bluuebunny/crossref_metadata_2025 huggingface dataset:
P0614URINARY EXOSOMAL MICRORNA-21 AS A MARKER OF SCRUB TYPHUS-ASSOCIATED ACUTE KIDNEY INJURY
Authors: Sun In O , Lee Kwang Young , Cho A Young
Published: June 2020

Background and Aims

Urinary microRNA (miRNA)-21 is reported to be a biomarker for detection of acute kidney injury (AKI). Analysis of urinary exsome may serve as a novel diagnostic approach in kidney disease. The aim of this study is to investigate the clinical significance of urinary exosomal miRNA-21 for AKI in patients with scrub typhus.

Method

In a cross-sectional study, we collected 138 urine samples at the time of admission from 145 patients with scrub typhus. For 25 patients with scrub typhus-associated AKI and 25 age, sex-matched scrub typhus patient without AKI, we measured miRNA-21 in urinary exosomal fraction and compared diagnostic value in predictiong AKI.

Results

Compared with patients in the non-AKI group, patients in the AKI group were more likely to have one or more comorbidity such as diabetes (50% vs. 5%, P<0.01) and chronic kidney disease (8% vs. 0%, P<0.01). Total leukocyte count were higher in patients with AKI than in those without AKI (10.40 × 103/ mL vs. 6.40 × 103/mL, P<0.01). The levels of urinary miRNA-21 were higher in the AKI group than in the non-AKI group. Urinary exosomal miRNA-21 levels correlated directly with serum neutrophil gelatinase-associated lipocalin values and total leukocyte counts and inversely with estimated glomerular filtration rate. The receiver operator characteristics curve analysis for urinary exosomal miRNA-21 showed good discriminative power for the diagnosis of scrub typhus-associated AKI, with area under the curve value of 0.907.

Conclusion

Urinary exosomal miRNA-21 could be a surrogate markers for the diagnosis of scrub typhus–associated AKI.
P0618PREOPERATIVE LOW URINE SPECIFIC GRAVITY PREDICTS ACUTE KIDNEY INJURY AFTER CARDIAC SURGERY
Authors: Jo Wonji , Jung Chan-Young , Kim Jaeyoung , Kim Jihye , Lee Sangmi , Park Jung Tak
Published: June 2020

Background and Aims

Acute kidney injury (AKI) is a common and serious complication following cardiac surgery. However, strategies that effectively predict AKI risk before cardiac surgery are scarce. Recent investigations identified urinary osmolality to be associated with non-glomerular kidney damage in normal kidney function individuals, suggesting urine concentration ability to be a surrogate of early kidney damage. Therefore, hypothesizing that urine specific gravity (SG) could reflect asymptomatic kidney damage, the clinical implication of preoperative urine specific gravity on AKI occurrence after cardiac surgery was investigated in subjects with normal kidney function.

Method

A total of 4135 patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from were enrolled. Patients whose eGFR was lower than 60mL/min/1.73m2 were excluded. Fasting urinary SG was measured from the morning first void a day before the surgery. The patients were divided into tertiles based on urine SG. The primary outcome was occurrence of AKI within 48hours of cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria.

Results

The mean age of the patients was 60 years and 60% were male. Diabetes consisted of 25.6% of the patients and 54.5% were hypertensive. The mean eGFR and urine SG was 98.8mL/min/1.73m2 and 1.020, respectively. AKI developed in 1,089 (26.3%) patients. The incidence of AKI was highest in the lowest urine SG tertile group (410, 29.0%) and lowest in the highest tertile group (304, 23.5%) (P < 0.001). Multivariable logistic regression analysis revealed that being included in the lowest preoperative urine SG tertile group was significantly related with higher post cardiac surgery AKI incidence risk (odd ratio (OR), 1.33; CI, 1.12-1.57; P =0.001). This association was significant even after adjustments were made for confounding factors.

Conclusion

Low urine SG was associated with increased risk of cardiac surgery associated AKI in patient with normal renal function. Evaluating preoperative urine SG may be useful in stratifying post cardiac surgery AKI risk.
P0620OXIDANT-INDUCED RENAL PRECONDITIONING BIOMARKERS FOR AKI PREVENTION WITH RBT-1
Authors: Zager Richard , Johnson Ali , Ruiz Stacey , Guillem Alvaro , Keyser Jeff , Rasmussen Henrik , Singh Bhupinder
Published: June 2020

Background and Aims

Ischemic preconditioning has shown tissue protective effects in various organs including kidneys in animal models. However, the translation of these findings to human acute kidney injury (AKI) has not been successful, at least partly because of difficulty in simulating an ischemic state, as attempted by remote ischemic preconditioning (RIPC). RBT-1 is a novel therapeutic composed of SnPP (tin protoporphyrin) and FeS (iron sucrose) and was designed to induce non-ischemic, oxidant renal preconditioning to prevent AKI. It has shown efficacy in various models of AKI: glycerol-induced (rhabdomyolysis), maleate (ATP depletion), ischemia/reperfusion (I/R), and post-AKI progression to CKD (long-term progression). This study investigated the mechanism of action of RBT-1 in mice, and its translation to the clinical setting.

Method

Male CD-1 mice were pretreated with control or RBT-1 for 18 hours; animals were then sacrificed for assessment of biomarkers of cytoprotection. Nrf2-/- mice were treated for 18 hours with RBT-1 prior to indication of ischemia/reperfusion (I/R); AKI was assessed by blood urea nitrogen (BUN) and plasma creatinine (PCr). Patients with CKD (Stage 3 and 4) were enrolled in Phase 1 studies of FeS and SnPP and cytoprotective biomarkers were assessed.

Results

In mice, RBT-1 significantly increased several Nrf2-dependent antioxidant, anti-inflammatory genes, such as HO-1, NQO1, SRXN1, and GCLC. RBT-1 also increased cytoprotective heavy chain ferritin (Fhc) levels. Nrf2-/- mice were resistant to RBT-1-mediated protection against AKI. At baseline, CKD patients had elevated plasma HO-1 and urinary NQO1 levels. Ferritin and hemopexin levels were also elevated at baseline. RBT-1 components were shown to further increase HO-1, NQO1, ferritin, and hemopexin in patients with CKD.

Conclusion

RBT-1 represents a novel therapeutic approach for the prevention of AKI. It mediates kidney protection by upregulating antioxidant and anti-inflammatory genes. Translation of RBT-1-mediated upregulation of cytoprotective markers has been demonstrated in the clinic in patients with CKD. These data, along with the broad range of RBT-1 activity previously shown in various models of AKI, highlight the potential of RBT-1 in AKI and suggest oxidant-induced renal preconditioning may be protective in preventing AKI.
P0623ACUTE RENAL FAILURE IN HAPOLIDENTICAL HEMATOPOIETIC CELL TRANSPLANTATION. TWO GRAFT VS HOST DISEASE (GVHD) PROFILAXIS PROTOCOL COMPARISON
Authors: Solis Miguel Angel , Pérez Ys Aurora , Pérez Ariadna , Hernández-Boluda Juan Carlos , Juan-Garcia Isabel , Gimenez-Civera Elena , Hernani-Morales Rafael , Solano-Vercet Carlos , Torregrosa Maicas Isidro , Gorriz Jose Luis
Published: June 2020

Background and Aims

Haplo-hematopoietic cell transplantation (Haplo-HCT) assures a valid donor in short notice in over 95% of the patients with high risk haematological neoplasia. High doses of post-transplant cyclophosphamide, in combination with other inmunosupressive drugs like calcineurin inhibitors, rapamycine and micophenolate mofetil, is safe and useful in GVHD prevention.

The aim of the study was to analyze and compare acute kidney injury (AKI) in the first 100 days after transplantation, the characteristics of the patients who went on haplo-HCT, and prophylaxis for GVHD with cyclosporine (n=32) (group 1) or rapamycine (group 2), in combination with other immunossupresors.

Method

Fifty-two consecutive patients who recieved a Haplo-HCT at our institution between october/2012 and February/2019 were retrospectively reviewed.

Results

A total of 52 patients were included, 34 male (65.4%), with a median age median age of 52.8 years old (range 18-71). Co-morbidities: hypertension: 13 (25%), Diabetes: 13 (5.8%), previous neoplasia: 4(7.7%). 27 patients received previously platinum-based chemotherapy with and 50% had received a previous HCT. No chronic kidney disease (CKD) were present in any patient. Haematological diseases were :non Hodgkin lymphoma (28.8%), Hodgkin lymphoma (23.1%), acute myeloid leukemia (21.2%), myelodysplastic syndrome (13.5%), other (13.4%). 42 patients (80.8%) received reduced intensity conditioning. Major complications were: TMA: 7(13.5%), Sinusoidal Obstruction Syndrome: 3 (5.8%) and sepsis 27 (51.9%). During the first 100 days post-transplantation follow up, 26 patients (83.2%) in group 1 and 5 patients (25%) in group 2 developed AKI attending KDIGO classification (p<0.0005). At day 100 post-transplantation, 14.5% of survivors had renal failure, defined as increased of serum creatinine ≥ 0.3mg/dL with respect to their baseline. In group 2 none of the patients developed acute kidney injury (0%) at 100 days post-transplantation follow up.

Median serum Cr in survivors at day 100 was 0,65mg/dL in group 1 VS 0.62mg/dL in group 2, (p<0.001).

In the multivariate analysis, treatment with CI (p<0.01) and sepsis (p<0.05) were independent predictors of ARF.

Conclusion

Rapamycin use instead cyclosporine is associated with a significatively lower incidence of AKI in the first 100 days post-tansplantation in our group of patients. The findings of this study call for further research identifying if non cyclosporine group have similar results in term of prevention of GVHD and if this protocol has a better impact in renal function and surveillance in the follow up.
P0627INTRAOPERATIVE DIALYSIS DURING LIVER TRANSPLANTATION IS SAFE AND BENEFICIAL
Authors: Kościelska Małgorzata , Matuszkiewicz-Rowińska Joanna , Zieniewicz Krzysztof , Krawczyk Marek , Giercuszkiewicz Dorota , Sierdziński Janusz , Żebrowski Paweł , Malyszko Jolanta
Published: June 2020

Background and Aims

Orthotopic liver transplantation (OLt) is a technically complex surgical procedure associated with a major risk of hemodynamic instability and metabolic derangement, especially in patients with coexisting renal dysfunction. It remains uncertain if intraoperative renal replacement therapy (ioRRT) during OLt could be beneficial and in which subset of patients.

Method

A retrospective observational study of all adult patients undergoing intraoperative renal replacement therapy during OLt in our center from January 2010 till December 2018. IoRRT consisted of dialysis performed with the use of mobile Genius® single-pass batch dialysis system.

Results

1319 OLts were conducted during the study period and 129 patients (9,8%) were treated with intraoperative dialysis. Seven patients with incomplete documentation were excluded from the study. The mean age of the cohort was 47,8±14,7 years, and 73 (60%) of patients were men. The mean calculated MELD score was 33,7±12,5. 41 procedures (33,6%) were retransplantations and 7 patients underwent simultaneous liver and kidney transplantation. 18 (14,7%) recipients had fulminant liver failure. 66 (54,1%) of patients were admitted to Intensive Care Unit before transplantation. The mean preoperative serum creatinine level was 2,95±1,15 mg/dl and 95 (78%) patients were undergoing renal replacement therapy or had creatinine level ≥2 mg/dl preoperatively. Others required emergent ioRRT due to intraoperative complications and development of significant hyperkalemia or acidosis. The mean preoperative serum potassium concentration was 4,23±0,68 mmol/l and the mean bicarbonate level was 19,8±4,5 mmol/l. Intraoperative dialysis was performed without anticoagulation. The mean surgical time was 400±90,6 minutes and the mean ioRRT duration remained 308 ±109 minutes. Dialysis circuit clotting occurred in 9 (7,3%) cases. There were no other adverse events of ioRRT. Achieved mean arterial bicarbonate and potassium levels after graft reperfusion were 18,5±3,6 and 3,8±0,95 mmol/l, respectively. In 111 cases dialysis was initiated at least 15 minutes before reperfusion. 13% of this subgroup (16 pts) experienced post-reperfusion syndrome (defined as a decrease in the mean arterial pressure of more than 30% of the baseline, occurring within first 5 minutes after the reperfusion of the graft and lasting at least 1 minute).

Conclusion

Our data suggests that intraoperative dialysis in severely ill patients with high MELD score is safe and effective. Lower than expected post-reperfusion syndrome occurrence needs to be confirmed in a study designed with appropriate control group.
P0632RISK FACTORS FOR ACUTE KIDNEY INJURE AMONG PATIENTS WITH RHABDOMYOLYSIS
Authors: Yang Jia , Yang Lichuan , Wang Xin , Wang Siwen
Published: June 2020

Background and Aims

Rhabdomyolysis (RM) is a syndrome characterized by the abruption of the integrity of skeletal muscle cells with subsequent release of intracellular components into extracellular fluid and circulation. Acute kidney injury (AKI) is a life-threatening complication of rhabdomyolysis. The aim of this study was to assess patients at high risk for the occurrence of AKI defined by KDIGO criteria and in-hospital mortality.

Method

We performed a retrospective study of patients with creatine kinase levels in excess of 1000 U/L, admitted in West China Hospital of Sichuan University from January 2011 to march 2019. The sociodemographic, clinical and laboratory data of the patients were obtained in an electronic medical record database. Univariate and multiple regression analyses were conducted.

Results

329 patients were included in our study. The incidence of AKI was 61.4%, the overall mortality was 19.8%, and patients with AKI tend to have higher mortality than those without AKI (24.8% versus 11.8%, P < 0.01). The clinical conditions most frequently associated with rhabdomyolysis were trauma (28.3%), infection (14.6%), bee stings (12.8%), thoracic and abdominal operations (11.2%) and exercise (7.0%). Patients resulted from sepsis, bee stings and acute alcoholism were susceptible to AKI. The risk factors for the occurrence of AKI among rhabdomyolysis patients included age≥60 (OR 3.070), chronic alcoholism (OR 3.256), hypertension (OR 4.252), multiple organ dysfunction syndrome (OR 7.244), elevated white blood cell counts (OR 1.047) and serum phosphorus (OR 5.526). Age≥60 (OR 3.188), multiple organ dysfunction syndrome (OR 2.262), diabetes (OR 2.746) and elevated prothrombin time (OR 1.079) were independent risk factors for in-hospital mortality of rhabdomyolysis patients with AKI.

Conclusion

AKI is independently associated with mortality in rhabdomyolysis patients. Several risk factors were found to be associated with the occurrence of AKI and in-hospital mortality. The findings aiming to suggest early prevention of AKI should target on patients with high risk and more effective management to improve the quality of medical care.
P0634RISK OF HYDROELECTROLYTIC AND ACID-BASE DISORDERS INDUCED BY LIPOSOMAL AMPHOTERICIN B USE IN VISCERAL LEISHMANIASIS PATIENTS
Authors: Freire Bezerra Gabriela , Cavalcante Meneses Gdayllon , Bandeira Lima Danya , Bezerra da Silva Junior Geraldo , Nobre Jacinto Vittoria , Paula Magalhães Emanuel , Pereira da Rocha Thaiany , Prado de Azevedo Isabella Evelyn , De Francesco Daher Elizabeth , Costa Martins Alice Maria
Published: June 2020

Background and Aims

Visceral leishmaniasis (VL) is a serious illness if untreated. Liposomal Amphotericin B (L-AMB) is the more effectiveness treatment against LV and less nephrotoxic formulation. We aim to evaluate expression of kidney transporters in VL patients before and during L-AMB use.

Method

This is a prospective study with 9 selected VL patients that used only L-AMB during hospital stay. Renal transporter analyzes were from before and during the treatment and compared with a control group composed by healthy people. The urine transporters (AQP2, aquaporin 2; NKCC2, Na-K-2Cl cotransporter; NHE3, Na/H exchanger) and a constitutive exosome marker (TSG 101) expressions were measured after urinary exosomes isolation.

Results

No significant increase of TSG 101 was observed in all comparisons, including between both times and vs healthy controls. Additionally, were observed increased urinary protein expression in VL patients in both times (before and after L-AMB use) in comparison with healthy controls of the AQP2: (105.32 (22.90 – 140.27) vs 1362.97 (627.93-2620.09) or 846,20(552.60-1249.14) %, p<0.01); NHE3: (74.81 (57.17 – 126.33) vs 3373.36 (282.69-6877.97) or 462.67 (123.80-7280.21) %, p<0.01); and NKCC2: (90.98 (79.07 – 120.30) vs 634.45 (345.18-1588.41) or 545.74 (284.34-2183.87) %, p=0.03). Moreover, the patients treated with L-AMB showed a significant decrease in AQT2 (P=0.023) and NHE3 (P=0.008) expression.

Conclusion

We suggest that despite less nephrotoxic, the L-AMB use may be monitored to investigate patients at risk of hydroelectrolytic and acid-base disorders.
P0638COMPARISON OF CIRCUIT PATENCY AND EXCHANGE RATES BETWEEN THE ORIGINAL PRODUCTS AND THE GENERIC VERSIONS OF NAFAMOSTAT MESILATE IN ACUTE KIDNEY INJURY RECEIVING CONTINOUS RENAL REPLACEMENT THERAPY
Authors: Shin Ho Sik , Kim Jisu , Jeon Haesu , Kim Ye Na , Jung Yeonsoon , Rim Hark
Published: June 2020

Background and Aims

The generic versions have the same main component as the original products. But, due to the difference in additives or the level of impurities, it is questionable the the generic versions are completely identical to the original products. Nafamostat mesilate has been widely used as an anticoagulation in continuous renal replacement therapy (CRRT) with hemorrhagic diathesis. In this study, we performed comparison of circuit patency and exchange rates between the original products and the generic versions of Nafamostat mesilate in acute kidney injury patients receiving continuous renal replacement therapy

Method

We have conducted retrospective studies to compare the original product of nafamostat mesilate (n=732) with the generic version (n=328) on the CRRT running time.

Results

CRRT fiter life time of the generic version group was shorter than that of original product group although that was not significantly.

Conclusion

When generic versions of nafamostat mesilate are adopted in a hospital formulary, it must be emphasized that the effect these versions may be not completely identical to that of the original products.
P0643PROGNOSTIC IMPACT OF THROMBOCYTOPENIA IN THE RISK OF INTRAHOSPITAL BLEEDING IN ACUTE KIDNEY INJURY (AKI) PATIENTS
Authors: Dimitrijevic Zorica , Mitic Branka , Tasic Danijela , Paunovic Goran , Paunovic Karolina , Kostic Emina , Glogovac Stevan
Published: June 2020

Background and Aims

Low platelet count is a marker of adverse events in acute kidney injury (AKI) patients. Thrombocytopenia has often been reported as an indicator of underlying disease severity and worse patient outcomes; however, it’s role in the prediction of the risk of bleeding is not well defined. Our study aimed to assess the prognostic impact of admission thrombocytopenia in the risk of major bleeding in non-septic, non-post surgery AKI patients.

Method

This retrospective study enrolled patients with AKI hospitalized at tertiary care hospital during the three years. Admission thrombocytopenia was defined as a platelet count < 150x103/mL. The primary endpoint was major bleeding, as defined by the International Society on Thrombosis and Haemostasis.

Results

Of 178 included patients (age 61.7±11.1 years; 68.3% males), 26 (14.6%) had thrombocytopenia. These patients had more comorbidities: cancer (19.4 vs 9.6%; p=0.05); previous ulcer disease (17.6 vs. 8.8; p=0.04) and bleeding history (7.4% vs. 2.0%;p=0.04). While in a hospital, there was a trend for the use of more blood transfusions (7.4% vs. 2.7%; p=0.03) and more concomitant medications (12.7 vs. 5.1; p<0.05) in patients with thrombocytopenia. During a hospital stay (IQR: 7-29 days), 19 patients (10.7%) died), 22 (12.35%) had major bleeding, and 5 (2.8%) intracranial bleeding. After adjusting for age, presence of cancer, and use of oral anticoagulant medications, patients with thrombocytopenia had a higher risk of major bleeding (HR 3.34 95%CI: 1.57-7.26; p < 0.001).

Conclusion

Thrombocytopenia is a predictor of major intrahospital bleeding in the non-septic, non-post surgery AKI patients. It should be regarded in bleeding risk estimation and therapeutic strategy decisions.
P0644RELATIONSHIP BETWEEN THE PRESENCE OF INFECTION DISEASE AND CLINICAL OUTCOMES OF PATIENTS WITH CARDIORENAL SYNDROME TYPE 1
Authors: Chávez Jonathan , Valle-Rodríguez Adriana , Michell Jorge , De la Torre-Quiroga Andres , Aranda-G de Quevedo Andres , Yanowski-Ortega Ekhaterina , Cabrera Jose Said , García-García Guillermo
Published: June 2020

Background and Aims: Introduction

Cardiorenal Syndrome type 1 (CRS-1) can be triggered by an infection. The pathophysiological basis is vascular congestion, which is why it has been treated with different strategies of diuretics, but in the presence of infection, the inflammatory, neurohormonal and hemodynamic effects can compromise the efficacy of the diuretic therapy and potentially worsen clinical evolution. Here we compare the clinical evolution during the hospitalization of CRS-1 patients with and without infection.

Method

This is a retrospective cohort study conducted in the Hospital Civil of Guadalajara “Fray Antonio Alcalde”, from January 2015 to September 2018. Conducted in CRS-1 patients, we showed the clinical evolution and diuretic strategies analyzed according to the presence or absence of infection. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

Results

We identified 63 patients classified as having CRS-1, 28 (44.4%) were classified as having an infectious disease. The mean age was 62 years (±14.6) and 58 (±12.4) in the group with infection and no infection, respectively. There were no statistically significant differences between the clinical outcomes of both groups. The median length of hospital stay was 8 days in the group with infection and 7 days in the group without infection (p=0.065). Three patients (10.7%) of the group with infection received renal replacement therapy and 1 patient (2.9%) in the group without infection (p=0.315). In the group with infection, 2 patients died (7.1%), whereas in the uninfected group there were no deaths (p=0.194). sCr values tend to diminish in a similar manner in both groups. Serum sodium tend to increase during the hospitalization but there was no significant difference between the groups. We found that all patients received furosemide at least during the first five days of hospitalization and the strategy of the diuretic chosen was similar between groups.

Conclusion

We showed that the clinical evolution of patients with CRS-1 is similar in the presence or absence of infection. We anticipate that this study may be a reason to expand knowledge in patients with CRS-1 and the presence of infection.
P0646PREDICTABLE CAPACITY OF ACUTE KIDNEY INJURY OF NEPHROCHECK TEST IN EMERGENCY ROOM PATIENTS
Authors: Gomá Elena , Gonzalez-Martin Guillermo , López-López Juan Alfredo , Perez Gomez Maria Vanessa , Ortiz Alberto , Martin Catalina
Published: June 2020

Background and Aims

Acute kidney injury (AKI) is increasingly prevalent and it is associated to increased hospital stay and costs, higher risk of developing a chronic kidney disease, and also major morbidity and mortality. Prediction tools may identify patients at high risk of AKI, allowing early intervention. Nephrocheck quantifies biomarkers of AKI (TIMP-2 and IGFBP-7), providing results within 20 minutes. This may allow stratification of the risk of developing an AKI in the next 12 hours in critically cardiovascular or respiratory ill patients and therefore implement preventive measures. We aimed to assess Nephrocheck performance to predict AKI development within 12 hours to 5 days in incident Emergency Room (ER) patients.

Method

Prospective observational study of 52 incident ER patients. Data were collected from April 2017 to November 2018. Inclusion criteria: sepsis of any origin, or cardiopulmonary insufficiency without AKI at baseline. Nephrochek was performed at baseline, patients were stratified into low (Nephrocheck test < 0.3), moderate (Nephrocheck between 0.3-2) and high risk (Nephrocheck >2) of AKI and occurrence of AKI was assessed (diagnosed as an increase of 0.3 mg/dl of serum creatinine) at 12, 24, 48 h and 5 days.

Results

Mean age as 70±13 years, 22/52 (43%) were women, risk factors included hypertension (54%), DM (29%), Cirrhosis: 2/52 (4%), heat failure (27%), prior CKD (12%), nephrotoxic use (38%). 18/52 (35%) of patients were Nephrocheck low risk, 21/52 (40%) were intermediate risk and 13/52 (25%) were high risk. AKI developed in 7/18 (39%), 3/21 (14%) and 3/13 (23%) of low, intermediate and high risk, respectively. When comparing patients who developed AKI with those who did not, those who developed AKI had been exposed more frequently to nephrotoxins and had lower urinary osmolarity and higher MAP (Table 1). However, a high risk Nephrocheck score identified patients with significantly higher urine osmolality (672±139 vs 387±172 mOsm/L, P=0.005) and lower MAP (76.7 ± 18.4 vs 101.62±22.7 mmHg; P=0.002).

Conclusion

LIMITATIONS: knowledge of Nephrocheck results may have changed patient care. CONCLUSIONS: A high risk Nephrocheck score was not associated with a higher risk of AKI in a ER setting. More nephrotoxins were used in the AKI group. Presumabily, these were discontinued in the ER, thus lowering AKI risk. By contrast, a past history of nephrotoxin use and lower urine osmolarity were associated with a higher incidence of AKI.
P0659MULTIMODAL IMAGING OF MALDI MSI DATA
Authors: Hermann Juliane , Brehmer Kai , Thiele Herbert , Jankowski Vera , Jankowski Joachim
Published: June 2020

Background and Aims

MALDI mass spectrometric imaging (MALDI MSI) is a powerful histologic tool for the analysis of biomolecules in tissue samples. MALDI MSI measurements results in a high sensitivity and accuracy of spatial distribution of biomolecules in tissue samples The resolution information of MALDI MSI is in the range of 5-10 µm in the spatial distribution and has the ability to identify proteins, peptides, lipids and small biomolecules directly in tissue samples in one analytical step..For a more detailed analysis of MALDI MSI data and a correlation between the molecular and microscopic level, a combination of MALDI MSI data and histological staining is essential. By combining MALDI MSI data and histological data, much more information are obtained than from a single analysis of both methods. Therefore, MALDI MSI data sets and histological staining were fused to a 3D model presenting a biomolecule distribution of the whole organ and provide more information than a single tissue section. We developed, established and validate an algorithm for an automatic registration of MALDI data with different histological image data for the cross-process evaluation of multimodal data sets for creating 3D models. This multimodal image approach simplifies and improves molecular analyses of tissue samples clinical research and diagnosis.

Method

The data sets for the fusion and creating of a 3D model consist of mass spectrometric data as well as histological and Immunohistochemical staining methods. Histological tissue sections of a whole mice kidney were prepared. For MALDI MSI data the organ sections were coated and incubated with a trypsin solution were performed by using a sprayer for MALDI imaging. As matrix, α-cyano-4-hydroxycinnamic acid was used. MALDI MSI was performed using the Rapiflex. For histological staining the hematoxylin-eosin and Gomori staining were chosen. For Immunohistochemical double staining and immunofluorescence, were used for the detection of Collagen type I, smooth muscle actin and the cell nuclei.

Results

By using a mathematical registration, a perfect superposition of the individual histological sections mass spectrometric data was achieved. It is possible to combine mass spectrometric data, histological and Immunohistochemical data sets in a high number and to reconstruct the measured mice kidney. By using different imaging methods, a variety of information about tissue structure as well as tissue changes and protein distribution can be obtained. The fusion of the data also offers a virtual incision of the organ from any angle and level. The algorithms are adapted to take the data fusion automatically offering a high-throughput approach for clinical diagnostics and the possibility to involved artificial intelligence in its interpretation in research.

Conclusion

There is a successful fusion of MALDI MSI data and different histological and Immunohistochemical staining data sets of a whole organ
P0661DIAGNOSTIC VALUE OF FULL AGE SPECTRUM EQUATION AS A PREDICTOR OF MORPHOLOGICAL LESIONS IN PATIENTS WITH GLOMERULONEPHRITIS
Authors: Elena Saganova , Galkina Olga , Sipovskii Vasiliy , Kayukov, Ivan , Smirnov Alexei
Published: June 2020

Background and Aims

Glomerular filtration rate (GFR) is generally accepted as a best overall index of kidney function. However, it remains controversial to choose the optimal equation to estimate GFR in patients with glomerulonephritis (GN). Recent studies have reported that newly developed full age spectrum equation based on normalized serum creatinine (FASsCr) showed improved validity and was less biased, more accurate than currently recommended sCr-based eGFR equations. Our aim was to assess FASsCr equation as a predictor of various morphological lesions in patients with GN.

Method

100 patients [48 female, age Me 39 (27; 54) years] with biopsy proven primary GN and without acute kidney injury, infectious diseases, severe heart failure, respiratory insufficiency, cancer were included in the study. Minimal change disease was diagnosed in 9% of cases based on the results of kidney biopsy, in 28% – focal segmental glomerulosclerosis, in 26% – membranous nephropathy and in 37% – IgA-nephropathy. Serum creatinine (sCr) level was measured by enzymatic method (Uni Cel DxC 800 PRO, «Beckman Coulter»,USA). eGFR was calculated using FASsCr equation. The extent of global glomerulosclerosis (GS) was assessed quantitatively as a sum of full and focal sclerotic glomeruli. Tubulo-interstitial fibrosis (TIF) and tubular atrophy (TA) were assessed semi-quantitatively (0-lesions absent; 1-mild focal tubular and interstitial lesions; 2-moderate tubular and interstitial lesions; 3 - diffuse tubular and interstitial lesions). All patients consistently were separated into 2 groups according to the degree of each morphological lesion (GS, TIF or TA): “mild” (GS<25% or TIF/TA grade 0 or 1) and “severe” (GS ≥ than 25% or TIF/TA grade 2-3).

Results

eGFR using FASsCr equation positively correlated (p<0,001 in all cases) with GS (r=0,44), TIF (r=0,64) and TA (r=0,61) and was significantly higher in patients with “mild” GS, TIF and TA (p<0,001) in comparison with “severe” group.

Using ROC-analysis all patients were separated (p<0.001) in 2 groups using FASsCr equation according to the degree of morphological lesions (“mild” or “severe”):

GS (Sn – 48.8%, Sp – 88.1%, ACC – 72.0%, AUC – 0.696, cut-off value – 47 ml/min/1.73m2), TIF (Sn - 75.4%, Sp – 76.9%, ACC – 76.0%, AUC – 0.815, cut-off value – 72 ml/min/1.73m2), TA (Sn – 65.9%, Sp – 88.8%, ACC – 70.0%, AUC – 0.798, cut-off value – 74 ml/min/1.73m2), (Figure).

Conclusion

Our results show that FASsCr equation is a significant marker of various morphological lesions in patients with GN. FASsCr equation predominantly can be used as a predictor of mild degree of interstitial sclerosis and tubular atrophy with high diagnostic value.

Figure: ROC curves with 95% CI of BM panel for A – GS; B – TIF; C – TA
P0665RENAL FUNCTION ASSESSMENT IN A SMALL COHORT OF ADULT PROFESSIONAL SOCCER PLAYERS
Authors: Kirsanova Tatiana , Talibov Oleg , Bezuglov Eduard , Mikhail Butovskiy
Published: June 2020

Background and Aims

Signs of acute kidney injury (AKI) are registered in 10-60% of patients with exertional rhabdomyolysis. Most professional soccer players from the time to time meet the criteria for rhabdomyolysis in high season. Link between chronic high levels of myoglobin and AKI is well known, while 25% of people who had AKI subsequently develop chronic kidney disease (CKD) and in 0,3% end-stage renal disease is diagnosed over the next 3 years. Progression of renal decline depends on incomplete recovery and the amount of AKI episodes. In all studies renal function (estimated glomerular filtration rate - eGFR) was calculated by creatinine level (SCr), while usually sportsmen have greater body muscle proportion, which makes it difficult to assess eGFR by creatinine. Cystatin C level is relatively independent of body mass index and composition therefore this parameter more accurately represents kidney function

AIM: comparison of two different GFR evaluation methods, cystatin (GFRcys) and creatinine (GFRcr) in adult professional soccer players

Method

24 adult professional soccer players (age = 28±3.8 years, BMI=23±0.98) were included. Renal function was assessed by blood tests of serum creatinine (SCr) and serum cystatin C (SCys) performed on the next day of regular matches. Blood samples were collected fasting at 8:00 in the morning after 8-hour night sleep. eGFR levels was determined by CKD-EPI formula for SCr, and (eGFR=130xcystatin C-1.069 x age -0,117-7) for CysC.

Results

Since data was distributed normally parametric tests were used. eGFRcr was significantly higher than eGFRcys : SCr 1.1±0.094 mg/dl, GFRcr 96±11 ml/min;CysC 0.94±0.093 mg/dl, eGFRcys 88±11 ml/min (p=0.0045, paired T-test). Both GFR methods and both indicators (SCr and CysC) have moderate weak statistically significant correlation. Pearson’s r=0.438 (p=0.0323) for eGFR (Pic.) and 0.4047 (p=0.0498) for SCr vs Cys.

Conclusion

In professional sportsmen cystatin C based eGFR evaluation has certain advantages in comparison to creatinine based method. Probably regular high-level physical exertions reduce kidney function.
P0670DIFFUSIONAL KURTOSIS IMAGING PREDICTS THE PROGNOSIS OF CHRONIC KIDNEY DISEASE
Authors: Liu Yan , Zhang Gu-mu-yang , Peng Xiaoyan , Li Xuemei , Sun Hao , Chen Limeng
Published: June 2020

Background and Aims

Renal fibrosis is the strongest prognosis predictor of ESRD in chronic kidney disease (CKD), but non-invasive and repeatable imaging markers are missing. Magnetic resonance imaging (MRI) has wide range of applications in renal parenchymal diseases, and diffusional kurtosis imaging (DKI) is a new promising noninvasive method of MRI which can provide more information about non-Gaussian diffusion using a polynomial model. We had successfully used DKI to assess renal fibrosis in IgA nephropathy in our previous work. This study aimed to evaluate the prognostic value of DKI in CKD.

Method

We prospectively enrolled forty-two CKD patients in our study in Jan. 2017. On recruitment, the basic clinical data were documented, and DKI was performed on a clinical 3T MR scanner. Region-of-interest (ROI) measurements were performed to determine apparent diffusion coefficient (ADC), kurtosis (K) and diffusivity (D) of the cortex of the kidneys. We had followed up these patients for 3 years, and collected all the clinical data and outcomes. The prognostic value of DKI metrics and clinical parameters were investigated.

Results

Forty-two patients consisted of 26 males and 16 females with mean age of 41.3±15.4 years. The most common etiology was IgA nephropathy (25/42, 59.5%). At baseline, the mean value of serum creatinine (SCr) was 224.4±156.2μmol/L. Among them, 18 patients had eGFR≥45ml/min and 24 patients had eGFR<45ml/min. According to the etiology and CKD classification, all the patients had received appropriate treatment. Besides supportive treatment and management of CKD complications, 21 patients (50%) had received corticosteroid and/or immunosuppressants treatment. After 36 months follow up, 12 patients had progressed to end stage renal disease (ESRD), and the mean value of SCr of the remaining 30 patients was 153.0±78.8umol/L. The Kaplan-Meyer survival regression showed that the patients with eGFR<45ml/min had worse clinical outcomes (p=0.0006). ROC analysis and Kaplan-Meyer survival regression showed that DKI metrics (K≥0.66 or ADC<1.35) not only predicted severe renal fibrosis, but also had worse clinical outcomes (p=0.01 and p<0.0001) (Figure 1). According to the COX regression analysis, both K (K≥0.66, HR 4.676, 95%CI 1.262-17.325) and ADC (ADC<1.35, HR 13.118, 95%CI 3.499-49.178) values, but not age, gender and eGFR group (cut-off value: 45ml/min), were the independent risk factors for the progression to ESRD.

Conclusion

Renal ADC and K values obtained from DKI showed significant predictive value for the prognosis of CKD, could be a promising non-invasive technique in patients follow-up.
P0677CONTRAST-ENHANCED ULTRASOUND TO ASSESS RENAL MICROCIRCULATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Garessus Jonas , Brito Wendy , Loncle Nicolas , Vannelli Anna , Wuerzner Grégoire , Schneider Antoine , Pruijm Menno
Published: June 2020

Background and Aims

Vascular factors such as capillary rarefaction, increased vascular stiffness and reduced vasodilatation due to endothelial dysfunction probably play an important role in the pathophysiology of chronic kidney disease (CKD). However, our understanding of the underlying mechanisms is hampered by the lack of non-invasive techniques to quantify renal microvasculature in humans. The aim of this study was to assess whether contrast-enhanced ultrasonography (CEUS) can identify (1) differences in renal microcirculation and (2) the degree of nitroglycerin-induced vasodilatation (NIV) as a measure of renal flow reserve between CKD-patients and age-matched healthy volunteers.

Method

All participants underwent CEUS under standardized conditions. Sonovue© (0.015 ml/kg/min) was perfused as contrast agent until a steady state was obtained, followed by four destruction-refilling sequences. Outcome measure of CEUS was the mean (change in) perfusion index (PI) of the outer renal cortex (see figure for an example). In a subgroup of participants, CEUS was repeated before and five minutes after the sublingual administration of nitroglycerin (0.2mg). Renal resistive index (RRI) as a measure of vascular stiffness was also measured at each time point with Doppler ultrasound.

Results

A total of 38 healthy volunteers (aged 50±8 years, eGFR 95±13 ml/min/1.73 m, 69% women) and 18 CKD stage 2-3 patients (aged 55±15 years, eGFR 64±32 ml/min/1.73m, 56% women) were included. Renal PI was significantly lower in CKD patients (1304±762 vs 2989 ±2503 arbitrary units, p=0.034), whereas RRI did not differ (0.66± 0.07 vs 0.63± 0.04), p=0.10). PI was lower in CKD due to vascular nephropathy (n=3) or interstitial nephritis (n=4) than CKD due to diabetes (n=4) or other causes (7). In continuous analysis, PI correlated with eGFR (spearman’s r=0.54, p=0.005) but not with blood pressure. Renal PI did not change after nitroglycerin in both groups; RRI decreased in healthy (from 0.64±0.03 to 0.61±0.02, p=0.01) but not in CKD patients.

Conclusion

In this study, contrast-enhanced ultrasound identified important alterations in renal microperfusion in patients with moderate CKD. Whether a low perfusion index predicts renal function decline needs further study. Sublingual nitroglycerin seems to have limited potential as a new test of renal flow reserve.
P0679LOSARTAN REDUCES INFLAMMATION INDUCED BY TERTIARY LYMPHOID TISSUES IN ENSUING CKD AFTER ACUTE KIDNEY INJURY
Authors: SHAO YU-HAN , Chou Yu-Hsiang , CHENG SHUN-YANG , LIN SHUEI-LIONG
Published: June 2020

Background and Aims

Chronic inflammation and renin-angiotensin system (RAS) overactivation have been demonstrated as a central mechanism that results in the development of progressive chronic kidney disease (CKD). Evidences have indicated that tertiary lymphoid tissues (TLT) form after acute kidney injury (AKI), especially in old-aged mice. Heterogeneous fibroblasts which appear and secret proinflammatory cytokines after AKI underlie TLT formation. There is an association between TLT sizes and impaired renal function along with increase of proinflammatory cytokines, suggesting a probable cause of persistent inflammation after AKI. In this study, we explored the relationship between TLT development and RAS activity. The phenotypes of heterogeneous fibroblasts diversified after AKI is also investigated.

Method

Here we utilized ischemia-reperfusion injury to cause ensuing CKD both in a CD-1 and C57BL6J mice model. We also used staining of CD3 and B220 to label and confirm multiple TLTs which represents T and B lymphocytes respectively.

Results

Administration of losartan, a kind of RAS inhibitor, offered protection against subsequent CKD development and attenuated number and size of TLT besides blood pressure reduction. Moreover, heterogeneous fibroblasts diminished and proinflammatory cytokines such as CXCL13, CCL21 and CCL19 which trigger the initiation of TLT were downregulated. In experiments of several fibroblast cell lines, angiotensin II (Ang II) administration could induce differentiation of fibroblasts with distinct phenotypes expressing p75 neurotrophin receptor and retinaldehyde dehydrogenase 2 which contribute to TLT formation. These fibroblasts expressing PDGFRβ stimulated production of aforementioned proinflammatory cytokines and expression of pro-fibrotic genes.

Conclusion

Our data demonstrates that TLT plays an important role in AKI-CKD transition. We also verify that Ang II causes phenotypic change of fibroblasts which constitute TLT. Losartan can ameliorate TLT formation through inhibition of these distinctive fibroblasts. It is a plausible mechanism to reduce ensuing CKD.
P0680A POST-HOC ANALYSIS OF EFFICACY AND SAFETY OF TOLVAPTAN (TOL) IN DECREASING RATE OF RENAL FUNCTION DECLINE IN PATIENTS WITH VERY LATE-STAGE AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD)
Authors: Torres Vicente , Gansevoort Ronald , Perrone Ron , Chapman Arlene , Ouyang John , Lee Jennifer , Japes Hina , Wang Tao
Published: June 2020

Background and Aims

ADPKD is a progressive inherited disease that causes end-stage renal disease (ESRD) in ∼50% of the affected individuals by 60 years of age. TOL, a selective vasopressin V2-receptor antagonist, has been shown in randomized, placebo-controlled trials to slow the progression of renal function decline in ADPKD subjects with an eGFR of 25 mL/min/1.73m2 or higher. The efficacy and safety of TOL in subjects with lower eGFR remain understudied. This post-hoc analysis evaluated the efficacy and safety of TOL in subjects with stage 4 ADPKD (eGFR of <30 mL/min/1.73m2).

Method

This is a retrospective analysis of a subgroup of ADPKD subjects who enrolled in the TOL long-term open-label extension (OLE) trial (NCT02251275). Included subjects had a baseline eGFR of <30 mL/min/1.73m2, received ≥ 1 TOL dose, and were randomized to the placebo group in the REPRISE trial (NCT02160145). Two subgroups of subjects were analyzed, one with baseline eGFR of 25-30 (Subgroup 1) and one with <25 (Subgroup 2). The variables evaluated included: 1) demographics, 2) adverse event (AE) profile, 3) intra-subject comparison of change in annualized eGFR decline during the open-label study (treatment period) to that during placebo use in the REPRISE trial (control period). Annualized eGFR change slopes in the treatment period were calculated using eGFR values between Month 1 and 12 visits to compensate for the acute hemodynamic effect of tolvaptan. Comparison was made by linear mixed model.

Results

Of the 1,803 subjects enrolled, 159 (8.8%) subjects (76 in Subgroup 1 and 83 in Subgroup 2) met the selection criteria for analysis. Annualized eGFR change slopes for all subjects (n=148) were -5.28 (SE 0.27) in the control period and -3.16 (SE 0.30) in the treatment period with a treatment effect of 2.11 mL/min/1.73m2/year (95% CI 1.56, 2.66), p<0.0001). Demographic information, baseline eGFR, treatment duration and effects in the 2 subgroups are shown in the Table below. Treatment-emergent AEs were observed in 95% and 90% of the subjects in the 2 subgroups, respectively. Discontinuation due to AEs occurred in 15% and 17% of the 2 subgroups, respectively. The 5 most common AEs for all subjects were thirst (32%), polyuria (30%), renal pain (25%), blood creatinine increase (23%) and nocturia (22%); the rates were similar between the 2 subgroups. One incidence of hepatic enzyme increase, hemodialysis and death (unrelated to TOL) was observed in Subgroup 2, but not in Subgroup 1.

Conclusion

This post-hoc analysis demonstrated that TOL significantly decreases the rate of eGFR decline in ADPKD subjects with stage 4 CKD, including those with an eGFR of <25 mL/min/1.73m2.
P0683PATTERNS OF HYPERKALAEMIA RECURRENCE AMONG CHRONIC KIDNEY DISEASE PATIENTS IN UK CLINICAL PRACTICE
Authors: Hurst Michael , Hoskin Louise , Badora Karolina , Tafesse Eskinder , Sugrue Daniel , Qin Lei , James Glen , McEwan Phil
Published: June 2020

Background and Aims

Patients with chronic kidney disease (CKD) are at increased risk of hyperkalaemia, HK (high serum potassium concentration) due to impaired renal function. This medical condition is potentially life threatening if untreated or poorly managed. This study describes the characteristics of CKD patients in the UK who experience HK and assessed the frequency of recurrent HK and time between first (index) and subsequent events.

Method

A retrospective cohort study was conducted using linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) data from 01 January 2008 to 30 June 2018, with a five-year lookback period (2003-2007).

Patients were included if they were diagnosed with CKD stage 3+ (READ code or eGFR <60 mL/min/1.73m2 without prior dialysis) during the study or lookback periods and aged >18 years at diagnosis (index).

Patient demographics, clinical history and baseline medication use were described. HK was defined as serum K+ ≥5.0 mmol/L. HK events occurring during the study period, but after diagnosis of CKD, were assessed. Recurrent HK was defined as any event subsequent to the first event. Time to recurrence was calculated using Kaplan-Meier.

Results

In total, 297,702 CKD patients (mean age 74.7 years [standard deviation: 11.3], male [41.4%]) met eligibility criteria. At time of CKD diagnosis, 30.6% of the population had resistant hypertension. Other prominent comorbidities included diabetes (22.24%), CKD (7.9%) and cancer (7.8%). Approximately half of patients were in receipt of diuretics at baseline (49.2%), while 32.5% and 32.0% were in receipt of beta blockers and calcium channel blockers, respectively. During follow up, 67.0% of patients received a renin-angiotensin aldosterone system inhibitor (RAASi).

147,215 patients (49.5%) experienced at least one HK event, of which 53,695 (36.5%) had only one HK event, 93,250 (63.5%) had two or more HK events and 29,413 (20.0%) had six or more events. HK event incidence was predictive of subsequent events, with the probability of experiencing a HK event increasing from 49.5% to 63.5%, 70.7%, 74.1%, 76.5% and 78.6% for patients experiencing 2-6 events, respectively. There was an inverse relationship between the number of recurrent events and time to next event, with less time between the next event for those experiencing multiple events (Figure 1).

Conclusion

This study shows that approximately half of CKD patients experienced a HK event. Furthermore, patients who experienced a HK event were at increased risk of subsequent events. Frequent monitoring of serum potassium may help reduce the burden of HK in patients with CKD.