Baseline Glomerular Filtration Rate Research Articles

Outcomes of COVID-19 Among Hospitalized Patients With Non-dialysis CKD.

Background: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Corona Virus 2 has generated significant impact on global health worldwide. COVID-19 can cause pneumonia and organ injury. Chronic kidney disease (CKD) has been associated with increased mortality in previous epidemics, but there is a paucity of data regarding actual risks for non-dialysis CKD patients with COVID-19.Methods: Multicenter, observational cohort study including 136 non-dialysis CKD patients and 136 age- and sex-matched controls that required hospitalization due to COVID-19. Patients with end-stage renal disease, a kidney transplant or without registered baseline glomerular filtration rate prior to COVID-19 infection were excluded. CKD and acute kidney injury (AKI) were defined according to KDIGO criteria.Results: CKD patients had higher white blood cell count and D-dimer and lower lymphocyte percentage. No differences were found regarding symptoms on admission. CKD was associated with higher rate of AKI (61 vs. 24.3%) and mortality (40.4 vs. 24.3%). Patients with AKI had the highest hazard for death (AKI/non-CKD HR:7.04, 95% CI:2.87–17.29; AKI/CKD HR:5.25, 95% CI: 2.29–12.02), followed by CKD subjects without AKI (HR:3.39, 95% CI:1.36–8.46). CKD status did not condition ICU admission or length of in-hospital stay.Conclusions: CKD patients that require hospitalization due to COVID-19 are exposed to higher risk of death and AKI.

Abstract 13433: Predictors of Contrast Induced Nephropathy in Patients With Acute Coronary Syndromes and Normal Baseline Glomerular Filtration Rate

Background: The incidence and predictors of contrast-induced nephropathy (CIN) in patients with normal glomerular filtration rate (GFR) are not well ascertained. We aim to determine the incidence and predictors for CIN after coronary catheterization (CATH) for acute coronary syndromes (ACS). Methods: We combined the datasets of two studies. The AMI-QUEBEC was an observational cohort of patients with ST-segment elevation myocardial infarctions in 2003. The AMI-OPTIMA was a study of patients hospitalized with ACS in 2009 and 2012. For this analysis, we retained only patients with GFR > 60 ml/min who underwent CATH. We defined “hyperfiltrators” as patients with GFR above the 95th percentile age and sex-adjusted value. CIN was defined as an increase in serum creatinine >0.5 mg/dL (44.2 μmols/L) or > 50% from baseline serum creatinine. Results: There were 3,188 patients with GFR > 60 ml/min : 39 hyperfiltrators and 3,149 without hyperfiltration. The mean age was similar between the two groups of patients (62 years); 21% and 27% females in hyperfiltrators and non-hyperfiltrators (p<0.0001). The prevalences of diabetes mellitus and hypertension were 36% and 64%, respectively in hyperfiltrators compared to 20% and 46%, respectively in non-hyperfiltrators. The mean baseline GFR and creatinine were 112 ml/min and 50 μmols/L, respectively in hyperfiltrators; 84.2 ml/min and 80 μmols/L in non-hyperfiltrators. There were 225 CIN following CATH; 7.1% of the whole cohort with 35.9% in the hyperfiltrators and 6.7% in non-hyperfiltrators. Hyperfiltration was independently associated with a 13-fold increase in the risk of CIN (Table 1). Each year of increase in age was associated with a 5% increase in the risk of CIN. Shock was also associated with an 11-fold increase in the risk of CIN. Conclusion: Hyperfiltrators may be at high risk of CIN following CATH in ACS. The risk of CIN associated with hyperfiltration should be evaluated in other populations.

Abstract 14245: Fibroblast Growth Factor 23 and Long-term Cardiac Function: The Multi- Ethnic Study of Atherosclerosis

Background: While fibroblast growth factor 23 (FGF23) is associated with incident heart failure (HF) and atrial fibrillation (AF), the mechanisms driving these associations are unclear. FGF23 elevation leads to cardiomyocyte calcium handling abnormalities, suggesting that FGF23 may directly reduce myocardial function. Methods: In the Multi-Ethnic Study of Atherosclerosis, a cohort free of cardiovascular disease at recruitment, we evaluated the associations of serum FGF23 (2000-2002) with measures of left ventricular (LV) and left atrial (LA) mechanical function on cardiac magnetic resonance (CMR) at 10-year follow up (2010-2012). Results: Of 2,276 participants with baseline FGF23 and CMR at 10-year follow up, participants with higher FGF23 levels were more likely white race, taking anti-hypertensive medications, and had lower baseline glomerular filtration rate (GFR). After covariate adjustment, baseline FGF23 levels were independently associated with worse LV global circumferential strain, worse LV mid-wall circumferential strain, and lower LA total emptying fraction in later life ( Table ). The association of FGF23 and LV global circumferential strain was consistent across the spectrum of GFR ( Figure ). While higher FGF23 was associated with higher LV mass (β coefficient per SD higher: 1.14, 95% CI: 0.16, 2.12, P= 0.02), it was not associated with the presence of macroscopic myocardial scar (OR per SD higher: 1.12, 95% CI: 0.86-1.45, P= 0.42). Conclusions: Baseline FGF23 is independently associated with lower LV and LA systolic function in later life. These findings provide mechanistic insight driving the associations of FGF23 with development of both HF and AF.

Acute kidney injury and multivessel percutaneous coronary interventions in chronic renal disease: the AMICI study

Patients with chronic kidney disease (CKD) often have multivessel coronary artery disease and the risk of acute kidney injury (AKI) after percutaneous coronary interventions (PCI) is high. The aim of this study was to evaluate the risk of AKI in patients with CKD who underwent single vessel PCI versus multivessel PCI. We retrospectively screened all PCI performed from January 2011 to December 2017 and we included all the procedures performed in patients with a baseline glomerular filtration rate <60 mL/min/1.73 m2. PCI were divided in two groups according to the treatment of a single vessel (mono group) or multivessel PCI (multi group). The multi group was also divided in two subgroups according to the modality of PCI: multivessel PCI performed in one procedure (multi-single session group) or in multiple staged procedures (multi-staged group). From a total of 4517 PCI screened, 848 PCI were included, 530 in the mono group and 318 in the multi group. The global rate of AKI was around 15% without significant differences between the mono and the multi group (15.5% in the mono and 14.8% in the multi group, P=0.786). In the multi group, the risk of AKI was significantly higher in the Single session sub-group (21.4%) compared to the staged sub-group (11.2%, P=0.014). In patients with CKD, the risk of AKI did not differ in patients who underwent single vessel versus multivessel PCI, but multivessel PCI should be performed in multiple staged procedures rather than in a single session.

Urinary excretion of epidermal growth factor and rapid loss of kidney function.

Lower urinary excretion of the kidney tubule-specific biomarker epidermal growth factor (uEGF) is associated with increased risk of renal function [glomerular filtration rate (GFR)] loss in diabetes and in patients with established chronic kidney disease (CKD). We investigated whether uEGF is associated with rapid GFR decline or incident CKD in the general population. Subjects without CKD or diabetes were recruited from the general population in Tromso, Norway [Renal Iohexol Clearance Survey (RENIS); N = 1249] and Groningen, the Netherlands [Prevention of REnal and Vascular END-stage disease (PREVEND); N = 4534], with a median follow-up of 5.6 and 7.4 years, respectively. GFR was measured by iohexol clearance in the RENIS and estimated using the CKD Epidemiology Collaboration creatinine-cystatin C equation in the PREVEND study. Rapid GFR decline was defined as an annual GFR loss >3.0 mL/min/1.73 m2 and in sensitivity analyses as subjects with the 10% steepest GFR slope within each cohort. Lower baseline uEGF excretion was associated with rapid GFR loss in both cohorts {RENIS, odds ratio [OR] per 1 μg/mmol lower uEGF 1.42 [95% confidence interval (CI) 1.06-1.91], P = 0.02; PREVEND, OR 1.29 [95% CI 1.10-1.53], P < 0.01}, adjusted for baseline GFR, albumin:creatinine ratio and conventional CKD risk factors. Similar results were obtained using the outcome of the 10% steepest GFR slope in each cohort. Lower uEGF levels were associated with incident CKD in the combined analysis of both cohorts. Lower uEGF levels are associated with increased risk of rapid GFR loss and incident CKD in the general population. This finding, together with previous findings in CKD and high-risk populations, supports that uEGF may serve as a broadly applicable biomarker representing the tubular component of the current glomerulus-centric clinical risk assessment system.

Hepatitis C therapy with grazoprevir/elbasvir and glecaprevir/pibrentasvir in patients with advanced chronic kidney disease: data from the German Hepatitis C-Registry (DHC-R).

Grazoprevir/elbasvir and glecaprevir/pibrentasvir (G/P) are the two preferred treatment options for patients with chronic hepatitis C virus (HCV) infection and a glomerular filtration rate (GFR) <30 mL/min. Both therapies have been separately analyzed in different real-life cohorts; however, a direct comparison has not been performed so far. We, therefore, analyzed safety and effectiveness of both regimens in a concerted real-life population. The Germany Hepatitis C-Registry is a prospective national real-world registry. The analysis is based on 2773 patients with documented GFR at baseline treated with grazoprevir/elbasvir (N = 1041), grazoprevir/elbasvir + ribavirin (N = 53) and glecaprevir/pibrentasvir (N = 1679). A total of 93 patients with GFR <30 mL/min were treated with grazoprevir/elbasvir (N = 56), grazoprevir/elbasvir + ribavirin (N = 4), and glecaprevir/pibrentasvir (N = 33). They suffered significantly more frequent from diabetes mellitus, hypertension, and coronary heart disease than individuals with GFR >30 mL/min and showed the following baseline characteristics: 20.4, 55.9, 3.2, 12.9, and 5.3% were infected with HCV-genotypes 1a, 1b, 2, 3, and 4; 12.9% suffered from liver cirrhosis; 80.1% were treatment-naïve. Baseline characteristics except distribution of HCV-genotype 1b (n = 43/52 treated with grazoprevir/elbasvir) and sustained virologic response rates (SVR12) did not differ significantly between glecaprevir/pibrentasvir (SVR12: 100%) and grazoprevir/elbasvir (SVR12: 97.9%).Fatigue, headache, abdominal discomfort, and arthralgia were the most frequently reported adverse events without a statistical difference between grazoprevir/elbasvir and glecaprevir/pibrentasvir. In patients with chronic hepatitis C and a baseline GFR ≤30 mL/min grazoprevir/elbasvir and glecaprevir/pibrentasvir show an equally favorable safety profile and antiviral efficacy and can both be recommended for real-life use.

GFR slope as a surrogate endpoint for CKD progression in clinical trials.

There is a paucity of therapies for chronic kidney disease (CKD), in part because of the slow nature of the disease which poses challenges in selection of endpoints in randomized controlled trials (RCT). There is increasing evidence for the use of glomerular filtration rate (GFR)-based endpoints either as percentage decline using time-to-event analyses, or as difference in slope between treatment arms. We reviewed the rationale for using surrogate endpoints and optimal methods for their evaluation prior to their use and evidence for GFR-based endpoints and particularly GFR slope as validated surrogate endpoints and considerations for their use in RCTs. In an individual patient meta-analysis of 47 studies (60 620 participants), treatment effects on the clinical endpoint were accurately predicted from treatment effects on 3-year total slope [median R = 0.97 (95% Bayesian confidence interval (BCI), 0.78-1.00] and on the chronic slope [R = 0.96 (95% BCI, 0.63-1.00)]. In a simulation study, GFR slope substantially reduced the required sample size and duration of follow-up compared to the clinical endpoint given high baseline GFR and absence of acute treatment effect. In the presence of acute effect, results were more complicated. GFR decline is accepted, and GFR slope is being considered, by regulatory authorities as a validated surrogate endpoint for CKD RCTs.

COMPARISON OF LONG-TERM OUTCOMES AFTER CONVERSION TO BELATACEPT WITH EITHER TACROLIMUS (TAC) OR MYCOPHENOLATE (MMF) AND PREDNISONE

Purpose: To study the efficacy and side effects of converting to Belatacept-Based (Bela) therapy in recipients of kidney transplant (KT). Methods: we studied patient transplanted between 5/2011 and 8/2019. 39 patients were converted to Bela-Based therapy. Of these 39 patients only 16 completed 2 years of observation and were included in this study. Patients were stratified by two groups. Group 1, Bela + Tac + prednisone (n=5), Group 2, Bela + MMF + prednisone (n=11). All donor, recipient and demographic factors were examined. We compared these two groups in regard to rejection rates, estimated glomerular filtration rate (GFR), creatinine level and protein/Cr ratios before conversion and at 1, 3, 6, 12, 18 and 24 months after conversion. Result: Only one patient in group 2 developed acute cellular rejection. Mean base line GFR for group 1 was 43.6±8.6 ml/min and after 24 months therapy mean GFR was 39.25±10.3 ml/min (p=NS). In group 2, mean baseline GFR was 22.4±1.8ml/min and at 24 months after therapy the mean GFR was 42.04 ±5.5 ml/min (p<0.05). Protein/Cr. ration had not change after conversion in both groups. Conclusion: Conversion to Bela-based immunosuppressive therapy is safe and should be recommended to patients with severe drug intolerance, poor renal function or de novo donor specific antibodies. For renal dysfunction the use of Belatacept with MMF leads to improved renal function which was not seen in the tacrolimus arm.

Влияние наличия критериев метаболического синдрома на течение раннего и отдаленного постинфарктного периода у больных с инфарктом миокарда с элевацией сегмента ST

Цель работы – оценить клиническое значение наличия метаболического синдрома (МС) у больных с острым инфарктом миокарда (ОИМ) для течения постинфарктного периода и его влияния на прогноз на основе ретроспективного анализа сопоставимых пар пациентов. Материалы и методы. Ретроспективный анализ базы из 820 случаев ОИМ с элевацией сегмента ST включал: оценку наличия основных факторов риска согласно шкалам TIMI, GRACE, PURSUIT и компонентов МС при поступлении (наличие сахарного диабета и/или повышение уровня глюкозы &gt; 7 ммоль/л, избыточная масса тела, артериальная гипертензия, нарушение липидного спектра крови), а также оценку показателей клинического течения госпитального периода ОИМ, лечения и результатов отдаленного наблюдения за пациентами с учетом случаев кардиальной смерти.Результаты и обсуждение. Путем автоматизированного подбора пар были сформированы группа 1 (n=41, пациенты с МС) и группа 2 (n=123, пациенты без МС), сопоставимые по следующим 13 факторам риска: возраст, рост, наличие сердечной недостаточности, курение, снижение систолического артериального давления в 1-е сутки ОИМ, локализация поражения по ЭКГ, пиковый уровень МВ-фракции креатинфосфокиназы и АСТ, наличие в анамнезе стенокардии напряжения и периода нестабильной стенокардии перед ОИМ, наличие инфаркта миокарда в анамнезе, частота сокращений сердца в 1-е сутки ОИМ, скорость клубочковой фильтрации по формуле CKD-EPI в 1-е сутки ОИМ, мужской пол. Группа 1 характеризовалась более тяжелым клиническим течением ОИМ, а также более интенсивной госпитальной терапией (включавшей более частое назначение ингибиторов ангиотензинпревращающего фермента и статинов). К 10-м суткам заболевания больные группы 1 имели более низкие показатели конечнодиастолического индекса ((59,1±2,55) по сравнению с (66,50±2,38) мл/м2 в группе 2; p&lt;0,05), конечносистолического индекса ((31,90±1,79) по сравнению с (37,50±1,89) мл/м2 в группе 2; p&lt;0,05) и тенденцию к более низкой 3-летней смертности (4,9 % по сравнению с 17,1 %; p=0,05).Выводы. Наличие у больных с ОИМ сопутствующего МС сопряжено с более тяжелым течением острого периода заболевания, но в силу более интенсивной кардиальной терапии в этой группе больных отмечается более благоприятное течение постинфарктного периода.

Echocardiographic index E/e' in association with cerebral white matter hyperintensity progression.

Cerebral white-matter hyperintensities (WMHs) on MRI is associated with reduced compliance of the cerebral arterioles. We hypothesized that an echocardiography index for left ventricular (LV) diastolic function, E/e’, might reflect the cerebral arteriolar compliance and evaluated the association between E/e’ and long-term progression rate of the cerebral WMH volume. This retrospective study included individuals who were ≥ 50 years of age, with a preserved LV ejection fraction (≥ 50%) and neurological function status (modified Rankin scale score ≤1), and underwent initial and follow-up MRI evaluations within intervals of 34–45 months. Baseline clinical, laboratory, and echocardiography markers such as ejection fraction, LV mass index, and E/e' were obtained. WMH volume progression rate between the baseline and follow-up MRIs was designated as the outcome factor. 392 individuals (57.1% men; mean age: 66.7±8.4 years) were followed-up for 38.2±3.4 months. The mean WMH volume progression rate was 1.35±2.65 mL/year. The log-transformed value of WMH volume progression rate was linearly associated with the log-transformed E/e’ (B coefficient = 0.365; 95% confidence interval [CI] 0.180−0.551; P = 0.001), along with the log-transformed values of baseline WMH volume (B = 0.142; 95% CI 0.106−0.179; P<0.001) and glomerular filtration rate (B = -0.182; 95% CI -0.321−0.044; P = 0.010). Additionally, a subgroup with an E/e’ ≥15 exhibited a significantly higher WMH progression rate compared to the subgroups with lower E/e’ values (P<0.001), especially in the lower quartiles (quartiles 1 and 2) of the baseline WMH volume. We concluded that echocardiographic marker E/e’ is associated with the long-term progression rate of cerebral WMHs in population with preserved LV systolic function.

Características basales de los pacientes nonagenarios ingresados por fracaso renal agudo en comparación con otros grupos etarios

BackgroundThe increase in life expectancy leads to higher hospitalisation rates in elderly patients. The aim of this work is to study the characteristics of the population over 90 years of age that are admitted due to acute kidney injury (AKI). Material and methodsA cross-sectional study was conducted that included all patients admitted to hospital with AKI in the years 2013 and 2014. Epidemiological characteristics, comorbidity, medication and baseline analytical data were collected, and a comparison was made between patients with age over 90 years-old and the others. ResultsA total of 1733 patients were included, of whom 264 (15%) were over 90 years-old. A significantly higher proportion of these patients were women. The most frequent cause of AKI in patients older than 90 years was functional (81%) (p < 0.001 compared to other age groups). The main cause of hospital admission was infection. In the group of over 90 years of age, a higher prevalence was found for arterial hypertension (p = 0.005), chronic kidney disease (p = 0.014), congestive heart failure (p = 0.006), and cognitive impairment (p < 0.0001). The baseline glomerular filtration rate by CKD-EPI was lower in the group of patients older than 90 years (p < 0.0001). Patients under 90 years admitted to hospital due to AKI, had a higher prevalence of diabetes mellitus (p < 0.001), dyslipidaemia (p < 0.001), history of neoplasia (p < 0.001), and a higher Barthel index (p < 0.0001). ConclusionsNonagenarians admitted due to AKI have functional aetiology as the most common factor. These patients have a higher prevalence of hypertension, heart failure, chronic kidney disease, low functional status, and more cognitive impairment.

Survival and renal recovery after acute kidney injury requiring dialysis outside of intensive care units

The incidence of acute kidney injury requiring dialysis (AKI-D) is increasing globally and it is usually associated to chronic kidney disease (CKD) and high mortality. Literature is lacking in short- and intermediate-term data on recovery of renal function after acute kidney injury (AKI). The objective was to evaluate the overall survival and renal recovery after an episode of AKI requiring dialysis out of intensive care units (ICUs). Retrospective study including patients admitted in two nephrology units along a period of 2years. Patients admitted to ICUs and renal transplant patients were excluded. Baseline renal function, mortality and glomerular filtration rate (GFR) improvement were evaluated. 151 consecutive adult patients with AKI requiring renal replacement therapy (RRT) were included. Mean age was 70.5 ± 15.2years, 60.3% were males. Median baseline creatinine (bCr) and baseline GFR (bGFR) were 1.4mg/dL and 46mL/min/1.73m2, respectively. After 1year of follow-up, we completed the monitoring of 94 patients: 64.9% had died, 10.6% were alive on dialysis and 24.5% were alive without need for RRT. Patients with bGFR > 60mL/min/1.73m2 prior to AKI episode had a slower but sustained GFR improvement through the follow-up in comparison with patients with bGFR < 60mL/min/1.73m2 whose recovery was incomplete. Patients with AKI requiring RRT have high short- and intermediate-term mortality and some require maintenance dialysis. Patients with GFR > 60mL/min/1.73m2 prior to AKI had a renal recovery closer to the basal renal function than in patients with a previously diminished GFR.

Comparison of a Significant Decline in the Glomerular Filtration Rate between Ileal Conduit and Ileal Neobladder Urinary Diversions after Radical Cystectomy: A Propensity Score-Matched Analysis

Urinary diversion after radical cystectomy is associated with a risk of renal function impairment. A significant decline in the glomerular filtration rate (GFR) (i.e., a ≥30% decline in baseline GFR after 12 months) is associated with long-term renal function impairment. We compared the significant GFR decline between ileal conduit and ileal neobladder urinary diversions 12 months after radical cystectomy. We retrospectively included radical cystectomy patients. Propensity score-matched analysis was performed. The primary outcome was the incidence of a significant GFR decline in ileal conduit urinary diversion (ileal conduit group) and ileal neobladder urinary diversion (ileal neobladder group) 12 months after radical cystectomy. The secondary outcomes were the change of GFR and the incidence of end-stage renal disease (ESRD) in the two groups. After propensity score matching, the ileal conduit and neobladder groups had 117 patients each. The incidence of a significant GFR decline was not significantly different between ileal conduit and ileal neobladder groups (12.0% vs. 13.7%, p = 0.845). The change of GFR and ESRD incidence were not significantly different between the two groups (−8.4% vs. −9.7%, p = 0.480; 4.3% vs. 5.1%, p > 0.999, respectively). These results can provide important information on appropriate selection of the urinary diversion type in radical cystectomy.

Частота возникновения и факторы риска острого повреждения почек после радикальной цистэктомии

Various studies have revealed the negative impact of surgery or related factors on the risk of acute kidney injury (AKI). The risk factors and 6-months outcomes in patients with clinical or subclinical manifestations of AKI after radical cystectomy were analyzed. This prospective study included patients with normal renal function who underwent radical cystectomy. Urine and serum samples were collected to measure the level of neutrophil gelatinase-associated lipocalin (NGAL). Of the 186 patients, 43 (23.1%) had AKI in the postoperative period. The most reliable predictor was the concentration of NGAL in the urine 12 hours after surgery (threshold value of 156.87 ng/ml). In 53 (28.5%) patients with NGAL higher than this value, subclinical AKI was diagnosed. Patients with clinical AKI and patients with subclinical AKI were allocated to the AKI group. Independent risk factors for postoperative AKI were age and obesity. After 6 months the glomerular filtration rate (GFR) in the group with AKI was significantly lower than in the control group, although the baseline GFR was similar. Determination of NGAL concentration in urine is recommended for early diagnosis of postoperative AKI, as well as for predicting the functional state of the kidneys 6 months after oncourological procedures. A significant proportion of patients developed subclinical AKI; in this group there was a worse renal outcome in comparison with the group without AKI.

P0117DOSE ESCALATING TOXICOLOGY STUDY OF ELP-VEGF, A NOVEL BIOLOGIC FOR RENAL THERAPEUTIC ANGIOGENESIS

Abstract Background and Aims Chronic renal disease, irrespective of the etiology, is hallmarked by renal microvascular rarefaction. This rarefaction is associated with a reduced bioavailability of the pro-angiogenic cytokine vascular endothelial growth factor (VEGF). Recently, we developed a therapeutic intervention for ischemic renal conditions using therapeutic angiogenesis – supplementing renal VEGF levels. This was achieved by administration of a biopolymer-stabilized form of VEGF using a fusion protein between human VEGF-A121 and an elastin-like polypeptide carrier protein (ELP-VEGF). ELP-VEGF induced microvascular remodeling and increased microvascular density when administered intra-renally in swine models of unilateral renovascular disease (RVD) and chronic kidney disease (CKD), which was associated with improved renal function, reduced renal inflammation, and reduced renal fibrosis. Also, ELP-VEGF targeted the kidney when administered systemically and induced similar beneficial effects on renal function and renal vascular density. The therapeutic dose of ELP-VEGF in the swine models was 0.1 mg/kg when administered intra-renally and 1.0 mg/kg when administered intravenously. The aims of the present study were to determine the maximum tolerated dose of ELP-VEGF and assess its dose-related toxicity. We hypothesize that ELP-VEGF will not exhibit toxicity at therapeutic doses. Method A dose escalating toxicology experiment was performed in Sprague Dawley. Female rats were instrumented with either carotid catheters or carotid artery telemeters for blood pressure monitoring. After a recovery period, a baseline 24-hour urine sample was collected, and baseline glomerular filtration rate (GFR) was measured by monitoring FITC-sinistrin clearance via transdermal fluorescence. A single injection of saline control or ELP-VEGF (0.1, 1, 10, 100, or 200 mg/kg) was administered, and blood pressure was monitored by telemetry or by direct carotid arterial pressure measurements. Body weights were monitored daily throughout the study, and 24-hour urine collections and GFR measurements were repeated 7 and 14 days after protein injection. On day 14 after injection, blood was collected, one kidney was collected and fixed for histological examination, and the second kidney was perfused with Microfil vascular contrast agent for quantification of renal vascular density by micro-CT. Results ELP-VEGF caused no significant changes in body weight at any dose. At the highest doses there was an acute drop in blood pressure (20 – 30 mm Hg at 100 and 200 mg/kg dose, respectively) for approximately twenty minutes post-injection which then normalized. GFR was unchanged by ELP-VEGF at doses up to 100 mg/kg. However, GFR was significantly increased 14 days after treatment with 200 mg/kg ELP-VEGF (1.5 +/- 0.3 versus 2.7 +/- 0.3 mL/min/100 g body weight, p=0.0021). Plasma toxicology revealed no changes in markers of liver or kidney toxicity (AST, ALT, BUN, creatinine, LDH, bilirubin) at any dose or time point. Renal vascular density was unaffected by ELP-VEGF at doses up to 10 mg/kg. However, at 200 mg/kg ELP-VEGF, renal vascular density was significantly decreased for small (0 – 100 micron, p=0.0007) and intermediate (100 – 200 micron, p=0.028) sized vessels Conclusion ELP-VEGF has a proven therapeutic potential for treatment of RVD and CKD at therapeutic doses ranging from 0.1 – 1.0 mg/kg in swine models. Dose escalating toxicity assessment in rats found no effect of ELP-VEGF on body weight, blood pressure, plasma markers of liver and renal toxicity, GFR, or renal vascular density at these therapeutic doses. ELP-VEGF doses of 100 – 200 mg/kg caused transient hypotension immediately after the injection and were associated with increased GFR and loss of renal vascular density, possibly indicating renal damage at ultra-high doses. We conclude that the therapeutic window for ELP-VEGF is 100 – 1,000 times the effective therapeutic dose.

P0711CHRONIC KIDNEY DISEASE STAGES 3-5 PROGRESSION: PATTERNS AND OUTCOMES

Abstract Background and Aims We evaluated the natural history of chronic kidney disease with regard to progression to renal replacement therapy or death in a prospective cohort of patient. Few studies are published concerning patterns of kidney function decline before initiation of dialysis while decreasing glomerular filtration rate (GFR) trajectories can influence the outcomes of the following treatment. Method The analysis of Saint-Petersburg City nephrology center data among 5935 patients with GFR below 60 ml/min/1.73m with five and more follow-up visits. The outcomes data were collected from clinical and administrative databases. Results The most common causes of end stage renal failure were chronic glomerulonephritis (19%, decreasing over time 2009-2019), diabetes (16.9 %, stable), and hypertension (13.8 %, increasing). In 18.9% cases diagnosis was not established. 49% of patients show the rate in range 0-5 ml/min/1.73m per year; 33% had the rate more than 5 ml/min/1.73m per year; 17% of pts revealed slow but stable improvement of kidney function. Overall mean of the GFR change rates were -3.86±0.21 and -3.19±0.23 ml/min/1.73m per year for men and women; being significantly different for CKD stages: -1.23 (-1.93 ÷ - 0.61); -2.69 (-3.17 ÷ - 2.14); -4.91 (-5.55 ÷ - 4.47) and -6.42 (-7.52 ÷ - 5.63) for CKD 3A, 3B, 4 and 5. CKD progression rates differed between patients with various diagnoses and were associated with phosphate, calcium, anemia and iron deficiency, serum albumin and proteinuria levels. In women, total cholesterol levels out of normal range were linked with higher progression rates. In the multiple regression male gender was linked with higher GRF slope by 1.01 ml/min/1.73m per year. The reduced baseline GFR by 10 ml/min/1.73m per year; the reduced albumin - by 2 g/l, Hb - by 5 g/l, elevated phosphate - by 0.1 mmol/l, uric acid - by 0.2 mmol/l and proteinuria by 0.33 g/d were associated with similar increase of GFR slope (by about 10%). We found three different trajectories for GFR slope during three-year period before dialysis initiation: slow progression (-2.53, 95%CI -5.02÷-0.69 mL/min/1.73m per year) from CKD3B-CKD4 – 74% of patients, faster progression (-7.96, 95%CI -11.32÷-5.89) from CKD3 – 21% of patients, initially no progression (+0.24, 95%CI -1.54÷-2.05) with following acceleration of GFR slope (-19.2, 95%CI -29.7÷-10.8) from CKD3 – 5% of patients. Dialysis was started at eGFR 7±3 ml/min/1.73m in “slow” group (31% - urgent start), 6±4 ml/min/1.73m in “fast” group (58% - urgent start) and 5±4 ml/min/1.73m in “accelerated” group (61% - urgent start).The rate of renal replacement therapy initiation over the 5-year observation period was 0.9%, 2.1%, 12.9% and 46.3%, respectively, for CKD stages 2, 3, 4, 5 while the mortality rate was 20.1%, 30.2%, 51.9 and 41.3% mainly for cardiovascular reasons. Thus, death was far more common than dialysis at all stages but CKD5, where it was comparable. Conclusion The identifying of the modifiable factors linked to CKD progression gives the opportunity to improve comprehensive renoprotective therapy. The efforts to decrease mortality in CKD3-4 cohort should be focused on prevention and treatment of coronary artery disease, congestive heart failure, diabetes mellitus, phosphatemia and anemia.

P1641DONOR ACUTE KIDNEY INJURY HAS A DELETERIOUS IMPACT ON KIDNEY GRAFT SURVIVAL: THE DON-AKI STUDY

Abstract Background and Aims Acute kidney injury (AKI) during organ procurement represents an important cause of discarded kidneys. In the context of organ shortage, the evaluation of such grafts is needed in order to enlarge the donor pool. Although many studies showed an increased risk of delayed graft function when donors present with AKI, long-term impact on graft survival remains controversial. A recent large US registry study concluded that AKI during organ procurement had no deleterious effect on graft survival. However the definition of AKI in this latter study is questionable. Indeed the donor baseline serum creatinine (SCr), according to KDIGO recommendations, is often not available. In this situation, the KDIGO guidelines suggest to estimate the baseline SCr using the MDRD equation, assuming a baseline glomerular filtration rate at 75 mL/min/1.73m? This method was applied in the present study to assess the impact of donor kidney failure on long term kidney allograft survival. Method We analyzed the French national allocation system CRISTAL (Agence de la Biomédecine) data of all the recipients who received a deceased donor kidney graft from 2006 to 2017. 26786 transplant patients from 14899 deceased kidney donors were included. The donors were categorized into four groups. Ongoing AKI at the time of kidney procurement: n=1880 (3373 transplantations, AKI group), AKI with total recovery (normal SCr) at the time of kidney procurement: n=1332 donors (2392 transplantations, recovery group), elevated SCr all along the procedure: n=952 donors (1745 transplantations, unclassified AKI/CKD group) and normal SCr all along the procedure: n=10735 donors (19276 transplantations, no-AKI group). The main outcome was death censored graft survival. Results 4458 graft losses occurred during the study period (648 in the AKI group, 411 in the recovery group, 297 in the unclassified AKI/CKD group and 3102 in the no-AKI group) after a median follow-up time of 5.7 years (3 - 8.9). Multivariate analysis showed a significant increase risk of graft loss for each group when compared to the no-AKI group: HR 1.18 (1.04-1.34), HR 1.15 (1.04-1.28) and HR 1.22 (1.12-1.34) for the unclassified AKI/CKD, recovery and AKI groups, respectively. Regarding the AKI group, the risk of graft loss increased according to the AKI stage (KDIGO 2012): HR 1.20 (1.08-1.32) for stage I AKI and HR 1.31 (1.13-1.53) for stage II-III AKI. Conclusion Donor AKI represents a significant risk factor of graft loss, independently of SCr at the time of procurement. Stage II-III AKI carries a higher risk than stage I AKI suggesting a “dose-effect”. However, considering organ shortage, further studies are required to better allocate these sub-optimal kidneys.

The effect of urinary diversion on long-term kidney function after cystectomy

ObjectivesCystectomy with urinary diversion is associated with decreased long-term kidney function due to several factors. One factor that has been debated is the type of urinary diversion used: ileal conduit (IC) vs. neobladder (NB). We tested the hypothesis that long-term kidney function will not vary by type of urinary diversion. Methods and MaterialsWe retrospectively identified all patients who underwent cystectomy with urinary diversion at our institution from January 1, 2007, to January 1, 2018. Data were collected on patient demographics, comorbid conditions, perioperative radiotherapy, and complications. Creatinine values were measured at several time points up to 120 months after surgery. Glomerular filtration rate (GFR) (ml/min per 1.73 m2) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. A linear mixed model with inverse probability of treatment weighting (IPTW) was used to compare GFR between the IC and NB cohorts over time. Multiple sensitivity analyses were performed based on 2 different calculations of GFR (Chronic Kidney Disease Epidemiology Collaboration equation vs. Modification of Diet in Renal Disease), with and without excluding patients with preoperative GFR less than 40 ml/min per 1.73 m2. ResultsAmong 563 patients who underwent cystectomy with urinary diversion, a NB was used for 72 (12.8%) individuals. Patients who had a NB were significantly younger, had a lower American Society of Anesthesiologists score, greater baseline GFR, better Eastern Cooperative Oncology Group performance status, lower median Charlson comorbidity index, and were less likely to have received preoperative abdominal radiation (all P < 0.05). Both NB and IC patients had decreased kidney function over time, with mean GFR losses at 5 years of 17% and 14% of baseline values, respectively. The IPTW-adjusted linear mixed model revealed that IC patients had slightly more deterioration in kidney function over time, but this was not statistically significant (estimate, 0.12; P = 0.06). The sensitivity analyses yielded a similar trend, in that GFR decrease appeared to be greater in the IC cohort. This trend was statistically significant when using Modification of Diet in Renal Disease (P = 0.04). ConclusionsAmong highly selected patients with an NB, deterioration of kidney function may potentially be lower over time than among IC patients. However, the statistical significance varied between analyses and we cautiously attribute these observed differences to patient selection.

Direct acting antiviral HCV treatment does not influence renal function.

HCV infection is associated with chronic kidney disease due to several mechanisms. Patients treated with interferon-based regimens demonstrate improved renal function and reduced incidence of chronic kidney disease. There is scarce evidence on the effect of direct acting antiviral regimens (DAAs) on renal function.We evaluated serial measures of renal function in a cohort of HCV-infected participants following completion of DAA-based treatment regimens.Measures of glomerular filtration rate (GFR) were estimated by the CKD-EPI equation. Data was recorded at end of treatment, and at 6-12 months, 12-24 months, and greater than 24 months following treatment completion. Group-based trajectory modeling was used to determine distinct GFR trajectories. Predictors of group membership were determined by multinomial regression analysis.Six trajectories were identified. One trajectory comprising 27% of the cohort demonstrated declining renal function and the others demonstrated no change in renal function over time. Baseline GFR did not predict SVR. Diabetes was associated with lower post-treatment GFR but patients with diabetes did not demonstrate a decrease in GFR over the period of evaluation. Cirrhosis and SVR were not significant predictors of GFR or GFR trajectory.There is no clinically relevant change in renal function among the majority of HCV-infected patients following completion of DAA-based treatments. Renal function does not influence the efficacy of DAA-based regimens. No consistent effect of DAA treatment and/or SVR on renal function was observed over a 2-year period following treatment completion.

Longitudinal kidney injury biomarker trajectories in children with obstructive uropathy.

Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification. Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. "Cases" were defined as individuals receiving any kidney replacement therapy (KRT), while "controls" were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine. In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0-13.0) and 15.9 (13.9-16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38ng/ml per year and 0.20ng/ml per mg/dl per year, respectively, p= 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR). In children with OU, pNGAL and uL-FABP levels increased over the 5years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors.