bluuebunny/crossref_metadata_2025 huggingface dataset:
P1361IS THE INFLAMMATORY STATE A DETERMINING FACTOR OF THE PRIMARY PERMEABILITY OF ARTERIOVENOUS FISTULES?
Authors: PICCONE SAPONARA LUIS GUILLERMO , CASTRO FERNÁNDEZ MARIA PAZ , URIBE HEREDIA NANCY GIOVANNA , Carreno Agustin , ANAYA FERNANDEZ SARA , DIAZ LÓPEZ MARIA , SANCHEZ ESCUDERO PATRICIA , Siedel Diego , FERNANDEZ MELERO ALICIA , VOZMEDIANO POYATOS MARIA DEL CARMEN
Published: June 2020

Background and Aims

Clinical practice guidelines recommend an arteriovenous fistula (AVF) as the preferred vascular access for hemodialysis and are associated with a lower incidence of morbidity and mortality. However, primary vascular access (AV) failure is not uncommon. Low-grade inflammation is present in ERCT. We identify the inflammatory parameters that influence the primary permeability of vascular access for hemodialysis.

Method

Cross-sectional study; We include all the AVs performed in the HGUCR. We evaluate the initial operation after the creation of the AV. Demographic variables (age, sex), aetiology of CKD and associated comorbidity were collected. Statistical analysis with SPSS 25.0. Categorical variables are expressed as percentages and are compared using the Chi2 Test. Quantitative variables are expressed as mean ± standard deviation and the t-student was used to compare them. We performed a multivariate analysis to determine those factors involved in the primary failure of the VA. Statistical significance for a value of p <0.05.

Results

600 VA performed on 466 patients were reviewed between October 2009 and December 2019. 492 autologous VA (86.8%) and 75 prosthetic VA (13.2%) were performed. The mean age of the patients was 65.3 ± 14.2 years and 66.2% were male. The most frequent etiology of CKD was diabetic nephropathy (29.9%), followed by non-affiliated (18%) and glomerulonephritis (16.5%). 90.8% of the patients had arterial hypertension (HT), diabetes mellitus (DM) 48%. 77.2% of AV presented primary permeability. In the univariate analysis using Chi2 and T student, statistical age (p = 0.017), HT (p = 0.002), statin treatment (p = 0.002), antiplatelet therapy (p = 0.001), low ferritin levels (p = 0.011) and PCR (p = 0.019). When performing a multivariate analysis, the high CRP figures (OR: 0.64 95% CI 0.42-0.98 p = 0.043) and ferritinemia (OR: 1.04 95% CI 1.01-1.06 p = 0.013) are predictive factors of primary AV failure.

Conclusion

In our study, high CRP decreases the probability of primary functioning of AVFs by 36% and elevated ferritin levels are predictors of primary failure after adjusting for age and sex in the multivariate model.
P1362AN EXPERIENCE WITH PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY IN ARTERIO-VENOUS FISTULA DYSFUNCTION SECONDARY TO VASCULAR STENOSIS
Authors: Ahmed Khan Mohammed Shoeb , Mukthar Faiz , Kumar K Vinod , Prasannan Bipi , Nair Rohit P V , Sadananda Arjun , Unni V Narayanan
Published: June 2020

Background and Aims

Arterio-venous fistula (AVF) is the life line of a hemodialysis patient. Dialysis Outcomes and Practice Study (DOPPS) showed that one year patency for AVF in the USA is 68% and 83% in Europe. The maintenance of the vascular pathways are vital. Vascular stenosis in native AVF at the anastomotic sit, venous cannulation zone, outflow vein or the central vein can lead to loss of AVF. Stenosis necessitate vascular intervention or creation of a “de novo” AVF. The number of possible vascular access sites are limited.

Aim : To evaluate the outcome of percutaneous transluminal angioplasty (PTA) in arterio-venous fistula due to vascular stenosis.

Method

This is a retrospective study of two years (02.05.17 to 02.05.19). Records of patients admitted to our hospital were obtained from hospital archives and images from the hospital radiology archive system. Demographic characteristics, duration of dialysis, stenosis or occlusion level, patency rates of AVF were evaluated. All procedures were performed by interventional radiologists in a hybrid cath lab. Antegrade, retrograde, or both antegrade and retrograde punctures were used, depending on the site of the stenosis as deemed on preoperative ultrasound. A complete angiogram from the proximal arteriovenous anastomosis to the central venous outflow was performed in all cases. A successful percutaneous balloon angioplasty was defined when there was no more than 30% residual stenosis (KDOQI). Primary patency rates were assessed at six months and one year.

Results

Total number of patients studied were 16. The average age was 66.6 years. All were hypertensive and diabetics comprised 75% of study group. Coronary artery disease was established in 81.25%, and two patients were known to have chronic liver disease. Most common type of AVF was the left brachio-cephalic (62.5%), followed by radio-cephalic (37.5%). Average dialysis vintage of AVF at the time of procedure was one year. Previously failed AVF was present in two patients. There were 18 vascular stenosis in 16 patients. The most common site of stenosis was the venous cannulation zone (62.5%), followed by anastomotic site stenosis (31.5%) and central vein stenosis (18.75%). Successful PTA was done in 12 patients. There were no complications; hemodialysis was resumed within 24 hours after the procedure. The primary patency rate at three months was 100%, six months was 75% and at one year it was 37.5%. Four patients were lost to follow up. Mean follow up was 9.41 ±6.79 months. None underwent a repeat PTA.

Conclusion

Percutaneous transluminal angioplasty is effective for salvaging arterio-venous fistula in majority of hemodialysis patients.
P1370UNPOPULAR SOLUTIONS FOR VASCULAR ACCESS DIFFICULTIES IN HEMODIALYSIS PATIENTS: A CASE SERIES
Authors: Attiya Ahmed Mohamed Naguib , Elshahat Samar , Galalah Ibrahim , Elmowafy Ahmed , Eldahshan Khaled , Elwasif Salwa , Refaie Ayman
Published: June 2020

Background and Aims

Vascular access remains a significant challenge for patients on chronic hemodialysis (HD) and often requires creative thinking to preserve and construct durable long-term access. While AVFs continue to remain the gold standard for vascular access, HD access remains an ongoing challenge for surgeons and patients.

The cases

This report is about 4 ESRD patients on chronic hemodialysis with multiple closed A-V fistulas (left and right radiocephalic then left and right brachiocephalic). Also, they suffered from catheter related blood stream infection (CRBSI) when central lines were inserted so the vascular sureon had to find solutions for them. First patient was 36-year old hemodialysis patient since 1995 2ry to posterior urethral valve. In 1994, he sought renal transplantation from his motivated brother who was the only available living related donor but unfortunately the surgeon discovered a congenital anomaly in the donor side during surgery. So the patient was maintained on hemodialysis. After multiple thrombosed AVF and recurrent episodes of CRBSI with central lines, the vascular surgeons inserted a synthetic graft on left chest wall between axillary artery and axillary vein 3 years ago and it is well functioning with efficient dialysis. The 2nd case (figure 1) is a 42-year old graft failure patient since 2005 and In view of high PRA, 2nd renal transplantation was not an option. After multiple thrombosed AVF and recurrent episodes of CRBSI with central lines, the vascular surgeons created a new fistula in lower extremities between right great saphenous vein and common femoral artery 2 years ago and it is still functioning. The 3rd case (figure 2) is about 14-year old child who received renal allo-transplantation from his father 8 years ago. Now, he is on chronic hemodialysis. First, he underwent peritoneal dialysis. But he suffered from recurrent peritonitis, so he was shifted to hemodialysis. Unfortunately, he suffered from CRBSI with catheters and multiple AVF were thrombosed. So, vascular surgeons performed arterio-arterial synthetic graft using right subclavian artery which is well functioning over 2 years. The 4th case (figure 3) is about 43-year old graft failure case on chronic hemodialysis with widespread thrombosis and difficult central line fixation. Also,AV fistulas had short survival. So, vascular surgeons decided to create AVF in lower extremities between right greater saphenous vein and superficial femoral artery 2 years ago. The patient after that received warfarin and the graft is functioning well till now.

Conclusion

Hemodialysis access remains an ongoing challenge for surgeons and patients lives.
P1373ERYTHROPOETIN RESISTANCE IN PRE-DIALYSIS PERIOD AND ITS RELATION TO PROGNOSIS IN JAPANESE INCIDENT DIALYSIS PATIENTS
Authors: MORINAGA Takatoshi , FUKATSU Atsushi , ITO Takeshi , TAMAI Hirofumi
Published: June 2020

Background and Aims

Erythropoiesis stimulating agents (ESA) are essential for better quality of life and longer life expectancy in end-stage kidney disease patients (ESKD). Resistance to ESA leads to worse prognosis in hemodialysis and peritoneal dialysis patients. Resistance to ESA exists in pre-dialysis period. We studied the clinical significance of pre-dialysis resistance to ESA by investigating the erythropoietin resistance index (ERI) in patients with ESKD prior to dialysis induction and its association with mortality and cause of death in three-year follow-up after dialysis initiation.

Method

Subjects included 1,420 patients in 17 centers participating in Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) from Oct. 2011 to Sep. 2013. ESA responsiveness was estimated by using erythropoietin resistance index (ERI) (U/kg/week/g/dL), which was calculated as weekly weight-adjusted epoetin dose divided by the hemoglobin (Hb) concentration before starting dialysis. We excluded 302 patients because ERI was not available. Thus, 1,118 subjects were enrolled. Subjects were divided into four categories of ERI; ERI < 5, 5≤ ERI <10, 10≤ ERI <15 and 15≤ ERI. Cumulative survival rates from all-cause, cardiovascular disease (CVD), infection and malignancy were compared by Kaplan-Meier method according to ERI categories. Three-year mortality was analyzed by logistic regression analysis adjusted by age, gender, Charlson comorbidity index (CCI), and ERI categories.

Results

During three-year follow-up period, 191 (17.1%) patients died. Age and female gender share were higher in proportion to ERI. Diabetes, coronary artery disease (CAD), and values of albumin (Alb) and brain natriuretic peptide (BNP) were not correlated with ERI (Table 1). Kaplan-Meier survival curve showed that patients with the highest ERI (15≤ ERI) had a higher all-cause mortality (Log rank test p=0.002, Figure 1). Concerning the cause of death, mortality from infection (p=0.023, Figure 2) and malignancy (p=0.031) were high in the highest ERI category, however there was no significant difference in each ERI category regarding CVD mortality (p=0.33). According to multivariate analysis analyses by logistic regression model, all-cause (odd ratio [OD]: 1.65, 95% confidence interval [CI]: 1.14-2.38, p=0.008) and infection-related mortality (OR: 2.13, 95% CI: 1.08-4.11, p=0.029) were significantly correlated with the highest ERI category, but unexpectedly CVD mortality was not (OR: 1.04, 95% CI: 0.59-1.75, p=0.90). Mortality from malignancy did not reach the significant level (OR: 1.92, 95% CI: 0.96-3.73, p=0.063) and may require longer observation period for analysis.

Conclusion

Pre-dialysis ERI is a prognostic marker in Japanese dialysis patients and predicts the susceptibility to infection.
P1374DEVELOPMENT OF HEMOGLOBIN PREDICTION AND ERYTHROCYTE STIMULATING AGENT RECOMMENDATION ALGORITHM (HPERA) USING RECURRENT NEURAL NETWORK IN END-STAGE KIDNEY DISEASE PATIENTS
Authors: Yoo Tae-Hyun , Yun Hae-Ryong , Chang Jae Hyun
Published: June 2020

Background and Aims

The optimization of anemia management is a challenging task due to the complexities of underlying diseases and heterogeneous responses to erythropoiesis-stimulating agents (ESA) in patients with end-stage kidney disease (ESKD). Recent studies have shown that machine learning (ML) algorithms can be an effective tool to predict hemoglobin (Hb) levels and determine the ESA doses in these patients. However, most of the proposed ML approaches are not designed to handle multivariate longitudinal patient data. Thus, we developed Hb prediction and ESA doses recommendation algorithm (HPERA) using recurrent neural networks (RNN).

Method

A total of 466 participants, who underwent hemodialysis in 7 hospitals in the Republic of Korea, were included in the present study. We selected 15 variables from an extreme gradient boosting (XGBoost) algorithm. The outcome of the prediction algorithm was Hb levels in next month. In the recommendation algorithm, the outcome was the ESA dose for target Hb next month. Among various types of RNN families, gated recurrent units (GRU) were used to build both the prediction and recommendation algorithms. In addition to holding out a separate validation dataset, we used a Gaussian noise layer following each input layer to avoid overfitting. We also performed linear regression, multilayer perceptrons, and extreme gradient boosting with an extensive hyperparameter search to validate our GRU-based prediction algorithm. The performances of each model were evaluated in terms of the mean absolute error (MAE).

Results

The mean age of the study population was 57.8 years, 248 (53.2%) participants are male, and the mean observation period is 30.0 months. The best result of our prediction algorithm in terms of MAE was 0.59 g/dL and was obtained by two stacked GRU layers followed by a single hidden feedforward network with 6-month follow-up patient data. The best recommendation algorithm had 43.2 μg in MAE and this was obtained by one GRU layer followed by two layers of a feedforward network. The HPERA had a lower overall ESA dose (μg/months) [155 (80–240) vs. 140 (70–210), P<0.001], decreased Hb difference (g/dL) [0.8 (0.4–1.4) vs. 0.6 (0.3–1.0), P<0.001)], and had a higher success and a lower failure rates of reaching target Hb compared to those in real practice.

Conclusion

The GRU-based prediction model outperformed previous ML methodologies, though hyperparameter turning was much simpler. Using the HPERA showed the possibility of a reduced amount of ESA, decreased Hb difference, and increased the reaching rate of target Hb levels. Our study revealed a great potential direction of anemia management using ML in ESKD patients.
P1377ANEMIA MANAGEMENT IN DIALYSIS PATIENTS IN SWITZERLAND
Authors: Winzeler Rebecca , Ambühl Patrice Max
Published: June 2020

Background and Aims

Anemia is highly prevalent in dialysis patients and is associated with increased morbidity and mortality. The purpose of the present analysis is to evaluate current anemia management in dialysis patients in Switzerland collected from the Swiss Dialysis Registry (srrqap), which covers all dialysis patients in Switzerland.

Method

All medical establishments in Switzerland (both public and private; N=92) providing chronic treatment by either hemo- and/or peritoneal dialysis, had to provide relevant data for the year 2018. All individuals being on chronic dialytic therapy in the year 2018 were enrolled (N=4646). To calculate survival probabilities, all deaths from incident dialysis patients between 2014 and 2018 were analyzed.

Results: 65 percent of all dialysis patients receive iron and EPO. Regardless of anemia management, 82% of patients reach target hemoglobin levels 10 g/dL. In 18% of patients inadequate management to reach Hb targets may be suspected.

The distribution of iron and EPO substitution is similar in all age groups. However, 26% of the age group 20-44 years receive EPO, but no iron, compared to only 15% in the other age groups.

Survival analysis by Cox regression adjusted for age, Charlson score and treatment modality revealed that patients with Hb levels equal or greater than 11 g/dl have the best survival (reference group). In comparison, patients in the Hb categories below 9, 9-9.9 and 10-10.9 g/dl have an odds ratio of 3.9, 2.0 and 1.3, respectively, to die.

Conclusion

Anemia management to reach Hb target levels following KDIGO guidelines seems to be adequately implemented among dialysis patients in Switzerland. In 18% of patients treatment might be optimized to achieve Hb targets. As expected, patients with Hb levels equal or greater than 11 g/dl have better survival rates compared to patients with lower Hb values.
P1380A SYSTEM FOR FORECASTING OF DRUG DOSAGE FOR ANEMIA CORRECTION IN PATIENTS ON CHRONIC DIALYSIS
Authors: Zinovev Dmitriy , Novitskiy Vladimir , Malkoch Andrey
Published: June 2020

Background and Aims

Anemia is a most common complication of CKD in patients on chronic dialysis. Adequacy of anemia correction directly affects both patient’s life quality and patient’s long-term survival. The most important aspect of anemia correction is drug therapy. In this work, we present a system for forecasting of iron supplements and ESA (Epoetin alfa) dosage, that is based on logical rules and artificial intelligence (AI) models.

Method

As an input dataset, system uses patient’s anthropomorphic parameters, results of laboratory studies, and information on previous drug therapy. The output of the system are dosages of ESA an iron supplements that have to be administered in order to bring the patient’s hemoglobin as close as possible to target range of values (100-120 g/l). The system consists of two sequentially triggering forecasting models (for ESA and for iron supplements), where each model is a combination of logical rules and artificial neural network, that has been trained on a data, collected in more than 20 “Nefrosovet” hemodialysis clinics for the period of 3 years.

The effect of system usage was examined for the group of 356 hemodialysis patients with median follow-up time of 4 month. The primary end-point was a number of patients in target range of hemoglobin values (100-120 g/l).

Results

During the study we determined that as a result of using the dose forecasting system, number of patients in target range of hemoglobin values significantly increased from 239 patients at the beginning of system employment to 266 patients at the end of the study (p=.0318). Furthermore, we observed that there was a concomitant effect of system usage – significant reduction of average monthly ESA dosage from 14300 IU at the beginning of system employment to 13900 IU at the end of the study (p=.0331).

Conclusion

Employment of automated drug dosage forecasting system based on logical rules and AI models, allows to improve the efficiency of anemia correction in hemodialysis patients and reduce the dosage of administered ESA, which, in turn, reduces the risk of possible complications and treatment cost.
P1389MAJOR OSTEOPOROTIC FRACTURES AFTER INITIATION OF DIALYSIS: INCIDENCE, PREDICTORS AND ASSOCIATION WITH MORTALITY
Authors: Iseri Ken , Carrero Juan Jesus , Evans Marie , Felländer-Tsai Li , Berg Hans , Runesson Björn , Stenvinkel Peter , Lindholm Bengt , Qureshi Abdul Rashid Tony
Published: June 2020

Background and Aims

Major osteoporotic fractures (MOF) are common in dialysis patients. We investigated incidence, predictors and clinical outcomes associated with first MOF occurring after initiation of dialysis (MOFfirst).

Method

In Swedish Renal Registry of 9714 incident (2005 -2016) dialysis patients (median age 68 years, 67% men), we identified all MOFfirst in hip, spine, humerus and forearm. Using flexible parametric hazard models and Fine-Gray analysis, we estimated incidence, mortality rates and predictors of MOFfirst, and, in time-dependent analysis, risk of all-cause and cardiovascular disease (CVD) mortality following MOFfirst.

Results

During median follow-up of 2.2 years, the crude incidence rate of MOFfirst (n=835) was 24/1000 patient-years (pt-yrs) and that of hip fractures (n=470) 13/1000 pt-yrs. The multivariate-adjusted fracture incidence rates increased gradually after dialysis initiation and were 47% higher among women. Female sex, higher age, presence of comorbidities, and previous history of MOF (MOFprevious) were associated with increased risk for MOFfirst, whereas peritoneal dialysis as compared to hemodialysis was associated with decreased fracture risk. The adjusted fracture incidence rate of MOFfirst during the first 90 days following dialysis initiation was higher in patients with MOFprevious than in those without MOFprevious. MOFfirst independently predicted increased all-cause mortality (sub-distribution hazard ratio, sHR, 1.67(95%CI 1.47-1.91) and CVD-related mortality (sHR 1.49 (95%CI 1.22-1.84). Adjusted mortality rate following hip fractures was higher than for other types of MOF. Spline curves showed that mortality following MOFfirst was highest during the first 6 months of follow-up.

Conclusion

Major osteoporotic fractures are common and associated with increased mortality in incident dialysis patients.
P1393A SYSTEM FOR FORECASTING OF DRUG DOSAGE FOR BONE MINERAL DISORDERS CORRECTION IN PATIENTS ON CHRONIC DIALYSIS
Authors: Zinovev Dmitriy , Novitskiy Vladimir , Malkoch Andrey
Published: June 2020

Background and Aims

Bone and mineral disorders (BMD) is a common complication of CKD in patients on chronic dialysis. Timely and adequate correction of BMD is the most important aspect of patient's treatment. This work presents a system for forecasting of phosphate-binding agents (PBA) dosage and vitamin D receptor activators (VDRA) dosage. The system consists of sequentially triggering artificial neural network forecasting models (separate model for each drug type).

Method

As an input dataset, system uses patient’s results of laboratory studies (blood calcium, phosphate and PTH) for the period of 6 months, information on previous drug therapy and data on adequacy of patient’s dialysis therapy. The output of the system are dosages of PBA an VDRA that have to be administered in order to bring the patient’s parameters as close as possible to target range of values (2.1-2.5 mmol/l for calcium, 0.87-1.5 mmol/l for phosphate and 150-300 pg/ml for PTH). The system consists of two sequentially triggering forecasting models (for PBA and for VDRA), where each model is an artificial neural network, that has been trained on a data, collected in more than 20 “Nefrosovet” hemodialysis clinics for the period of 3 years.

The effect of system usage was examined for the group of 356 hemodialysis patients with median follow-up time of 3 month. The primary end-points were a number of patients in target range of values With respect to calcium (2.1-2.5 mmol/l), phosphate (0.87-1.5 mmol/l) and PTH (150-300 pg/ml).

Results

During the study we determined that as a result of using the dose forecasting system, number of patients in target range of values significantly increased with respect to calcium (from 178 to 209, p=.0196), phosphate (from 99 to 152, p=.0000), and PTH (from 83 to 109, p=.0281).

Conclusion

Employment of automated drug dosage forecasting system based on artificial neural network models, has a positive effect on BMD correction quality, which, in turn, reduces the risk of possible complications.
P1397LONG-TERM EFFICACY AND SAFETY OF ETELCALCETIDE IN HEMODIALYSIS PATIENTS WITH SEVERE SECONDARY HYPERPARATHYROIDISM
Authors: Massimetti Carlo , Micarelli David , Feriozzi Sandro
Published: June 2020

Background and Aims

Currently the therapeutic strategies most frequently used in the treatment of secondary hyperparathyroidism (SHPT) are represented by vitamin D receptors activators (VDRAs) and cinacalcet. However, both drugs have side effects that limit their use. Recently, in the treatment of SHPT has been introduced the etelcalcetide, a second generation calcimimetic given intravenously (i.v.). This new route of administration could improve adherence to therapy and reduce gastrointestinal side effects. The aim of the study was to evaluate the efficacy and safety of the etelcalcetide in hemodialysis (HD) patients with SHPT inadequately controlled with traditional therapy (cinacalcet and/or VDRAs), or who had side effects with cinacalcet, or that were not adherent to cinacalcet therapy.

Method

For this purpose we have selected 28 HD patients with inadequate control of SHPT (PTH > 500 pg / ml; range 502-2148 pg/ml). Serum albumin-corrected calcium (sCa), phosphate (P), calcium–phosphate product (Ca x P), and PTH were assessed monthly. Baseline 19 patients were taking stable doses of active vitamin D analogs and all patients were taking phosphate binders. Etelcalcetide was administered three times a week after each hemodialysis session. The starting dose was 2.5 or 5.0 mg and then adjusted between 2.5 and 10.0 mg according to sCa and PTH levels. Treatment was temporarily withheld for sCa <7.5 mg/dl, or symptomatic hypocalcemia and was subsequently resumed at a lower dose. The primary endpoint was a PTH reduction > 30% compared to baseline levels.

Results

At present 12 months have passed since the beginning of etelcalcetide therapy. In most patients PTH levels were reduced immediately after the start of therapy. After 12 months we observed a reduction > 30% in 82% of patients, meanly -54% with a range between – 22% and – 81%. On average PTH levels decreased from 1167±444 to 558±310 pg/ml (P<.001). Serum calcium significantly reduced already after one month of therapy settling on stable levels from the third month onward, sCa decreased from 9.7±0.4 to 9.2±0.5 mg/dl (P<.01). However, the percentage of patients treated with calcium salts rose from 21% at baseline to 44% at F-U, mean dose at F-U 1.8 ± 0.9 g/d, while the percent of patients treated with VDRAs increased from 68% to 91%. Serum phosphate decreased from 6.4±1.4 to 4.6±1.3 mg/dl (P<.001), Ca x P decreased from 60±13 to 42±12 mg2/dl2 (P<.001). The median average dose of etelcalcetide at F-U was 6.2 ± 1.7 mg/HD, with a range of 2.5-10.0 mg/HD. Throughout the study, the only side effect was asymptomatic hypocalcemia that required the use of calcium salts. There were no gastrointestinal adverse effects.

Conclusion

Our results confirm that in hemodialysis etelcalcetide therapy is effective and safe in the control of SHPT refractory to conventional therapy over a 1-year treatment period.
P1408PAIN MANAGEMENT IN CALCIPHYLAXIS: A KNOWLEDGE,ATTITUDE AND PRACTICE SURVEY AMONG PHYSICIANS
Authors: Chinnadurai Rajkumar , Miller Mary , Lowney Aoife , Sinha Smeeta
Published: June 2020

Background and Aims

Calciphylaxis is a rare disease usually seen in patients with end-stage renal disease. Pain is a hallmark of this disease and can be extremely difficult to control. Anecdotal data suggests that pain management in calciphylaxis is unsatisfactory with differing practice, variable across the United Kingdom (UK) and also around the world. This knowledge, attitude and practice (KAP) survey aims to gather information on the current practice in the management of pain in patients with calciphylaxis.

Method

A pre-tested online questionnaire was circulated among physicians (renal and palliative care) involved in the management of pain in calciphylaxis. (https://www.gmann.co.uk/ website/calciphylaxis-pain-management-survey.cfm). The questionnaire included a mix of open-ended questions and questions with drop down options.

Results

One hundred and six clinicians responded to the survey of which 60 (57%) respondents were from palliative medicine and the remainder 46 (43%) were from renal medicine. There were 31 (30%) respondents, across both specialties who had not encountered any patients with a diagnosis of calciphylaxis (renal-2, palliative care-29). 18% of renal physicians refer patients to palliative care team, 32% refer to pain team and 50% refer to both. Only 3% of the palliative medicine respondents indicated that they’d received a referral from the renal team at the time of diagnosis. Opioids were the preferred initial drug of choice for the management of all types of pain although the preferred drug varied with the specialities (Fig–1). Paracetamol was universally selected as the preferred first-choice adjuvant agent for management of all types of pain. Additional procedures to aid pain management (epidural analgesia and nerve blocks) were used by 6.6% of respondents. A majority (83%) felt the presence of infection impacts on the effectiveness of pain control. The importance of advanced care planning was also highlighted with 72% undertaking advanced care planning discussions often or most of the times.

Conclusion

In conclusion, there was wide variation in the current practice of management of pain in calciphylaxis, with variation between renal specialists and palliative care specialists. Referral to pain specialists is not universal despite the severe nature of the pain experienced by patients with calciphylaxis. The data generated will enable to us to develop practice guidelines to support complex pain management in a group of patients with multiple comorbidities.
P1413EFFECT OF PULSE ORAL VERSUS INTRAMUSCULAR VITAMIN D REPLACEMENT IN HEMODIALYSIS PATIENTS WITH VITAMIN D DEFECIENCY
Authors: Shaarawy Abdelbassit , Anwar Waleed , Abdelmoneim Behairy Said Maha , Khedr Lina , Elsharabasy Reem , Mahmoud Zinab
Published: June 2020

Background and Aims

Low 25-hydroxyvitamin D (25(OH)D) level is common in patients with chronic kidney disease and hemodialysis (HD) patients . It has been associated with high bone turnover, secondary hyperparathyroidism (SHPT), and decreased bone mineral density (BMD). We aimed to investigate the efficacy of equivalent doses of pulse oral cholecalciferol (25,000 IU weekly for 12 weeks) versus single intramuscular cholecalciferol (300,000 IU) in correcting serum 25 (OH) D levels in HD patients.

Method

Prospective randomized open label Clinical trial. 40 prevalent HD patients with vitamin D deficiency were enrolled. Serum 25 hydroxy-vitamin D (25 (OH) D) level < 20 ng/m and Serum parathyroid hormone level ( iPTH) >100 pg/ml. Exclusion Criteria were serum calcium > 10 .5mg/dl, Calcium phosphorus product ≥ 55, tertiary hyperparathyroidism and Parathyroidectomy among others. Patients were randomized equally into two groups. 36 patients were compliant and completed the study. Group I :17 HD patients received oral cholecalciferol 25000 IU weekly of (Vidrop® 2800 IU/ml ) for 12 weeks. Group II: 19 HD patients received a single intramuscular injection (IM) of cholecalciferol 300,000 IU (Devarol® 200000 IU/ ampoule). Vitamin D supplements were stopped if serum calcium >10.5mg/dl or 25(OH) D level > 100 ng /ml (toxic level) during study. Serum calcium (albumin-adjusted), phosphorus, 25(OH) D by ELISA, Alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) were monitored at baseline, 6 and 12 weeks of intervention. Both groups were maintained on their regular medications used to control mineral bone disorder as: alfacalcidol, sevelamer or a calcium-based chelator.

Results

Significant increase in serum 25(OH) D level in group II patients who received single dose IM Cholecalciferol after 12 w. Means of 25 (OH)D levels basal and 12 w of study were (10.54±5.14 and 13.45 ±5.72) ng/ml respectively. There was a significant increase in the mean of serum calcium basal and at 12 w (8.19±0.69 and 8.42 ±0.54) mg/dl respectively. No significant reduction in the iPTH level or any significant change in the serum phosphorus level was noticed.

compared to group I with oral vitamin D, there was an insignificant change in the mean of serum 25(OH) D basal and at 12 w were (11.91±6.13 and 9.30±5.29) ng/ml respectively, associated with insignificant increase in serum calcium and an insignificant change in either the level of phosphorus or iPTH level.

Conclusion

Cholecalciferol 300,000 IU IM single dose showed better response on serum 25 (OH) D and calcium levels as a treatment of hemodialysis patients with Vitamin D deficiency compared to weekly oral dose for 3 months.
P1416EFFECT OF SWITCH FROM CINACALCET TO ETECALCETIDE IN HEMODIALYSIS PATIENTS WITH A POOR CONTROL OF SECONDARY HYPERPARATHYROIDISM
Authors: Rivero Garcia Karen , Tamayo Arroyo Sebastian , Tamayo Sebastian , Martin-Centellas Jesus , Rodríguez Campón Alejandro , Fraile Gómez Pilar , Correa Marcano Luis , Tabernero Fernandez Guadalupe , Martin Arribas Alberto , Lerma Marquez Jose Luis , González Zhindon Gabriela , Menacho Miguel Jose Antonio , Heras Benito Manuel
Published: June 2020

Background and Aims

Patients on hemodialysis (HD) show a high incidence of secondary hyperparathyroidism (SHPT). An inadequate control of this condition increases morbidity and mortality, most of the times due to lack of adherence to the treatment. There is currently an available intravenous calciomimetic drug that could be an alternative to improve the prognosis and management of SHPT.

Objectives

To analyze the switch from cinacalcet to etelcalcetide in patients with a poor control of SHPT.

Method:

A descriptive observational study was carried out with patients on HD with iPTH levels over 400 pg/mL who had previously been treated with cinacalcet for at least 6 months and then with etelcalcetide for a year. The analysis assessed their basal characteristics, the evolution of their analytical parameters (calcium/phosphorus/iPTH) and their comorbidity, and a questionnaire was completed to observe their adherence to treatment.

Results

The study included 34 patients; average age 65±15 years (58% men); hemodialysis time 84±69 months. The main comorbidities were: 97% hypertension; 44% diabetes; and 47% heart disease. The average basal dose of cinacalcet was 62±26 mg/session, and the average dose of etelcalcetide was 2.8±2.6 mg/session. Over the 12 months of treatment with etelcalcetide a better control of iPTH was observed (from 681±279 to 291±190, p=0.004), with a decrease of iPTH by >50% in 79% of the patients. There were no significant changes in the levels of albumin, calcium or magnesium, but a significant decrease was observed in the levels of phosphorus, Ca x P product and alkaline phosphatase. 44% of the patients showed hypocalcemia after 6 months of treatment, which was asymptomatic in all cases and was corrected with an increase in the oral administration of calcium (44%) or with a change of dialysate [Ca] concentration (50%). None of the patients reported clinical intolerance with etelcalcetide. Table 1:

Conclusion
P1417ALTERED CATHEPSIN-K LEVELS REFLECT SEVERITY OF MINERAL BONE DISEASE AND INFLAMMATION IN CHRONIC HEMODIALYSIS PATIENTS
Authors: Coppolino Giuseppe , Greco Marta , Leonardi Giuseppe , Provenzano Michele , Tripolino Omar , Arcidiacono Valentina , Donato Cinzia , Chiarella Salvatore , Russo Emilio , Foti Daniela , Fuiano Giorgio , Andreucci Michele , Bolignano Davide
Published: June 2020

Background and Aims

Mineral bone disease (MBD) and chronic inflammation are key triggers of the exceeding cardiovascular risk that characterizes dialysis patients. Cathepsin-K (Cts-K) is a lysosomal cysteine protease involved in bone remodeling and resorption, whose expression is promoted particularly by inflammation and whose involvement in bone and cardiovascular disorders has previously been demonstrated. We set out to undertake an exploratory, observational study to assess the possible clinical significance of Cts-K in dialysis patients.

Method

Eighty-five chronic HD patients (mean age 67±12, median dialysis vintage 3.2 yrs) with stable dry weight were studied. Cts-K was measured in peripheral blood samples before a mid-week dialysis session together with standard biochemical parameters. Twenty-six healthy subjects, matched with HD patients for age and gender, served as controls.

Results

Cts-K was statistically higher in HD patients than in controls (median 340, IQR 170-835 vs. 190 IQR 20-120 pg/mL, p<0.0001). At univariate analyses, Cts-K levels were significantly associated with ALP (r=0.50, p<0.001), CRP (r=0.46, p<0.001), PTH (r=0.24,p=0.02), presence of diabetes (r=0.28,p<0.001),peripheral vasculopathy (r=0.20, p=0.05) and dialysate calcium concentration (r=-0.28,p<0.001). In a multivariate model including all univariate predictors (R2=61%, p<0.001) only ALP (β=0.70,p<0.001), CRP (β=0.49,p<0.001) and dialysate calcium concentration (β -0.40,p=0.04) remained significantly associated with Cts-K levels. Interestingly, Cts-K levels were significantly higher among individuals who were under active calcimimetic therapy (n=28; p<0.001) but significantly lower among those who previously underwent parathyroidectomy (n=8; p<0.001) (Figure 1).

Conclusion

Cathepsin-K is a biomarker at the crossroads of bone and inflammatory disorders in chronic hemodialysis patients. Future research is needed to clarify the exact pathophysiological role of this protein and to test its potential usefulness as a marker for managing MBD therapy and complications.
P1419U- SHAPED ASSOCIATION OF SERUM PARATHYROID HORMONE AND COGNITIVE DYSFUNCTION IN MAINTENANCE HAEMODIALYSIS PATIENTS
Authors: Ammar Yaser
Published: June 2020

Background and Aims

Primary hyperparathyroidism (HPT) is linked with several cognitive and affective disorders in the general population that tend to improve following parathyroidectomy. Most end- stage renal disease (ESRD) patients treated with maintenance haemodialysis (MHD) have 2ry/3ry HPT encompassing a broad range of serum intact parathyroid hormone (S. iPTH) values. They commonly suffer some degree of cognitive dysfunction (CODY) that impairs medication adherence and quality of life. This CODY results from the interplay of multiple factors, including HPT. However, relative hypoparathyroidism may as well cause CODY in the setting of adynamic bone disease and increased cerebrovascular calcification. Therefore, the relationship between S. iPTH and CODY in MHD patients needs to be clearly characterized across the whole spectrum of iPTH values.

Method

Seventy two stable ESRD patients (39 males, median age 50y) treated with thrice weekly low flux MHD for > 6 months underwent Montreal cognitive assessment- basic version (MoCA-B) and pre-dialysis assessment of S. iPTH, vitamin D3, alkaline phosphatase, urea, creatinine, calcium, phosphorus and haemoglobin (Hb).

Results

CODY, defined by a MoCA-B score < 24/30, occurred in 37/72 (51%) patients. MoCA-B score had a statistically significant positive correlation with Hb level. A quadratic inverted U-shaped curve provided the best estimate for the relation between S. iPTH and MoCA-B score (P = 0.019, Figure). Among patients in the highest S. iPTH tertile, S. iPTH has a statistically significant negative linear correlation with MoCA-B score (r = - 0.565, P = 0.004). This correlation was attenuated but persisted after controlling for Hb level (r = - 0.516, P = 0.012).

Conclusion

Anaemia and HPT are important contributors to the high prevalence of CODY in MHD patients. Both markedly high and relatively low (still above normal) S. iPTH levels are associated with lower MoCA-B scores, indicating a U- shaped relation between S. iPTH and CODY. Contrary to other populations, some degree of mild (permissible) HPT is most compatible with near normal cognitive function in MHD patients. Our results emphasize the recommendation of avoiding overzealous suppression of PTH secretion in these patients.
P1421SERUM OSTEOPROTEGERIN LEVEL IS NEGATIVELY ASSOCIATED WITH BONE MINERAL DENSITY IN PATIENTS UNDERGOING HEMODIALYSIS
Authors: Lu Chia-Wen , Hou Jia-Sian , Hsu Bang-Gee
Published: June 2020

Background and Aims

Osteoprotegerin, a potent osteoclast activation inhibitor, decreases bone resorption and positively affects bone mineral density (BMD). Our aim was to evaluate the relationship between BMD and fasting serum osteoprotegerin concentration in hemodialysis patients.

Method

Fasting blood samples were obtained from 75 chronic hemodialysis patients. BMD was measured by dual energy X-ray absorptiometry in lumbar vertebrae (L2-L4). Serum osteoprotegerin levels were measured using a commercial enzyme-linked immunosorbent assay.

Results

A total of 7 patients (9.3%) had osteoporosis and 20 patients (26.7%) had osteopenia in hemodialysis patients. Older age (p = 0.023), increased serum osteoprotegerin (p < 0.001), urea reduction rate (URR, p = 0.021), Kt/V (p = 0.027), while decreased height (p < 0.001), body weight (p < 0.001), body mass index (BMI; p < 0.001), and logarithmically transformed triglyceride (log-triglyceride, p = 0.020) was significantly correlated with low lumbar T-score cut-off points between groups (normal, osteopenia, and osteoporosis) in hemodialysis patients. Female patients had lower lumbar BMD than male hemodialysis patients (p = 0.002). Univariate linear regression analysis indicated lumbar BMD were positively correlated with height (p < 0.001), body weight (p < 0.001), BMI (p < 0.001), log-triglyceride (p = 0.004), creatinine (p = 0.016), while negatively correlated with age (p = 0.001), alkaline phosphatase (p = 0.016), URR (p = 0.012), Kt/V (p = 0.013), and osteoprotegerin (p < 0.001) among the hemodialysis patients. Multivariate forward stepwise linear regression analysis of the significant variables revealed that female hemodialysis patient (adjusted R2 change = 0.040; p = 0.003), body weight (adjusted R2 change = 0.126; p = 0.001), kt/V (adjusted R2 change = 0.024; p = 0.034) and osteoprotegerin (adjusted R2 change = 0.332; p < 0.001) were the independent predictors of lumbar BMD values in the hemodialysis patients.

Conclusion

Our study results revealed that increased serum osteoprotegerin levels were independently associated with decreased BMD in the lumbar spine, and with increased risk of osteoporosis in hemodialysis patients.
P1424IMPACT OF DIRECTLY OBSERVED TREATMENT OF ONE ALFACALCIDOL ON MINERAL BONE DISORDER PROFILE IN DIALYSIS PATIENTS-A SINGLE UNIT PILOT STUDY
Authors: Baig Mirza Yasar , Chinnadurai Rajkumar , Chrysochou Tina
Published: June 2020

Impact of directly observed treatment of one-alfacalcidol on mineral bone disorder profile in dialysis patients- A single unit pilot study

Background and Aims

Secondary hyperparathyroidism (SHPT) is a common mineral bone disorder observed in patients with end-stage renal disease. Management of SHPT can be challenging mainly due to poor medication compliance. Directly observed treatment (DOT) has shown to improve management outcomes in other conditions like tuberculosis. We conducted a pilot study to investigate the impact of DOT with one alfacalcidol for SHPT in our cohort of dialysis patients.

Method

This prospective observational study was conducted on 21 end stage renal disease patients on dialysis from a single centre who were commenced on one alfacalcidol on dialysis days under direct observation .All patients had not shown any improvement in PTH despite increase in one alfacalcidol either admitted to or were suspected to have medication non-adherence. Serum bone mineral profile including parathormone (PTH), corrected calcium, phosphate and alkaline phosphatase were recorded before and after initiation of DOT. Treatment outcome was measured by comparing the mean change in the biochemical profile prior DOT initiation and at the lowest PTH value achieved on DOT. Data was analysed by paired t test using SPSS software.

Results

The mean age of our sample at the time of commencing DOT therapy was 52 years. Our sample had a predominance of males (67%) and Asian ethnicity (62%). 71% had a history of hypertension and 43% were diabetic. DOT one alfacalcidol therapy produced a significant reduction in the mean PTH value (pre-DOT- 92.2 vs post DOT-36.1 pmol/L, p<0.001). There was a significant rise in the corresponding mean corrected calcium levels (pre-DOT- 2.22 vs post-DOT-2.45 mmol/L, p=0.001) (table–1). Over a mean follow up of 8 months, a significant reduction in the one alfacalcidol dose requirement was observed in 52.38% of our cohort.

Conclusion

DOT one alfacalcidol therapy produced a significant improvement in the mineral bone profile in our cohort of dialysis patients. DOT approach can help to improve the outcomes in dialysis patients with poor compliance.
P1427ROLE OF ETECALCETIDE IN THE MANAGEMENT OF SECUNDARY HYPERPARATHYROIDISM
Authors: Moliz Candela , Canllavi Elisabeth , Redondo Beatriz , Fernandez-Vidal Maria , Bada Bosch Teresa , Trujillo Hernando , Aubert Lucia , Sandino Justo , Gutiérrez Vilchez Elena , Mérida Evangelina
Published: June 2020

Background and Aims

Secondary Hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD). Etelcalcetide is the first intravenous calcimimetic authorized for the treatment of SHPT in haemodialysis (HD). It has proven to be effective in lowering parathyroid hormone (PTH), with an acceptable and comparable safety profile. The aim of this descriptive study was to evaluate the results of using etelcalcetide in patients on HD with SHPT.

Method

Thirty patients on HD received etelcalcetide were enrolled (figure 1). The minimum observation period was 6 months. Fifteen (50%) were previously with cinacalcet (group 1) and 15 (50%) received etelcalcetide at onset (group 2). We analyzed change of serum iPTH, calcium (Ca) and phosphorus (P) in both cohorts; as well as the dosage of calcium carbonate, non-calcium (phosphate binders) and / or vitamin D analogs. The presence of adverse effects were also recorded.

Results

Thirty patients on HD received etelcalcetide were enrolled (figure 1). The minimum observation period was 6 months. Fifteen (50%) were previously with cinacalcet (group 1) and 15 (50%) received etelcalcetide at onset (group 2). We analyzed change of serum iPTH, calcium (Ca) and phosphorus (P) in both cohorts; as well as the dosage of calcium carbonate, non-calcium (phosphate binders) and / or vitamin D analogs. The presence of adverse effects were also recorded.

In global, serum iPTH levels were significantly decreased during therapy compared to baseline levels. When comparing both groups, we found a significant decrease of Ca, P and iPTH in group 2. However, we only found significant decrease of Ca in group 1 (figure 2). When we analyzed the reducton of PTH >30% in both groups, we observed that 46.6% of patients treated with etecalcetide compared to 33.3% of patients treated with cinacalcet, achieved this reduction in PTH. The dosage of calcium binders (33.3% pretreatment vs 56.7% at the end of follow-up, p 0.054), non-calcium binders (40% pretreatment vs 63.3% at the end of follow-up, p 0.02) and vitamin D analogues (56,7% pretreatment vs 66,7% at the end of follow-up, p 0,3) were increased when etelcalcetide treatment was started. No changes were made in dialysate calcium concentration. Six patients, presented hypocalcemia (Ca < 7.5 mEq/l).

Conclusion

In our cohort, etelcalcetide has shown to be effective in reducing serum iPTH. In addition, etecalcetide was noninferior to cinacalcet reducing PTH>30%. An increase in the use of vitamin D analogues, calcium binders and non-calcium binders has been observed, probably due to the hypocalcemia.