Dialysis Transplantation Research Articles

Examining the Role of HIPPO/YAP and AMOT Dysregulation and Imbalance in Autosomal Dominant Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder, most commonly caused by mutations in Polycystin-1 and Polycystin-2 (PC1 and PC2), in which many large lumenal cysts develop in the kidney epithelium. The disease is progressive and ultimately leads to renal dialysis and/or kidney transplant given the lack of efficacious therapeutic intervention. Current research has implicated HIPPO/YAP pathway dysregulation and AMOT imbalance following defects in cell-cell adhesion and contact inhibition as the molecular basis for ADPKD. To test this hypothesis as to the minimum cellular changes necessary to produce cystogenesis, the Bacallao lab microinjected normal human kidney epithelial (HK2) cells in order to drive ectopic expression of Cadherin-8 (CAD-8). Our Imaging with confocal microscopy and subsequent image analysis indicates CAD-8, a cadherin abnormally expressed in renal epithelial cells of ADPKD patients, is sufficient to cause formation of cysts albeit with uncharacteristically small lumens compared to typical ADPKD cysts. However, these cells exhibit significantly larger cyst expansion when they are transduced for coexpression of CAD-8 and constitutively active YAP5SA. Cells modified for heterozygosity with respect to a defective PC1 gene (PKD) also exhibited significantly larger lumen cysts when transduced with YAP5SA reinforcing the role of Yap in lumen size control. Finally, PKD cells transduced with AMOTL1 exhibited significantly smaller lumen sizes. AMOTL1 belongs to a family of adapter proteins which bind and inhibit Yap activity thus showing conclusively that positive and negative modulation of Yap activity correlates with cyst lumen size expansion and reduction respectively.
 “This project was funded, in part, with support from the O’Brien Center for Advanced Renal Microscopic Analysis funded, in part by P30 DK079312 from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”

Comparison of Two Methods for Estimation of Glomerular Filtration Rate: Double Plasma Sampling Method and Renography with 99mTc-DTPA

: Glomerular filtration rate (GFR) is a crucial metric that is widely used to evaluate kidney function. A method with high accuracy to estimate GFR is renal scintigraphy using radiopharmaceutical 99m-technetium diethylenetriamine pentaacetic acid (99mTc-DTPA) in SPECT (single-photon emission tomography) system. In addition, there is another method, the double plasma sampling method (DPSM) using the same radiopharmaceutical to determine GFR. This study aims to evaluate and compare GFR results collected from 42 patients by the two methods. The result indicates that the two methods have a high correlation with r = 0.857 and r = 0.711 (p<0.05), respectively in the two patient groups. Therefore, DPSM shows a high possibility for clinical application in certain situations.
 Keywords:
 99mTc-DTPA, glomerular filtration rate, renography.
 References
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208.7: Impact of Preemptive Transplantation on Long-term Outcomes After Simultaneous Pancreas-Kidney Transplantation

Introduction: Simultaneous Pancreas-Kidney transplantation (SPK) is an established treatment option for patients with End-Stage Kidney Disease (ESKD) and diabetes, which provides multiple benefits related to patient survival and cardiovascular risk when compared to kidney transplantation alone. Previous studies have suggested that, also in SPK, a preemptive approach is associated with a significant survival advantage when compared to non-preemptive SPK, although available information on the impact of preemptive SPK on recipient and grafts outcomes remains controversial. Methods: we explore the influence of preemptive SPK on recipient, kidney and pancreas graft survival through a retrospective study with 9690 SPK recipients from the OPTN/UNOS database between 2000 and 2017. An Inverse probability of treatment weighting (IPTW) was used to account for covariate imbalance between preemptive and dialysis transplant recipients. Results: A total of 1796 (19%) patients were preemptively transplanted. After inverse probability of treatment weighting, recipient (97.6%, 91.7% and 78.9% vs 96.6%, 88.8% and 71.8% at 1, 5 and 10 years for preemptive vs dialysis, respectively, P<0.0001) and death-censored kidney graft survival (97.8%, 91.4% and 84.3% vs 97.63%, 88.1% and 75.4% for the preemptive and dialysis at 1, 5 and 10 years, respectively, P<0.0001) were higher for the preemptive group. No differences were observed neither for pancreas graft survival nor patients with Type 2 Diabetes. Dialysis (HR 1.66 [95%CI 1.32–2.09], P<0.0001) and dialysis duration ≥12 months (HR 1.78 [95%CI 1.42–2.24], P< 0.0001) were associated with an increased risk of recipient death and kidney graft failure (HR 1.46 [95%CI 1.18–1.81, P<0.001 and HR 1.53 [95%CI 1.23–1.91], P<0.0001 for dialysis and dialysis duration ≥12 months, respectively). Discussion/Conclusions: In a cohort of 9690 SPK recipients, dialysis was associated with an increased risk of recipient death and kidney graft loss of up to 66% and 46% when compared with recipients transplanted preemptively. Furthermore, this risk increased with the dialysis duration prior to the SPK. Interestingly these results were observed in T1D, but not in T2D recipients. Overall, our findings suggest that preemptive SPK is associated with a significant survival advantage for SPK recipients, thus reinforcing the need for an early referral of ESKD and diabetes patients to be evaluated as potential SPK recipients.

Lifestyle behaviors associated with the initiation of renal replacement therapy in Japanese patients with chronic kidney disease: a retrospective cohort study using a claims database linked with specific health checkup results

BackgroundChronic kidney disease (CKD) is an independent risk factor for progression to an end-stage renal disease requiring dialysis or kidney transplantation. We investigated the association of lifestyle behaviors with the initiation of renal replacement therapy (RRT) among CKD patients using an employment-based health insurance claims database linked with specific health checkup (SHC) data.MethodsThis retrospective cohort study included 149,620 CKD patients aged 40–74 years who underwent a SHC between April 2008 and March 2016. CKD patients were identified using ICD-10 diagnostic codes and SHC results. We investigated lifestyle behaviors recorded at SHC. Initiation of RRT was defined by medical procedure claims. Lifestyle behaviors related to the initiation of RRT were identified using a Cox proportional hazards regression model with recency-weighted cumulative exposure as a time-dependent covariate.ResultsDuring 384,042 patient-years of follow-up by the end of March 2016, 295 dialysis and no kidney transplantation cases were identified. Current smoking (hazard ratio: 1.87, 95% confidence interval, 1.04─3.36), skipping breakfast (4.80, 1.98─11.62), and taking sufficient rest along with sleep (2.09, 1.14─3.85) were associated with the initiation of RRT.ConclusionsAmong CKD patients, the lifestyle behaviors of smoking, skipping breakfast, and sufficient rest along with sleep were independently associated with the initiation of RRT. Our study strengthens the importance of monitoring lifestyle behaviors to delay the progression of mild CKD to RRT in the Japanese working generation. A substantial portion of subjects had missing data for eGFR and drinking frequency, warranting verification of these results in prospective studies.

Chronic kidney disease and cognitive impairment.

Chronic kidney disease (CKD) affects 25% of people over the age of 70. Neurocognitive disorders (NCDs) are frequent in patients with CKD and affect 30% to 60% of patients treated by haemodialysis. The link between CKD and NCD is explained by common risk factors, such as hypertension and diabetes, but also by CKD-specific risk factors through vascular, degenerative, and toxic mechanisms. In patients with non-dialysed CKD, albuminuria is more strongly linked to the occurrence of NCD than glomerular filtration rate. Vascular dementia is the main cause of NCDs in patients with CKD, but the incidence of Alzheimer's disease has also been found to be higher in patients with end-stage renal disease (ESRD) than in the general population. Executive functions, orientation and attention are the most frequently affected cognitive domains in patients with CKD. The occurrence of NCDs in older patients with CKD could be prevented by controlling blood pressure or by using anticoagulant drugs in the case of atrial fibrillation, which is particularly frequent in patients with CKD, in order to prevent cerebrovascular lesions. Nephrological care could also influence the occurrence of neurological complications. Anticholinesterase drugs and memantine should be used with caution in patients with CKD, as most of these drugs accumulate due to a low glomerular filtration rate. Due to the poor prognosis of patients with NCD and ESRD treated by dialysis or kidney transplantation, a cognitive assessment should be proposed in older patients with severe CKD in order to discuss the initiation and type of renal replacement therapy with both patients and caregivers.

Dental health assessed using panoramic radiograph and adverse events in chronic kidney disease stage 4-5 patients transitioning to dialysis and transplantation-A prospective cohort study.

Oral health could potentially be a modifiable risk factor for adverse outcomes in chronic kidney disease (CKD) patients transitioning from predialysis treatment to maintenance dialysis and transplantation. We aimed to study the association between an index of radiographically assessed oral health, Panoramic Tomographic Index (PTI), and cardiovascular and all-cause mortality, major adverse cardiovascular events (MACEs) and episodes of bacteremia and laboratory measurements during a three-year prospective follow-up in CKD stage 4-5 patients not on maintenance dialysis at baseline. Altogether 190 CKD stage 4-5 patients without maintenance dialysis attended panoramic dental radiographs in the beginning of the study. The patients were followed up for three years or until death. MACEs and episodes of bacteremia were recorded during follow-up. Laboratory sampling for C-reactive protein and leukocytes was repeated tri-monthly. PTI was not associated with baseline laboratory parameters or C-reactive protein or leukocytes examined as repeated measures through the 3-year follow-up. During follow-up, 22 patients had at least one episode of bacteremia, but only 2 of the bacteremias were considered to be of oral origin. PTI was not associated with incident bacteremia during follow-up. Thirty-six patients died during follow-up including 17 patients due to cardiovascular causes. During follow-up 42 patients were observed with a MACE. PTI was independently associated with all-cause (HR 1.074 95% CI 1.029-1.122, p = 0.001) and cardiovascular (HR 1.105, 95% CI 1.057-1.157, p<0.0001) mortality, as well as, incident MACEs (HR 1.071 95% CI 1.031-1.113, p = 0.0004) in the multivariable Cox models adjusted for age and kidney transplantation or CKD treatment modality during follow-up. Radiographically assessed dental health is independently associated with all-cause and cardiovascular mortality and MACEs but not with the incidence of bacteremia in CKD stage 4-5 patients transitioning to maintenance dialysis and renal transplantation during follow-up.

La realidad del paciente en hemodiálisis antes de la pandemia COVID-19

In a pilot test carried out in the department of Lambayeque (Peru) about the profile of patients who entered hemodialysis for the first time with grade five chronic kidney disease (CKD 5), evidence was found different from other Latin American. The treatment modality for CKD 5 patients increased through hemodialysis according to the Latin American Registry of Dialysis and Kidney Transplantation from 2000 to 2008. In Peru, 84.75% of patients are registered with this form of treatment still in force in our country and others.

Island medicine: using data linkage to establish the kidney health of the population of Tasmania, Australia.

ObjectiveTo report (using linked laboratory data) the incidence, prevalence and geographic variation of chronic kidney disease (CKD) across the whole island population of Tasmania, Australia.MethodsA retrospective cohort study (the Tasmanian Chronic Kidney Disease study (CKD.TASlink)) using linked data from five health and two pathology datasets from the island state of Tasmania, Australia between 1/1/2004 and 31/12/2017. We used data on 460,737 Tasmanian adults (aged 18 years and older, representing 86.8% of the state’s population) who had a serum creatinine measured during the study period. We defined CKD as per Kidney Disease Outcomes Quality Initiative, requiring two measures of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2, at least three months apart. Kidney replacement therapy (KRT) included dialysis or kidney transplantation.ResultsWe identified 56,438 Tasmanians with CKD during the study period, equating to an age-standardised annual incidence of 1.0% and a prevalence of 6.5%. These figures were higher in women, older Tasmanians and people living in the North-West region of Tasmania. Testing for urinary albumin:creatinine ratio is increasing, with 28.5% of women and 30.8% of men with stage 3 CKD having both an eGFR and uACR in 2017. Use of KRT was consistently seen in >65% of Tasmanians with eGFR <15 mL/min/1.73m2.ConclusionThere is geographic and gender variation in the incidence and prevalence of CKD, but it is reassuring to see that the majority of people with end-stage kidney failure are actually receiving treatment with dialysis or transplantation.

Kidney, limb and ophthalmic complications, and death in patients with nonvalvular atrial fibrillation and type 2 diabetes prescribed rivaroxaban or warfarin: an electronic health record analysis

Background Patients with nonvalvular atrial fibrillation (NVAF) and type 2 diabetes are at risk of kidney, limb, and ophthalmic complications. We evaluated the rate of these complications and death in patients with NVAF and type 2 diabetes prescribed rivaroxaban or warfarin. Methods We analyzed Optum de-Identified electronic health record (EHR) data from 11/2010–12/2019. We included adults with NVAF and T2D newly initiated on rivaroxaban or warfarin with ≥12 months of prior EHR activity. Patients with another indication for anticoagulation, valve disease, history of end-stage renal disease, major adverse limb events (MALE), diabetic retinopathy or pregnancy were excluded. We evaluated the incidence rate of developing a composite outcome of >40% decrease in estimated glomerular filtration incidence rate (eGFR) from baseline, eGFR < 15 mL/minute/1.73 m2, need for dialysis or kidney transplant, MALE, diabetic retinopathy or death. Overlap weighting was used to balance baseline characteristics between cohorts while preserving sample size. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted Cox regression. Results We included 24,912 rivaroxaban and 58,270 warfarin users. The mean ± standard deviation (SD) CHA2DS2VASc score was 4.3 ± 1.5 and modified HASBLED score was 1.5 ± 0.8. Thirty percent of rivaroxaban patients were started on 15 mg once daily, with the rest prescribed 20 mg once daily. Warfarin patients had a mean time in therapeutic range of 47 ± 28%. Patients were followed for a mean of 2.89 ± 1.95 years. Rivaroxaban was associated with a reduced hazard of the composite outcome (HR = 0.93, 95%CI = 0.91–0.95; absolute risk reduction = 1.97 events per 1000 patient-years; number needed-to-treat = 51) versus warfarin. Rivaroxaban was also associated with significant reductions in the relative hazard of > 40% decrease in eGFR from baseline (HR = 0.96), need for dialysis or renal transplant (HR = 0.81), and limb revascularization or major amputation (HR = 0.85). Death occurred at a lower incidence rate with rivaroxaban (HR = 0.92, 95%CI = 0.89–0.95). Conclusions Rivaroxaban was associated with reduced incidence rates of kidney and limb complications, and death in NVAF patients with type 2 diabetes compared to warfarin. ClinicalTrials.gov Identifier: NCT04509193

Effect of Hemodialysis on Diabetic Retinopathy

Diabetes mellitus is a serious health problem in both developed and developing countries. It is expected that by 2040 the incidence of diabetes mellitus in the world will increase to 642 million people. With the increase in the incidence of diabetes mellitus, the incidence of diabetic vascular complications increases, which worsen the quality of life of patients and triple the risk of death. Diabetic retinopathy is one of the most common microvascular complications of diabetes mellitus, leading to progressive loss of visual function. Diabetic retinopathy occurs in conjunction with diabetic nephropathy. This fact is associated with the anatomical similarity of the blood-retinal barrier and the glomerular filtration barrier, as well as with the general pathogenetic mechanisms of the effect of hyperglycemia on peripheral microcirculation. On average, after 10–15 years, patients with decompensated diabetes mellitus develop end-stage renal failure, requiring renal replacement therapy, such as peritoneal dialysis, programmed hemodialysis, and kidney transplantation. This article highlights the latest data on the effect of programmed hemodialysis on the morphofunctional state of the retina in patients with diabetes mellitus.

COVID-19 Pandemic and Hemodialysis: Disease Parameters and Outcome: Single Center Study

Background: Coronavirus disease 2019 (COVID-19) has significantly affected the provision of medical services. The hemodialysis (HD) facilities together with other medical facilities faced challenges in safely providing clinical care to patients and staff during the pandemic. Objective: To describe our experience during the COVID-19 pandemic as regard infection, mortality rate, clinical manifestations, illness duration and the efficacy of our local infection control measures in our Hemodialysis Unit, Ain Shams University Hospital, Cairo, Egypt. Patients and Methods: followed the interim guidance provided by the US Centers for Disease Control and Prevention (CDC) together with the European Renal Association– European Dialysis Transplantation Association (ERA-EDTA) for dealing with the emerging COVID19 pandemic in HD centers. The study included 238 patients on regular HD from Dialysis Unit in Ain Shams University Hospitals. We monitored all patients and staff members for any symptoms or signs of respiratory tract infection and those confirmed to have COVID-19 infection were followed up through their illness. Results: 42 out of total 238 patients were diagnosed to have COVID19 infection by combination of symptoms, chest imaging and SARS COV PCR. Their mean age was 49.8 ± 8.9 years, 19 were males, the mean ± SD total illness duration for all COVID-19 positive patients was 17 ± 8.7. Patients were further subdivided based on survival into cure group (34 patients) and death group (8 patients). CRP and D-dimer were all significantly higher in death group while O2% were significantly lower in death group compared to cure group. Conclusion: COVID 19 pandemic still a major health problem worldwide with significant morbidity and mortality among hemodialysis patients. © 2021, Ain Shams University Faculty of Medicine. All rights reserved.

Underlying Causes and Risk Factors of Chronic Renal Allograft Dysfunction Among Renal Transplant Recipients

Objective: Dialysis or renal transplantation are the two treatment options for end-stage renal disease patients. Renal transplantation from an appropriate donor increases survival and quality of life compared to treatment with dialysis. Recent advances in immunosuppressive therapy have significantly improved the success in 1-year graft survival. However, the long-term graft survival remains the same. Therefore, we aimed to determine the underlying causes and risk factors of chronic allograft dysfunction in renal transplant recipients.&#x0D; Materials and Methods: From 2000 to 2012, all consecutive renal transplant recipients followed in our tertiary referral center who underwent renal biopsy due to an increase in serum creatinine level were enrolled. Etiologies of chronic allograft dysfunction were assessed according to pathologic results of renal biopsy specimens and laboratory findings. The immunological and non-immunological risk factors of chronic allograft dysfunction were screened and recorded retrospectively.&#x0D; Results: Eighty (80) renal transplant recipients with a mean age of 38±10 years were included in the study. Delayed graft function (p=0.007), history of acute rejection (p&lt;0.001), positive panel reactive antibody (p=0.033) (Class I (p=0.013), Class II (p=0.006)), positive donor specific antibodies (p=0.001), number of recurrent acute rejections (p&lt;0.001), number of human leukocyte antigens mismatches (p=0.051), cold ischemia time (p=0.001) were found to be risk factors for chronic allograft dysfunction. The donor specific antibodies positivity (p&lt;0.001) and the panel reactive antibody positivity (Class I (p=0.003), Class II (p=0.001)) were significantly higher in patients with antibody mediated rejection than patients without antibody mediated rejection (p=0.002).&#x0D; Conclusion: Delayed graft function, presence and the number of acute rejections, increased cold ischemia time, panel reactive antibody positivity, donor specific antibodies positivity, and the number of human leukocyte antigens mismatches were risk factors for chronic allograft dysfunction.

MO138ASSOCIATION OF NT-PROBNP WITH OBESITY IN CKD PATIENTS

Abstract Background and Aims Obesity is associated with lower circulating levels of N-terminal pro-BNP (NT-proBNP) both in the general population and in patients with heart failure. In asymptomatic patients with CKD, NT-proBNP levels are generally elevated. The prevalence of obesity is markedly increasing among patients with CKD. However, whether obesity affects NT-proBNP levels and thresholds for increased risk of clinical outcomes is unclear. Method We examined the associations between NT-proBNP and obesity in 408 stage 3–5 CKD patients (268 men and 140 women; mean age 65±13 years) free of heart failure at baseline, who were categorized into 3 groups according to body mass index (BMI; kg/m2) as normal (&amp;lt;24.0), overweight (24.0–27.9), and obese (≥28.0). Multivariate Cox proportional hazards models were used to compare the risk associations of NT-proBNP with the composite of ESKD (needing chronic dialysis or kidney transplantation) or all-cause mortality across BMI categories. Results NT-proBNP levels were significantly lower in obese patients than in normal weight and overweight subjects (P &amp;lt;0.001). Within each CKD stage, NT-proBNP levels decreased with increasing BMI. In a multivariate analysis, NT-proBNP was inversely associated with obesity, as well as BMI and its fat and lean body mass components (all P &amp;lt;0.001), independent of demographics, comorbidities, and severity of CKD. During a median follow-up of 2.2 years, 117 patients progressed to ESKD and 46 patients died. Overall, higher NT-proBNP levels were independently associated with ESKD or death (HR, 1.52; 95% CI, 1.22–1.89). Specifically, higher NT-proBNP levels were consistently associated with poor outcomes in all BMI categories (P for interaction = 0.096). Conclusion Obese CKD patients have significantly lower NT-proBNP levels. Nevertheless, BMI category did not modify the relationship between NT-proBNP and clinical outcomes. Increased risk may be seen at relatively lower levels of NT-proBNP in obese CKD patients.

MO878THE DYNAMICS OF THE COLLABORATION BETWEEN GENRAL PRACTITIONER AND NEPHROLOGIST DURING PRE-DIALYSIS CARE: A MIXED METHOD STUDY

Abstract Background and Aims Nephrologists and General Practitioners (GP) are critical in the care trajectory of patients with CKD through the medical work they provide: screening, referral, follow-up, slowing down CKD progression and renal replacement therapy preparation. They often intervene simultaneously in a collaborative context. Several guidelines define this medical work and collaborative care models. However, evidence suggests that the implementation of such models is limited and suboptimal. For example, 18% of patients who started dialysis in 2018 in France did not see a nephrologist before.The objectives of this study were 1) to quantitatively describe the practices of both French nephrologists and GPs through drug and biology lab test prescriptions for patients with CKD and its evolution before and after dialysis start, 2) to qualitatively describe how they see each other’s role and from this 3) identify the factors interfering with optimal care trajectory Method All incident 2015 dialysis patients from France were identified using the national REIN registry. Healthcare consumption of those patients 2 years before and 1 year after dialysis start was retrieved from the French national health insurance database (SNDS) via indirect record linkage. The items of interest were drug and lab test prescriptions as well as the prescriber medical specialty. Prescription frequencies and percentages per months and per prescriber specialty were reported. Anatomical Therapeutic Chemical (ATC) classification level 2 was used for drugs. Semi-structured interviews with general practitioners and nephrologists exploring their practices surrounding CKD care were performed in a sample from the Bretagne region. Thematic analysis was performed on the transcripts. Results A total of 2 263 935 drug prescriptions were found for 8679 patients who started dialysis in 2015 in France in the span of 2 years before and 1 year after dialysis start. The place of each professional changed through time: drug prescribed by GPs decreased from 83.6% of the total during the 2 years before dialysis start to 62.6% during the year following dialysis start. Nephrologist’s place increased from 4.9% of the total prescriptions to 21%. Although GPs and nephrologists had differences between the drugs they prescribe (nephrologists prescribed more frequently vitamins and antianemic preparations whereas GPs prescribed more frequently analgesics and drugs used in diabetes), they also had similarities (frequencies of beta blocking agents, calcium channel blockers and lipid modifying agents). Similarly, the interviews highlighted that despite the unique technical nature of a large part of nephrologists’ practice (nephropathy aetiology, dialysis and kidney transplantation, nephrotoxicity) another part was similar to GPs’, including the long-term holistic care of patients with multiple comorbidities as well as diet and lifestyle advices. This appears to blur the perimeter of the role of each professionals regarding CKD care and favours an increased presence of nephrologists, as suggested by the quantitative prescription analysis. In turn, as interviews revealed, some GPs expressed a fear of losing their patients and regretted a decreased communication from specialists. Nephrologists’ description of the role of GPs ranged from a strict addressor to nephrologists, to an intermediary support to reduce uncertainties, to a constant partner with transfer of therapeutic objectives. Conclusion Combining the crossed point of view of GPs and nephrologists and robust prescription data, this study highlights an overlap in the roles and practices and suggests a competition in the control of therapeutic strategies that might hinder an optimal care trajectory for patients. Development of integrated renal care network could address these obstacles

MO462TIME-TRAJECTORIES OF RENAL FUNCTION AND OUTCOMES IN ELDERLY INDIVIDUALS WITH CKD OF VARIOUS ETIOLOGY

Abstract Background and Aims Despite hypertension ranks among the leading causes of chronic kidney disease (CKD), the impact of chronic hypertensive nephropathy, the so-called “nephrosclerosis” (NS), on CKD progression towards end-stage kidney disease (ESKD) is often unpredictable, particularly in older populations. We run a prospective, observational study to define renal function patterns and outcomes in elderly individuals with or without NS-related CKD. Method 304 elderly patients with already established CKD (mean age 69±4 y; mean eGFR 44.2±19.6 mL/min/1.73 m2; male= 64.1%), followed in our outpatients’ clinic were categorized according to the etiology of CKD. NS was defined as the presence of CKD associated with long-term essential hypertension, hypertensive retinopathy, left ventricular hypertrophy and minimal proteinuria. Time-trajectories in eGFR (CKD-Epi) were computed over a 4-year follow-up. In addition, we analysed the occurrence of a composite outcome of doubling of serum creatinine, eGFR reduction≥ 25% and/or ESKD needing dialysis or kidney transplantation. Results CKD was secondary to nephrosclerosis (CKD-NS) in 220 (72.3%) patients. Among the remaining 84 (27.7%), glomerular/diabetic diseases were the most frequent cause of CKD (47.6%). In the whole cohort, the average estimated annual GFR slope was of 1.8 mL/min/1.73 m2. eGFR decline was slower in CKD-NS as compared with the one of others (1.4 vs. 3.4 mL/min/1.73 m2; p&amp;lt;0.001. Figure 1). The composite renal outcome during follow-up (median 36 mo.; range 6-48) occurred less frequently among elderly with CKD-NS (16/204 vs 14/70; p=0.01 Crude HR 0.43, 95%CI 0.22-0.85) and was associated at logistic analyses with etiology of CKD, serum total cholesterol, serum LDL cholesterol levels and glycemia (p ranging from 0.01 to 0.04). Conclusion Despite being highly prevalent in the elderly, NS is associated with a more favorable renal disease course as compared with other conditions. Therapeutic efforts to delay CKD progression in older populations should go beyond just optimizing blood pressure control and focus more on concomitant diseases.

MO889COST OF ILLNESS OF CHRONIC KIDNEY DISEASE IN LEBANON: FROM THE SOCIETAL PERSPECTIVE

Abstract Background and Aims Chronic Kidney Disease (CKD) is the 12th leading cause of death worldwide and a high societal burden. Cost-of-illness studies of CKD are scarce in developing countries. Identifying factors associated with the highest cost can help decision makers adapt health policies and sustain kidney health services, especially in limited resources' settings. This study aims to estimate the cost of illness of CKD in Lebanon, from the early stages of CKD until dialysis and kidney transplant and identify cost components related to the highest financial burden. Method This is a cross-sectional study of all CKD patients who presented to two nephrology clinics during the first two weeks of November 2020. The sample size required for the study to be representative was 154 patients. The medical and administrative records were reviewed to collect the demographics and CKD characteristics of patients as well as the direct medical costs (medications, diagnostic tests, hospitalizations, inpatient care, outpatient care), direct non-medical costs (transportation) and indirect costs (productivity losses) for one year between 1st June 2019 and 1st June 2020. Kruskal Wallis test was used to compare the costs between different CKD stages and categories. The study got the approval of the ethics committee of Saint-Joseph University. Results The sample included a total of 160 patients: 102 non-dialysis CKD patients, 40 hemodialysis, 8 peritoneal dialysis and 10 kidney transplant patients. Their mean age was 66.74 ±15.36 years, 57.5% were males and 42.5% diabetics. The mean number of daily medications was 8.75 ±3.38, mean frequency of blood tests per year 6.86 ±6.4 and mean number of hospital admissions per year 0.79 ±1.43. The mean total annual cost of CKD per patient across all categories was assessed at 19,900,164 ±27,893,591 Lebanese Pounds (1 $USD= 1515 LP in 2019). Statistical analysis showed a higher total cost among dialysis patients compared to other categories of CKD (p&amp;lt;0.001), higher cost of medications in transplant patients (p&amp;lt;0.001) and higher cost of technique modality in peritoneal dialysis patients (p&amp;lt;0.001). These differences are summarized in Figure 1. Conclusion Similar to previous studies from other countries, this cost of illness analysis showed a high burden of dialysis annual costs compared to non-dialysis CKD and transplant patients. It revealed as well a great burden of medications' costs at the level of dialysis and transplantation. It is thus crucial that governments and health policies in low- and middle-income countries target interventions that prevent end-stage kidney disease, reduce medications' costs and most of all create programs that encourage kidney transplantation.

MO285CLINICAL PRESENTATION OF IGA NEPHROPATHY AND LONG-TERM RENAL OUTCOME

Abstract Background and Aims There is a wide range of clinical presentation of IgA nephropathy (IgAN), from asymptomatic microscopic hematuria to rapidly progressive glomerulonephritis. However, there is little epidemiologic data on the relationship between the clinical pattern at diagnosis and long-term renal outcome. Method We performed a unicentric retrospective study on 299 consecutive IgAN patients (age 43 [35-56] years, 71% male, eGFR 42.1 [25.2-62.8] mL/min, proteinuria 1.3 [0.6-2.6] g/g creatinine) - kidney biopsy proven - between 2010-2017. Patients were followed until composite endpoint (doubling of serum creatinine, ESKD (dialysis or renal transplant) or death, whichever came first) or end of study (May 2018). Results Patients were followed for a mean of 41 (95%CI 38, 44) months, and 80 (27%) patients experienced the composite endpoint. The most frequent clinical presentation at diagnosis regardless of age was nephritic syndrome (68%), followed by asymptomatic urinary abnormalities (AUA) (19%), macroscopic hematuria (15%), acute kidney injury (AKI) (14%) and nephrotic syndrome (10%). The clinical pattern varied in frequency with age: macroscopic hematuria had a bimodal distribution in the 20- and 60-years groups, AKI was more frequent in the 50 to70 years groups, AUA was more often present in the 30 to 50 years groups (Figure 1). Mean renal survival time for the entire cohort was 70 (95%CI 65, 75) months; patients with AKI (40 (95%CI 27, 54) vs 75 (95%CI 69, 80) months, p&amp;lt;0.001), nephrotic syndrome (42 (95%CI 26, 57) vs 73 (95%CI 67,78 months, p&amp;lt;0.001)) at diagnosis had significantly shorter renal survival time. In multivariate Cox regression analysis adjusted for IgAN progression factors, presence of nephritic syndrome at diagnosis was associated with good renal outcome, while clinical presentation as AKI or nephrotic syndrome were associated with poor renal survival (Table 1). Conclusion Although AKI and nephrotic syndrome are uncommon in IgAN at diagnosis, their presence seems to be associated with poor renal survival.

A validation study of the kidney failure risk equation in advanced chronic kidney disease according to disease aetiology with evaluation of discrimination, calibration and clinical utility

BackgroundThe Kidney Failure Risk Equation (KFRE) predicts the 2- and 5-year risk of end-stage renal disease (ESRD) in patients with chronic kidney disease (CKD) stages 3a-5. Its predictive performance in advanced CKD and in specific disease aetiologies requires further exploration. This study validates the 4- and 8-variable KFREs in an advanced CKD population in the United Kingdom by evaluating discrimination, calibration and clinical utility.MethodsPatients enrolled in the Salford Kidney Study who were referred to the Advanced Kidney Care Service (AKCS) clinic at Salford Royal NHS Foundation Trust between 2011 and 2018 were included. The 4- and 8-variable KFREs were calculated on the first AKCS visit and the observed events of ESRD (dialysis or pre-emptive transplantation) within 2- and 5-years were the primary outcome. The area under the receiver operator characteristic curve (AUC) and calibration plots were used to evaluate discrimination and calibration respectively in the whole cohort and in specific disease aetiologies: diabetic nephropathy, hypertensive nephropathy, glomerulonephritis, autosomal dominant polycystic kidney disease (ADPKD) and other diseases. Clinical utility was assessed with decision curve analyses, comparing the net benefit of using the KFREs against estimated glomerular filtration rate (eGFR) cut-offs of < 20 ml/min/1.73m2 and < 15 ml/min/1.73m2 to guide further treatment.ResultsA total of 743 patients comprised the 2-year analysis and 613 patients were in the 5-year analysis. Discrimination was good in the whole cohort: the 4-variable KFRE had an AUC of 0.796 (95% confidence interval [CI] 0.762–0.831) for predicting ESRD at 2-years and 0.773 (95% CI 0.736–0.810) at 5-years, and there was good-to-excellent discrimination across disease aetiologies. Calibration plots revealed underestimation of risk at 2-years and overestimation of risk at 5-years, especially in high-risk patients. There was, however, underestimation of risk in patients with ADPKD for all KFRE calculations. The predictive accuracy was similar between the 4- and 8-variable KFREs. Finally, compared to eGFR-based thresholds, the KFRE was the optimal tool to guide further care based on decision curve analyses.ConclusionsThe 4- and 8-variable KFREs demonstrate adequate discrimination and calibration for predicting ESRD in an advanced CKD population and, importantly, can provide better clinical utility than using an eGFR-based strategy to inform decision-making.

Development and validation of a prediction model for kidney failure in long-term survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

10047 Background: Kidney failure (need for dialysis or kidney transplantation, or death due to kidney disease) is a rare but serious late effect for survivors of childhood cancer. We aimed to develop a model using demographic and treatment characteristics to predict individual risk of kidney failure among five-year survivors of childhood cancer. Methods: CCSS survivors without kidney failure at five years after cancer diagnosis (n = 25,483) were assessed for subsequent kidney failure by age 40. Outcomes were self-reported and corroborated by the Organ Procurement and Transplantation Network and the National Death Index. A sibling cohort (n = 5045) served as a comparator. Piecewise exponential models with backward selection estimated the relationships between potential predictors and kidney failure and were converted to integer risk scores. Additional results from the St. Jude Lifetime Cohort Study (SJLIFE, n = 2490) and the National Wilms Tumor Study (NWTS, n = 6760) validated the models. Results: Among CCSS survivors, 204 developed late kidney failure. We developed a model with sex, race/ethnicity, age at cancer diagnosis, nephrectomy, exposure to specific chemotherapy, any abdominal radiation, presence of genitourinary anomalies, and early-onset hypertension (Table). Risk scores achieved an area under the curve (AUC) and concordance (C) statistic of 0.65 and 0.68 for kidney failure by age 40. Validation cohort AUC and C statistics were 0.83/0.86 for SJLIFE (8 cases) and 0.61/0.63 for NWTS (91 cases). An alternative model with specific chemotherapy doses and kidney-specific radiation dosimetry had similar AUC and C statistic (0.67/0.70). Integer risk scores were collapsed to form statistically distinct low (score &lt;3; 87 cases of 17,326), moderate (score 3-5; 63 cases of 4667), and high (score 6+; 18 cases of 401) risk groups. These groups corresponded to cumulative incidences in CCSS of kidney failure by age 40 of 0.6% (95% CI 0.4-0.7%), 2.3% (95% CI 1.6-3.2%), and 9.4% (95% CI 4.4-16.7%), compared with 0.2% (95% CI 0.1-0.5%) among siblings. Conclusions: Using readily available information, we were able to identify low, moderate, and high risk groups for developing kidney failure following treatment for childhood cancer. These prediction models may help guide screening and interventional strategies for higher risk survivors.[Table: see text]

Application Of Predialytic Exercise To Reduce Fatigue In-Patient Undergoing Hemodialysis

Chronic kidney disease is an irreversible and slow-progressing disorder of kidney function so that the kidneys are unable to maintain the body's metabolism, fluid and electrolyte balance and cause uremia which requires dialysis or kidney transplantation. Hemodialysis is management to treat chronic kidney disease that is carried out for life so that the complications that often arise are fatigue, cramps, anxiety, pain. The phenomenon found in the Hemodialysis Room of the Tugurejo Hospital Semarang, there were 34% of the 84 patients who experienced fatigue which was characterized by lethargy, weakness, drowsiness, dizziness. This research is a quantitative study with a quasi-experimental design. The sample size is 4 respondents in the intervention group without a control group. Measurement of the level of fatigue (pre and post-test) using the PFS (Piper Fatigue Scale) which contains 22 subjective statements. Predialytic Exercise intervention is given for 5 sessions with a duration of 10-15 minutes. The results of this study indicate that the fatigue level of hemodialysis patients has decreased after the intervention of predialytic exercise for 5 sessions. The fatigue score of respondents 1 has decreased from a score of 4.8 (moderate fatigue) to 3.2 (mild fatigue), respondent 2 from a score of 6.3 (moderate fatigue) to 4.3 (moderate fatigue), respondent 3 from score 9 (severe fatigue) to 7 (severe fatigue), and respondent 1 from a score of 4.9 (moderate fatigue) to 2.4 (mild fatigue). The results of this study indicate that there is a decrease in each dimension of fatigue levels so that predialytic exercise intervention is effective to reduce fatigue in patients undergoing hemodialysis.