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Background and aims: Acute Kidney Injury (AKI) is the most frequent complication after respiratory failure in COVID-19 patients. AKI increases mortality risk, length of hospital stay and healthcare costs with possibile progression toward CKD. Study aims: 1) evaluation of AKI incidence in 1020 COVID-19 hospitalized patients;2) comparison of AKI incidence in COVID-19 vs. pre-pandemic period;3) establishment of out-patient follow-up for monitoring kidney, lung, motor and immune function;4) creation of a biobank for biomarker discovery studies. Methods: AKI incidence was calculated matching laboratory and administrative data of 26214 hospitalized patients in 2018-2019 and in 1020 COVID-19 patients in 2020-2021: KDIGO algorithms were applied for AKI grading. After 12 months from discharge, 232 COVID AKI patients and relative controls matched for age and gender were evaluated for kidney (eGFR, biomarkers of tubular damage NGAL, CCl-14, DKK-3), lung (DLCO, CT scan) and neuro-motor (SPPB, 2-min walking test, post-traumatic stress test-IES) function. Results: Before pandemic, in-hospital AKI incidence was 18% (10% KDIGO 1, 5% KDIGO 2, 3% KDIGO 3): median age of AKI patients was 69. In-hospital mortality was 3.5 % in non-AKI group vs. 15% in AKI group in accordance with KDIGO stages. In COVID patients, AKI incidence increased to 37% (20% KDIGO 1,11% KDIGO 2, 6% KDIGO 3): median age of patients was 54. In-hospital mortality was 31 % in AKI group. After 12 months from hospital discharge, COVID AKI patients showed a persistent reduction of respiratory function (severe DLCO impairment <60%) related to the extent of CT scan abnormalities. AKI patients also presented motor function impairment and a worse posttraumatic stress response. GFR reduction was 1.8 ml/min in non AKI vs. 9.7 ml/min in AKI COVID patients not related to age. Urinary DKK-3 and CCL-14 were also higher in the AKI group. Last, IgG response after SARS-CoV-2 vaccination was significantly lower in the AKI group. Conclusion: AKI incidence was significantly increased during COVID-19 in respect to pre-pandemic period with an association with higher mortality in class 2-3 KDIGO. In the post-COVID follow-up, AKI was associated with lung and neuro-motor function impairment, a defective antibody response and a sudden GFR decline concomitant to the persistence of tubular injury biomarkers. These results suggest the importance of a nephrological and multidisciplinary follow-up of frail patients who developed AKI during hospitalization for COVID-19.
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BACKGROUND AND AIMS: AKI is the most frequent complication after respiratory failure in COVID-19. AKI increases mortality risk, length of hospital stay and healthcare costs, with possible progression towards CKD. Study aims: (1) evaluation of AKI incidence in 1020 COVID-19 hospitalized patients;(2) comparison of AKI incidence in COVID-19 versus pre-pandemic period;(3) establishment of out-patient follow-up for monitoring kidney, lung, motor and immune function;(4) creation of a biobank for biomarker discovery studies. METHOD: AKI incidence was calculated matching laboratory and administrative data of 26 214 hospitalized patients in 2018-2019 and in 1020 COVID-19 patients in 2020-2021: KDIGO algorithms were applied for AKI grading. After 12 months from discharge, 232 COVID AKI patients and relative controls matched for age and gender were evaluated for kidney (eGFR, biomarkers of tubular damage NGAL, CCl- 14, DKK-3), lung (DLCO, CT scan) and neuro-motor (SPPB, 2-min walking test, post-traumatic stress test-IES) function. RESULTS: Before the pandemic, in-hospital AKI incidence was 18% (10% KDIGO 1, 5% KDIGO 2, 3% KDIGO 3): median age of AKI patients was 69. In-hospital mortality was 3.5% in non-AKI group versus 15% in AKI group in accordance with KDIGO stages. In COVID patients, AKI incidence increased to 37% (20% KDIGO 1.11% KDIGO 2, 6% KDIGO 3): median age of patients was 54. In-hospital mortality was 31% in the AKI group;AKI is an independent risk factor for death. After 12 months from hospital discharge, COVID AKI patients showed a persistent reduction of respiratory function (severe DLCO impairment < 60%) related to the extent of CT scan abnormalities. AKI patients also presented the motor function impairment and a worse post-traumatic stress response. GFR reduction was 1.8 mL/min in non-AKI patients versus 9.7 mL/min in AKI COVID patients not related to age. Urinary DKK-3 and CCL-14 were also higher in the AKI group. Last, IgG response after SARS-CoV-2 vaccination was significantly lower in the AKI group. CONCLUSION: AKI incidence was significantly increased during COVID-19 in respect to the pre-pandemic period, with an association with higher mortality in class 2-3 KDIGO. In the post-COVID follow-up, AKI was associated with lung and neuromotor function impairment, a defective antibody response and a sudden GFR decline concomitant to the persistence of tubular injury biomarkers. These results suggest the importance of nephrological and multidisciplinary follow-up of frail patients who developed AKI during hospitalization for COVID-19. (Table Presented).
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BACKGROUND AND AIMS: The mass vaccination for COVID-19 has raised new concerns for patients with immune-mediated nephropathies: there is a small but growing literature of case-reports linking SARS-CoV-2 vaccines with heightened off-target immune responses leading to De novo or relapsing glomerular diseases [1, 2]. Aim of this study was to evaluate how many and how severe were the relapses of immune-mediated nephropathies after the SARS-CoV-2 vaccine in a single center. METHOD: This is a retrospective study held in Italy from the start of the vaccination campaign (late December 2020) to December 31st 2021. We included all patients with an immune-mediated nephropathy (either on or off immunosuppressive therapy-IS), excluding patients with an end-stage renal disease or kidney transplant. In Italy we used mRNA (Comirnaty by Pfizer-BioNTech or Spikevax by Moderna) or adenoviral vector vaccines (Vaxzevria by AstraZeneca or Janssen), without any preference for patients with kidney disease, but those on active IS were given preferentially an mRNA vaccine. There was no active surveillance of lab tests after vaccination and post-vaccine tests were either concomitant to programmed visits or suggested on a patient by patient basis. Recurrence was defined as relapse of nephrotic or nephritic syndrome, doubling of urinary proteins with a max value > 1 g/24h, acute kidney injury with an active urinary sediment, or positivization or 5-fold increase of serological markers of disease activity (i.e.: ANCA in AAV). RESULTS: A total of 38 patients (M: F 28:10, age at vaccine 45.9 ± 19.1 years) completed the vaccination protocol: among them, the most common nephropathy was membranous nephropathy (n = 12, 31.6%), followed by IgA nephropathy (n = 7, 18.4%), minimal change disease (n = 6, 15.8%) and ANCA-associated vasculitis (n = 6, 15.8%);26 patients (68.4%) had at least one other comorbidity. We observed six relapses (4 MN, 1 IgA, 1 AAV), of which only one (MN) developed a mild oedema. The mean time from the first vaccine dose to the relapse was 101 ± 71 days (5-199 days) and only two episodes occurred within 4 weeks from a vaccine dose. We could not find an association between recurrences and maintenance IS at the time of vaccine or any other variable. The overall post-vaccine incidence rate of relapses was 35.8/100 patient-years, as compared with 14.0/100 patient-years historically observed in the same cohort [IRR 2.55, 95% confidence interval (CI) 0.89-5.97]. CONCLUSION: Relapses of immune-mediated nephropathies are not common after SARS-CoV-2 vaccine and we did not observe any clinically relevant relapse. However the overall rate of relapse seems to be a little higher than prior vaccination [3], but only 2/6 patients recurred soon after a vaccine dose. As these relapses seem to be self-limiting, a post-vaccine monitoring could be useful in patients at high risk of severe disease.
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BACKGROUND AND AIMS: The development and massive use of mRNA COVID- 19 vaccine BNT162b2 has raised new concerns on triggering De novo immunemediated diseases, in particular rare diseases as glomerulonephritis (GN), even if the security profile is excellent and severe reactions have been rare. In literature few similar cases were recently described [1, 2]. We report six cases of newly diagnosed GN after a two-dose regimen of SARS-CoV-2 vaccine, from a single tertiary care institution in Northern Italy. METHOD: We described six cases of De novo GN occurring after massive use of Pfizer-BioNTech BNT162b2 COVID-19 vaccine from March 2021 to December 2021. All cases were biopsy proven. Baseline characteristics and laboratory findings, treatments and outcomes were based on review of medical records. RESULTS: From April 2021, we observed two IgA nephropathies (IgA-N), one membranous nephropathy (MN), one membranoprolipherative GN (MPGN), one acute interstitial nephritis (aTIN) and one minimal change disease (MCD). Of note, one IgA-N presented with diffuse purpura as in IgA-vasculitis. The median age at vaccination was 52.8 years (min-max 18-67) and three (50%) were female;arterial hypertension was the most common comorbidity (50%). Only one subject contracted COVID-19 before vaccine (16.6%). None of the points showed any sign of renal disease before vaccine;at the time of disease onset, the median creatinine was 1.49 mg/dL (min-max 0.6-10.5 mg/dL) and proteinuria 3.0 g/24 h (min-max 0.9-13.8 g/24 h). All cases presented after the second dose (1 day to 6 months thereafter) and three (50%) were within 3 weeks from the vaccine. Of note, the aTIN developed after the vaccine during a long-time therapy with statins and relapsed after a rechallenge with a statin few months later. All the nephropathies were treated as per center practice, with an overall good response (four partial remissions and one complete remission). Given a target population of about 100 000-200 000 residents in our area, we could estimate an incidence rate of 4-8 cases/100 000 patient-years. CONCLUSION: This small series has a lot of limitations including the small number of patients and we probably missed some cases in our area. Furthermore, we could not investigate a causal association, even if the timing of disease onset might be suspicious in three cases and the incidence seemed to be almost twice as the expected in Europe (about 2-4/100.000 patient-years). As for SARS-CoV-2 vaccines, it is likely that the mRNA vaccine will result in a more potent inflammatory stimulus than the one observed after inactivated virus-vaccine: maybe some patients had already a subclinical GN and the vaccine constituted a flare leading to the full-blown disease [3].
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BACKGROUND AND AIMS: Very few information about COVID-19 in kidney transplant recipients (KTRs) are known and the available evidence are based on limited case series. In KTRs, Acute Kidney Injury (AKI) of different causes is known to be associated with a decreased graft survival: direct viral infection and local inflammation may potentially lead to a premature loss of graft function and to an increased risk of death in COVID-19 patients. To evaluate prevalence, stage, causes of AKI and mortality in KTRs with a positive pharyngeal swab for SARS-CoV-2 in our transplant center located in a 500-bed University Hospital. METHOD: In March-June 2020, we evaluated in 25 COVID-19 KTRs demographic and transplant characteristics, comorbidities, immunosuppressive therapies (IT). Patients were screened for type of symptoms, management of IT, complications and outcome. AKI was graded according to 2012 KDIGO guidelines and causes were investigated basing on both clinical and laboratory variables. AKI prevalence in KTRs was compared to that observed in the whole hospitalized COVID-19 patients. RESULTS: During the first wave of pandemic, a total of 945 patients were admitted to our hospital with a reported AKI prevalence of 37%. AKI classified using 2012 KDIGO guidelines associated with an increased mortality risk in the whole population. In this setting, we observed that 25 KTRs followed-up in our University Hospital had a positive molecular diagnosis for COVID-19: median age was 58 years and 80% were males. Considering the most frequent comorbidities, 100% of KTRs had hypertension and 7/25 (29%) had diabetes. Clinical symptoms at enrollment were fever (95%), cough (47%), dyspnea (30%). Regarding IT, 100% of patients were taking CNI, 64% antimetabolite agents and 76% steroids. Of note, 19/25 patients (76%) were hospitalized and 6/19 (31.5%) were admitted to Intensive Care Unit (ICU). Mean length of hospital stay was 23 days. At admission, all KTRs stopped MMF and increased steroid doses, concomitantly decreasing CNI levels. AKI occurred in 60% of KTRs (12/25), AKI KDIGO grading as follow: stage 1 4/12 (33.3%), stage 2 3/12 (25%), stage 3 5/12 (41.7%);development favored by low eGFR/ increased serum creatinine (mean serum creatinine 2.06 mg/dl): 4/25 (16%) required hemodialysis and the most frequent cause of AKI was sepsis or septic shock. Overall mortality in KTRs was 37,5% (9/25): of note, 88% (8/9) of patients with a worse outcome had developed AKI. CONCLUSION: AKI prevalence was significantly higher in KTRs than in nontransplanted COVID-19 patients. AKI development was associated with an increased risk of mortality: of note, mortality rate in KTRs was significantly higher than that observed in the non-transplanted patients. COVID-19 lead to a difficult management of IT, in particular for elevated tacrolimus levels due to associated antiviral and antibiotic therapies. COVID-19-associated AKI in KTRs may lead to an increased risk of rejection and premature loss of graft function with the need of skilled nephrological follow-up.
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BACKGROUND AND AIMS: In 2020, SARS-CoV-2 pandemic had a devastating impact on individuals and on national health systems worldwide. Although being primarily a lung disease, COVID-19-associated systemic inflammation and activation of coagulation/complement cascades lead to multiple organ dysfunction including Acute Kidney Injury (AKI). Our aim is to evaluate AKI prevalence and mortality in hospitalized patients during COVID-19 pandemic in a 500-bed University Hospital. METHOD: Observational study on 945 COVID-19 patients (March-May 2020). Data collection from Board Hospital Discharge and serum creatinine (Lab database). AKI stratification in accordance to KDIGO criteria and evaluation of outcome in the different subgroups. The same methodology was adopted to assess AKI prevalence and outcome in 2018-2019. RESULTS: 351/945 (37.14%) of all hospital admissions for COVID-19 showed AKI further sub-classified as follows: 173 (18.3%) stage 1, 112 (11.9%) stage 2 and 66 (6.9%) stage 3: the control NO AKI group was 594/945 (62.86%). COVID-associated AKI prevalence was higher than that observed in 2018 (total AKI 17.9%, stage 1 10.7%, stage 2 4.5%, stage 3 2.7%) and 2019 (total AKI 17.2%, stage 1 10.1%, stage 2 4.5%, stage 3 2.6%). During COVID-19 pandemic, in-hospital mortality was 27% for NO AKI group, 28% for total AKI group, further subdivided 24% for stage 1, 45% for stage 2 and 42% for stage 3 group, respectively. Mortality was different from that observed during 2018 (NO AKI 3.77%, total AKI 15.2%, stage 1 9.69%, stage 2 17.24%, stage 3 18.9%) and 2019 (NO AKI 3.56%, total AKI 18.35%, stage 1 10.6%, stage 2 20.1%, stage 3 24.3%). In COVID-19 patients, mean age of NO AKI group was 64.6 ys vs. 71.7 ys of total AKI group divided in 71.6 ys for stage 1, 74.3 ys for stage 2 and 67.9 ys for stage 3, respectively. Mean eGFR at admission was 74.2 ml/min for NO AKI group, 61.3 ml/ min for total AKI group divided in 64.3 ml/min for stage 1, 57.8 ml/min for stage 2 and 52.5 ml/min for stage 3. Mean serum creatinine at admission was 1.17 mg/dl in NO AKI group, 1.43 mg/dl for total AKI group divided in1.22 mg/dl for stage 1, 1.4 mg/dl for stage 2 and 2.25 mg/dl for stage 3. Among evaluated comorbidities, only diabetes (p=0,048) and cognitive impairment (p=0,001) were associated with a significant increased risk for AKI development. ICU admission rate was 5% for NO AKI group and 18% for total AKI group divided in 14% for stage 1, 22% for stage 2 and 44% for stage 3. Mean length of hospital stay for NO AKI group was 7.22 days vs 15.08 days for total AKI group divided in 13.67 for stage 1, 15.83 for stage 2 and 21.82 for stage 3. Of note, all different therapies administered to COVID-19 patients did not correlate with AKI incidence. Mean eGFR at discharge was 76 ml/min for NO AKI group vs 66 ml/min for total AKI group divided in 68.7 ml/min for stage 1, 59.3 ml/min for stage 2 and 59.3 ml/min for stage 3. Mean serum creatinine at discharge was 1.14 mg/dl for NO AKI group vs 1.45 mg/dl for total AKI group divided in 1.28 mg/dl for stage 1, 1.58 mg/dl for stage 2 and 2.05 mg/dl for stage 3. CONCLUSION: COVID-19 pandemic is associated with an increased AKI prevalence in hospitalized patients (2-fold increase in all KDIGO stages). AKI associated with an increased risk of mortality: of note, AKI stage2-3 had a strong impact on mortality in comparison to NO AKI group (OR 2.59 and 2.11, respectively). The presence of eGFR >60 ml/min and serum creatinine < 1.2 mg/dl at admission were associated with a lower risk of AKI development: reduced eGFR levels were observed at discharge particularly in AKI stage 2-3. The length of hospital stay and risk of ICU admission depended on AKI incidence and severity. COVID-19 lead to an increased burden for Nephrologists due to increased AKI prevalence: a nephrological follow-up is needed to avoid progression from AKI to chronic kidney disease (CKD).
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Introduction: The ongoing SARS-COV-2 pandemic hit the world’s population since the first trimester of 2020. Since the beginning it has been clear that the elderly and chronic patients were at greater risk ofmorbidity and mortality. The aim of the study was to monitor the spread and outcomes amongpatients in kidney replacement therapy treated in Nephrology-Dialysis units in Piedmont and Valled’Aosta Regions, North-West Italy. Methods: A web platform accessible by Dialysis coordinators across the first and second wave of the pandemic is still being used to collect and regularly update demographic and clinical data of patients. We present preliminary results on cumulative incidence, risk estimates and measures of association. Data were analyzed using SPSS version 19 and Wizard 1.9.47 for Mac. Results: An overall of 599 cases has been monitored since March 2020 till November 2020. The cumulative incidence is 10% compared to 3,3% of the general population. A higher cumulative incidence has been observed among Hemodialysis patients (14%), while in peritoneal dialysis patients and transplant receivers’ sub-groups it is 5,3% and 6,6%, respectively. Compared to the general population, among dialysis patients, cumulative incidence grew at a slower rate in the first than in the second wave of pandemic (incidence rate ratio of 1,65 for patients compared to 5,9 for the rest of the population). A higher fatality risk is observed among dialysis patients and transplant receivers (17% and11%, respectively) compared to that of the general population of 3,7%. Fatality is associated with age and cardiovascular diseases in both groups. Conclusions: The study of an overall population of 599 showed a higher susceptibility to SARS-COV-2 infection and worse outcomes compared to the general population. We observed increased risks for hemodialysis patients, who are older on average and more exposed to in-hospital infections. No conflict of interest