bluuebunny/crossref_metadata_2025 huggingface dataset:
P0625CONTINUOUS RENAL REPLACEMENT THERAPY WITHOUT ANTICOAGULATION IN CRITICALLY ILL PATIENTS AT HIGH RISK OF BLEEDING-A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Sun Shiren , Zhang Wei , Bai Ming , Zhao Lijuan , Chen Xiaolan , Yu Yan
Published: June 2020

Background and Aims

Continuous renal replacement therapy (CRRT) has been widely used in the critical care setting and anticoagulation is usually necessitated. However, critically ill patients are commonly at incremental risk of bleeding, which contributed to the hesitation of anticoagulant use for CRRT in clinical practice. The current guideline recommended CRRT proceed without anticoagulation in patients with contraindication to citrate and increased bleeding risk. Nevertheless, the efficacy of anticoagulation-free CRRT remains inconsistent. Therefore, the purpose of our present systematic review is to evaluate the efficacy and safety of anticoagulant-free CRRT based on the current literatures.

Method

We conducted a comprehensive search of PubMed (US National Library of Medicine, Bethesda, MD, USA), Cochrane Library databases and EMBASE from database inception to January 12, 2019 for potential candidate studies. Studies included adult critically ill (age > 18 years) patients with increased bleeding risk, and underwent CRRT without anticoagulation were considered for the inclusion.

Results

Finally, 17 observational studies and 3 randomized controlled trials with 1615 patients were included in our present meta-analysis. There was no significant difference in filter lifespan between the anticoagulation-free and systemic heparin group. The filter lifespan was significantly prolonged in the citrate (WMD -23.01, 95%CI [-28.62, -17.39], P < 0.001; I2 = 0%, P = 0.53) and nafamostat (WMD -8.4, 95%CI [-9.9, -6.9], P < 0.001; I2 = 33.7%, P = 0.21) groups, compared with anticoagulation-free group. The averaged filter lifespan of the anticoagulation-free CRRT ranged from 10.2 to 52.5 hours.

Conclusion

The filter lifespan in anticoagulation-free patients with increased bleeding risk was comparable to that in patients without increased bleeding risk underwent systemic heparin anticoagulation CRRT. Nafamostat was not recommended for CRRT anticoagulation due to its drawbacks. Currently, the optimal choice of anticoagulation strategy for critically ill patients without citrate contraindications at high risk of bleeding should be regional citrate anticoagulation. Further studies should focus on the special cut-off value of activated partial thromboplastin time (APTT), international normalized ratio (INR) and platelet (PLT) count, at which the anticoagulation-free CRRT would be beneficial.
P0626THE RISK FACTORS OF ACUTE KIDNEY INJURY CAUSED BY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
Authors: Wang Siwen , Zhou Jiaojiao , Yang Jia , Yang Lichuan , Wang Xin
Published: June 2020

Background and Aims

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome caused by uncontrolled natural killer (NK) cell and cytotoxic T cell activation, resulting in the overproduction of proinflammatory cytokines and hemophagocytosis. Acute kidney injury (AKI) characterized by rapid loss of renal excretion function is the most common complication of HLH in the kidney. In this retrospective study, we aimed to find the risk factors of AKI in patients with HLH.

Method

This study included adult patients with HLH admitted in West China Hospital of Sichuan University from January 2009 to June 2019. Patients with HLH were excluded from the study if they had a functioning kidney transplant, received renal replacement therapy (RRT) in the past month, suffered from end-stage renal disease (ESRD) or had the renal malignant tumor. The diagnosis of HLH was based on the HLH diagnostic criteria revised by the Histocyte Society in 2004 and AKI was defined according to the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) guideline. We collected basic information, clinical manifestations and laboratory data of patients from electronic medical records.

Results

We analyzed 294 patients this time, of whom 95 (32.3%) developed AKI. The patients were divided into two groups according to the occurrence of AKI. The mortality rate in the AKI group was significantly higher than that in the non-AKI group (40.0% VS 12.6%; p<0.001). The risk factors of AKI in patients with HLH were hyperphosphatemia [Odds Ratio (OR) 3.825; 95% Confidence Interval (CI) 1.647-8.886; p=0.002] ,heart failure (OR 2.972; 95% CI 1.029-8.584; p=0.044), increased heart rate (OR 1.025; 95% CI 1.008-1.043; p=0.004), prolonged prothrombin time (OR 1.025; 95% CI 1.001-1.049; p=0.041), elevated total bilirubin level (OR 1.003; 95% CI 1.000-1.007; p=0.030), and hypoproteinemia (OR 0.915; 95% CI 0.842-0.994; p=0.035).

Conclusion

The incidence of AKI in HLH patients is frequent, and the risk of death in HLH patients with AKI is significantly higher. The occurrence of AKI in patients with HLH is related to hyperphosphatemia, heart failure, increased heart rate, prolonged prothrombin time, elevated total bilirubin level, and hypoproteinemia.
P0628CREATININE-CYSTATIN C RATIO IS ASSOCIATED WITH MORTALITY IN ICU PATIENTS UNDERGOING CONTINUOUS RENAL REPLACEMENT THERAPY
Authors: Jung Chan-Young , Jo Wonji , Kim Jaeyoung , Park Jung Tak
Published: June 2020

Background and Aims

Development of acute kidney injury (AKI) in intensive care patients considerably increases the risk of mortality. Although several factors that are related to outcome have been recognized in this patient group, stratifying mortality risk still remains a challenge. While serum creatinine levels are confounded by muscle wasting in critical illness, cystatin C is expected to be less modulated by muscle mass. Speculating that the ratio between serum creatinine and cystatin C may reflect muscle mass in critically ill AKI patients, we evaluated the association between creatinine-cystatin C ratio and mortality in patients requiring continuous renal replacement therapy (CRRT) in the intensive care unit (ICU).

Method

Retrospective analyses were conducted on 443 ICU patients who underwent CRRT between August 2009 and October 2016 at Severance Hospital of Yonsei University Health System, Seoul, South Korea. The patients were divided into four groups based on creatinine-cystatin C ratio at the time of CRRT commencement. The primary outcome was 90-day mortality after CRRT initiation.

Results

The mean age was 64 ± 15 years, and 57.3% of patients were male. The most common cause of AKI was sepsis. The median and range of the creatinine-cystatin C ratio was 0.83 (0.13-6.20). The 90-day mortality rate for each creatinine-cystatin C ratio quartiles 1, 2, 3, and 4 were 76.6%, 73.9%, 61.3%, and 51.8%, respectively. Multiple Cox proportional hazard models revealed that the creatinine-cystatin C ratio was an independent predictor of 90-day mortality even after adjusting for confounding factors (Hazard ratio, 0.97; 95% confidence interval, 0.95-0.99, P<0.01). The prediction of mortality was significantly improved when creatinine-cystatin C ratio was considered compared to APACHE-II or SOFA scores alone.

Conclusion

Creatinine-cystatin C ratio is associated with mortality in ICU patients undergoing CRRT, and may be a practical marker in predicting survival among ICU patients with AKI.
P0630EARLY CHANGES OF SEQUENTIAL URINE SEDIMENT ANALYSIS ARE INDICATIVE FOR DEVELOPMENT OF ACUTE KIDNEY INJURY AFER CARDIAC SURGERY
Authors: Schanz Moritz , Schricker Severin , Oberacker Tina , Göbel Nora , Alscher Dominik M , Kimmel Martin , Ketteler Markus
Published: June 2020

Background and Aims

Microscopic examination of urine sediment is a well-established and inexpensive technique for differential diagnosis of acute kidney injury. Especially renal tubular epithelial cells (RTEC) and granular casts (GC) have been shown to be a strong predictor of acute tubule necrosis (ATN), the assumed most common cause for AKI in cardiac surgery patients. So far, no study evaluated urine sediment before manifest AKI is evident. Therefore, the aim of this prospective trial was to evaluate if early changes of urine sediment parameters are indicative for development of acute kidney injury.

Method

Sequential urine sediment specimens were analyzed on day 0 (d0), day 1 (d1) and day 4 or 5 (d5) after cardiac surgery in n=37 patients. Urine analysis was conducted immediately after collection of urine specimens. Analysis includes detection of RTEC and GC as well as hyaline casts (HC), squamous epithelium (SE), erythrocyte count (EC) and leucocyte count (LC). Urine score (US) - consisting of RTEC and GC - which is described as indicative for ATN, was calculated as described previously. For detection of AKI, serum creatinine, serum cystatin c and urine output were recorded. Urine sediment changes over time were analyzed using differences between day of surgery (d0) and day 1 (d0-d1 = Δd1) or day 5 (d0-d5 = Δd5), respectively.

Results

Of the 37 included patients n=10 (27%) developed AKI within 5 days. According to the definition of KDIGO 2012, two patients developed Stage 1 (20%), six patients Stage 2 (60%) and two patients Stage 3 (20%) AKI. Median age was 67 years (IQR: 63.5-73.0). Mean HC, GC, RTEC and US tended to be higher in AKI patients from day one after surgery. Looking at the urine sediment changes over time (Median; IQR), Δd1 of RTEC (AKI: 0.65; 0.00 – 1.15 vs. No AKI: 0.00; -0.03 – 0.03; p=0.010), GC (AKI: 0.25; 0.00 – 0.50; No AKI: 0.00; -0.20 – 0.00; p=0.002) and US (AKI: 0.00; -0.25 – 0.00 vs. No AKI: 0.00; 0.00 – 1.00; p=0.047) were significant higher in AKI group. Also HC (AKI: 1.00; 0.00 – 1.00; No AKI: 0.00; -1.25 – 1.00; p>0.05) tended to be higher in AKI on Δd1, whereas SE, EC and LC did not show any trend between both groups. Δd5 did not show any significant result between AKI and non-AKI. Because all of these patients were catheterised, the results on urinary erythrocyte count were interpreted with appropriate caution.

Conclusion

This is the first study evaluating sequential urine sediment measurements for early detection of AKI in cardiac surgery. According to these preliminary data, Δd1 of RTEC, GC and US is significant higher in AKI, suggesting that an increase from day of surgery to day 1 may be indicative for the development of AKI right before manifest AKI is evident. Therefore sequential urine sediment measurements could be useful for early detection of AKI after cardiac surgery.
P0633EFFECT OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS ON CISPLATIN-INDUCED ACUTE NEPHROTOXICITY IN CANCER PATIENTS WITH DIABETES MELLITUS: A RETROSPECTIVE STUDY
Authors: Iwakura Takamasa , Fukasawa Hirotaka , Kitamura Atsushi , Ishibuchi Kento , Yasuda Hideo , Fujigaki Yoshihide , Furuya Ryuichi
Published: June 2020

Background and Aims

Cisplatin is a highly effective chemotherapeutic agent. However, acute kidney injury (AKI) limits its subsequent use, resulting in poor cancer prognosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to attenuate cisplatin-induced AKI in animal models, but the effect in human patients remains to be clarified. We hypothesized that DPP-4 inhibitors can prevent cisplatin-induced AKI in diabetic-cancer patients.

Method

We retrospectively reviewed all consecutive cancer patients who were treated with a first cycle of cisplatin-containing regimen between January 2011 and October 2019. We analysed data of diabetic-cancer patients treated with high-dose cisplatin (> 50 mg/m2)-containing regimens. The change of estimated glomerular filtration rate (eGFR) within 2 weeks after cisplatin treatment was compared between the patients treated with DPP-4 inhibitors and those treated without DPP-4 inhibitors.

Results

A total of 455 patients were treated with cisplatin during the period. Of these, 35 patients were eligible for the analysis. The change of eGFR was significantly less in the patients treated with DPP-4 inhibitors, compared to those without DPP-4 inhibitors [Fig.1; the percentages of eGFR decline (mean ± SD) was 23.6 ± 20.3% vs 41.2 ± 20.6%, respectively; P=0.016]. Furthermore, the incidence of AKI was significantly less in the patients treated with DPP-4 inhibitors (25% vs 60%, respectively; P=0.040).

Conclusion

DPP-4 inhibitors may decrease the risk of cisplatin-induced AKI in diabetic patients. Therefore, the use of DPP-4 inhibitors may be one of supportive therapies for cancer patients treated with high-dose cisplatin.
P0639COMPARISON OF SIRS AND QSOFA CRITERIAS IN RECOGNITION OF SEPSIS RELATED ACUTE KIDNEY INJURY
Authors: Alkan Özlem , Arıkan İzzet Hakkı
Published: June 2020

Background and Aims

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Epidemiological studies have shown that the incidence of sepsis is increasing and therefore it is a public health problem. AKI is often associated with critical illnesses such as sepsis, and is associated with prolonged hospital stay, need for intensive care, increased morbidity and mortality. Although the mechanism of sepsis-induced AKI is not fully understood, it is thought that it has a different pathogenesis and requires a different approach and therefore it has been the focus of the studies. The aim of this study was to compare the criteria of SIRS and qSOFA in patients with suspected infection to determine which is more valuable in predicting sepsis associated AKI.

Method

SIRS and qSOFA scores of 120 patients with sepsis who were admitted to the Emergency Department of Marmara University Hospital were calculated at the time of admission. Age, gender and chronic diseases were recorded. The laboratory values at the time of admission and follow-up were recorded and the factors associated with the development of AKI were investigated by statistical analysis.

Results

Of the patients evaluated in the study, 60.8% (n = 73) were male and 39.2% (n = 47) were female. The median age was 66 (18-89) years. About 96% (n = 116) of the patients met the SIRS criteria, 54.2% (n = 65) met the qSOFA criteria, and 51.7% (n = 62) met both the SIRS and qSOFA criteria. AKI was found in 62.5% (n = 75) of the patients. According to AKIN staging, 40 (53.3%) patients had stage 1, 19 (25.3%) patients had stage 2 and 16 (21.4%) patients had stage 3 AKI. There was no correlation between SIRS criteria and development of AKI. However, all patients who received 3 points from qSOFA criteria developed AKI. According to the results of multivariate analysis, age, abnormal mental status and procalcitonin were associated with development of AKI.

Conclusion

Sepsis-associated AKI is related with deterioration in clinical outcomes, early diagnosis and treatment is important. According to our results, the risk of AKI is higher in patients with qSOFA score 3 but not SIRS criterias.
P0640DIAGNOSTIC AND TREATMENT OF THE SEVERE FORMS OF ACUTE RENAL FAILURE DURING MALARIA UNDER LIMITED CONDITIONS
Authors: Pilcevic Dejan , Kojic Miroslav , Milic Veljko
Published: June 2020

Background and Aims

To explore clinical features and outcome of the most severe forms of acute renal failure (ARF) during Plasmodium falciparum malaria in United Nations personnel stationed in Central African Republic, during “MINUSCA ” mission. ARF is one of the most important negative predictive criteria for outcome of malaria.Etiology is multifactorial, but most often is consequence of prerenal dehydration and tubular damages with hemoglobinuria during severe hemolysis

Method

We analyzed records of 54 inpatients with complicated forms of Plasmodium falciparum malaria who were treated in the Serbian level 2 hospital during 2017. Diagnosis of ARF was estimated based on RIFLE criteria. Having in mind the occasional lack of diagnostic kits for creatinine, at the almost one third of patients we used daily diuresis monitoring (with follow up of volume status) to diagnose this complication (according with RIFLE criteria).

Results

Total of 19 patients (35,19%) have developed ARF. Beside parenteral treatment with Artemisin, they were treated with parenteral solutions and diuretics. Despite therapy, 8 patients (14,81%) developed progressive and dialysis depended form of ARF (one had hemolytic-uremic syndrome) and they have been urgently evacuated accompanied by AMET into a senior medical institution. Based on provided back information, average creatinine on admission was 1242+/-342 µmol/l, Hb level 10,6 g/dl, potassium 6,8mmol/l. Six out of 8 patients completely recovered renal function (they needed average 7+/- 2 HD procedures; patient with HUS performed 5 plasma exchange sessions), one developed CRF grade 3 and one developed ESRD with necessity for chronic HD treatment. There were not lethal outcomes.

Conclusion

Early recognition of systemic complications including parameters of acute renal failure (decreasing urine output or changing of urine color could be useful markers under limited medical conditions)is necessaryin the purpose of timely recognition and promptly evacuation into higher medical facilities for further treatment.
P0647ACUTE KIDNEY INJURY SECONDARY TO SUCROSE CONTAING INTAVENOUS IMMUNOGLOBULIN
Authors: Al Lawati Sadiq , Al Salmi Issa , Hannawi SUAD
Published: June 2020

Background and Aims

Intravenous immunoglobulins (IVIG) are pooled polyvalent IgG antibodies extracted from the human plasma. While the initial indications were mainly immune deficiency states and some autoimmune diseases, the usage has been widened to include several immune mediated diseases, viral infections, and organ transplant rejection. Stabilizers in IVIG may include sugars, such as sucrose, glucose, or maltose. Sucrose in IVIG preparations may cause acute kidney injury. We report the case of a renal transplant patient who developed acute kidney injury due to sucrose nephropathy following the administration of sucrose containing IVIG.

Method

Four months after transplantation he was referred to our Hospital for deterioration of kidney function with eGFR (by MDRD formula) of 27ml/min. Cytomegalovirus virus (CMV) PCR turned positive (3300 copies/ml). Cyclosporine levels were high (C2: 2937 ng/ml) and hence, cyclosporine dose was adjusted. Induction therapy with Injection Ganciclovir for 2 weeks, followed by therapeutic dose of oral Valganciclovir was administered for the treatment of CMV infection. Skin examination revealed annular purple patches, suspicious of Kaposi Sarcoma, on the upper limbs. Skin biopsy confirmed the diagnosis.

It was planned to give total IVIG of 2 gm/ kg in four daily divided doses. After completion of the second dose, serum creatinine increased to 370 µmol/L. He was clinically asymptomatic, euvolumic, vital signs were stable, and his urine output remained normal and his urinalysis was inactive.

Results

The ultrasound of the transplant kidney was normal with normal resistivity index. IVIG was stopped. He was well hydrated and underwent ultrasound guided biopsy. The graft biopsy showed acute tubular injury with flattening and vacuolation of tubular epithelial cells. Mitosis indicating tubular regeneration was seen. There was mild focal interstitial inflammation (20%) with mild lymphocytic tubulitis not amounting to graft rejection. Immunohistochemistry for C4d and polyomavirus (BKV) were both negative. The features were most consistent with sucrose induced nephropathy (Figure 1).

Subsequent visits showed a decrease in BKV-PCR serum level and eventually undetected serum level of BKV-PCR at follow up about a month later.

Conclusion

In this paper, we presented a case of a living unrelated kidney transplant recipient who developed BKV nephropathy and developed impaired kidney function. The patient also had new onset diabetes mellitus after kidney transplantation (NODAT) but was otherwise in good general health. Treatment included sucrose containing IVIG. The patient subsequently developed acute kidney injury.

The outcome was favorable with recovery of filtration rate to the baseline within 21 days without the need for dialysis.

We conclude that the administration of sucrose containing IVIG may lead to acute kidney injury. We recommend the use of sucrose-free IVIG whenever possible. In all cases, caution is required when administrating IVIG.
P0652THYMOSIN BETA 4 AND KIDNEY FUNCTION: AN INVERSE RELATIONSHIP?
Authors: He Tianlin , Schanstra Joost , Siwy Justyna , Beige Joachim , Latosinska Agnieszka , Mischak Harald
Published: June 2020

Background and Aims

Thymosin β4 (Tβ4) is an abundant peptide in urine and plasma, involved in multiple processes including cell morphology, wound healing, and inflammation. A major, yet not well defined role of Tβ4 was described in the context of kidney and cardiovascular disease. Knock out of Tβ4 resulted, among others, in increased albuminuria in a nephrotoxic nephritis model. In animal models it has been shown that Tβ4 can modify renal and cardiovascular disease, fibrosis and inflammation. However, most of the data are derived from animal models and the relevance of Tβ4 in human is less clear. As a first step towards investigating the potential relevance of Tβ4 in chronic kidney disease (CKD) in human, we investigated the abundance of Tβ4 in human urine.

Method

We investigated human urine in 2240 subjects with a wide spread of kidney function for the presence of Tβ4 using capillary-electrophoresis coupled mass spectrometry (CE-MS) and tandem mass spectrometry. In addition, we evaluated the presence of Tβ4 abundance in hemodialysis fluid of 10 subjects.

Results

The full length acetylated Tβ4 peptide could be identified in human urine in high abundance (molecular mass 4960.485 Da). In addition, an oxidized isoform could also be observed at high abundance. When investigating the distribution of both isoforms in control subjects and patients at different stages of CKD, a highly significant inverse association of the abundance of Tβ4 with eGFR could be observed for both, with rho -0.388 for the non-oxidized and -0.387 for the oxidized isoform, p<0.0001 in each case. In hemodialysate, Tβ4 is found as the most abundant peptide in 2 of the 10 analyzed subjects, on average the second most abundant peptide, with β2 microglobuline being the most abundant one.

Conclusion

Tβ4 is highly significantly inversely associated with kidney function, suggesting a role of Tβ4 in kidney disease and/or its complications. Based on the experimental data published from animal models, the increase in Tβ4 may reflect a potential physiological mechanism to counteract CKD and its complications. Investigation of association of Tβ4 levels with progression in CKD, cardiovascular complications and death may inform on a potentially beneficial effect of Tβ4, is currently ongoing in longitudinal datasets and will be presented.
P0657CHANGES IN CREATININE MAY NO REFLECT MEASURED RENAL FUNCTION CHANGES IN PREDIALYSIS
Authors: Beatriz Escamilla Cabrera , Sánchez Dorta Nuria Victoria , Negrã­n Mena Natalia , Luis-Lima Sergio , Gonzalez Rinne Federico , Porrini Esteban , Torres Ramírez Armando
Published: June 2020

Background and Aims

Serum creatinine is the most used biomarker of renal function in clinical practice. However, the correlation between creatinine and measured GFR is poor with a variability as wide as 200%. The causes of this phenomena are not clear. Some studies observed tubular handling (reabsorption and secretion) as well as intestinal secretion of creatinine, and depends of nutritional status . Importantly, these changes increased with the loss of renal function, masking changes in the evolution of real renal function. However, scarce evidence is available about the reliability of creatinine in reflecting the changes of renal function over the time in predialysis patients, compared to measured GFR. This information is relevant in the setting of clinical decisions.

Method

Spanish unicenter study developed at the Hospital Universitario de Canarias (Tenerife). In the pre-dialysis outpatient clinic, subjects are followed with measured GFR (clearance of iohexol by DBS). Measured GFR is performed at baseline and repeated as suggested by the clinical evolution. For this study we included all patients with repeated determinations of creatinine and measured GFR. The changes of creatinine in terms of increase (>10%), decrease (<10%) and stability (±10%) were compared with the changes in measured GFR.

Results

89 cases with repeated measurement of GFR and creatinine were evaluated. In 61 cases (68.53%) discrepancies between changes in creatinine and measured GFR were evident. Graphic 1 shows differents discordancing cases with 39 cases (43.8%) overestimation, 7 (7.8%) of infraestimation and 15 cases (24.7%) not change of mGFR with changes on Cr.

Conclusion

Changes in creatinine do not reflect real changes in real renal function in about 70% of the cases. Whenever possible, the measurement of GFR by whichever method available should be considered in the renal care and follow-up of these patients.
P0658MATRIX AND FLOW MODULATE GENE EXPRESSION IN A 3D VASCULARISED TUBULE MODEL
Authors: Williams Julie , Robinson Sanlin , Alaei Babak , Homan Kimberly , Clausen Maryam , Hicks Ryan , Belfield Graham , William-Olsson Lena , Bak Annette , Lewis Jennifer , Laerkegaard Hansen Pernille
Published: June 2020

Background and Aims

Questions abound regarding the translation of in vitro 2D cell culture systems to the human setting. This is especially true of the kidney in which there is a complex hierarchical structure and a multitude of cell types. While it is well accepted that extracellular matrix plays a large part in directing cellular physiology emerging research has highlighted the importance of shear stresses and flow rates too. To fully recapitulate the normal gene expression and function of a particular renal cell type how important is it to completely reconstitute their in vivo surroundings?

Method

To answer this question, we have cultured proximal tubular (PT) epithelial cells in a 3-dimensional channel embedded within an engineered extracellular matrix (ECM) under physiological flow that is colocalised with an adjacent channel lined with renal microvascular endothelial cells that mimic a peritubular capillary. Modifications to the system were made to allow up to 12 chips to be run in parallel in an easily handleable form. After a period of maturation under continuous flow, both cell types were harvested for RNAseq analyses. RNA expression data was compared with cells cultured under static 2-dimensional conditions on plastic or the engineered ECM. Additionally, the perfusion of glucose through this 3D vascularised PT model has been investigated in the presence and absence of known diabetes modulating agents.

Results

PCA of RNAseq data showed that a) static non-coated, b) static matrix-coated and c) flow matrix-coated conditions separated into 3 distinct groups, while cell co-culture had less impact. Analysis of transcriptomic signatures showed that many genes were modulated by the matrix with additional genes influenced under flow conditions. Several of these genes, classified as transporters, are of particular importance when using this model to assess drug uptake and safety implications. Co-culture regulated some interesting genes, but fewer than anticipated. Preliminary experiments are underway to monitor glucose uptake and transport between tubules under different conditions.

Conclusion

We have developed a medium throughput system in which matrix and flow modulate gene expression. This system can be used to study the physiology of molecular cross-talk between cells. Ongoing analysis will further consider relevance to human physiology.
P0662A NOVEL NOMOGRAM TO PREDICT THE RELIABILITY OF ESTIMATED GLOMERULAR FILTRATION RATE FORMULA IN ONCOLOGY PATIETNS
Authors: Cheng Yichun , Huang Liu , Han Yunfeng , Vanisha Chummun , Ge Shu-wang , Xu Gang
Published: June 2020

Background and Aims

Formulae of estimated glomerular filtration rate (eGFR) based on serum creatinine (Scr) are routinely used in oncology patients, however, they are inaccurate in some populations. Our aim was to identify population characteristics where eGFR formulae performed poorly and thereby build a nomogram to predict the reliability of estimates.

Method

Measured GFR (mGFR) using isotope from 444 oncology patients were compared with eGFR from four formulae (Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration and Wright). Multivariate logistic regression was applied to identify characteristics associated with inaccurate eGFR and construct a predictive nomogram.

Results

The Cockcroft–Gault formula exhibited estimates with lowest bias and highest precision. Nonetheless, it was still unreliable in a relevant proportion of patients. The percentage of patients within 30%, 20%, and 10% of the accurate percentage error (APE) was seen in only 62.8%, 47.7% and 24.8% of patients respectively. Inaccuracy was found in overweight patients or in patients with BUN/Scr ratio greater than 20 or with eGFR greater than 120 ml/min. A novel nomogram was constructed to help oncologists to predict the risk of inaccuracy of eGFR. The calibration curve showed good agreement.

Conclusion

Our results suggest that all eGFR formulae tend to overestimate the eGFR in oncology patients. Our nomogram may assist oncologists in decision-making when mGFR is needed.
P0681TIMP-1 DEFICIENCY DAMPENS RENAL GALECTIN-3 RESPONSE IN DIABETES
Authors: Kokeny Gabor , Popovics Helga , Mikone Krisztina , Mozes Miklos
Published: June 2020

Background and Aims

Overexpression of tissue inhibitors of metalloproteases (TIMPs) are a hallmark of renal fibrosis, and elevated TIMP-1 has been reported in experimental and human diabetes. Also, renal galectin-3 (Lgals3) overproduction might link macrophages to fibrosis progression. However, the possible association of renal Lgals3 with TIMP-1 in diabetes is still unclear. Thus, we investigated nephropathy and renal Lgals3 in type-1 diabetic wild type and TIMP-1 knockout (KO) mice.

Method

Type-1 diabetes was induced in 6 week-old male TIMP-1 KO (DM KO, n=7) and wild type (DM, n=6) mice with daily intraperitoneal streptozotocin (50 mg/kg/day) injections for 5 consecutive days. Non-diabetic controls (CTL, n=5) were injected with vehicle. Fasting blood glucose was monitored, and after 8 weeks kidneys were analyzed for histology and mRNA expression.

Results

Both diabetic groups developed similar hyperglycemia (CTL: 6±2, DM: 29±5, DM KO: 33±7 mmol/l, p<0.01). However, serum creatinine was elevated only in wild type diabetic mice (CTL: 9±2, DM: 47±28, DM KO: 11±2 ug/dl, p<0.001). Histology revealed significant tubular damage in DM mice (score: CTL: 0.4±0.1, DM: 2.3±0.2, DM KO: 1.6±0.2, p<0.05), accompanied by 10-fold lipocalin-2 (CTL: 1.0±0.3, DM: 10.9±6.2, DM KO: 3.3±1.7, p<0.05) and 2-fold collagen-1 overexpression (CTL: 1.0±0.2, DM: 1.9±0.7, DM KO: 1.2±0.4, p<0.05), practically absent in diabetic KO kidneys. Similarly, TIMP-1 deficiency was associated with twofold decrease in renal Lgal3 (CTL: 1.0±0.6, DM: 2.0±1.1, DM KO: 0.8±0.3, p<0.05) and tenfold decrease in CCL2 expression levels (CTL: 1.0±0.3, DM: 20.2±4.2, DM KO: 2.3±1.5, p<0.01) as compared to DM.

Conclusion

In our model of type-1 diabetes, TIMP-1 deficiency attenuated the development of renal fibrotic and inflammatory response by reducing galectin-3 and CCL2 (MCP-1), preserved tubular integrity and renal function. This might implicate TIMP-1 to be a possible therapeutic target in the future.
P0682PSYCHOLOGICAL STRESS AS A RISK FACTOR FOR RENAL FUNCTION DECLINE
Authors: Kim Jaeyoung , Kim Jihye , Jung Chan-Young , Jo Wonji , Park Jung Tak
Published: June 2020

Background and Aims

Accumulating evidences propose that psychological stress leads to changes in biological processes or behavioral patterns that effects disease risks. Supporting this possibility, recent animal experiments and population studies show a probable link between psychological stress and cardiovascular and metabolic diseases. However, the association between psychological stress and kidney function is not well elucidated yet.

Method

Data were retrieved from a prospective community-based cohort study (Korean Genome and Epidemiology Study). Psychological distress was assessed as the primary exposure using PWI-SF (psychosocial well-being index short form) scores. The decline rate of estimated glomerular filtration rate (eGFR) over time was calculated using linear regression analysis of serial eGFR measurements for each subject. Rapid eGFR decline was defined as an average decline in eGFR ≥3 ml/min/1.73 m2 per year.

Results

In total, 6,968 participants were analyzed. During a median follow-up of 10.49 years, rapid eGFR decline was observed in 886 (12.7%) participants. When the participants were categorized into tertiles according to PWI-SF score, rapid eGFR decline was more prevalent in the highest PWI-SF score group (14.0%) compared to the lowest PWI-SF score group (11.1%). Multivariate logistic regression analyses revealed that the risk of rapid eGFR decline was significantly increased in the highest PWI-SF score group compared to the lowest group (odds ratio, 2.04; 95% confidence interval 1.27-3.27). When PWI-SF score was treated as a continuous variable, each 1 standard deviation increase in PWI-SF was associated with a 12% increased risk of rapid eGFR decline.

Conclusion

The amount of psychological stress was significantly associated with an increased risk of rapid renal function decline in participants with normal renal function.
P0696CHARACTERIZATION OF A DAPA-CKD-LIKE POPULATION USING A CONTEMPORARY US HEALTHCARE SYSTEM: COHORT CHARACTERISTICS AND CLINICAL OUTCOMES
Authors: Olufade Tope , Lamerato Lois , Garcia Sanchez Juan Jose , Jiang Like , Huang Joanna , Nolan Stephen
Published: June 2020

Background and Aims

The Sodium Glucose Co-Transporter 2 inhibitor (SGLT-2i) class of drugs have demonstrated significant cardiorenal benefits in patients with type 2 diabetes (T2D), including reducing the composite renal outcome of significant eGFR decline, End Stage Kidney Disease (ESKD) or renal death in patients with T2D and preserved renal function and also in patients with overt Diabetic Kidney Disease. In addition, SGLT-2i have proven to have beneficial effects on cardiovascular (CV) outcomes in patients with heart failure with reduced ejection fraction (HFrEF) independent of glycaemic status. The DAPA-CKD Trial (A study to evaluate the effect of dapagliflozin on renal outcomes and CV mortality in patients with CKD) is the first SGLT-2i renal outcome trial to test the efficacy and safety of an SGLT-2i, dapagliflozin, in patients with diagnosed CKD with and without T2D.

In order to appropriately evaluate the future results and aid clinical interpretation of the DAPA-CKD trial, the present study assessed the renal and CV outcomes of a “DAPA-CKD-like population” (eGFR 25-75ml/min/1.73m2 and UACR 200-5000mg/g) in a contemporary US real healthcare system.

Method

Administrative data from the Henry Ford Health System was used to identify persons with CKD stages 2 through 4 between 2006 and 2016 based on eGFR lab reading (n=38,376). Exclusions included no confirmatory eGFR > 90 days from index date, death within 30 days, history of renal transplant, and evidence of renal replacement therapy, or progression to CKD stage 5 during the baseline period (6 months pre or post index date). Within that cohort, 17,742 had eGFR (25-75ml/min/1.73m2) and 9,177 had a UACR (0-5000 mg/g) within 12 months of index date. Additional exclusions included type 1 diabetes (n=2,546), lupus nephritis (n=1) and polycystic kidney disease (n=20). Patients were followed through December 31st, 2018.

Results

Of the 6,557 patients that met the eligibility criteria and were included in the study cohort, the mean age was 62.9 years and 46.2% were male. The population was stratified by UACR (0-<30, 30–199, 200–5,000mg/g). Across all outcomes assessed, the clinical outcomes were highest in the DAPA-CKD-like cohort (UACR 200-5000mg/g) (HF 36.1%; MI 11.3%, Stroke 8.9%; ESKD 18.6%; Mortality 18.5%; see Figure 1). The greatest increase was observed for renal outcomes particularly ESKD, increasing from 0.9% (UACR 0-<30mg/g) to 3.4% (UACR 30-199mg/g) to 18.6% (UACR 200-5000mg/g).

Conclusion

In a contemporary US healthcare system, there remains significant adverse renal, CV and mortality outcomes among patients fitting the DAPA-CKD study inclusion criteria. These results highlight the unmet need existing for additional therapies to delay disease progression and improve patient outcomes and survival in this population.
P0704PROTECTIVE EFFECT OF DUAL ACTING LIGAND TARGETING A2A AND A3 ADENOSINE RECEPTOR ON OBSTRUCTION-INDUCED KIDNEY INJURY IN MICE
Authors: Pak Eun Seon , Lee Jiyoun , Ha Hunjoo
Published: June 2020

Background and Aims

Chronic kidney disease (CKD) has been a worldwide public health problem, and the current therapeutic strategies against CKD are limited. Adenosine plays a significant role in protection against cellular damage in the regions with high metabolism. All 4 known subtypes of adenosine receptors such as A1AR, A2AAR, A2BAR, and A3AR are expressed in the kidney. While A2AAR agonists protect the kidney against inflammation, our previous study has demonstrated that an A3AR regulator effectively prevented diabetic kidney injury. The present study examined the preventive effect of LJ-4459, a newly synthesized dual acting ligand targeting A2AAR and A3AR, on unilateral ureteral obstruction (UUO)-induced kidney injury in mice.

Method

UUO surgery was performed in 6-week-old male C57BL/6 mice. LJ-4459 was administered by oral gavage at dose of either 1 or 10 mg/kg per day. The control group was administered an equal volume of vehicle (0.25% carboxymethyl cellulose).

Results

LJ-4459 effectively prevented tubular damage presented by significantly reduced NGAL expression and tubular necrosis in the obstructed kidney. LJ-4459 effectively inhibited elevation of a-SMA, collagen I, and collagen IV protein expression as well as picro sirius red staining in the obstructed kidney, suggesting antifibrotic effect of LJ-4459. LJ-4459 also inhibited inflammation as estimated by significantly reduced F4/80 positive-stained area and protein expression of p-NF-kB and ICAM1.

Conclusion

The results suggest that LJ-4459 may become a potential therapeutic agent against interstitial fibrosis, a common feature of CKD.
P0715SUPERB MICROVASCULAR IMAGING: AN INNOVATIVE ULTRASOUND TECHNIQUE FOR EARLY DETECTION OF KIDNEY DYSFUNCTION AND RENAL FIBROSIS
Authors: Abu-rahme Munai , Artul Suheil , Kinaneh Safa , Abassi Zaid , Armaly Zaher
Published: June 2020

Background and Aims

Superb microvascular imaging (SMI) is an innovative ultrasound image processing technique that shows greater details and better visualization of small branching vessels by using a unique algorithm that offer high frame rates, less clutter, and fewer tissue motion artefact that were not previously possible without the use of contrast agent. We assume that SMI provides superb information regarding the severity of chronic kidney disease (CKD) and associated the fibrotic changes. Therefore, the present study was designed to examine whether SMI can detect early renal fibrosis as compared with the reference standard renal biopsy.

Method

The SMI was performed in patients (n=47) with CKD stage 2-4, where some of them underwent biopsy proven chronic renal dysfunction and fibrosis as part of the diagnosis and therapeutic judgment as needed. In addition, biochemical tests were performed in order to obtain the serum parameters of kidney function (BUN, Serum Creatinine), a urine collection test for the assessment of proteinuria, and estimation of GFR by MDRD formula in patients with CKD of various severity and healthy controls (n=17). In addition, all patients underwent SMI US imaging, where vascularity is expressed as SMI index (low index reflects low vascularity/fibrosis and vice versa).

Results

As expected, SMI vascular index was significantly lower in CKD patients as compared with healthy control (72.2±3.1 Vs 49.1±2.6 %, P<0.001). Interestingly, strong correlation between the SMI index and eGFR was found among the CKD patients (r=0.595, P<0.001). Similarly, a keen correlation was found between the SCr and SMI index of the diseased subjects. Among those who underwent renal biopsy, SMI index corresponds with the histological alterations as well as CKD staging.

Conclusion

This study demonstrates that in patients with CKD of various stages, SMI imaging may be utilized as a simple and practical method for evaluation of the chronic renal morphological changes and for the differentiation between CKD grades.
P0718HEALTH CARE COSTS IN CHRONIC KIDNEY DISEASE: A LONGITUDINAL STUDY FROM THE PIRP COHORT
Authors: Rucci Paola , Gibertoni Dino , Voci Claudio , Fantini Maria Pia , Mandreoli Marcora , Santoro Antonio
Published: June 2020

Background and Aims

Health care costs in patients with chronic kidney disease (CKD) vary widely according to patients’ severity. In patients followed up in a community-based project, it is of interest to determine cost variations over time, as a result of treatment and CKD progression. The aim of the study was to estimate the costs incurred by the health care system for CKD patients in an Italian region.

Method

Patients recruited in the Emilia-Romagna (Italy) PIRP project in the years 2007-2014 with CKD stage 3a to 5 were included in the study. Patients were stratified at baseline into 7 groups at different risk of progression according to the CT-PIRP classification (Rucci et al., A clinical stratification tool for chronic kidney disease progression rate based on classification tree analysis, NDT 2014). To calculate the annual medical costs, we multiplied the number of services used by the respective unit cost. Per capita costs were obtained dividing overall costs by person-years. We used DRG tariffs as a proxy of costs for hospital admissions, the regional nomenclator for outpatient visits and lab tests, and cost unit for prescribed drugs. Mixed effects generalized linear models were used to estimate the annual direct costs of CT-PIRP groups, adjusted for calendar year of entry in PIRP and local health authority of residence.

Results

The study cohort includes 7737 CKD patients, aged 73.2±11.6 years, 64.5% males, mostly in CKD stage 4 (3136, 40.5%) and 3b (2799, 36.2%); 697 patients (9.0%) entered the study at stage 5. The CT-PIRP classification and frequency distribution is shown in Tab.1. After 4 years, 5017 (64.8%) were still alive, 1743 (22.5%) died, 546 (7.2%) were on ESKD and 422 (5.5%) were lost. The overall direct costs of patients while still enrolled in the PIRP project decreased from 36.89 million € in the first year to 32.22 in the fourth year, while the per capita annual median costs were stable around 2200 €. The cost breakdown showed a decrease of hospitalization and drugs costs and an increase in specialty visits costs (Fig.1).

The model-estimated average annual costs were significantly higher for proteinuric, low GFR patients of CT-PIRP groups 2 and 3 (7239 € and 8825 € respectively), while non-diabetic, younger patients of group 5 determined a significantly lower burden (3350 €).
P0721PPAR-GAMMA ACTIVATION INHIBITS TGF-BETA INDUCED RENAL COMPLEMENT AND GALECTIN-3 EXPRESSION IN VIVO AND IN VITRO
Authors: Popovics Helga , Mikone Krisztina , Mozes Miklos , Kwon JiYeon , Hansmann Georg , Kokeny Gabor
Published: June 2020

Background and Aims

Reduced peroxisome proliferator-activated receptor-γ (PPARγ) activity has been observed in chronic kidney disease and fibrosis. We have recently shown that the PPARγ agonist pioglitazone dampens TGF-β induced renal pro-fibrotic transcription factors in vivo. Several studies have shown that renal complement expression is associated with fibrosis, yet the role of galectin-3 (Lgals3) remains controversial. However, the effect of PPARγ agonists on renal complement (C3, C4b) and Lgals3 expression has not been studied. We investigated how pioglitazone treatment affects TGF-β–driven renal inflammatory molecule expression in transgenic mice and in primary tubular epithelial cell (PTEC) culture.

Method

Ten weeks-old male C57Bl6 control (CTL) and TGF-β transgenic mice (with elevated circulating TGF-β1 level) were divided in two sets. The first set of mice received regular chow (CTL and TGFβ, n=4/group). The second set of mice were treated orally with pioglitazone (20mg/kg/day) for 5 weeks (CTL+Pio and TGFβ+Pio, n=5/group), when the kidneys were analyzed for mRNA and protein expression. PTEC were isolated from 4-weels old CTL mouse kidneys using graded sieving and characterized by immunoblot. Isolated cells were maintained in DMEM/F12 medium supplemented with 2% FBS and insulin/transferrin/selenium, and cells of passage 4-6 were used in triplicate for the experiments. Cells were treated for 24h with 10 ng/ml TGF-β and/or 5 µM pioglitazone, then mRNA expression levels were assessed. Statistical significance was verified using Mann-Whitney test.

Results

TGFβ kidneys depicted 13-fold and 4-fold overexpression of C3 and C4b mRNA (p<0.05), respectively, accompanied by a 1.7-fold Lgals3 expression (p<0.05). Oral treatment with the PPARγ agonist pioglitazone inhibited the TGF-β1 induced overexpression of C3, C4b, Lgals3, as well as IL-6 and CCL2 (MCP-1) mRNA (p<0.01). This was accompanied by reduced alfa-SMA (Actca2) and fibronectin mRNA expression. Renal Lgals3 showed significant correlation with alfa-SMA expression (p<0.01, see Figure). PTEC treated with TGF-β also depicted increased C3aR, alfa-SMA and collagen-1 mRNA expression by 1.7-fold, 2-fold and 2.1-fold, respectively (p<0.01), that were reduced to control levels by pioglitazone treatment (p<0.05).

Conclusion

Our data indicate that PPARγ activation exert strong anti-inflammatory effects in the renal tubular epithelial cells, implicating its possible therapeutic benefit by attenuating renal EMT and fibrosis in CKD patients.