bluuebunny/crossref_metadata_2025 huggingface dataset:
P0508NEPHROTIC SYNDROME DUE TO HEAVY AND LIGHT CHAIN (AHL) AMYLOIDOSIS
Authors: Markóth Csilla , Bidiga László , Pettendi Piroska , Rékasi Éva , Ujhelyi László , Balla Jozsef , Mátyus János
Published: June 2020

Background and Aims

Kidney diseases with heavy chain deposition are rare, including AHL amyloidosis also. The mutation/deletion of the constant domain (CH1/CH2) of the heavy chain causing high tissue affinity seems most likely in its pathogenesis. The very low serum level is responsible for the difficult diagnosis, which is often based on kidney biopsy or laser microdissection / mass spectrometry.

Method

Case study of a 76-year-old male patient, examined in January, 2019.

Results

Besides treatment for Ménière syndrome and benign prostatic hyperplasia there was no other important event in patient’s history. Significant proteinuria and microscopic haematuria were observed from May 2016, but eGFR was 70 ml/min/1,73 m2 at that time. By April, 2018 nephrotic range proteinuria (10 g/day) with full nephrotic syndrome developed. Screening tests for cancer were negative. Despite symptomatic treatment, half year later eGFR decreased to 27 ml/min/1,73 m2, therefore he was referred to nephrology. Serum protein electrophoresis verified IgG lambda (8,1 g/l) and free lambda (0,5 g/l) monoclonal light chains, and in addition the possibility of IgG heavy chain accumulation. Urine electrophoresis showed also IgG lambda (1720,1 mg/l), and free lambda light chain (552,1 mg/l) monoclonality. Serum free lambda and kappa light chain ratio was 0,06, complement serology was normal. Kidney biopsy was done, which showed IgG heavy and light chain restriction, Congo red stain positivity and apple green birefringence under the polarized microscope in the expanded mesangium, in the interstitium and along the tubular basement membrane and the blood vessels. The electron microscope detected fibrillary deposits (10 nm) in the same structures, therefore diagnosis of AHL amyloidosis was established. He had no extrarenal symptoms. Bone marrow aspiration flow cytometry verified 1,11% plasma cell accumulation, 93% of them had pathological immunphenotype. Bone marrow morphology assay showed 30-40% plasma cell infiltration, and chromosome assay detected monoallelic deletion of IgH and MAF and gains of 1q region, suggesting myeloma multiplex in the background of AHL amyloidosis. VCD (bortezomib-cyclophosphamide-dexamethason) treatment was started, so far he has received 8 cycles. He is asymptomatic, proteinuria decreased, kidney function stabilized, eGFR 23 ml/min/1,73 m2.

Conclusion

only about 20 cases of AHL amyloidosis have been reported in the literature so far. In the context of longstanding kidney failure with nephrotic syndrome, we should consider renal disease associated with plasma cell dyscrasia also. If case of an AHL amyloidosis caused by myeloma multiplex, effective anti-plasma cell therapy can improve the hematological and the renal outcome.
P0539NICOTIFLORIN ATTENUATES RENAL ISCHEMIA/REPERFUSION INJURY THROUGH REDUCING CELL APOPTOSIS
Authors: Wang Lin , Xu Yan
Published: June 2020

Background and Aims

Renal ischemia/reperfusion (I/R) is the main cause for acute kidney injury, Nicotiflorin can ameliorate ischemia/reperfusion injury in other organs, just like in cerebral ischemic damage. Therefore, this article intends to explore whether Nicotiflorin has protective effects on renal tubular epithelial cell after ischemia-reperfusion. On the one hand, We use C57 mice to establish the Nicotiflorin group, DMSO group, AKI group, sham group and control group to investigate whether Nicotiflorin can ameliorate ischemia-reperfusion injury of kidney. In other hand, we use CCK8 to explore the optimal concentration of Nicotiflorin in renal tubular epithelial cells and find optimal hypoxia oxygenation time, in order to analysis the influence of Nicotiflorin. The results indicate that Nicotiflorin can alleviate ischemia-reperfusion injury by reducing apoptosis of renal tubular epithelial cells.

Method

In this study, we investigated the protective mechanism of Nicotiflorin on ischemic acute kidney injury by analyzing gene chip in patients with acute kidney injury and proving in vitro and in vivo experiments. The main methods are as follows: (1) Multiple nucleus ischemia-reperfusion model transcriptase data were selected from the NCBI GEO Datasets database and analyzed to screen out related proteins that may be involved in ischemia-reperfusion kidney injury; (2) The tertiary structure of Nicotiflorin and related proteins was obtained from the SWISS-MODEL database and the PubChem compound database. The molecular docking between protein and Nicotiflorin was performed using Autodock software, and the binding energy between Nicotiflorin and the selected protein was analyzed to determine Nicotiflorin binds to each other; (3) We set different groups, such as control group, sham group, AKI group, Nicotiflorin group and DMSO group in animals. The blood function was used to detect renal injury related function indicators 24 hours after modeling. Renal tissue samples were collected for real-time fluorescent RT-PCR, Western blotting and histopathological analysis; (4)Renal tubular epithelial cells were treated with different concentrations of Nicotiflorin, CCK8 was screened for the most appropriate concentration, and the hypoxic and reoxygenated cells were intervened at the concentration to explore the interaction between Nicotiflorin and the docking protein, and to observe the protective mechanism of Nicotiflorin on the kidney

Results

Conclusion

Nicotiflorin binds to ATF3 and promotes the expression of Cyr61 through protein interactions to improve renal ischemia-reperfusion injury.
P0550ISCHEMIC PRECONDITIONING ATTENUATES RENAL ISCHEMIA-REPERFUSION INJURY THROUGH ACTIVATING THE NRF2/HO-1 PATHWAY ENHANCED AUTOPHAGY
Authors: Hwang Jeong Kye , Choi HyunSu , Kim Mi-hyeong
Published: June 2020

Background and Aims

Ischemic preconditioning (IPC), which is a brief and nonlethal episode of ischemia, confers protection against subsequent ischemia-reperfusion (I/R) through the up-regulation of endogenous protective mechanisms. Recent studies have reported that the activation of autophagy is associated with IPC. However, the underlying mechanisms still need to be determined. In this study, we investigated the role of IPC in renal I/R injury and demonstrated that IPC could ameliorate renal I/R injury by activating the Nrf2/HO-1 pathway and induction of autophagy.

Method

In order to gain insights into IPC–induced alterations at the cellular level, an in vitro model for IPC was designed using the human proximal tubule epithelial cell line HK-2. In vitro I/R was induced by layering mineral oil (for 60 min) over a thinfilm of media covering the cells followed by 120 min of reperfusion in normal media. IPC was performed by a 10-min period of incubation of cells under mineral oil followed by a 30-min recovery period prior to the 120 min reperfusion. To further determine the role of autophagy in IPC-induced renoprotection, the cells were treated with bafilomycin A1 (200 nM), prior to I/R injury. In a renal I/R injury model, mice were subjected to 30 min of renal ischemia followed by 24 h of reperfusion. IPC was produced by 5 min of ischemia followed by 10 min of reperfusion prior to sustained ischemia.

Results

We found that IPC significantly attenuated I/R-induced kidney injury and suppressed oxidative stress and inflammatory responses. IPC also increased LC3-II and decreased SQSTM/p62 and cleaved caspase-3 during renal I/R injury, as well as increased the number of intracellular double-membrane vesicles in injured renal cells. IPC-induced renal protection was efficiently attenuated by pretreatment with Bafilomycin A1 (0.3 mg/kg, IP). Pretreatment with IPC also dynamically affected the expression of Nrf2/HO-1 signaling components. The beneficial effects of IPC were abolished by Brusatol (2 mg/kg, IP), potent inhibitors of Nrf2. Moreover, the Nrf2 agonist t-BHQ (50 mg/kg, IP) showed similar activity as IPC.

Conclusion

In summary, the present study shows that Nrf2 plays a critical role in regulating the HO-1 production induced by I/R. Also, upregulation of Nrf2 expression might represent one of the major mechanisms whereby IPC confers protection against I/R-induced kidney injury. The beneficial effects of IPC could be attributed to its antioxidative stress and anti-inflammatory properties
P0560POST-DISCHARGE FOLLOW UP AFTER AKI. AN EXTERNAL VALIDATION AND DECISION CURVE ANALYSIS OF TWO RISK MODELS
Authors: Sawhney Simon , Tan Zhi , Black Corri , Hemmelgarn Brenda , Marks Angharad , Mclernon David , James Matthew
Published: June 2020

Background and Aims

There is limited evidence to inform which people should receive follow up after AKI and for what reasons. Here we report the external validation (geographical and temporal) and potential clinical utility of two complementary models for predicting different post-discharge outcomes after AKI. We used decision curve analysis, a technique that enables visualisation of the trade-off (net benefit) between identifying true positives and avoiding false positives across a range of potential risk thresholds for a risk model. Based on decision curve analysis we compared model guided approaches to follow up after AKI with alternative strategies of standardised follow up – e.g. follow up of all people with AKI, severe AKI, or a discharge eGFR<30.

Method

The Alberta AKI risk model predicts the risk of stage G4 CKD at one year after AKI among those with a baseline GFR>=45 and at least 90 days survival (2004-2014, n=9973). A trial is now underway using this tool at a 10% threshold to identify high risk people who may benefit from specialist nephrology follow up. The Aberdeen AKI risk model provides complementary predictions of early mortality or unplanned readmissions within 90 days of discharge (2003, n=16453), aimed at supporting non-specialists in discharge planning, with a threshold of 20-40% considered clinically appropriate in the study. For the Alberta model we externally validated using Grampian residents with hospital AKI in 2011-2013 (n=9382). For the Aberdeen model we externally validated using all people admitted to hospital in Grampian in 2012 (n=26575). Analysis code was shared between the sites to maximise reproducibility.

Results

Both models discriminated well in the external validation cohorts (AUC 0.855 for CKD G4, and AUC 0.774 for death and readmissions model), but as both models overpredicted risks, recalibration was performed. For both models, decision curve analysis showed that prioritisation of patients based on the presence or severity of AKI would be inferior to a model guided approach. For predicting CKD G4 progression at one year, a strategy guided by discharge eGFR<30 was similar to a model guided approach at the prespecified 10% threshold (figure 1). In contrast for early unplanned admissions and mortality, model guided approaches were superior at the prespecified 20-40% threshold (figure 2).

Conclusion

In conclusion, prioritising AKI follow up is complex and standardised recommendations for all people may be an inefficient and inadequate way of guiding clinical follow-up. Guidelines for AKI follow up should consider suggesting an individualised approach both with respect to purpose and prioritisation.
P0575TIME TO NEPHROLOGY CONSULTATION AND MORTALITY RISK IN COMMMUNITY ACQUIRED AKI
Authors: Acosta-Ochoa Isabel , Coca Armando , Lorenzo Arturo , Mendiluce Alicia
Published: June 2020

Background and Aims

Acute Kidney Injury (AKI) is the most frequent cause of Nephrology consultation. Although time to nephrology consultation (TNC) has been object of study, few works focus on its influence on in-hospital mortality in patients with community acquired AKI (CA-AKI).

Method

We picked cases of CA-AKI, and divided individuals in dead in-hospital and survivors. We analyzed clinical and epidemiological variables, and categorized AKI with the KDIGO-2012 stages. We compared clinical outcomes and influence of TNC in mortality.

Results

We included 420 patients, 92 (22%) in the mortality group. These individuals were older, had higher Charlson’s Index, were hospitalized in critical care units, and were classified in KDIGO-2012 Stage 3 more frequently (Table 1). TNC was higher in the dead patients and was significantly associated with mortality HR 1.28 (CI 95% 1.03-1.55, P=0,009). In KDIGO Stages 1 and 2 TNC was shorter in the survivors group, and in Stage 3 we found no differences. In general wards (medical and surgical), TNC was higher in the mortality group, with no differences in the consults from critical units (Table 1). In the survival curves we observe a decline in survival in patients with TNC ≥2 days since admission (Figure 1).

Conclusion

We found that a longer TNC was associated with a poorer survival. This finding would indicate that earlier nephrology attention could impact in-hospital mortality. We interpret the longer TNC in less severe AKI stages as a warning of the unawareness and late recognition of AKI in other specialties. More well designed and larger studies are needed to prove that electronic alerts offer a survival benefit.
P0583RED CELL DISTRIBUTION WIDTH PREDICTS CONTRAST-INDUCED NEPHROPATHY IN PATIENTS UNDERGOING ENHANCED COMPUTED TOMOGRAPHY
Authors: Li Youqi , Shi Yongjun , Li KeXuan , Shen Jian , Xiao ShaoBing
Published: June 2020

Introduction

Contrast-induced nephropathy (CIN) is an major complication of enhanced computed tomography(CT) procedures.Development of CIN after enhanced CT may lead to worse clinical outcomes. Thus, markers are used to identify the risk of patients ,who undergo enhanced CT with CIN.Red cell distribution width(RDW) is a measurement of erythrocyte variability and heterogeneity, and it is obtained routinely in standard complete blood cell counts.Current researches indicate that RDW is the independent predictor of AKI after patients receiving percutaneous coronary intervention (PCI).However, the correlation of RDW and CIN after enhanced CT are yet to be determined.In this study we investigated whether RDW levels correlate with development of CIN in patients after enhanced CT.

Method

A total of 633 patients undergoing enhanced CT from June 2015 to June 2018 at Huizhou Central Municipal Hospital were enrolled. Patients were divided into CIN group and no-CIN group. The diagnostic criteria for CIN is an increase in serum creatinine(Scr) more than 44.2μmol/L or 25% higher than the baseline value within 72 hours after contrast administration.

Results

The study population consisted of 633 patients ,25(3.95%) patients developed into CIN. Patients who got CIN were older and had a higher prevalence of active smoking compared with those were without CIN. The range of the baseline serum creatinine and red cell distribution width was significantly higher in CIN groups.However,baseline eGFR,red blood cell counts,hemoglobin and albumin levels were significantly lower in patients who developed CIN(all P<0.05).Multivariate logistic regression analysis revealed that baseline RDW level(OR=2.325,95% CI 1.521∼3.556,P<0.001),albumin(OR=0.888,95%CI 0.803∼0.982, P=0.021)and eGFR(OR=0.921,95%CI 0.849∼0.999,P=0.047)were independent risk factors in the development of CIN in patients after enhanced computed tomography.The area under the ROC curve for RDW was 0.803(95% CI 0.706∼0.900,p<0.001),and an RDW of 13.85% or higher predicted CIN with a sensitivity of 72% and specificity of 75.80%(Figure 1).

Conclusion

Increased baseline of RDW, decreased eGFR and lower albumin are independently related with a higher risk of CIN in patients undergoing enhanced CT.RDW is possibly a predictive biomarker for the early diagnosis of CIN.
P0584A COMPARATIVE STUDY ON THE INCIDENCE OF CONTRAST INDUCED NEPHROPATHY FOLLOWING INTRA-ARTERIAL VERSUS INTRAVENOUS CONTRAST ADMINISTRATION
Authors: Moideen Adel
Published: June 2020

BACKGROUND

Contrast-induced nephropathy (CIN) / Contrast induced-acute kidney injury (CI-AKI), defined as a relative increase of ≥25% or an absolute increase of ≥0.5 mg/dL in S.Cr levels assessed at 48 hours post procedure, is a well described following an administration of Intra-arterial (IA) iodinated contrast agent, but its occurrence after Intravenous (IV) contrast is being questioned.

AIMS

To compare the incidence of CIN following IV and IA contrast procedures and to identify its risk factors.

METHOD

This is a prospective, single center study of 774 patients (449 males and 325 females with mean age of 48.85 ± 14.05 years) who underwent contrast studies with nonionic, low-osmolar iodinated contrast agent (Iomeprol) via IV and IA routes were included in the study. We recorded baseline characteristics along with laboratory parameters; underlying renal injury risk factors; contrast administration volume, type, and route of administration; incidence of CIN and requirement of renal replacement therapy (RRT). Univariate and multivariate models were used to determine predictors of CIN.

RESULTS

The total incidence of CIN was 14.85% (115 patients). Baseline eGFR was lower for patients undergoing intra-arterial contrast procedures (66.02 ± 23.70 ml/min/1.73m2 vs 71.31±24.07 ml/min/1.73m2, p=0.002). Simple logistic regression showed a statistically significant difference in the rate of CIN in patients who received IV vs. IA iomeprol (6.2% vs 25.1%). The total risk of RRT was 1.7% with the incidence being more in the IA group than the IV group (3.1% vs 0.5%, p=0.005). Advanced age, dehydration and hypotension, CCF, anemia, proteinuria, diabetes mellitus, preexisting renal disease (i.e. baseline serum creatinine>1.5mg/dl), baseline eGFR<60ml/min/1.73m2), use of nephrotoxic antibiotics and route of contrast correlated significantly with CIN. Proteinuria ≥1 g/day and hypoalbuminemia was significantly higher in the intra-arterial group than the intravenous group (p=0.001).

CONCLUSION

We found that administration of both IV and IA iodinated contrast agents is associated with a risk of CIN with a significant higher risk of CIN as well as RRT following IA contrast. Proteinuria may be a new risk factor for the development of CIN.
P0596LONG TERM FOLLOW UP OF CONTRAST INDUCED ACUTE KIDNEY INJURY IN A TERTIARY JORDANIAN HOSPITAL
Authors: Oweis Ashraf , Alshelleh Sameeha
Published: June 2020

Background and Aims

Contrast induced acute kidney injury (CI-AKI) is potentially preventable and reversable cause of acute kidney injury (AKI).

Multiple factors are associated with the development of CI-AKI, some are modifiable such as drugs, type and amount of contrast, others are not like preexisting chronic kidney disease (CKD), heart failure.

Though it’s usually a reversable condition, there is increasing evidence of adverse long-term outcome (increasing morbidity and mortality).

The aim of this study to evaluate the long-term outcome of CI-AKI on mortality, the rate of re-catheterization and the development of CKD.

Method

In a prospective observational study design, we evaluated all patients admitted for cardiac catheterization between June 2015 and January 2016. A total of 326 patients signed the consent to participate in the study.

Patients had blood withdrawn 48 hours after the procedure for their creatinine level.

CI-AKI was defined as an increase in serum creatinine by >25% or 44 mmol/l from the baseline level (48-72) hours after contrast administration, without any other obvious cause.

We used only low osmolality contrast media (CM) (Lopamidol, Bayer, Germany).

Of the 326 patients included, 202 patients had their second sample taken, thus, were eligible to continue in the study.

Patients were followed for at least 3 years.

Results

The incidence of CI-AKI was 14.8% (30 patients), for baseline characteristics see table 1.

At the end of follow up; a total of 7 patients died; 6 in the non CI-AKI group vs. 1 in the CI-AKI group (p= ), though the difference between the mean eGFR was not statistically significant by the end of the follow up (85.4ml/min for the CI-AKI vs. 79.2ml/min for the other group (P=0.31)), but the decline in eGFR for the CI-AKI was significant ( a drop from 105.4 ml/min to 85.4ml/min vs. 85.2ml/min to 79.2ml/min, P=0.004).

The rate of re-catheterization was not statistically significant between the two groups (61 for the non CI-AKI vs. 12 for the other group; P=0.63).

Conclusion

CI-AKI carries a higher negative long-term effect on eGFR, while did not affect the mortality in our cohort.
P0619POINT OF CARE CREATININE FOR EARLY DIAGNOSIS OF COMMUNITY ACQUIRED ACUTE KIDNEY INJURY IN NIGERIA. TECHNOLOGY EVALUATION AND DESIGN OF QUALITY IMPROVEMENT PROJECT
Authors: Poulikakos Dimitrios , Erekosima Ibi , Emem-Chioma Pedro , Fakrogha Prelador , Oko-Jaja R I , Utein Nkoyo , Wokoma F S , David-West Manda , Ndu Victor , Ugochukwu Duru Stephen , Ohiri John , Harry Agba M , Kalra Philip A , Lewis David
Published: June 2020

Background and Aims

Acute Kidney Injury (AKI) in low- and middle-income countries is mostly a community-acquired potentially reversible syndrome and has high morbidity and mortality. Due to limited laboratory infrastructure diagnosis of AKI is often delayed until life threatening complications have developed and dialysis treatment is largely unavailable. Decisions for hospital referral from primary health care centers and triage decisions for hospital admission are not based on laboratory results in Port Harcourt Nigeria. To address the need for early diagnosis and treatment of AKI we established a collaboration between the Renal Unit of the University of Port Harcourt Teaching Hospital, Primary Health Care Board Rivers State and the Renal Department of Salford Royal NHS Foundation Trust, aiming at the evaluation of the use of point of care (POC) Creatinine (Cr) for early detection and management of community acquired AKI.

Method

The first stage of the project evaluated the accuracy of POC Cr technology. Following informed consent patients underwent concurrent measurement of Cr using the central laboratory (Lab) assay (Jaffe) from a venous sample and a point of care Cr measurement using a capillary sample (fingerstick) with the NOVA Stasensor Xpress Cr analyser. Pearson Correlation and Bland-Altman plots were used to assess correlation and agreement between the two methods. During the second stage, the results were discussed at a focused AKI workshop and guidance for the use of POC Cr was developed.

Results

During the first phase 96 concurrent POC Cr capillary and venous Lab Cr samples were analysed. Mean age was 49±14 years and 66 subjects were females. POC Cr values were 127±122 umol/l and Lab Cr values were 100 ±85 umol/L, mean positive bias of 27.2±47.94 umol/L. Overall, correlation between POC Cr and Lab Cr was very good, with Pearson correlation r=0.956) Figure 1A. All 4 out of 96 values that were outside the limits of agreement (set at mean ±2 standard deviations) were for Lab Cr values >200 umol/L. A Bland-Altman Plot is presented for paired samples with Lab Cr values <200 umol/L (Figure 1B).
P0645EDARAVONE MAY DECREASE THE INCIDENCE OF CONTRAST INDUCED ACUTE KIDNEY INJURY (CI-AKI)
Authors: Ivanov Dmytro , Ivanova Mariia , Burlachenko Illia
Published: June 2020

Background and Aims

Edaravone is a low-molecular-weight antioxidant drug targeting peroxyl radicals of reactive oxygen species and has shown clinical efficacy in patients with acute ischemic stroke.

We have conducted a multicenter open prospective randomized controlled study to evaluate the efficacy of edaravone in preventing AKI in patients with CKD 3b-4 stages.

Method

The study included 2 groups of patients aged 46 to 68 (55 ± 3): group A (n=16) with CKD stage 3b or 4 (eGFR EPI 32 ± 4 ml/min) that received intravenous edaravone 30 mg bid on 0,1,2 day of contrast media infusion and control group B (n=20) with CKD stage 3b or 4 (eGFR EPI 33 ± 3 ml/min) with no edaravone intervention during CT coronarography. Patients of both groups received intravenous hydration with 0.9% sodium before CT. Primary endpoint: CIN onset in 48 hours after contrast media infusion and need for RRT. Secondary endpoint: serum potassium level above 5.5 mmol/l.

Results

CIN onset was obtained in 4 patients of group A and 12 patients of group B (p>0,05, RR 0.417, RRR 0.583, RD 0.350, NNT 2.857). Other results are presented in table
P0653THE USE OF URINARY EPIDERMAL GROWTH FACTOR FOR EVALUATION OF KIDNEY GRAFT FUNCTION
Authors: Chan Joe , Eide Ivar Anders , Jenssen Trond Geir , Waldum-Grevbo Bård , Tannæs Tone Møller , Svensson My
Published: June 2020

Background and Aims

Follow-up after kidney transplantation requires repeated, reliable glomerular filtration rate (GFR) measurements. Measured GFR (mGFR), using urinary or plasma clearance of an exogenous filtration marker such as iohexol, provides precise measurements but are expensive and time consuming. Instead, estimated GFR (eGFR) based on serum creatinine is most commonly used in clinical practice. Epidermal growth factor is produced in the kidney and promotes tubular cell regeneration and recovery of kidney function after injury. Low levels of urinary epidermal growth factor (uEGF) are linked to progression of chronic kidney disease and increased risk of kidney graft failure. The aim of this study was to investigate uEGF as an additional marker to evaluate graft function in kidney transplant recipients (KTRs).

Method

Participants in the Omega-3 fatty acids in Renal Transplantation (ORENTRA) trial were examined with mGFR by iohexol clearance at 1 year after kidney transplantation. The concentration of iohexol in serum was measured 3 and 4 hours after iv injection. On the same day, fasting blood and urine samples were obtained in the morning. Serum creatinine was measured and eGFR calculated with the MDRD formula. uEGF and a pre-specified selection of inflammation and fibrosis markers were measured with multiplex immunoassay technique and normalized with urinary creatinine. Principal component analysis (PCA) was used to explore clustering of markers. Correlations were calculated with Pearson’s correlation coefficient R.

Results

Fifty-nine participants had complete measurements of mGFR (57.2 ± 15.2 mL/min/1.73m2), eGFR (68.6 ± 23.0 mL/min/1.73m2) and uEGF. The correlation between mGFR and eGFR was strong (R=0.783, P<0.001). Measurements of uEGF had a coefficient of variation below 10% for all participants, with a mean value of 22.0 ± 12.1 μg/g creatinine. There was a significant correlation between mGFR and uEGF (R=0.678, P<0.001). The component score of uEGF and eGFR calculated with PCA (74% of variance) had the strongest correlation with mGFR (R=0.845, P<0.001).

Conclusion

Combining uEGF with eGFR into one component score by PCA gives a greater correlation with mGFR compared to eGFR alone in this cohort of KTRs. These findings need to be validated in other patient populations.
P0660COMPARISON OF BIAS AND ACCURACY OF CREATININE AND CYSTATIN C-BASED CKD-EPI EQUATIONS FOR GFR ESTIMATION
Authors: Sun Ling , Zou Luxi , Nicholas Susanne B , Lu Yan , Sinha K Satyesh , Hua Ruixue
Published: June 2020

Background and Aims

Glomerular filtrate rate (GFR) is a key index of kidney function, and directly measured GFR (mGFR) is the gold standard, but it is invasive and costly. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have been widely used to estimate GFR with high accuracy. However, the comparative accuracy of estimated GFR (eGFR) using creatinine and cystatin C in CKD-EPI equations remains unclear. This study aimed to systematically assess the bias and accuracy of eGFR using equations of CKD-EPIcrea, CKD-EPIcys, and CKD-EPIcrea/cys in adult populations relevant to primary health care.

Method

Pubmed, Web of Science, EMBASE, and the Cochrane Library were searched from inception until December 2019 for studies comparing mGFR with simultaneous eGFR using CKD-EPI calculated from standardized serum creatinine and cystatin C. We pooled data on bias (difference between mGFR and eGFR), accuracy (P30; proportion of eGFR within 30% of mGFR), and correlation coefficient (R; between mGFR and eGFR), using random-effects models.

Results

A total of 35 studies with 23,667 participants, which reported the data on the bias, and/or P30, and/or R were included (Figure 1). The difference in the bias of eGFR using CKD-EPIcys was 4.84 mL/min/1.73 m2 (95% CI, 1.88∼7.80) lower than using CKD-EPIcrea, and 1.50 mL/min/1.73 m2 (95% CI, 0.05∼2.95) lower than using CKD-EPIcrea/cys. These gaps increased in subgroups of low mGFR (<60 mL/min/1.73 m2) (Figure 2). CKD-EPIcrea/cys eGFR achieved the highest accuracy (Figure 3), 7.50% higher than CKD-EPIcrea (95% CI, 4.81∼10.18), and 3.21% higher than CKD-EPIcys (95% CI, -0.43∼6.85) (Figure 4); and the best correlation with mGFR, with Fisher's z transformed R of 1.20 (95% CI, 0.89-1.50) (Figure 5).

Conclusion

CKD-EPIcrea/cys and CKD-EPIcys equations gave less bias and more accurate estimates of mGFR than CKD-EPIcrea equation. Our findings validated and strengthened the use of cystatin C alone or in combination with creatinine in CKD-EPI equations. More variables and coefficients could be added in CKD-EPI equations to achieve less bias and more accuracy in future research.
P0688GREATER MUSCLE STRENGTH IS ASSOCIATED WITH LOWER RISK OF CHRONIC KIDNEY DISEASE
Authors: Jhee Jong Hyun , Lee Gang Yoon , Yoon Songuk , Choi Hoon Young , Park Hyeong Cheon
Published: June 2020

Background and Aims

Frailty is a known risk factor for chronic disease and mortality. However, the association between frailty assessed by hand grip strength (HGS) and chronic kidney disease (CKD) among adults has not been elucidated. This study evaluated the association between muscle strength and the risk of CKD.

Method

Data were retrieved from a nationwide cohort study (Korean National Health and Nutrition Examination Surveys VI-VII, 2014-2017) and participants aged 40 to 80 years were included in the study analysis (male=6,660, female=8,195). HGS was measured using digital hand dynamometer and normalized to body mass index (BMI). The association between the risk of CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 or the presence of proteinuria) and quartile of HGS per BMI was evaluated among male and female subjects.

Results

The mean age was 58.8 ± 11.6 years and mean eGFR level was 88.2 ± 18.7 mL/min/1.73 m2. The mean levels of HGS per BMI were 1.5 ± 0.3 and 0.9 ± 0.2 in male and female subjects, respectively. Those in higher quartile of HGS per BMI showed lower prevalences of advanced CKD stages than lowest quartile among both male and female subjects. When univariable logistic regression analysis for the risk of CKD was performed, higher quartile of HGS per BMI was significantly associated with lower risk of CKD in both male and female subjects. After adjustment for confounding factors including age, systolic blood pressure, smoking and alcohol intake, education and income levels, history of hypertension, diabetes, or arthritis, physical activity, baseline eGFR, total cholesterol, hemoglobin, and daily protein intake, the higher quartile of HGS per BMI were associated with lower risk of CKD in both male and female subjects (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.49-0.88 in Q4; OR, 0.64; 95% CI 0.49-0.83 in Q3 in male; OR, 0.59; 95% CI, 0.43-0.81 in Q4; OR, 0.61; 95% CI, 0.47-0.80 in Q3; OR, 0.70;95% CI, 0.55-0.90 in Q2 in female, Q1 as reference group). These associations were consistent when the HGS per BMI was treated as continuous variable that 34% and 54% of risk was reduced as 1 m2 increase in male and female subjects.

Conclusion

Greater muscle strength normalized to BMI is associated with lower risk of CKD in adults. These findings suggest that frailty in adults is an important risk factor for CKD development.
P0692NON-PROTEINURIC DIABETIC NEPHROPATHY AND THE RISK OF MORTALITY IN PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD)
Authors: Santoro Antonio , Gibertoni Dino , Mandreoli Marcora
Published: June 2020

Background and Aims

Diabetes (DM) is considered one of the major causes of progressive CKD even when it does not induce proteinuria. However, the condition of diabetes without proteinuria is not universally considered to be accompanied by a reduced survival of the patient.

The aim of the study was to verify whether non-proteinuric diabetic CKD patients presented a different risk of mortality compared to non-diabetic and non-proteinuric CKD patients.

Method

Two matched cohorts of CKD patients were obtained from the PIRP database, that contains clinical and laboratory data from about 30,000 patients who have been followed since 2005 in the Emilia-Romagna Region (Italy). In the period 2005-2017, 2651 subjects with DM2 in CKD-EPI stages 3a to 5 and without evidence of proteinuria that entered the PIRP register surveillance were matched with as many non-diabetics patients without proteinuria by gender, age class, CKD stage. To assess the presence of a differential mortality risk in diabetic patients, a multivariable Cox regression model was fit, adjusted for several potential clinical confounders, using multiple imputation to estimate missing data and taking into account patients’ clusterization into nephrology units to correct standard error estimates.

Results

In the 13 years examined, deaths were more frequent in patients with DM2 (38.7% vs 30.7%, p<0.001) as well as CV events before and after PIRP enrolment (52.2% vs. 42.9%, p<0.001), while dialysis initiation rate was lower (Fig.1). Furthermore, in diabetics there was a higher percentage of overweight or obese patients (38.9% vs 19.7%, p<0.001), lower levels of hemoglobin (12.3 g/dl vs 12.7 g/dl, p<0.001) and higher values of triglycerides 163 mg/dl vs 132 mg/dl, p<0.001). 10-year survival was significantly lower in diabetics (22.9% vs 36.4%, log-rank test: p <0.001, Fig.1). Multiple Cox regression identified a higher mortality risk for diabetics (HR = 1.326, p<0.001) after adjusting for sex, age, baseline eGFR, hemoglobin level, BMI, smoking status, presence of tumors or cardio-vascular comorbidities and cohort effect (5-years period indicator).

Conclusion

In patients with CKD and non-proteinuric nephropathy, concurrent diabetes was associated to a higher frequency of CV events and represented an independent risk factor for overall mortality. Thus, in diabetic patients, even in absence of proteinuria, we have to intensify therapeutic strategies to control the so-called CV intermediate risk factors (tobacco use, low-density lipoprotein cholesterol, hypertension, hypercoagulable states, obesity, etc.)
P0698STRESS RELATED DISORDERS AND THE RISK OF KIDNEY DISEASE: A MATCHED COHORT STUDY BASED ON THE STOCKHOLM CREATININE MEASUREMENTS (SCREAM) PROJECT
Authors: Su Guobin , Song Huan , Lanka Vivekananda , Liu Xusheng , Fang Fang , Valdimarsdóttir Unnur A , Carrero Juan Jesus
Published: June 2020

Background and Aims

Psychiatric reactions to life stressors are common in the general population and may increase the risk of acute (AKI) and chronic kidney disease (CKD). The aim of this study is to evaluate the association between stress related disorders and subsequent risk of AKI or CKD progression.

Method

Population-matched retrospective cohort study conducted in the Stockholm CREAtinine Measurement project (SCREAM), Sweden from 2006 to 2012. The cohort included 31,137 exposed patients with stress related disorders (ie, posttraumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions, defined by 10th international Classification of diseases, ICD-10: F43) and known kidney function (estimated glomerular filtration rate, eGFR), and 117,144 unexposed matched by age, sex and eGFR category. The primary outcome was CKD progression, defined as a sustained relative decline in eGFR of more than 40% or commencement of kidney replacement therapy. The secondary outcome was acute kidney injury (AKI), defined by death or hospitalization attributed to AKI or detected transient plasma creatinine elevations (KDIGO classification). Conditional Cox models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

During a medium follow-up of 3.3 years and compared with the unexposed population, patients with stress related disorders were at increased risk of CKD progression (HR 1.16, 95% CI 1.04-1.30) and AKI (HR 1.17, 95% CI 1.01-1.37). While the relative risk of CKD progression remained constant over follow-up, the association with AKI was most evident during the first year after stress diagnosis (HR: 1.31, 95% CI 1.04-1.66), disappearing thereafter. Among 9 prespecified subgroups, there was suggestion of heterogeneity with possible lack of association in patients with psychiatric comorbidity.

Conclusion

Exposure to a stress related disorder was associated with the long-term risk of CKD progression and the short-term risk of AKI. Studies are needed to better understand underlying mechanisms.
P0701LONG-TERM RETROSPECTIVE OBSERVATION STUDY TO EVALUATE EFFECTS OF ADIPONECTIN ON SKELETAL MUSCLE IN KIDNEY TRANSPLANT RECIPIENTS
Authors: Adachi Hiroki , Fujimoto Keiji , Kagaya Yu , Kumano Syo , Fujii Ai , Matsuura Kazutoshi , Okada Keiichiro , Okino Kazuaki , Kengo Furuichi , Yokoyama Hitoshi
Published: June 2020

Background and Aims

Although it is reported that chronic kidney disease participates some roles in progression of sarcopenia, mechanisms of the progression of sarcopenia are unclear so far. In this observational study, we focused on serum adiponectin levels, that is a marker of metabolic syndrome, cardiovascular disease, and skeletal muscle mass in patients with kidney transplantation.

Method

Fifty-one patients who underwent renal transplantation at our hospital in and after 1998 (31 males and 20 females; aged 29-52 years at the time of transplantation) were retrospectively examined the relationships between the psoas muscle index (PMI), intramuscular adipose tissue content (IMAC), serum adiponectin fractions (high-/low-molecular-weight), and new-onset diabetes after transplantation (NODAT).

Results

Age at kidney transplantation negatively correlated with PMI before transplantation and positively correlated with IMAC before transplantation (rS=-0.427, p<0.01; rS=0.501, p<0.01, respectively). Both in one and five years after transplantation, PMI was higher than before transplantation (p<0.01). In contrast, IMAC transiently decreased one year after kidney transplantation, but subsequently recovered five years after kidney transplantation. Multivariate analyses identified that the mean increases of high-molecular-weight adiponectin concentrations was exacerbating factor for the mean change in PMI (p=0.003). Moreover, the mean increases of PMI and IMAC were exacerbating factors for the newly development of post-transplantation diabetes mellitus.

Conclusion

PMI increased associated with high-molecular-weight adiponectin levels after renal transplantation. In addition, PMI increased suppressed the development of NODAT.
P0720CARVEDILOL AND NON-DIHYDROPYRIDINE CALCIUM CHANNELS BLOCKERS DELAY THE PROGRESSION OF CHRONIC KIDNEY DISEASE BEYOND ACE-INHIBITION IN KWAZULU-NATAL (SOUTH AFRICA)
Authors: Reddy Verushka , Assounga Alain
Published: June 2020

Background and Aims

Chronic kidney disease (CKD) is on the rise worldwide. It is associated with increased morbidity and mortality and places a huge burden on cost constrained health systems in developing countries such as South Africa. ACE inhibition is well established as major factor of reduction of the decline of renal function. The aim of this study to evaluate carvedilol, non-dihydropyridine calcium channel blockers (NDCCB) as potential renal protection factor beside ACE inhibition.

Method

This is a retrospective cohort study using the medical records of 300 patients attending the outpatient renal clinic department at Inkosi Albert Luthuli Central Hospital for the period January 2007 – December 2009. The average patient age was 43 years. The patients were followed up for 24 months following their first clinic visit. Socio-demographic (age sex, residence) and clinical characteristics including eGFR, blood pressure, BMI (body mass index), proteinuria, haemoglobin, cholesterolemia, were recorded. Treatments received including ACE inhibitors, carvedilol, non-dihydropyridine calcium channel blockers (NDCCB), Beta blockers were also recorded. Patients were divided into 2 outcome categories, according to changes in eGFR (estimated glomerular filtration rate): patients with eGFR decline of 1ml/min/year or less and those with accelerated eGFR decline (>1ml/min/year). Data analysis using SPSS version 23 (IBM) comprised of descriptive tests and logistic regression analysis (expressed as OR (odd ratio) and confidence interval) for the study of the association of above characteristics with patients’ outcome.

Results

ACE inhibition was used by 92% of patients. The use of carvedilol and NDCCB was associated with a reduction of the decline of eGFR with OR: 0.144[0.207-0.953] p=0.037 and OR: 0.543[0.329-0.884], p=0.016 respectively. No significant association was found between eGFR change and daily proteinuria or cholesterolemia. The aetiology of the chronic kidney disease did not affect rate of progression of eGFR. In addition, the rate of progression was not dependent on eGFR.

Conclusion

These results suggest that beyond ACE inhibition, the control of BMI, and use of carvedilol and NDCCB further delay the progression of chronic kidney disease in KwaZulu-Natal.
P0722VITAMIN D-DEFICIENT RATS RECOVER RENAL ALTERATIONS AFTER VITAMIN D REPLACEMENT FOLLOWING ISCHEMIA-REPERFUSION INJURY
Authors: Seguro Antonio Carlos , Santos Michele S , Denelle Bernardo Desiree Rita , Canale Daniele , Shimizu Maria Heloisa Massola , Volpini Rildo Aparecido , De Braganca Ana Carolina
Published: June 2020

Background and Aims

Several studies have been linking vitamin D deficiency (VDD) as a non-traditional risk factor to acute kidney injury (AKI). It has been shown that VDD associated with AKI potentiates the injury and may accelerate the progression of kidney disease. Conversely, some lines of evidence have been describing that vitamin D sufficiency can be considered as a renal protective factor. Thus, we aimed to verify the effect of vitamin D replacement (R) on the renal disease progression post ischemia-reperfusion injury (IRI) in vitamin D deficient rats.

Method

We performed bilateral 45 min IRI on day 30 in all animal groups. Male Wistar rats were randomized into three groups: 1- IRI (fed a standard diet for 120 days); 2- VDD+IRI (fed a vitamin D-free diet for 120 days); and 3- VDD+IRI+R (fed a vitamin D-free diet for 30 days and just after IRI, on day 31, we reintroduced the standard diet for more 90 days). We evaluated inulin clearance (Cin); mean arterial pressure (MAP); renal blood flow (RBF); plasma levels of Vitamin D2+D3 [25(OH)D] and Parathormone (PTH) by ELISA. In addition, we performed histomorphometrical studies for CD3+ cells, fibronectin and vimentin as well as the fractional interstitial area (FIA). Moreover, we run qPCR studies and immunoblotted for vitamin D receptor (VDR) and Klotho. All the results are described in table 1.

Results

Vitamin D replacement restored the plasma levels of 25(OH)D and PTH in VDD+IRI+R group. Also, VDD+IRI+R presented an improvement of renal function and hemodynamic parameters. In addition, we observed more evident alterations in tubulointerstitial compartment, featuring interstitial expansion (renal fibrosis and inflammatory cell infiltrates) and fibronectin and vimentin expression in VDD+IRI rats. These alterations were recovered by vitamin D replacement. Concerning VDR and Klotho data, our results revealed a decreased expression of these targets in VDD+IRI group. On the other hand, vitamin D replacement retrieved the expression of VDR and Klotho.

Conclusion

Our study suggests that vitamin D replacement improved the recovery of renal function, hemodynamics, inflammatory and morphological alterations. In addition, vitamin D replacement was able to reestablish the expression of VDR and Klotho in IRI-AKI associated with vitamin D deficiency. Thus, it is recommendable that vitamin D levels should be observed as well as its reposition should be taken into account in renal patients.
P0725INDICATORS OF AGING KIDNEY, MEDIATORS OF EXTRACELLULAR MATRIX REMODELING
Authors: Cha Dae , Han Jee Young , Park Jeong Hoon , Kang Young Sun , Ghee Jung Yeon , Yoo Ji Ae , Cha Jin Joo
Published: June 2020

Background and Aims

The main characteristics of aging kidney are age dependent glomerulosclerosis, tubular atrophy and interstitial fibrosis, therefore aging is now considered as an independent risk of chronic kidney disease. Extracellular matrix accumulation (ECM) is an early indicator of aging. Therefore in order to search for early indicator of aging kidney, we examined the expressions of regulators of ECM in the kidney in biologically aging and disease aging mice.

Method

C57BL/6 mice were studied at 2, 6, 12, 24 months of age, and leptin-deficient db/db mice were studied at 3, 6, 9 months of age. Gene and protein expressions of the kidney were examined as well as kidney injury markers in blood and urine.

Results

As expected, the biologically aging B6 mice exhibited progressive microalbuminuria during the lifespan. Systemically, the aging mice showed decreased levels of adiponectin, insulin and cholesterols. In the kidney tissue, proinflammatory and profibrotic gene expressions, in association with its regulators were significantly increased in age-dependent manners. At 24months, MCP-1, PAI-1, Collagen IV, MMP7, MMP9, angiotensin II, FGF23 and β-catenin gene expressions were significantly increased, whereas MMP2 and Snail, a direct activator of MMP-2 were significantly decreased. Protein expressions showed similar patterns. In high glucose condition, several markers showed diverse features in aging mice. As compared to db/m control, gene expressions of proinflammatory, profibrotic molecule as well as its regulators were all significantly increased in diabetic condition. Angiotensin II, FGF23, MCP-1, MMP7 and MMP9, TIMP-1 were significantly upregulated in diabetic kidney according to ages and interestingly Klotho was significantly downregulated in aged diabetic kidney. Snail and MMP2 showed no significant differences.

Conclusion

MMPs are involved in the crosstalk of the cells and surrounding extracellular matrix and can be considered as the marker of aging kidney. The regulators of ECM matrix seems to be different according to its’ pathological conditions. Human clinical data is needed to render the clinical significance.