Pregnancy-Related Acute Kidney Injury, Dialysis Versus Conservative Management in the Nephrology Ward

Aim: To determine the overall frequency of patients suffering from P-AKI in the third trimester requiring dialysis as compared to conservative management. Study Design: Prospective study Place and Duration: Nephrology department of Fatima Jinnah Medical University/Sir Ganga Ram Hospital, Lahore from 3rd June 2017 to 31st December 2017. Methodology: 106 pregnant women having age 15 to 45 years with AKI during the third trimester or postpartum period (42 days of delivery) who were hemodynamically stable and shifted to the Nephrology department without any surgical intervention or ICU requirements were included in the study. For the diagnosis of AKI, KDIGO guidelines were utilized. After taking informed consent from patients, current clinical data, baseline S. Cr before pregnancy, and current renal function tests were recorded. Clinical progress was monitored, and patients were treated as per SOPs of the department. Records of conservative management and dialysis were made. Patients were followed up from the day of admission to the date of discharge. Results: The mean age of the patients was 27 ± 4.169 years. Almost 70% (n=74) of the patients had age 15-29 years, while 30 % (n=32) of patients had age 30-45 years. The mean creatinine of the patients was 4.76 ± 3.55 mg/dl. The frequency of patients requiring dialysis was 23.6% (n=25) and 76.4% patients (n=81) were treated conservatively. Patients who received conservative management, 55 patients (67.9%) had full recovery of renal functions, 25(30.9%) had mildly raised serum creatinine (1.3 to 2mg/dl), and only 1.2% had S. Cr of more than 3mg/dl. 14(56%) were off hemodialysis while 11(44%) were needed regular hemodialysis. Of those who were off hemodialysis, 6(24%) had complete recovery, 5(20%) had mildly raised serum creatinine and 1(4%) had moderate derangement of S.Cr. Of those patients who were discharged on dialysis 13(52%) had severely deranged serum creatinine. Conclusion: It is concluded that conservative treatment is effective for renal recovery with short hospital stay. Sepsis is leading cause of P-AKI in third trimester. HD is required only in 23.6% of P-AKI patients in Nephrology ward. Keywords: Pregnancy, Acute Kidney Injury, Conservative Management, Dialysis

Ambiguous definitions for baseline serum creatinine affect acute kidney diagnosis at the emergency department

Background Acute kidney injury (AKI) incidence is increasing, however AKI is often missed at the emergency department (ED). AKI diagnosis depends on changes in kidney function by comparing a serum creatinine (SCr) measurement to a baseline value. However, it remains unclear to what extent different baseline values may affect AKI diagnosis at ED. Methods Routine care data from ED visits between 2012 and 2019 were extracted from the Utrecht Patient Oriented Database. We evaluated baseline definitions with criteria from the RIFLE, AKIN and KDIGO guidelines. We evaluated four baseline SCr definitions (lowest, most recent, mean, median), as well as five different time windows (up to 365 days prior to ED visit) to select a baseline and compared this to the first measured SCr at ED. As an outcome, we assessed AKI prevalence at ED. Results We included 47,373 ED visits with both SCr-ED and SCr-BL available. Of these, 46,100 visits had a SCr-BL from the − 365/− 7 days time window. Apart from the lowest value, AKI prevalence remained similar for the other definitions when varying the time window. The lowest value with the − 365/− 7 time window resulted in the highest prevalence (21.4%). Importantly, applying the guidelines with all criteria resulted in major differences in prevalence ranging from 5.9 to 24.0%. Conclusions AKI prevalence varies with the use of different baseline definitions in ED patients. Clinicians, as well as researchers and developers of automatic diagnostic tools should take these considerations into account when aiming to diagnose AKI in clinical and research settings.

Defining AKD: The Spectrum of AKI, AKD, and CKD

Kidney Disease Improving Global Outcomes (KDIGO) guidelines address the definition, classification, and management of acute kidney injury (AKI) and chronic kidney disease (CKD). In practice, some clinical presentations of acute kidney diseases and disorders (AKD) do not meet the criteria for AKI or CKD. In principle, these presentations may be caused by the same diseases that cause AKI or CKD, which could be detected, evaluated, and treated before they evolve to AKI or CKD. In 2020, KDIGO convened a consensus conference to review recent evidence on the epidemiology of AKD and harmonize the definition and classification of AKD to be consistent with KDIGO definitions and classifications of AKI and CKD.

The importance of the urinary output criterion for the detection and prognostic meaning of AKI

Most reports on AKI claim to use KDIGO guidelines but fail to include the urinary output (UO) criterion in their definition of AKI. We postulated that ignoring UO alters the incidence of AKI, may delay diagnosis of AKI, and leads to underestimation of the association between AKI and ICU mortality. Using routinely collected data of adult patients admitted to an intensive care unit (ICU), we retrospectively classified patients according to whether and when they would be diagnosed with KDIGO AKI stage ≥ 2 based on baseline serum creatinine (Screa) and/or urinary output (UO) criterion. As outcomes, we assessed incidence of AKI and association with ICU mortality. In 13,403 ICU admissions (62.2% male, 60.8 ± 16.8 years, SOFA 7.0 ± 4.1), incidence of KDIGO AKI stage ≥ 2 was 13.2% when based only the SCrea criterion, 34.3% when based only the UO criterion, and 38.7% when based on both criteria. By ignoring the UO criterion, 66% of AKI cases were missed and 13% had a delayed diagnosis. The cause-specific hazard ratios of ICU mortality associated with KDIGO AKI stage ≥ 2 diagnosis based on only the SCrea criterion, only the UO criterion and based on both criteria were 2.11 (95% CI 1.85–2.42), 3.21 (2.79–3.69) and 2.85 (95% CI 2.43–3.34), respectively. Ignoring UO in the diagnosis of KDIGO AKI stage ≥ 2 decreases sensitivity, may lead to delayed diagnosis and results in underestimation of KDIGO AKI stage ≥ 2 associated mortality.

MO548PREVALENCE AND INCIDENCE OF ANAEMIA IN PATIENTS WITH NON-DIALYSIS DEPENDENT (NDD) CHRONIC KIDNEY DISEASE (CKD), AND EVALUATION OF TREATMENT PATTERNS WITH ERYTHROPOIESIS-STIMULATING AGENTS (ESAS): A RETROSPECTIVE DATABASE STUDY IN ITALY

Background and Aims Anaemia is a common complication in patients with NDD-CKD, and its prevalence increases with advancing CKD stage.1,2 It is a risk factor for both CKD progression and other adverse outcomes, including major adverse cardiac events, hospitalisation and all-cause mortality.1 We aim to report the prevalence of NDD-CKD stage 3a–5 in Italy, and to evaluate the prevalence and incidence of anaemia among patients with NDD-CKD. Of those patients with anaemia, we seek to establish the size of the patient pool eligible for ESAs, and consequently, the proportion of patients treated with ESAs. Method Patients ≥18 years of age with a record of NDD-CKD stage 3a–5 between 1 January 2014 and 31 December 2016 were identified from databases of five Local Health Units (LHUs) across Italy. NDD-CKD stage 3a–5 in our study was defined as either ≥1 hospitalisation record with discharge diagnosis of CKD (ICD-9-CM 585.x, where x = 3, 4, or 5) or ≥1 record of estimated glomerular filtration rate (eGFR) <60 mL/min. eGFR values were estimated using the Modification of Diet in Renal Disease method and were as reported by LHUs. Patient classification into CKD stage 3a–5 based on eGFR was done according to KDIGO guidelines.3 Anaemia was defined as Hb <13 g/dL (males) or <12 g/dL (females). Prevalence was defined as the presence of ≥1 record of NDD-CKD stage 3a–5 or anaemia in the entire period preceding the timepoint of interest, or as incident NDD-CKD/anaemia; incidence was defined as a first record of the condition in the year of interest (no record of the condition in the patient’s history). Point prevalence (at 31 December of each reported year) and annual incidence were age- and sex-standardised using census data from 1 January of the following year. Among patients with anaemia of NDD-CKD stage 3a–5, eligibility for ESA was defined as at least one record of Hb <10 g/dL,4 and patients with a record of ESA prescription were categorised as ESA treated. Results For 2016, the prevalence of NDD-CKD stage 3a–5 in the population aged ≥18 years was 5.6% (83,625/1,507,391): CKD stage 3a was the most common (4.2%; 62,683/1,507,391), while the prevalence of each of the stages 3b–5 was ≤1.0% (Table). The prevalence and incidence of anaemia among patients with NDD-CKD stage 3a–5 in 2016 was 33.8% and 11.4%, respectively. The prevalence of anaemia increased with CKD stage: from 28.2% among patients with stage 3a to 78.9% among those with stage 5. A similar trend was observed for incidence, which increased from 9.3% for stage 3a to 32.8% for stage 5. The proportion of patients with NDD-CKD stage 3a–5 and anaemia who were eligible for ESA treatment from 2014–2016 ranged from 51.9% to 75.6% across the CKD stages. In 2016, the proportion of patients with incident NDD-CKD anaemia who were eligible for ESAs but not treated was 42.3%. This proportion was similar across the CKD stages, except for stage 5, for which the proportion of patients who were eligible but not ESA treated was 51.1%. Conclusion In Italy, we found that higher CKD stages are associated with increased prevalence and incidence of anaemia in NDD-CKD, a finding which is supported by previous research in other countries worldwide.1,2 Despite this, almost half of patients with anaemia of NDD-CKD stage 3a–5 were eligible for ESA treatment but did not receive ESAs. This suggests that anaemia may not be adequately controlled in patients with NDD-CKD stage 3a–5, and may need further attention and treatment.

MO292MALIGNANT DISEASE IS MORE COMMON WITH DETERIORATING KIDNEY FUNCTION IN PATIENTS WITH MEMBRANOUS NEPHROPATHY

Background and Aims Membranous nephropathy (MN) can be associated with tumor and present a paraneoplastic condition. Recently, development of tumors during the course of follow up is more in focus. It is especially interested whether patient with MN are prone to tumors, or tumors are condition indipendent of membranous nephropathy or consequence of imunosupressive therapy (IS). Method Retrospective data of all adult patients diagnosed with MN from 1987 to 2017 at the Department of Nephrology of University Hospital Centre Zagreb were analysed. Medical data regarding antropometric measeures and preexsisting comorbid disease at presentation and during follow up were derived from medical records and hospital informatic system. Furthermore, data regarding kidney function were used, namely serum creatinine (SCr), proteinuria. Renal function was assessed using CKD-EPI equation. CKD stages, partial and complete remission were defined according to KDIGO guidelines. Results From 1987 till 2017 a total of 122 patients were diagnosed with MN. Eighty nine (72.9%) were treated with imunosupressive therapy. Most commonly prescribed initial therapy was combination of corticosteroids and cyclophosphamide (N=66; 74%). Three (0,02%) patients had history of tumor with median of 3y (min – max 1-4 y) before glomerular disease presentation, two solid tumor, adenocarcinoma pulmonum and carcinoma prostatae, and one condition after allogenic haematopoetic transplantation due to acute myeloid leukemia. There was no difference in clinical presentation between those with positive history of malignant disease and others (proteinura 11.7 g/du (25-75C 3.4-15.7) vs. 5.8 g/dU (25-75C 3.4 – 8.5); p=0.232 and eGFR 57 ml/min/1,73m2 (25C-75C 14 – 59) vs. 81 ml/min/1.73m2 (25-75C 54 – 100); p=0.066). During follow up 11 (9%) patients developed tumor, median age of pts 67 y (min – max 59 – 71); nine solid tumors most comonly of gastrointestinal origin (pancreas, colon N=5 (45%)), then pulmonum (N=2(18%)) and urogenithal origin (ca renis and prostate N=2 18%). Also two hematological malignancies (B-ALL, B-NHL) occurred. Median time till confirmed malignant disease was 9 y (min – max 5 -24). At the time of detecting the tumor six (54%) patients were in complete and partial remission (4 and 2) and 2 (18%) patients had nephrotic syndrome. No difference was observed in proteinuria between those with malignant condition and other MN patients (1,4 g/dU (25 – 75C 0.2 – 5.6) vs. 0,29 g/dU (25 – 75C 0.13 – 0.74); P=0.154). MN patients with malignant disease during follow up had lower estimated glomerular filtration rate (eGFR 45 ml/min/1,73m2 (25 – 75C 22 – 70) vs. 77 (25 – 75C 58 – 92); p=0.010). There was no difference in cummulative dose of cyclophosphamide between those who developed tumor with others (24 g(25 – 75C13.5 – 30) vs. 27 g(25 – 75C 15 – 38)p=0.592). Conclusion Our data emphasize the need for long term follow up of patients with membranous nephropathy despite accomplishing remission of MN and period screening for malignant disease, especially in those with deteriorating kidney function.

MO1006COMPARISON OF DIFFERENT DEFINITION OF PARTIAL AND COMPLETE REMISSION IN A COHORT OF CHILDREN WITH LUPUS NEPHRITIS*

Background and Aims Lupus Nephritis (LN) occurs in up to 80% of children with SLE and it affects the long term outcome and the overall survival. Achieving and maintaining renal remission is crucial. However definition of remission in children is not clearly defined. We compared the outcomes using different published definitions of complete and partial remission. Method 248 children with biopsy proven LN class III or higher (ISN/RPS) diagnosed and treated in 23 international centers in the last 10 years were included. Data regarding their renal outcome were collected for twenty-four months after the start of induction therapy. We applied seven definitions of remission to compare the number of children achieving partial and complete remission. Definitions applied have been adapted from the Bristol-Myers Squibb (BMS) trial, the American College of Rheumatology (ACR) recommendations, the Lupus Nephritis Assesment with Rituximab (LUNAR) trial, the Aspreva Lupus Management Study (ALMS) trial, the Abatacept and Cyclophosphamide Combination: Efficacy and Safety Study (ACCESS) trial, the Kidney Disease Improving Global outcomes (KDIGO) guidelines and the Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis (BLISS-LN). We also focused on the BMS trial, the ACCESS trial and the KDIGO guidelines definitions to analyse the importance of gender, age, ethnicity and the economic income of the country (as defined by the World Bank) where patients had been treated. Results The mean age at diagnosis was 11 years and 4 month. 71.4% were females. They were mainly East-Asian (34.3%), South-Asian (24.6%) and Caucasian (18.6%). 42.7 % were from middle income countries and 57.3% high income countries. The kidney biopsies showed LN class III in 35.5%; class IV in 45.6% and class V in 18.9%. The different definitions varied significantly in terms of outcomes, with that of the ACCESS trial having the highest percentages of complete remission and the BMS trial the lowest (Figure 1). A relatively small percentage of children achieved partial remission during the follow-up for all the definitions (Figure 2). Focusing on the BMS, ACCESS and KDIGO definitions, we found no statistically significant differences of gender and age in the rate of children entering complete remission at 6, 12 and 24 months. East Asian children did however achieve remission more often than other ethnic groups (p < 0.05) (Figure 3). Children treated in high income countries showed a statistically significant higher percentage of complete remission at 12 and 24 months (p < 0.05) (Figure 4). Conclusion Rate of complete and partial remission varied considerably when using the different definitions. Ethnicity and income of the country where the patients were treated did influence outcome. The findings of our study can help in deciding how to define remission in urgently needed future treatment studies in children.

MO962EPIDEMIOLOGY AND CLINICAL RELEVANCE OF ACUTE KIDNEY INJURY IN KIDNEY TRANSPLANT RECIPIENTS

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 non-transplanted 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.