Infection in Patients with Suspected Thrombotic Microangiopathy Based on Clinical Presentation

Background and objectivesIn contrast to shigatoxin-associated Escherichia coli (STEC) causing hemolytic uremic syndrome, STEC-unrelated infections associated with thrombotic microangiopathy are less characterized.Design, setting, participants, & measurementsOur retrospective study in a four-hospital institution of 530 consecutive patients with adjudicated thrombotic microangiopathies during the 2009–2016 period studied STEC-unrelated infections’ epidemiology and major outcomes (death, acute dialysis, and major cardiovascular events).ResultsSTEC-unrelated infection was present in 145 of 530 (27%) patients, thrombotic microangiopathies without infection were present in 350 of 530 (66%) patients, and STEC causing hemolytic and uremic syndrome was present in 35 of 530 (7%) patients. They (versus thrombotic microangiopathy without infection) were associated with age >60 years (36% versus 18%), men (53% versus 27%), altered consciousness (32% versus 11%), mean BP <65 mm Hg (21% versus 4%), lower hemoglobin and platelet count, and AKI (72% versus 49%). They were associated with more than one pathogen in 36 of 145 (25%) patients (either isolated [14%] or combined [86%] to other causes of thrombotic microangiopathy); however, no significant clinical or biologic differences were noted between the two groups. They were more frequently due to bacteria (enterobacteria [41%], Staphylococcus aureus [11%], and Streptococcus pneumonia [3%]) than viruses (Epstein–Barr [20%], cytomegalovirus [18%], influenza [3%], hepatitis C [1%], HIV [1%], and rotavirus [1%]). STEC-unrelated infections were independent risk factors for in-hospital death (odds ratio, 2.22; 95% confidence interval, 1.18 to 4.29), major cardiovascular event (odds ratio, 3.43; 95% confidence interval, 1.82 to 6.69), and acute dialysis (odds ratio, 3.48; 95% confidence interval, 1.78 to 7.03). Bacteria (versus other pathogens), and among bacteria, enterobacteria, presence of more than one bacteria, and E. coli without shigatoxin were risk factors for acute dialysis.ConclusionsInfections are frequent thrombotic microangiopathy triggers or causes, and they are mostly unrelated to STEC. Infections convey a higher risk of death and major complications. The most frequent pathogens were enterobacteria, S. aureus, Epstein–Barr virus, and cytomegalovirus.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_09_07_CJN17511120.mp3

IN-HOSPITAL MORTALITY OF ACUTE KIDNEY INJURY: AN EXPERIENCE FROM SOUTH RAJASTHAN.

INTRODUCTION: There are few studies on in-hospital mortality among medical intensive care unit (MICU) patients with acute kidney injury (AKI). We assessed the clinical characteristics of AKI at MICU admission, its impact on mortality during the current hospitalization, and whether the inuence of AKI varied in subgroups of AKI patients. METHODS: We identied all adult aged 12 years and above having medical etiology related community acquired AKI who were admitted to MICU at Pacic Medical College and Hospital, Udaipur, India; from 2015 to 2019. AKI was dened based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria; based on serum creatinine (SCr). Dialysis requiring AKI (D-AKI) was dened as needing acute dialysis at or after MICU admission. Among 2440 MICU patients; 516 patients (21.1%) had AKI. We analyzed in-hospital mortality for subgroups of AKI: stage1, stage2 and stage3: with different etiology, comorbidity levels, acute risk factors, primary hospital diagnosis, and treatment with mechanical ventilation, vasopressors and dialysis. RESULTS: Maximum number of AKI patients (57.8%) were in KDIGO Stage3, while stage1 and stage2 had 17.8% and 24.4% respectively. 51.4% patients were male, median age was 54.81 years and average length of ICU stay was 11.73 days. The most common primary diagnosis and etiology was sepsis (31.4%), the most common acute risk factor was hypovolemia (18.8%), the common chronic comorbidity were diabetes (17.0%) and hypertension (10.0%). The most common presenting symptoms was oliguria (43.8 %), while commonest sign on admission was edema (28.1%). Common indications for dialysis were oliguria (75%), hyperkalemia (38.2%), refractory uid overload (36.2%) and metabolic acidosis (35.2%). Overall common critical care treatment required in AKI patients were acute dialysis (58.9%), vasopressor support (16.5%) and ventilator support (14%). The requirement of dialysis was 0.0%, 4.8% and 100%; among stage1, stage2 and stage3 respectively. The overall AKI mortality was 9.9% (95% condence interval (CI) 7% to 12% ). The associations between AKI and mortality were 10.87% (95% CI 5% to 17%) for the AKI-stage1, 13.49% (95% CI 8% to 19% ) for the AKI-stage2 and 8.05% (95% CI 5% to 11%) for the AKI-stage3. The mortality in D-AKI group was 8.6% (95% CI 5 % to 12 %) compared to the mortality in ND-AKI group 11.8% (95% CI 7 % to 16 %). The association between AKI and in-hospital mortality was evident in all subgroups of AKI; association was more pronounced in stage2 AKI, mostly due to worsening of complications which suggests that KDIGO stage2 AKI is a transition zone among D-AKI and ND-AKI groups. Further, it may be needed to lower the threshold for dialysis criteria in AKI. CONCLUSIONS: Any degree of AKI was associated with increased mortality. Timely and early initiation of dialysis in AKI was an important prognostic factor for the reduction of in-hospital mortality.

Clinical Profile, Pharmacological Treatment, and Predictors of Death Among Hospitalized COVID-19 Patients With Acute Kidney Injury: A Population-Based Registry Analysis

Introduction: One of the worst clinical outcomes of the coronavirus disease 2019 (COVID-19) pandemic was acute kidney injury (AKI).Methods: This manuscript presents results from a population-based registry study assessing treatment, comorbidities, and predictors of hospital death among COVID-19 patients with AKI from March 1st to May 31th, 2020. Death, oxygen delivery and ventilation, acute dialysis need, use of medications, and various clinical outcomes, in addition to the length of stay in the hospital and intensive care unit (ICU), were evaluated.Results: In Castile and Leon, the largest region of Spain, 10.87% of the patients admitted for COVID-19 (n = 7,307) developed AKI. These patients were known by having hypertension (57.93%), cardiovascular disease (48.99%), diabetes (26.7%) and chronic kidney disease (14.36%), and they used antibiotics (90.43%), antimalarials (60.45%), steroids (48.61%), antivirals (33.38%), anti-systemic inflammatory response syndrome (SIRS) drugs (9.45%), and tocilizumab (8.31%). Mortality among patients with AKI doubled that observed in patients without AKI (46.1 vs. 21.79%). Predictors of hospital death in COVID-19 patients with AKI were ventilation needs (OR = 5.9), treatment with steroids (OR = 1.7) or anti-SIRS (OR = 2.4), severe acute respiratory syndrome (SARS) occurrence (OR = 2.8), and SIRS occurrence (OR = 2.5).Conclusions: Acute kidney injury is a frequent and serious complication among COVID-19 patients, with a very high mortality, that requires more attention by treating physicians, when prescribing medications, by looking for manifestations particular to the disease, such as SARS or SIRS.

Renal Dysfunction following Direct Current Cardioversion of Atrial Fibrillation: Incidence and Risk Factors

<b><i>Introduction:</i></b> Emerging data suggest that cardioversion for atrial fibrillation (AF) may be associated with acute kidney injury (AKI). However, limited data are available regarding the incidence and risk factors for AKI after direct current cardioversion (DCCV) of AF. <b><i>Methods:</i></b> All patients undergoing DCCV at Mayo Clinic between 2001 and 2012 for AF were prospectively enrolled in a database. All patients with serum creatinine (SCR) values pre- and post-cardioversion were reviewed for AKI, defined as a ≥25% decline in eGFR (estimated glomerular filtration rate) from baseline value within 7 days of the DCCV. <b><i>Results:</i></b> Of the 6,427 eligible patients, 1,256 (19.5%) patients had pre- and post-DCCV SCR available and formed the cohort under study. The mean age was 70.4 (SD 11.7) years, and 67.3% were male. During the study period, 131 (10.4%) patients suffered from AKI following DCCV. AKI was independently associated with inpatient status (OR 26.79; 95% CI 3.69–194.52), CHA₂DS₂-VASc score (OR 1.25; 95% CI 1.11–1.41), prior use of diuretics (OR 1.59; 95% CI 1.03–2.46), and absence of CKD (OR 1.61; 95% CI 1.04–2.49), and was independent of the success of the DCCV. None of the patients required acute dialysis during the study outcome period. <b><i>Conclusion:</i></b> AKI following DCCV of AF is common, self-limited, and without the need for replacement therapies.

Hematuria Is Associated with More Severe Acute Tubulointerstitial Nephritis

Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury. Although haematuria is a risk factor for the development of renal disease, no previous study has analyzed the significance of haematuria in ATIN. Retrospective, observational analysis of 110 patients with biopsy-proven ATIN was conducted. Results: Haematuria was present in 66 (60%) ATIN patients. A higher percentage of ATIN patients with haematuria had proteinuria than patients without haematuria (89.4% vs. 59.1%, p = 0.001) with significantly higher levels of proteinuria (median (interquartile range) protein:creatinine ratio 902.70 (513–1492) vs. 341.00 (177–734) mg/g, p <0.001). Moreover, those patients with more haematuria intensity had a higher urinary protein:creatinine ratio (1352.65 (665–2292) vs. 849.60 (562–1155) mg/g, p = 0.02). Those patients with higher proteinuria were more likely to need renal replacement therapy (22.7 vs. 0%, p = 0.03) and to suffer relapse (4 vs. 0%, p = 0.03). At the end of follow up, haematuric ATIN patients had higher serum creatinine levels (3.19 ± 2.91 vs. 1.91 ± 1.17 mg/dL, p = 0.007), and a trend towards a higher need for acute dialysis (7 vs. 1%, p = 0.09) and renal replacement therapy (12.1 vs. 2.3%, p = 0.12). Haematuria is common in ATIN and it is associated with worse renal function outcomes.

P0471DIALYSIS TREATMENT AT THE TIME OF DIAGNOSIS PREDICTS OUTCOMES IN ANCA ASSOCIATED VASCULITIS PATIENTS - DATA FROM CROATIAN REFERRAL CENTER

Background and Aims Dialysis dependence and ESRD are known complications of ANCA associated vasculitis (AAV) with renal involvement. What is not so often discussed is the role of dialysis treatment at the time of diagnosis and how it affects patient outcomes as well as characteristics of such patients. We present data showing the importance of dialysis treatment at the time of diagnosis as the predictor of clinical outcomes. Method This study included 106 consecutive AAV patients with renal involvement in the period from 2007-2017. We performed renal biopsy on patients using automatic 16 Gauge needle. Light, immunofluorescent and electronic microscopy were performed. Primary outcomes were combined outcome progression to end-stage renal disease, defined as persistent (more than three months) need for renal replacement therapy or permanent reduction of EGFR to &lt;15ml/minute (according to CKD EPI formula) and/or death (ESRDD), death (D) and ESRD alone, and disease relapse. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between phenotypes and finding significant predictors regarding outcomes. Results Out of 106 patients (55,6% female, median age 61; IQR 51-70) there were 66 (61,1%) microscopic poliangitiis (MPA), 20 (18,5%) granulomatosis with angitiis and 20 (18,5%) with renal limited vasculitis (RLV). Out of those 14 (13%) were PR3-ANCA positive patients, 57 (52,8%) MPO ANCA positive, 5 (4,6%) PR3-ANCA+MPO-ANCA positive and 32 (29,6%) ANCA negative patients. Average serum creatinine (SCr) levels was 316,5 μmol/l (IQR 207,0-548,5), 24-hour proteinuria median was 1,7g/24h (IQR 0,8-2,8). According to the Berden classification 43 (39,8%) patients had crescentic, 19 (17,6%) focal, 34 (31,5%) mixed and 12 (11,1%) sclerotic class. Follow up time ranged from 1 to 127 months. Median follow up time was 21 months (IQR = 7-44). Median time to diagnosis was 3 months (IQR 2,0-6,0). Patients requiring dialysis treatment at the time of diagnosis were more often MPO – (p=0,04), had more severe anemia (p=0,001), higher CRP (p=0,003), and more pronounced hypoalbuminemia (serums albumin &lt;30g/l; p=0,006).Such patients were older than those not requiring dialysis (p=0,055) na had shorter time to diagnosis (p=0,001). Clinically such patient s presented more often with RPGN (p&lt;0,001) which is in a way expected thus having higher SCr levels (p=&lt;0,001). Histologically dialysis treated patients predominantly had crescentic class, while non-dialysis group had focal class (p&lt;0,001). Of note dialysis group had more acute tubular damage (p=0,007). Interestingly enough there was slightly more positive C3 deposition in dialysis group (p=0,09). In univariate analysis the need for acute dialysis at the time of diagnosis of AAV was significant predictor for combined ESRDD, D, ESRD and relapse rate. In multivariate analysis the need for acute dialysis at the time of diagnosis of AAV remained significant predictor for ESRD (HR = 4,674, 95% CI =1,996-10,946; p = &lt; 0,001) and relapse rate (HR = 59,545, 95% CI =3,467-1022,665; p = 0,005). Conclusion The need for dialysis at the time of AAV diagnosis is a strong predictor for ESRD and relapse rate. It is also interesting to further study differences between patients needing dialysis at the time of diagnosis and those who don’t need it.

P0456LONG TERM PATIENT SURVIVAL AND RELAPSE RATE IN ANCA ASSOCIATED PATIENTS WITH RENAL INVOLVMENET - DATA FROM CROATIAN REFERRAL CENTER

Background and Aims The aim of the research was to evaluate patient and renal as well as relapse free survival in ANCA associated vasculitis (AAV) patients in our center. Despite the advances in understanding pathogenesis of AAVs and advances in treatment, the outcomes of AAV patient differ in various centers. Method This study included 106 consecutive AAV patients with renal involvement in the period from 2007-2017. We performed renal biopsy on patients using automatic 16 Gauge needle. Light, immunofluorescent and electronic microscopy were performed. All the patients were treated with cyclophosphamide and steroids in induction treatment with adjuvant PLEX and dialysis depending on renal function and lung manifestations. Primary outcomes were combined outcome progression to end-stage renal disease, defined as persistent (more than three months) need for renal replacement therapy or permanent reduction of EGFR to &lt;15ml/minute (according to CKD EPI formula) and/or death (ESRDD), death (D) and ESRD alone, and disease relapse. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between phenotypes and finding significant predictors regarding outcomes. Out of 106 patients (55,6% female, median age 61; IQR 51-70) there were 66 (61,1%) microscopic poliangitiis (MPA), 20 (18,5%) granulomatosis with angitiis and 20 (18,5%) with renal limited vasculitis (RLV),There were 14 (13%) PR3-ANCA positive patients, 57 (52,8%) MPO ANCA positive, 5 (4,6%) PR3-ANCA+MPO-ANCA positive and 32 (29,6%) ANCA negative patients. Histologically (Berden classification) 43 (39,8%) patients had crescentic, 19 (17,6%) focal, 34 (31,5%) mixed and 12 (11,1%) sclerotic class. Follow up time ranged from 1 to 127 months. Median follow up time was 21 months (IQR = 7-44). Median time to diagnosis was 3 months (IQR 2,0-6,0). Results During follow up 21 (19,8%) patients died, 26 (24,5%) patients reached ESRD and 10 (9,4%) patients relapsed. There was no significant difference in outcomes between clinical, serological or histological phenotypes. In multivariant analysis independent predictors for death were age (HR = 1,059, 95% CI =1,001-1,120; p = 0,046), anemia (HR = 0,952, 95% CI =0,908-0,998; p = 0,040) and BVAS (HR = 1,093, 95% CI =1,030-1,159; p = 0,003), for ESRD. the need for acute dialysis (HR = 4,674, 95% CI =1,996-10,946; p = &lt; 0,001), and interstitial fibrosis and tubular atrophy (IFTA) percentage over 50% (HR = 2,652, 95% CI =1,157-6,081; p = 0,021). and for relapse rate younger age (HR = 0,924, 95% CI = 0,870-0,981; p =0,010), lower serum creatinine levels (HR = 0,996, 95% CI = 0,992-1,000; p = 0,033), and the need for acute dialysis (HR = 59,545, 95% CI =3,467-1022,665; p = 0,005). Event free survival after 12, 24, 36 and 60 months was for death 83,9, 81,2, 79 and 74,7%, for ESRD 80,6, 77,9, 76,1 and 71% and for relapse 95,3, 88,4, 88,4 and 85%. Conclusion Timely diagnosis and treatment can ensure better outcomes in AAV patients. Though there is an overlap in predictive factors between different cohorts, there are still distinctive differences especially between cohorts from clinical trials and those from observational studies. Our study is among few to show significance of anemia as clinical predictor and IFTA percentage as pathohistological predictor.