians should continue using this medication for its mortality benefits in patients with kidney dysfunction and its cardioprotective effects.

Evaluation of the Diagnostic Utility of Urine Biomarkers Timp-2 and Igfbp-7 in Predicting Aki and Short-Term Outcomes among High Risk, Critically Ill Patients

Introduction: Acute kidney injury (AKI) is a common complication of critical illness that often leads to increased mortality and morbidity. Biomarkers detect AKI earlier, providing a window of opportunity for timely intervention. Of the recent biomarkers in literature, the cell cycle arrest biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) were found to be superior in predicting AKI. Our study aims to evaluate the diagnostic performance of urine TIMP-2/IGFBP-7 in its ability of predict AKI and major adverse kidney events within 30 days (MAKE30) among high-risk patients for AKI. MAKE30 is a composite outcome comprised of all-cause mortality, use of renal replacement therapy (RRT), or persistent renal dysfunction at hospital discharge truncated at 30 days Methods: We conducted a prospective, cross-sectional study which included 135 adult, non-COVID ICU patients. Baseline urine TIMP-2/IGFBP-7 results were used to dichotomize the population into low risk (<0.3 ng/mL) or high risk (>=0.3 ng/mL) for AKI. Participants were then observed for 30 days and monitored for MAKE30 outcomes. ROC curves were created to calculate the sensitivity, specificity, NPV, PPV, and the AUC of the 0.3 ng/mL cut-off to predict the AKI and MAKE30. Result(s): Urine TIMP-2/IGFBP-7 cutoff of 0.3 ng/mL predicted AKI with a sensitivity 82.4%, specificity 79.2%, PPV 57.1%, NPV 93% and AUC 0.81. MAKE30 was detected with a sensitivity 62.8%, specificity 76.1%, PPV 55.1%, NPV 81.4% and AUC 0.69. Elevated levels of urine TIMP-2/IGFBP-7 were found to be associated with AKI (p<0.01), MAKE30 (p<0.01) and all of its subcomponents. Survival or discharge after 30 days were found to be associated with lower urine TIMP-2/IGFBP-7 levels (p<0.01). [Formula presented] Figure 1. Receiver operating characteristic (ROC) curves for predicting AKI across urine TIMP-2/IGFBP-7 levels [Formula presented] Figure 2. Receiver operating characteristic (ROC) curves for predicting MAKE30 across urine TIMP-2/IGFBP-7 levels Conclusion(s): Urine TIMP-2/IGFBP-7, at its current cut-off at 0.3 ng/mL, can predict the likelihood of developing AKI and major adverse kidney events among high-risk patients for AKI. It can serve as a useful adjunct to existing methods, such as serum creatinine, in the early diagnosis and prognosis of acute kidney injury and expanding the therapeutic window to prevent disease progression and improve outcomes. 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

Nocturnal hypoventilation and respiratory muscle/cough weakness in COVID-19 ICU survivors

Background: The impact of severe COVID-19 in nocturnal hypoventilation and respiratory muscles/cough strength is unknown. Aim(s): Characterize respiratory function in post-ICU COVID-19 patients and correlate these findings with COVID-19 associated outcomes. Method(s): Retrospective study with 55 post-ICU COVID-19 patients admitted to a rehabilitation center (RC). Clinical data were collected and patients performed arterial blood gas analysis, nocturnal oxy-capnography, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP) and peak cough flow (PCF) at admission. Result(s): Mean age was 64.4+/-10.2 years, 39 (70.9%) were male. Co-morbidities were present in 50 (90.9%): 39 (70.9%) hypertension;20 (36.4%) diabetes;3 (5.5%) OSA;1 (1.8%) COPD. None had neuromuscular disorders. Median of ICU length was 25.5 (min 5;max 190) days. Fifty-three (96.4%) needed mechanical and invasive ventilation, 6 (10.9%) ECMO and 22 (40%) tracheostomy (all decannulated before admission to our RC). Eighteen (32.7%) had criteria of nocturnal hypoventilation, 17 (30.9%) inspiratory, 16 (29.1%) expiratory and 17 (30.9%) cough weakness. Sepsis correlated with increased length of ICU stay (p=0.007) and with lower PCF values (p=0.048). Neurologic disfunction was associated with lower minimum SpO2 and more time of SpO2<88% (p=0.032;p=0.035). Renal disfunction was associated with higher values of mean and maximum TcCO2 (p=0.003;p=0.011). Patients with previously diagnosed OSA had higher values of MIP and PCF (p=0.006;p<0.001) at evaluation. Conclusion(s): In COVID-19 ICU survivors, nocturnal hypoventilation, inspiratory/expiratory muscle and cough weakness are common and may have an impact in rehabilitation outcomes.

Isolated Colonic Histoplasmosis in Renal Transplant Recipient Post Covid-19 Infection

Introduction: Histoplasmosis is caused by the dimorphic fungus - Histoplasma capsulatum. The presentation of histoplasmosis is often disseminated, though primary intestinal involvement can rarely be seen in patients with cell mediated immune dysfunction like in patients with AIDS. We report a case of renal allograft recipient, who had history of COVID 19 infection and also underwent anti-rejection treatment for renal graft dysfunction, presented with chronic diarrhea and was diagnosed as a case of colonic histoplasmosis. Method(s): We report a case of 45 years old male who underwent renal transplant surgery one and a half year prior (February 2021) and was having stable graft function on tacrolimus, mycophenolate and steroid. He had history of fever and diarrhea in February 2022 and was diagnosed COVID-19 positive with RT-PCR, and was treated conservatively with intravenous dexamethasone and lowering of immunosuppressants. He had mild graft dysfunction in April 2022;renal graft biopsy had acute T-Cell mediated rejection (Banff Grade 1 B) and was treated with pulse steroids for 3 days. He had complaint of intermittent diarrhea, weight loss and intermittent fever since May 2022. He was evaluated and treated on outpatient basis with empirical oral antibiotics. He was admitted in June 2022 with complaint of high grade fever, loose stools leading to hypovolemic shock and renal dysfunction. He had marked thrombocytopenia and neutrophilic leukocytosis. He showed initial response to intravenous broad spectrum antibiotics and crystalloids, but intermittently symptoms of increased stool frequency and altered consistency were still persisting. Stool studies for ova, cyst, parasites and clostridium difficile were negative. Indian ink staining of stool sample had no evidence of Cryptococcosis. Serum PCR for cytomegalovirus was also negative. CT abdomen showed normal visualized bowel and other viscera. Upper GI endoscopy was unremarkable. Colonoscopy revealed multiple small ulcers with erythematous hue and clean base particularly in ceacum and along ascending colon. Multiple colonic biopsies were taken. Histopathology showed lymphoplasmacytic infilterate in the lamina propria. It also showed increased presence of foamy histiocytes, several of which also showed interacellular organism bearing a pseudocapsule. PAS stain also confirmed budding of these interacellular organisms which is consistent with Histoplasmosis. His HRCT chest revealed hyperinflated lungs, cylindrical bronchiectasis in left upper lobe. Urine for histoplasma antigenuria was negative. Result(s): He was treated with intravenous liposomal amphotericin B for initial two weeks followed by oral itraconazole. His symptoms responded remarkably to the treatment. In view of persisting thrombocytopenia and histoplasmosis his mycophenolate was stopped and tacrolimus was titrated as per trough levels Conclusion(s): Colonic histoplasmosis is associated with significant mortatlity and morbidity. Prolonged use of immunosuprresants, use of antirejection therapies (like high dose pulse methyl prednisolone and bortezomib) and even in some case reports COVID 19 infection have shown to increase the risk of histoplasmosis. Primary and isolated colonic histoplasmosis like in this case can be the atypical presentation which emphasizes the importance of maintaining a low threshold for consideration of histoplasmosis in renal allograft recipients. No conflict of interestCopyright © 2023

Acute Kidney Injury and Covid-19

Introduction: COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This emerging disease has become a public health emergency worldwide. Acute Kidney Injury (AKI) secondary to COVID-19 has been described in different studies, but information characterising patients with subsequent AKI is limited. The cause of kidney involvement in COVID-19 is thought to be multifactorial. Cardiovascular comorbidity and predisposing factors (e.g. sepsis and nephrotoxins) are considered as important contributors. The tubular damage has been linked to the cytopathic effects of kidney-resident cells and cytokine storm syndrome. To gain better understanding of the effect of COVID-19 on renal function, large clinical and register based studies have been requested. The objective of this study was to quantify the risk of acute kidney injury during and after covid-19. Method(s): This was a Swedish prospective cohort study where Generalised Estimating Equation methods (GEE) was used to map the kinetics of kidney injury markers such as serum-creatinine (s-creatinine), cystatin and eGFR for the hospitalised patients in the cohort, comparing patients with moderate and severe COVID-19 during and after the acute infection. Furthermore, we will investigate if patients with kidney dysfunction during COVID-19 have more severe disease outcome compared with the whole cohort, adjusting for age, sex, and comorbidities. We will also compare start values of kidney injury markers with the latest values and count the percentage worsening among all disease severity groups. Cohort: Approximately 550 COVID-19 patients were recruited to the study following informed and signed consent at 2 Swedish University Hospitals. A case report form was filled in at pre-specified time points, and samples collected consecutively. A database was then created containing dates and information regarding symptoms, laboratory samples, complications, and disease severity (e.g., need of oxygen, intensive care, mechanical ventilation, death). Result(s): There was a significant increase in s-creatinine among hospitalised and intensive care unit patients (n=126) during the acute phase of COVID-19 (day 0-6 post disease onset) when compared to the follow up samples after 90 days from disease onset. There was also a decrease in s-creatinine in day 11-21 and 31-70 among hospitalised and intensive care unit COVID-19 patients when compared to the same follow up samples. This analysis was adjusted for age and sex. See figure 1. [Formula presented] Conclusion(s): Our preliminary results show that s-creatinine was increased during the first days of COVID-19 followed by decreased levels compared to baseline. The higher levels of s-creatinine day 0-6 of COVID-19 could be an effect of the acute infection, but it could also be caused by other factors such as dehydration or medication. The lower levels of s-creatinine might be caused by dietary changes or loss of muscle mass due to immobilisation during hospitalisation. Knowledge about fluctuations in s-creatinine in COVID-19 patients may be of use for treating physicians. Conflict of interest Potential conflict of interest: Funding from: Swedish Kidney Foundation Central and local ALF funding Vasterbotten County Council, Sweden Arnerska Research Fund, Umea University, SwedenCopyright © 2023

MALIGNANT HYPERTENSION AFTER COVD-19 VACCINE INJECTION

Case;40 y/o male. Clinical course;The patient was transferred to our university hospital because of DOE and severe headache. He had been well and had no history of hypertension or obesity. He had experienced the COVID-19 vaccine injection two week before this visit. After the injection he had been experienced high fever and general fatigue as well as 7 kg of weight loss. On examnation, it was found that he had severe hypertension (190/110 mmHg) and hypertensive optic fundi. On chest X-ray, cardiomegaly and bilateral lung infiltrations was evident and biochemical data indicated renal dysfunction (serum creatinine 2.35 mg/dl), high levels of plasma renin activity (39.1 ng/ml/hour normal;0.6-3.9) and aldosterone concentration (176 pg/ml normal;4.0-82.1), and inflammatory changes (CRP = 23 mg/dl). We also found that increased levels of LDH and decreased levels of hemoglobin which indicated hemolytic anemia and thrombotic microangiopathy. After the control of high blood pressure by intravenous administration of Calcium channel blockades, We performed renal biopsy, which had a finding of diffuse findings of onion skin lesion and global glomerular sclerosis compatible with the diagnosis of malignant hypertension. Any secondary etiologies including renal artery disease or collagen disease had not been identified. Seven days after the admission, we started hemodialysis for this patient because of the renal failure was not resolved. We also had startred ACE inhibitors. We stopped the diuretics and minimized the ultrafiltration. Twenty-five days after the admission the patients was withdrawn from dialysis with the urine volume around 2000 ml/day and the serum creatinine concentration 5.29 mg/dl. He was discharged without any aid of dialysis and with small number of anti-hypertensives. Four months after the discharge, his serum creatinine concentration was 3.36 mg/dl and his blood pressure was 139/85 mmHg with the ACE inhibitor and calcium channel blockades. Conclusions;The case suggested that the malignant hypertension might be triggered by COVID-19 vaccine injection, which is of clinical importance.

Simultaneous Lung and Kidney Transplant in a Young Patient with COVID-19

Purpose: Lung transplant is the last resort for COVID-19 refractory ARDS. Dual organ transplant is seen as a relative contraindication at many institutions. We describe a case of simultaneous Lung-Kidney transplant (SLK) in a patient with COVID-19 ARDS. Method(s): A 24-year-old patient with no PMH presented to an outside hospital with a week of shortness of breath, cough, and fever. Despite treatment with Remdesivir and dexamethasone, the patient developed hypoxemic respiratory failure with acute renal injury requiring ICU care and intubation, V-V ECMO, and dialysis. Additionally, Intravenous and inhaled Aviptadil were given under emergency use authorization. While oxygenation improved, the patient could not be weaned off ECMO. With a LAS score of 90.29, the patient underwent an SLK transplant on HD 53, requiring standard induction and maintenance immunosuppression therapy. The patient was treated post-operatively for PGD as well as for subclinical AMR. After successful inpatient rehabilitation, the patient was discharged home after four months and had a one-month follow-up on room air and normal creatinine clearance. Result(s): Patients with pre-existing renal dysfunction who have undergone lung transplants have a significantly higher one- and three-year mortality than patients with normal GFR. The patient's survival after SLK was similar to isolated lung transplants at one and five years, according to an analysis of the UNOS/OPTN database. Still, dual organ transplant in the COVID-19 ARDS population is considered a contraindication at many centers, given these patients' critical illness and frailty. However, the frailty in this population is reversible due to the rapid onset of disease in an otherwise previously healthy younger population with minimal comorbidities. Thus, multiorgan transplantation should be considered in such a patient population. Our patient received Aviptadil as part of an EIND to stabilize patients and improve oxygenation while waiting on the transplant list. Conclusion(s): We propose that SLK transplantation should be considered for carefully selected patients with COVID-19 ARDS.

DAPTOMYCIN-INDUCED EOSINOPHILIC PNEUMONITIS

SESSION TITLE: Drug-Induced Lung Injury Pathology Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Daptomycin is an antibiotic that exerts its bactericidal effect by disrupting multiple aspects of bacterial cell membrane function. It has notable adverse effects including myopathy, rhabdomyolysis, eosinophilic pneumonitis, and anaphylactic hypersensitivity reactions. CASE PRESENTATION: A 46-year-old male with a history of type 2 diabetes presented with a 1-week history of dyspnea and productive cough. 2 weeks prior, he was started on vancomycin for MRSA osteomyelitis of the right foot, but was switched to daptomycin due to vancomycin induced nephrotoxicity. On presentation he was afebrile, tachycardic 100, hypertensive 183/109, tachypneic to 26, hypoxemic 84% on room air, which improved to 94% on nasal cannula. Chest exam noted coarse breath sounds in all fields and pitting edema of lower extremities were present. Labs showed leukocytosis of 15.2/L, Na of 132 mmol/L, and creatinine 3.20mg/dL (normal 1 month prior). COVID-19 testing was negative. Chest X-ray noted new bilateral asymmetric opacifications. Daptomycin was discontinued on day 1 of admission, he was started on IV diuretics and ceftaroline. Further study noted peripheral eosinophilia. Computed tomography of the chest showed bilateral centrally predominant ground-glass infiltrates with air bronchograms and subcarinal and paratracheal lymphadenopathy. On day 4, he underwent bronchoscopy with bronchoalveolar lavage. Cytology noted 4% eosinophil with 43% lymphocytes. Eventually, oxygen requirements and kidney function returned to baseline. He was discharged on ceftaroline for osteomyelitis DISCUSSION: Daptomycin-induced acute eosinophilic pneumonitis (AEP) often results in respiratory failure in the setting of exposure to doses of daptomycin >6mg/kg/day. It is characterized by the infiltration of pulmonary parenchyma with eosinophils and is often associated with peripheral eosinophilia. AEP has been associated with certain chemicals, non-steroidal anti-inflammatory agents, and antibiotics including daptomycin. Renal dysfunction is associated with an increased risk for developing AEP. The mechanism for daptomycin-induced lung injury is unknown but is believed to be related to daptomycin binding to pulmonary surfactant culminating in epithelial injury. Diagnostic criteria include recent daptomycin exposure, fever, dyspnea with hypoxemic respiratory failure, new infiltrates on chest radiography, BAL with > 25% eosinophils, and clinical improvement following daptomycin discontinuation. Our patient met four out of six criteria;we believe that BAL results were due to discontinuing daptomycin days before the procedure was performed. Sometimes stopping daptomycin is enough for recovery, however, steroids may be beneficial and were used in some of the cases reported in the literature CONCLUSIONS: Clinicians should consider AEP in a patient on Daptomycin presenting with respiratory failure, as timely discontinuation favors a good prognosis Reference #1: Uppal P, LaPlante KL, Gaitanis MM, Jankowich MD, Ward KE. Daptomycin-induced eosinophilic pneumonia - a systematic review. Antimicrob Resist Infect Control. 2016;5:55. Published 2016 Dec 12. doi:10.1186/s13756-016-0158-8 Reference #2: Kumar S, Acosta-Sanchez I, Rajagopalan N. Daptomycin-induced Acute Eosinophilic Pneumonia. Cureus. 2018;10(6):e2899. Published 2018 Jun 30. doi:10.7759/cureus.2899 Reference #3: Bartal C, Sagy I, Barski L. Drug-induced eosinophilic pneumonia: A review of 196 case reports. Medicine (Baltimore). 2018;97(4):e9688. doi:10.1097/MD.0000000000009688 DISCLOSURES: No relevant relationships by Chika Winifred Akabusi No relevant relationships by Shazia Choudry No relevant relationships by Hector Ojeda-Martinez No relevant relationships by Mario Torres

COVID-19-ASSOCIATED THROMBOTIC THROMBOCYTOPENIA PURPURA (TTP)

SESSION TITLE: COVID-Related Critical Care Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a rare medical emergency with mortality rates reported to be as high as 90% if untreated. We report a case of severe TTP in an immunocompetent patient diagnosed with COVID 19 infection. CASE PRESENTATION: A 34-year-old morbidly obese female not vaccinated for COVID presented to PCP 2 weeks prior with complaints of fatigue. CBC showed Hb 12.2, platelet count 108 (baseline > 200), and covid resulted positive. The patient was reluctant for further workup at the time. After 2 weeks she felt short of breath prompting ICU admission for high flow oxygen with blood work showing hemoglobin of 8.8, platelet count of 11, Reticulocyte count 3.9%, LDH 763, fibrinogen 639, schistocytes on peripheral smear, MCV < 90, INR<1.5, Creatinine 1 giving her a PLASMIC Score of 7. For concerns of TTP, she was urgently started on plasmapheresis, prednisone 1 mg/kg, and remdesivir for COVID. ADAMTS13 was sent prior to the initiation of plasmapheresis resulted at 5% indicating severe deficiency and a high risk of relapse. She underwent 3 cycles of plasma exchange and was also started on Caplacizumab. Rituximab was not started in the setting of active COVID infection and negative COVID IgG. Repeat ADAMTS13 level at 2-week interval increased to 43%. The patient was discharged on steroids and completed 1 month of Caplacizumab. On outpatient follow up the patient was asymptomatic but repeat ADAMTS13 declined to 16%. COVID IgG now resulted positive, and she was started on Rituximab. Ultimately patient was treated with 4 months of steroids and 4 doses of weekly Rituximab with the final two ADAMTS 13 levels normalized above 100. DISCUSSION: TTP is caused by decreased activity of the plasma metalloproteinase ADAMTS 13, the key enzyme involved in the cleavage of ultra-large von Willebrand Factor (vWF) multimers into smaller less procoagulant multimers. It is reported that COVID-19 infection is associated with almost a five-fold increase in vWF levels which the body's ADAMTS-13 enzyme activity cannot adequately regulate, resulting in an excess of unchecked ultra-large vWF, diffuse microthrombi, and systemic ischemia. The presentation of this disease is often characterized by the pentad of fever, thrombocytopenia, hemolytic anemia, renal dysfunction, and neurologic dysfunction. However, the full pentad is often not present in many patients Plasma exchange and immunosuppression are the mainstays of treatment for TTP. A high index of suspicion is required for a timely diagnosis. Early diagnosis is crucial as without treatment TTP is associated with a high mortality rate. CONCLUSIONS: Health care providers should be aware of this life-threatening complication of COVID-19 so that prompt and appropriate interventions can be undertaken if it is suspected or confirmed. Rituximab should be delayed until the acute COVID-19 infection has cleared, and neutralizing antibodies have been produced. Reference #1: Hindilerden F, Yonal-Hindilerden I, Akar E, Kart-Yasar K. Covid-19 associated autoimmune thrombotic thrombocytopenic purpura: Report of a case. Thromb Res. 2020;195:136-138. doi:10.1016/j.thromres.2020.07.005 DISCLOSURES: No relevant relationships by Hanish Jain No relevant relationships by Dragos Manta No relevant relationships by Parth Sampat No relevant relationships by Garima Singh No relevant relationships by Simant Thapa

The effect of renal dysfunction on mortality rates for patients on VVECMO for ARDS due to COVID-19 infection

Extracorporeal membrane oxygenation (ECMO) has been used within the SARS-Cov-2 (COVID-19) pandemic to support patients with severe COVID-19 related acute hypoxemic respiratory failure that is refractory to lung-protective mechanical ventilation. The decision to offer and support patients with ECMO therapy comes from selection criteria which is more likely to demonstrate a positive outcome. However, providers may be faced with challenges regarding discontinuation of therapy when recovery appears unlikely. The in-hospital mortality rate for COVID-19 ECMO patients as reported by ELSO's registry is 47%. This retrospective single-institution study sought to determine the effect of the development of renal dysfunction on mortality rates for COVID-19 ECMO patients. In a cohort of 53 patients, 22 of these patients (41.5%) experienced mortality while receiving ECMO therapy, with a total of 26 (49.1%) experiencing mortality during ECMO therapy or within 90 days after ECMO decannulation. Correlating the outcome of mortality with the stages of severity of AKI as defined by KDIGO guidelines, this study demonstrated a significantly lower percentage of study participants in the No AKI group experienced mortality (12.5%;n=2) relative to all other categories of renal dysfunction, X2(4)=4.96, p<.05. Additionally, bivariate analysis indicated that a significantly higher percentage of study participants who required CRRT experienced mortality (77.8%;n=14) relative to all other categories of renal dysfunction, X2(1)=9.00, p<.01. This demonstrates patients requiring CRRT while on ECMO therapy for ARDS related to COVID-19 are 6.71 times more likely to experience mortality relative to those in other categories.

The Effects of SARS-CoV-2 Infection on Renal Function in Patients with Hemodialysis

Objective: This study aims to demonstrate the impact of "SARS-CoV-2" infection on renal function in patients who have undergone hemodialysis in the past. Methodology: Telomerase Reverse Polymerase Chain Reaction in Real Time (RT-Real time PCR) To verify "SARS CoV-2" infection, RT-PCR was used, moreover pre and post urea and creatinine tests were confirmed by COBAS INTEGRA 400 plus analyzer was automated qualitative assays rapidly detected Creatinine, urea, and diabetes Mellitus levels. Result(s): The mean of pre-creatinine levels was 7.3336. The post-creatinine levels (11.8276) significantly increased after "SARS-CoV-2" infection with a P-value of 0.001. The mean of pre-urea levels was 163.6724. The post-urea levels (213.706897) significantly increased after "SARS-CoV-2" infection with a P-value of 0.001. Conclusion(s): SARS-CoV-2 infection in patients with pre-existing hemodialysis leads to increasing kidney dysfunction with or without comorbidities (diabetes mellitus and hypertension). Moreover, the old patients with pre-existing hemodialysis are found to be at higher risk of renal dysfunction during "SARS-CoV-2" infection than the younger groups. Copyright © 2022, Bahrain Medical Bulletin. All rights reserved.

Relapse of Membranous Nephropathy and Renal Sarcoidosis Following Exposure to SARS-CoV-2 Vaccine (Johnson & Johnson)

The role of infectious agents derived antigens including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recognized as a trigger for development of autoimmune mediated disorders following natural infection or immunization. However, there is a scarcity of reports of occurrence of autoimmune associated kidney disorders or flare ups following exposure to a SARS-CoV-2 vaccine. A 65-year-old female presented to a nephrology clinic for evaluation of worsening renal dysfunction. The patient is well known to have systemic sarcoidosis under complete remission on low dose prednisone and likely membranous nephropathy (no previous kidney biopsy) with mildly elevated phospholipase A2 receptor (PLA2R) antibodies. Her membranous nephropathy was in partial remission on angiotensin receptor blockage, with urine to protein creatinine ratio (UPCR) of 1.5 g/g . Five months after receiving the single dose SARS-CoV-2 vaccine (Johnson & Johnson®), she started having a flare up of her systemic sarcoidosis with worsening joint, skin and respiratory symptoms. Blood chemistry revealed worsening renal dysfunction with elevated creatinine up to 1.7 mg/dL from her baseline of 1.0 mg/dL. UPCR was also elevated at 3.4 g/g. Urine sediment revealed no red blood cells or casts, only several calcium oxalate dihydrate crystals. A kidney biopsy was performed and showed a combination of membranous nephropathy (PLA2R positive) along with granulomatous interstitial nephritis with well-formed epithelioid granulomas characteristic of sarcoidosis. She was started on high dose prednisone and her renal function improved to 1.2 mg/dL, UPCR decreased to 1.8 g/g and serum PLA2R antibodies became undetectable. She is still being monitored. After many years of renal sarcoidosis and membranous nephropathy remission, the relapse of renal disease after receiving the SARS-CoV-2 vaccine (Johnson & Johnson®) suggests the association between receiving the vaccine and the recurrence of renal sarcoidosis and membranous nephropathy.

The negative impact of the pandemic on hospital admissions, morbidity and 30-day mortality for acute cirrhosis decompensation: a tertiary care perspective

Background and aims: The global pandemic has inevitably diverted resources away from management of chronic diseases, including cirrhosis, where up to 40% of patients are readmitted with new cirrhosis decompensation events. Whilst there is increasing knowledge on COVID-19 infection in liver cirrhosis, little is described on the impact of the pandemic on decompensated cirrhosis admissions and outcomes, which was the aim of this study. Method: A single-centre, retrospective study, evaluated decompensated cirrhosis admissions to a tertiary London hepatology and transplantation centre, from October 2018 to February 2021. Patients were included if they had an admission with cirrhosis decompensation defined as new onset jaundice or ascites, infection, encephalopathy, portal hypertensive bleeding or renal dysfunction. Admissions were excluded if they lasted <24 hours,were elective or occurred post liver-transplant. Results: Therewere 351 admissions in the pre-COVID period (October 2018 to February 2020) and 240 admissions during the COVID period (March 2020 to February 2021), with an average of 20.4 admissions per month throughout. Patients transferred in from secondary centres had consistently higher severity scores during the COVID period (UKELD 58 versus 54;p = 0.007, MELD Na 22 versus 18;p = 0.006, AD score 55.0 versus 51.0;p = 0.055). The proportion of ITU admissions pre versus during-COVID stayed constant (22.9% versus 19.2%), but there was a trend towards increased ICU admissions with acute-on-chronic liver failure (ACLF) (73.9% versus 63.8% prepandemic). Of those admitted to the intensive care without ACLF, there was a significant increase in EF-CLIF acute decompensation (AD) scores during the COVID period (58 versus 48, p = 0.009). In addition, there was a trend towards increased hospital re-admission rates during the COVID period (29.5% versus 21.5%, p = 0.067). When censored at 30 days, time to death post discharge was significantly reduced during the COVID period (p < 0.05) with a median time to death of 35 days compared to 62 days pre-COVID.(Figure Presented)Conclusion: This study provides a unique perspective on the impact that the global pandemic had on the clinical course and characteristics of decompensated cirrhosis admissions. The findings of increased early mortality and re-admissions, and higher AD scores, indicating increased disease morbidity, highlight the need to maintain resourcing on providing high-level hepatology care. Given that COVID-19 will likely be a chronic issue, alternative care pathways such as remote monitoring may need adoption to facilitate continuity of care post-discharge and to reduce readmission rates and morbidity in the future

FORTUNATELY, NOT A TTP (THROMBOTIC THROMBOCYTOPENIC PURPURA). A CASE OF COVID INFECTION WITH EXTREME THROMBOCYTOPENIA (PLATELETS 5K/UL) AND SEVERE DEFICIENCY OF ADAMTS 13 (<2 %) WITHOUT TTP SYMPTOMS AND WITHOUT NEED FOR PLASMAPHERESIS

CASE: 54-year-old female presented with 1 week of generalized weakness, headache, congestion, cough with dark- colored phlegm, and several days of decreased smell and taste. She was unvaccinated and had positive sick contacts. Patient tested positive for Covid and found to have severe thrombocytopenia with platelets of 5K/uL, very rare schistocytes on smear, and no other notable abnormalities. She received platelet transfusion and was treated for presumed immune thrombocytopenia with IVIG and dexamethasone. The patient had no petechiae, bleeding, or other symptoms concerning for secondary TMA, notably TTP. The platelet count was 93 K/uL by day 5 and she was discharged home. Later that day her ADAMTS13 test resulted at <2% and the ADAMTS13 antibody was elevated. The patient was asked to return to the hospital for monitoring of TTP symptoms. She reported improvement in her weakness. Her thrombocytopenia and oxygen saturation remained normal. Bilateral lower extremity ultrasound showed no lower extremity VTE. On the day of discharge, 10 days after her original thrombocytopenia identified, she had a platelet count of 373 K/uL and repeated ADAMTS13 of 14.8%. IMPACT/DISCUSSION: ADAMTS13 is known as von Willebrand factor (VWF) protease as it cleaves prothrombotic and highly adhesive to platelets ultra-large multimers of VWF into smaller multimers, thus modulating VWF activity and regulating the adhesive function. A severe deficiency of ADAMTS13 characterizes TTP, a rare but potentially fatal disorder associated with thrombosis due to accumulation of prothrombotic ultra-large VWF multimers. There are literature reports of TTP and TTP-like syndromes in Covid-19. It is speculated that in COVID-19, the excess of VWF released in response to endothelial activation likely exhausts the available reserves of ADAMTS13, which may then propagate formation of microthrombi in different organs. We report an extreme thrombocytopenia, marked decrease of ADAMTS 13 and elevated ADAMTS13 antibodies, which would be confirmative evidence of TTP should our patient have clinical features of it. Our patient did not have fever, neurologic abnormalities, renal dysfunction, or active hemolysis. She was followed in outpatient clinic after the discharge. The platelet count recovered and ADAMTS 13 trended up without need for plasmapheresis. Our case is a good example of a fortunate outcome without any complications despite threatening presenting criteria. CONCLUSION: Covid-19 associated endothelial stimulation and damage could mimic a life-threatening disorder without expected fatal complications. On the other hand, it can ultimately lead to the most severe form of thrombotic microangiopathy, TTP, for which the mortality rate is close to 90%. It is hard to know which outcome to expect in different circumstances. Therefore, it is crucial for physicians to promptly recognize clinical picture of TTP as treatment is lifesaving.

The RELIEHF registry & clinical trial design (Relieving Increasing Oedema due to Heart Failure)

Background: Water retention leading to worsening congestion is a common reason for heart failure (HF) hospitalisation. Increases in aldosterone, due to increased secretion (driven by angiotensin and hyperkalaemia) and reduced degradation (due to hepatic dysfunction), contribute to congestion. Mineralocorticoid receptor antagonists (MRA) reduce morbidity and mortality in advanced HF. However, use of MRA is often limited by hyperkalaemia, renal dysfunction and hypotension. Hyperkalaemia can be corrected by potassium binding agents. Methods: An open-label, randomised, multi-centre (up to 100 UK sites) trial investigating the use of a potassium binding agent, patiromer, to facilitate higher doses of MRA for HF with worsening congestion requiring treatment with ≥80mg/day of furosemide (or equivalent). Patients are first entered on an unconsented screening-log (approved by the UK Health Research Authority) and then asked to consent to a registry (no exclusion criteria). If they agree, and are eligible (systolic blood pressure ≥90mmHg, eGFR ≥30mL/min/1.73 m2, no other terminal disease, no active infection or myocardial ischaemia), they are invited to participate in a randomised trial. Patients who consent for the trial enter a run-in phase of ≤35 days, when they receive ≤100mg/day of spironolactone. If serum potassium rises to >5.0mmol/L, the patient is randomised either to receive an MRA at guideline recommended doses or to have spironolactone increased ≤200mg/day, using patiromer to manage hyperkalaemia, providing eGFR remains ≥30mL/min and the patient does not become hypotensive. The primary outcome of the first phase of the trial (n = 400) is severity of congestion at 60-days but patients will be followed The RELIEHF Registry & Randomised Trial long-term for morbidity and mortality. An adaptive trial design allows recruitment to be increased up to 2.000 patients. Results: The conduct of the trial has been disrupted by COVID. As of January 2022, from 10 sites, >300 patients (40% women;median age 76 (65-83) years have been screened, >100 (37% women;median age 72 (62-80) years) have consented for the registry and >25 for the randomised trial. Of patients screened, about 50% were asked for registry-consent, of whom one third refused. The main reason for not asking was that the care-team considered it inappropriate due to patient frailty and/or cognitive dysfunction. Most patients who consented for the registry agreed, in principle, to participate in a randomised trial. Most patients have tolerated 100mg of spironolactone during the run-in period. Conclusions: For a high proportion of patients admitted to hospital with worsening HF, research staff do not deem it appropriate to approach them to ask for research consent. Most patients with HF who were asked to participate in research were willing to do so and to participate in a randomised trial, although a substantial proportion were not eligible for this trial. Of those who were, the majority tolerated spironolactone at a dose of 100mg/day.