bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO012IS IT SAFE TO USE INTERLEUKIN-2 RECEPTOR ANTAGONIST INDUCTION THERAPY IN 2DR MISMATCH RENAL TRANSPLANTS IN TACROLIMUS ERA?
Authors: Ali Hatem Kaies Ibrahim Elsayed , Daoud Ahmed , Mohamed Mahmoud , Soliman Karim 
Published: June 2020

Abstract

Background and Aims
2DR HLA mismatch indicates high immunological risk renal transplant. Induction therapy with rabbit Anti-thymocyte Globulin (r-ATG) and IL-2 Receptor Antagonist (IL-2RA) resulted in marked reduction of acute allograft rejection rate and improved graft survival. However, the outcomes in 2DR (HLA-DR) mismatched renal transplant recipients (RTRs) in the era tacrolimus-mycophenolate mofetil maintenance immunosuppression remains understudied.

Method
Using data from the United States organ procurement and transplantation network, all 2 DR mismatched RTRs with panel reactive antibodies &lt;20% maintained on tacrolimus and mycophenolate mofetil immunotherapy between 2000 and 2017 were retrospectively reviewed. Data including age, sex, gender, ethnicity, functional status, diabetes, body mass index, cold ischemia time, number of previous transplants, panel reactive antibodies, donor type, donor age, HLA-mismatches, number of acute rejection episodes, induction therapies, maintenance immunotherapy, recipients and graft survival were collected. Based on induction therapies administered, RTRs were divided into 2 groups: (r-ATG) and IL-2RA groups. Poisson regression analysis was used to assess effect of induction therapies on acute rejection episodes. Cox hazard regression analysis was used to assess effect of different induction therapies on patient and graft survival

Results
3379 patients received IL2-RA while 3677 patients received ATG for induction. There were no significant differences between both groups in terms of acute rejection episodes (95% CI ranges from 0.95 to 1.068, P=0.805), graft survival (95% CI: 0.91 - 1.06, P=0.712), or patient survival (95% CI: -0.949 - 1.12, P=0.43) .

Conclusion
This study revealed no significant difference in acute rejection episodes, patient or graft survival when utilizing ATG vs IL-2RA in 2DR HLA mismatched renal transplant recipients with PRA&lt;20%, in the tacrolimus-based maintenance immunosuppression era. Therefore, IL2-RA is a safe induction therapy in this group of patients and non-inferior to –ATG induction therapy.
MO013PATERNAL SAFETY OF THE USE OF MYCOPHENOLIC ACID BY KIDNEY TRANSPLANT RECIPIENTS. RESULTS OF THE EMVARON STUDY
Authors: Martin-Moreno Paloma Leticia , Sánchez-Fructuoso Ana I , Mazuecos Auxiliadora , Mir Marisa , López López Isabel , González-Rinne Ana , Coca Armando , Ridao Natalia , Rosalía Valero , Ventura Galiano Ana , Toapanta Néstor , Fernández-Tagarro Ernesto José , Pérez-Mir Mónica , Cruzado-Vega Leónidas , Jimenez Carlos 
Published: June 2020

Abstract

Background and Aims
Mycophenolic acid (MPA) is one of the most used immunosuppressive drugs. It is teratogenic in women with a typical embryopathy profile. Regarding its effect on the children of male kidney transplant recipients, although clinical evidence does not indicate a greater risk of malformations, the European Medicines Agency and the Spanish Agency for Medicines and Health Products introduced in 2015 the recommendation to use contraceptive methods because of their genotoxic potential.
For this reason, we propose to study the results of the Spanish Kidney Transplant Centers.

Method
Multicenter retrospective observational study in which 15 Kidney Transplant Centers have participated. Of 3934 men ≤ 60 years old that received a kidney transplant between 2000 and 2015, 3023 were contacted, and 159 men who fathered at least one post-transplant pregnancy (total 252 fetuses) were included. We compared the incidence of abortions and live births with malformations among those who received MPA at the time of conception vs. those who did not.

Results
In the 252 fetuses (characteristics in table 1) there was an exitus and no differences were detected in the incidence of abortions between the group exposed to MPA (n = 230) and the unexposed group (n = 22), 11.3% vs 18.2%, p = 0.31. Among the 221 live-born fetuses, no differences were found in congenital malformations between the group exposed to MPA (n = 203) and the unexposed (n = 18) 4.9% vs. 16.7%, p = 0.07. Among the malformations described, the typical embryopathy profile of the MPA was not found.

Conclusion
According to the data of this retrospective national multicenter study, the use of MPA in male kidney transplant recipients does not cause a greater number of abortions or congenital malformations.
For these reasons, and given the evidence also published by other groups, it seems necessary to reevaluate the recommendation given on contraception in men treated with MPA.
MO016MYOCARDIAL INFARCTION IN THE PIVOTAL STUDY OF IV IRON IN HAEMODIALYSIS: A PRE-SPECIFIED SECONDARY ANALYSIS
Authors: Petrie Mark , Jhund Pardeep , Robertson Michele , Mark Patrick , Connolly Eugene , Macdonald Michael , White Claire , Reid Chante , Anker Stefan D , Bhandari Sunil , Farrington Kenneth , Kalra Philip A , Tomson Charles R V , Wheeler David , Ford Ian , McMurray John , Macdougall Iain 
Published: June 2020

Abstract

Background and Aims
Coronary artery disease is prevalent in patients with CKD but how often a myocardial infarction (MI) occurs in patients on maintenance haemodialysis, and the prognostic importance of these MIs, is uncertain. The PIVOTAL trial investigated the effects of proactive high-dose versus reactive low-dose intravenous (IV) iron in incident haemodialysis patients. We now report the rates of MI, sub-types of MI, and the prognostic importance of these MIs, as well as the effect of high versus low dose iron on this event.

Method
This was a pre-specified secondary analysis of 2141 patients enrolled in the PIVOTAL trial. All potential endpoints in the trial, including MIs were adjudicated by a blinded Endpoint Adjudication Committee. The outcomes of time-to-first MI (type 1 or type 2 MI, STEMI or NSTEMI) and the composite outcome of MI and death due to MI were reported. In addition to time-to-first MI, we also analysed recurrent events, to account for the cumulative burden of events over time, as well as case-fatality related to MI. The time-to-event analyses of the primary, secondary and post hoc outcomes were performed in the intention-to-treat population using Cox proportional hazards regression, with treatment group as the only explanatory variable. The Kaplan–Meier method was used to estimate event rates. Recurrent events were analysed using the proportional-means model of Lin et al. and described in the form of mean frequency functions.

Results
8.4% of patients experienced a MI over a median of 2.1 years follow-up. Rates of type 1 MIs (3.2/100 patient years) were 2.5 times higher than type 2 MIs (1.3/100 patient years). NSTEMIs (3.3/100 patient years) were 6.6 times more common than STEMIs (0.5/100 patient years). Mortality was high after non-fatal MI (30-day and 1-year mortality were 11.3% and 39.8%, respectively). In time-to-first event analyses, proactive high-dose IV iron reduced the rate of non-fatal MI (HR 0.69, 95% CI 0.51-0.93; p=0.01) and the composite endpoint of non-fatal and fatal MI (HR 0.69, 95% CI 0.52-0.93, p=0.015) (Figure) when compared to low dose reactive IV iron. The benefits of a proactive high-dose IV iron strategy were seen in type 1 MIs but not type 2 MIs.

Conclusion
Most MIs in patients on HD were type 1 and NTEMIs. Patients randomised to the high-dose group of PIVOTAL had a substantial reduction in fatal and non-fatal MI compared to those in the low-dose group.
MO031EFFECTS OF PREDICTIVE MODELLING RISK DIRECTED INTERVENTIONS ON HOSPITALIZATION RATES IN HAEMODIALYSIS PATIENTS
Authors: Chaudhuri Sheetal , Rosen Sophia , Larkin John , Usvyat Len A , Sweet David , Vinson Allison , Johnstone Steinberg Stephanie , Maddux Franklin 
Published: June 2020

Abstract

Background and Aims
End Stage Kidney Disease (ESKD) patients have high hospitalization rates. We have developed and deployed a predictive model to identify in-centre haemodialysis (HD) patients at an increased risk for all-cause hospitalization within the next 12 months. The model was used in a pilot called Dialysis Hospitalization Reduction Program (DHRP) to identify patients predicted to be at risk of &gt;=6 hospital admissions and provide additional interdisciplinary team intervention. We investigated the impact of the DHRP on hospitalization rates in HD patients.

Method
We used data from 45 clinics in South Alabama/Florida Panhandle regions of the United States who participated in DHRP pilot starting January 2016. The predictive model used more than 200 variables to stratify patients as high risk (&gt;=6 admissions), medium high risk (&gt;=3 admissions) and medium low risk (&gt;=1 admission) and low risk (&lt;1 admission). For patients identified at high risk of hospitalization, social workers assessed psychosocial barriers and offered additional psychosocial intervention to target those barriers. Dietitians utilized a high risk assessment looking at weight, nutrition, and access to food and supplements. Resident nurses assessed high risk patients focusing on anaemia, adequacy, access, blood pressure, fluid management, prior hospitalizations, glycaemic control and risk of skin ulcers and blood stream infection Data from patients at the participating clinics was collected and yearly hospital admission and day rates per patient year were calculated 2 years prior to (2014, 2015) and 3 years after (2016-2018) pilot start. Comparison clinics were chosen from neighbouring regions in South and North Florida (43 and 45 clinics respectively).

Results
Over the study period the number of patients ranged from 4661 to 5672 in the DHRP pilot clinics, 5416 to 5947 in South Florida control clinics, and 6087 to 7596 in North Florida control clinics. Hospitalization rates in pilot clinics during the first year of the DHRP remined similar to the rates during the two years preceding the pilot start. In the second and third years of the DHRP, pilot clinics showed reductions in hospital admission and day rates. At control clinics in both regions the hospital admissions and day rates showed increasing trends while DHRP clinics showed decreasing trends over the study period (Figures 1a and 1b).

Conclusion
These findings suggest predictive model risk directed interdisciplinary team interventions associate with lower hospitalization rates in HD patients, compared to controls. Further studies are needed to confirm these results.
MO048MULTICENTRE PROSPECTIVE VALIDATION OF THE URINARY PEPTIDOME-BASED CLASSIFIER CKD273 AS A PREDICTOR OF RENAL FUNCTION DECLINE IN SUBJECTS WITH TYPE 2 DIABETES
Authors: Lindhardt Morten , Tofte Nete , Currie Gemma , Frimodt-Moeller Marie , Von der Leyen Heiko , Delles Christian , Mischak Harald , Rossing Peter , For the PRIORITY Investigators  
Published: June 2020

Abstract

Background and Aims
In the PRIORITY study, it was recently demonstrated that the urinary peptidome-based classifier CKD273 was associated with increased risk for progression to microalbuminuria. As a prespecified secondary outcome, we aim to evaluate the classifier CKD273 as a determinant of relative reductions in eGFR (CKD-EPI) of 30% and 40% from baseline, at one timepoint without requirements of confirmation.

Method
The ‘Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial’ (PRIORITY) is the first prospective observational study to evaluate the early detection of diabetic kidney disease in subjects with type 2 diabetes (T2D) and normoalbuminuria using the CKD273 classifier.

Setting
1775 subjects from 15 European sites with a mean follow-up time of 2.6 years (minimum of 7 days and a maximum of 4.3 years).

Patients
Subjects with T2D, normoalbuminuria and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2. Participants were stratified into high- or low-risk groups based on their CKD273 score in a urine sample at screening (high-risk defined as score &gt; 0.154).

Results
In total, 12 % (n = 216) of the subjects had a high-risk proteomic pattern. Mean (SD) baseline eGFR was 88 (15) ml/min/1.73m2 in the low-risk group and 81 (17) ml/min/1.73m2 in the high-risk group (p &lt; 0.01). Baseline median (interquartile range) urinary albumin to creatinine ratio (UACR) was 5 (3-8) mg/g and 7 (4-12) mg/g in the low-risk and high-risk groups, respectively (p &lt; 0.01).
A 30 % reduction in eGFR from baseline was seen in 42 (19.4 %) subjects in the high-risk group as compared to 62 (3.9 %) in the low-risk group (p &lt; 0.0001). In an unadjusted Cox-model the hazard ratio (HR) for the high-risk group was 5.7, 95 % confidence interval (CI) (3.9 to 8.5; p&lt;0.0001). After adjustment for baseline eGFR and UACR, the HR was 5.2, 95 % CI (3.4 to 7.8; p&lt;0.0001).
A 40 % reduction in eGFR was seen in 15 (6.9 %) subjects in the high-risk group whereas 22 (1.4 %) in the low-risk group developed this endpoint (p&lt;0.0001). In an unadjusted Cox-model the HR for the high-risk group was 5.0, 95 % CI (2.6 to 9.6; p&lt;0.0001). After adjustment for baseline eGFR and UACR, the HR was 4.8, 95 % CI (2.4 to 9.7; p&lt;0.0001).

Conclusion
In normoalbuminuric subjects with T2D, the urinary proteomic classifier CKD273 predicts renal function decline of 30 % and 40 %, independent of baseline eGFR and albuminuria.
MO050GLYCEMIC CONTROL AND THE RISK OF AKI IN PATIENTS WITH DIABETES AND CKD: PARALLEL POPULATION-BASED COHORT STUDIES IN U.S. AND SWEDEN ROUTINE CARE
Authors: Xu Yang , Surapaneni Aditya , Alkas Jim , Chang Alexander , Grams Morgan , Carrero Juan Jesus 
Published: June 2020

Abstract

Background and Aims
Patients with diabetes and chronic kidney disease (CKD) have increased susceptibility to acute kidney injury (AKI), but the underlying mechanisms are not well known. We here explore the association between glycemic control and risk of AKI.

Method
We created two parallel observational cohort studies of Swedish (SCREAM project, Stockholm, 2006-2011) and U.S. (Geisinger Heath system, Pennsylvania, 1996-2018) adult patients with diabetes mellitus and confirmed CKD stages G3-G5. Glycemic control was evaluated through repeated HbA1c measurements, which were categorized into 5 levels of glycemic control intensity, with HbA1c 6-6.9% as referent category, and continuously using cubic splines. We evaluated the association between baseline and time-varying HbA1c levels with AKI (defined as increase in creatinine &gt;=0.3 mg/d over 48 hours or 1.5x creatinine over 7 days) using Cox proportional hazards regression and, in sensitivity analyses, Fine and Gray competing risk models accounting for death.

Results
In the Swedish cohort, there were 13932 patients with median age 76 years, 51% women, median eGFR 50.8 (Interquartile Range (IQR) 41.4-57.1) ml/min/1.73. In the U.S. cohort, there were 26520 patients with median age 71 years, 55% women and 52.1 (IQR 43.4-57.5) ml/min/1.73 m2. During a median of 2.3 and 3.1 years of follow up, 3172 and 8671 AKI events were recorded in the Swedish and US cohorts, respectively. The adjusted association between baseline HbA1c and AKI was similar in both cohorts, with the lowest risk between 6-6.9% and higher risk at higher levels of HbA1c. Compared to baseline HbA1c 6-6.9%, baseline HbA1c&gt;9% associated with a 1.28 fold (95% CI 1.11-1.47) higher risk of AKI in the Swedish cohort, and a 1.14 (95% CI 1.04-1.25) higher risk in the U.S. cohort. Conversely, baseline HbA1c&lt;6% did not associate with AKI. When using time-varying HbA1c, AKI risk was higher for HbA1c&gt;9% (HR 1.18, 95% CI 1.03-1.37 in Swedish cohort and 1.27, 1.17-1.37 in U.S. cohort); AKI risk was also higher for HbA1c&lt;6% in the U.S. cohort (1.12, 1.04-1.19), but not in the Swedish cohort (1.06, 0.97-1.16)).

Conclusion
Higher A1c was associated with AKI in adults with diabetes and CKD, suggesting that better glycemic control may also reduce risk of AKI.
MO052BIOPSY PROVEN KIDEY DISEASES IN TYPE 2 DIABETIC PATIENTS WITH IMPAIRED RENAL FUNCTION
Authors: Paek Jin Hyuk , Kwon Ohyun , Kim Yaerim , Park Woo Yeong , Han Seungyeup , Yoon Jeongsoo , Jin Kyubok 
Published: June 2020

Abstract

Background and Aims
Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus (DM) and the most common cause of end stage of renal disease worldwide. The nature of kidney disease in type 2 DM is more complex than type 1 DM. However, the usefulness of kidney biopsy in type 2 DM is still controversial and there are few reports about the biopsy proven kidney disease, especially in patients with impaired renal function.

Method
We retrospectively reviewed 1454 patients who received native kidney biopsy at Keimyung university Dongsan medical center between 2005 and 2018. Among 1454 patients, 92 patients were diagnosed with type 2 DM before kidney biopsy. Fifty-three patients with impaired renal function (estimated glomerular filtration rate &lt; 60 mL/min/1.73 m2 using Modification of Diet in Renal Disease formula) were finally enrolled in this study. We categorized the pathologic diagnoses as DN, non-diabetic renal disease (NDRD), and NDRD mixed with DN (Mixed).

Results
The mean age at kidney biopsy was 58.4 ± 11.2 and mean eGFR was 28.6 ± 14.6 mL/min/1.73 m2. Nineteen patients (35.8%) had diabetic retinopathy and mean duration of DM before kidney biopsy was 102.1 ± 82.2 months. Of the 53 patients, there were 28 NDRD (52.8%), 18 DN (34.0%), and 7 Mixed (13.2%). Diabetic retinopathy was more common in DN, following Mixed and NDRD (72.2%, 42.9%, and 10.7%, respectively, p &lt; 0.001). Multivariable logistic regression analysis revealed that diabetic retinopathy was significantly associated with DN (OR, 23.672; 95% CI, 4.290-130.609; p &lt; 0.001). In multivariable cox proportional hazard models, creatinine level (HR, 1.779; 95% CI, 1.404-2.255; p &lt; 0.001) and dipstick albuminuria ≥ 2+ (HR, 22.721; 95% CI, 4.670-110.542; p &lt; 0.001) were identified as independent prognostic factors for renal survival.

Conclusion
Kidney disease of type 2 diabetic patients were various and clinical parameters could not completely predict. Kidney biopsy is an important tool for the definite diagnosis and the proper treatment of kidney disease in diabetic patients with impaired renal function.
MO053INHIBITION OF SODIUM PHOSPHATE TRANSPORTER NPT2A IMPROVES EXPERIMENTAL VASCULAR CALCIFICATION AND PHOSPHATE HOMEOSTASIS IN RATS
Authors: Klar Juergen , Anja Giese , Ehrmann Alexander , Thiel Christoph , Riedl Bernd , Eitner Frank 
Published: June 2020

Abstract

Background and Aims
A dysregulated phosphate homeostasis is strongly associated with mortality, cardiovascular events and vascular calcification, particularly in patients suffering from CKD. Inhibition of the tubular phosphate transporter Npt2a provides a novel and unique mechanism to address phosphate homeostasis imbalance and vascular calcification.

Method
Npt2a activity was measured in a cell-based assay, using a stable CHO cell line with inducible Npt2a expression. Male Wistar rats were used for all experiments. Healthy rats were treated orally with BAY 767, a potent Npt2a inhibitor developed at Bayer AG to assess urinary phosphate excretion. Vascular calcification was induced by administration of a pan-FGFR inh. (25mg/kg) for 10 days. Calcium content in the aorta was measured as surrogate for vascular calcification. Blood samples were withdrawn at the end of the study to determine the plasma levels of FGF-23, parathyroid hormone and phosphate with commercially available assay systems according to the manufactures protocols (FGF-23 and PTH: ELISA Kit, Immuntopics; phosphate: Pentra400 system).

Results
BAY 767 was identified as potent Npt2a inhibitor, with an IC50 of 2.9/6 nM on rat/ human Npt2a, respectively, selective over Npt2b, Npt2c and Pit-1. Single dose treatments of healthy rats resulted in a significant, dose-dependent increase in urinary phosphate excretion within 16h. In an experimental vascular calcification model, massive vascular calcification and hyperphosphatemia was induced by daily oral administration of a FGFR inh. Simultaneous treatment with the Npt2a inhibitor BAY 767 significantly inhibited vascular calcification in comparison to untreated rats. In this set-up the plasma phosphate level was increased after 10 days up to 3.7 mmol/L in the FGFR inh. treated group compared to 1.9 mmol/L in control animals, whilst treatment with BAY 767 reduced plasma levels to 2.7 mmol/L. In addition, FGF-23 and PTH were also reduced under compound BAY 767 treatment. However, in the same model 2.2% lanthanum carbonate was not beneficial with respect to vascular calcification.

Conclusion
Our results show for the first time that treatment with a Npt2a inhibitor improves vascular calcification by addressing urinary phosphate excretion and phosphate homeostasis in rats.
Npt2a inhibition may provide a new therapeutic principle for patients suffering from disbalanced phosphate homeostasis and vascular calcifications, including CKD patients.
MO055STABLE CALCIUM ISOTOPES: A NOVEL BIOMARKER OF BONE MINERAL CONTENT IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Shroff Rukshana , Heuser Alex , Lalayiannis Alex , Karabay Bayazit Aysun , Jankauskiene Augustina , BACCHETTA JUSTINE , Askiti Varvara , Schmitt Claus , Mitsioni Andromachi , Crabtree Nicola , Fewtrell Mary , Biassoni Lorenzo , Fischer Dagmar-Christiane , Eisenhauer Anton 
Published: June 2020

Abstract

Background and Aims
In CKD dysregulated calcium (Ca) homeostasis is common and causally associated with reduced bone mineral density (BMD) and vascular calcification. Currently available radiological measures and biomarkers do not allow accurate evaluation of BMD.
The aim of our study was to determine the sensitivity and specificity of stable Ca isotopes in determining bone mineral content.

Method
We measured stable Ca isotopes 44Ca and 42Ca by plasma-ionization mass-spectrometry in blood and urine. The relationship between bone Ca gain and loss is calculated using a compartment model based on Ca kinetics, and expressed as δ44/42Ca. Ca absorption from bones increases δ44/42CaBlood and δ44/42CaUrine, and resorption decreases these fractions.
104 children in CKD4-5 and on dialysis (CKD4-5D), 40 matched controls and 100 adults underwent Ca isotope measurement, bone biomarkers, dual energy x-ray absorptiometry (DXA) and tibial peripheral quantitative CT scan (pQCT), an accurate measure of cortical BMD.

Results
In healthy children the δ44/42CaBlood and δ44/42CaUrine were higher than in adults (p&lt;0.0001), reflecting avid Ca uptake during bone formation. Since urinary Ca excretion is impaired in CKD, δ44/42CaBlood was higher and δ44/42CaUrine lower in children with CKD4-5D compared to controls (p&lt;0.001 for both); Figure 1.
In CKD2-5D δ44/42CaBlood positively correlated with cholecalciferol (p=0.01) and alfacalcidol (p=0.002) doses, implying increased bone Ca uptake when Ca bioavailability is increased. δ44/42CaBlood positively correlated with biomarkers of bone formation (alkaline phosphatase, p=0.05) and negatively with bone resorption markers (PTH, p=0.013; TRAP5b, p&lt;0.001 and CTX, p=0.006). δ44/42CaBlood positively correlated with tibial cortical BMD-Z-score (p=0.006, R2=0.39), and DXA hip BMD-Z-score (p=0.02). On multivariable linear regression analysis significant and independent predictors of tibial cortical BMD-Z-score were δ44/42CaBlood (β=0.68, p=0.006) and PTH (β-0.39, p=0.04), together predicting 67% of the variability in BMD.

Conclusion
Ca isotope ratios provide a novel, non-invasive method of assessing bone mineralization. Further studies are in progress to define optimal levels of δ44/42CaBlood that can guide safe and effective treatment to prevent Ca deficiency or overload.