MO722PHOSPHATE-BINDER THERAPY WITH SUCROFERRIC OXYHYDROXIDE REDUCES ENDOGENOUS CALCIPROTEIN PARTICLE FORMATION AND CRYSTALLIZATION IN A POST-HOC ANALYSIS OF A RANDOMIZED CONTROLLED TRIAL IN DIALYSIS PATIENTS

Abstract Background and Aims Calcification propensity of serum can be measured with the so-called T50-test, which integrates the complex biological interplay of promoters and inhibitors of calciprotein particle formation in blood into a single readout. Calcification propensity is associated with the risk for cardiovascular events and death in dialysis patients. As we have recently demonstrated in a randomized, controlled, cross-over study in 39 chronic hemodialysis patients with hyperphosphatemia, lowering serum phosphate with high-dose phosphate-binder therapy with 2000 mg/d of sucroferric oxyhydroxide (SO) over two weeks reduces calcification propensity as determined by the T50-test compared to a two-week wash-out phase. Based on these results, we hypothesized that SO would influence endogenous calciprotein particle (CPP) formation and crystallization, i.e. conversion from primary to secondary CPP. Method To test this hypothesis, we conducted post-hoc analyses of the previously reported RCT (74% men, mean age 63±27 years, median dialysis vintage 24, IQR 16-36 months). Native serum CPP levels were measured by a fluorescent probe-based flow cytometric assay. Moreover, hydrodynamic radii (Rh) of secondary CPP formed after enrichment with exogenous calcium and phosphate was assessed by three-dimensional cross-correlation dynamic light scattering. Results Phosphate-binder therapy with SO lead to a reduction in serum phosphate levels from 2.28±0.5 mmol/l to 1.63±0.43 mmol/l (p<0.0001), accompanied by a significant reduction of endogenous calciprotein particle load and crystallization. Median (IQR) number of primary CPP decreased from 9.2x105 (7.7x105 - 12x105) particles/ml to 3.8 x105 (2.7x105 - 4.4x105) particles/ml (p<0.0001) and secondary CPP decreased from 5.4x104 (3.6x104 - 7.5x104) particles/ml to 3.2x104 (2.4x104 - 4.2x104) particles/ml (p<0.01, both by Wilcoxon matched-pairs test). Upon SO therapy we also observed a significant reduction of secondary calciprotein particle size as determined by Rh compared to phosphate-binder wash-out (214±55 nm vs. 231±52 nm, p<0.01 by paired t-test). Conclusion In chronic hemodialysis patients, lowering serum phosphate with SO is associated with a reduction in the load of primary and secondary CPP and a smaller size of secondary CPP.

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P1308PHOSPHATE-LOWERING USING SUCROFERRIC OXYHYDROXIDE: CALCIFICATION PROPENSITY (T50) IN HEMODIALYSIS PATIENTS. POST-HOC ANALYSES OF A RANDOMIZED, CONTROLLED CLINICAL TRIAL

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1308 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Ursula Thiem ◽

Rodrig Marculescu ◽

Andreas Pasch ◽

Maria Haller ◽

Daniel Cejka

Keyword(s):

Phosphate Binder ◽

Hemodialysis Patients ◽

Serum Phosphate ◽

Controlled Clinical Trial ◽

High Dose ◽

Randomized Controlled Clinical Trial ◽

Current Standard ◽

Laboratory Parameters ◽

Randomized Controlled ◽

Post Hoc

Abstract Background and Aims Lowering serum phosphate with sucroferric oxyhydroxide (SO) therapy reduces calcification propensity (measured with the T50 test) in hemodialysis patients (Cejka et al. Abstract FR-PO149, ASN Kidney Week 2019). Intriguingly, we observed considerable inter-patient variability for changes in T50 in response to SO treatment, despite similar reductions in serum phosphate. Method Post-hoc analysis of a randomized, controlled cross-over study investigating the effects of serum phosphate lowering using oral phosphate binder therapy with SO on calcification propensity (T50). Patients with changes of serum phosphate of approximately -0.5 mmol/l between phosphate binder wash-out and high dose (2000 mg/d) SO and were selected and classified as “responders” (showing profound changes in T50) and “non-responders” (showing very little change in T50). Data are shown as means ± SD. Results “Responders” (N=4) and “non-responders” (N=4) showed similar degrees of lowering of serum phosphate with high-dose SO treatment (-0.47 ± 0.06 vs. -0.49 ± 0.01 mmol/l). “Responders” showed marked increases in T50 (+108 ± 26 min), but “non-responders” did not (+6 ± 24 min). When comparing other laboratory parameters during the wash-out phase between “responders” and “non-responders”, no obvious difference in single parameters or pattern of laboratory parameters was apparent for ionized calcium (1.11 ± 0.1 vs. 1.01 ± 0.1 mmol/l), phosphate (1.76 ± 0.31 vs. 2.06 ± 0.47 mmol/l), T50 (285 ± 82 vs 271 ± 38 min), albumin (3.9 ± 0.2 vs. 4.1 ± 0.4 g/dl), magnesium (1.07 ± 0.17 vs. 0.98 ± 0.14 mmol/l), bicarbonate (22.0 ± 3.6 vs. 24.1 ± 3.0 mmol/l), iPTH (301 ± 156 vs. 463 ± 303 pg/dl) or iFGF23 (6903 ± 9480 vs. 1097 ± 927 pg/ml). Conclusion Similar degrees of phosphate lowering do not lead to a similar improvements in T50. T50 “responders” versus “non-responders” cannot be identified using current standard laboratory parameters.

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Effects of education on low-phosphate diet and phosphate binder intake to control serum phosphate among maintenance hemodialysis patients: A randomized controlled trial

Kidney Research and Clinical Practice ◽

10.23876/j.krcp.2018.37.1.69 ◽

2018 ◽

Vol 37 (1) ◽

pp. 69-76 ◽

Cited By ~ 14

Author(s):

Eunsoo Lim ◽

Sunah Hyun ◽

Jae Myeong Lee ◽

Seirhan Kim ◽

Min-Jeong Lee ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Phosphate Binder ◽

Controlled Trial ◽

Hemodialysis Patients ◽

Serum Phosphate ◽

Maintenance Hemodialysis ◽

Randomized Controlled ◽

Control Serum ◽

Maintenance Hemodialysis Patients

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P1417ALTERED CATHEPSIN-K LEVELS REFLECT SEVERITY OF MINERAL BONE DISEASE AND INFLAMMATION IN CHRONIC HEMODIALYSIS PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1417 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Giuseppe Coppolino ◽

Marta Greco ◽

Giuseppe Leonardi ◽

Michele Provenzano ◽

Omar Tripolino ◽

...

Keyword(s):

Bone Disease ◽

Calcium Concentration ◽

Cathepsin K ◽

Hemodialysis Patients ◽

Chronic Hemodialysis ◽

Future Research ◽

Dialysis Session ◽

Dialysis Patients ◽

Dialysis Vintage ◽

Dialysate Calcium

Abstract 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.

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Prescription characteristics of phosphate binders in a high pill burden for hemodialysis patients

Renal Replacement Therapy ◽

10.1186/s41100-021-00322-2 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Nobuo Nagano ◽

Kyoko Ito ◽

Takashi Ono ◽

Yuichi Ariyoshi ◽

Soichiro Masima ◽

...

Keyword(s):

Significant Negative Correlation ◽

Hemodialysis Patients ◽

Chronic Hemodialysis ◽

Phosphate Binders ◽

Pill Burden ◽

Dialysis Patients ◽

Oral Drugs ◽

Dialysis Vintage ◽

The Mean ◽

The Relationship

Abstract Background Dialysis patients have to take many oral drugs, causing a high pill burden. Phosphate binders (PBs) account for a large proportion of daily pill burden; however, the relationship between patient background and prescription status of PBs is not clear. Methods We clarified the characteristics of PBs in the total daily pill burden by analyzing the drugs prescribed for 533 chronic hemodialysis patients in our facility. Results An average of nine different types of oral drugs was prescribed for each patient. The mean and median values of total pill burden were 15.1 and 14.1 pills/day/patient, respectively. The total pill burden showed a significant negative correlation with age and a significant positive correlation with dialysis vintage. In addition, the total pill burden was significantly higher in males than in females. However, there was no difference in the pill burden between patients with and without diabetes mellitus (DM). PBs were prescribed to 409 patients (76.7%), and the mean pill burden derived from PBs was 6.44 pills/day/patient. This was by far the highest of all 35 different drug categories and accounted for 32.84% of all pills. Multiple regression analysis demonstrated that independent predictors of total pill burden were age, dialysis vintage, DM, and serum phosphorus (P) levels, and all these variables, except DM, were also independent predictors of pill burden from PBs. These variables were also selected when considering the use of calcimimetics. Conclusions A high pill burden is more likely to occur in younger patients with longer dialysis vintage, DM, higher serum P levels, and prescription of calcimimetics. In addition, PB was the single largest contributor to the total pill burden that positively and linearly linked to serum P levels. Therefore, P management is a high-priority issue in the mitigation of high pill burdens in dialysis patients.

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The effect of phosphate binder therapy with sucroferric oxyhydroxide on calcification propensity in chronic haemodialysis patients: a randomized, controlled, crossover trial

Clinical Kidney Journal ◽

10.1093/ckj/sfaa154 ◽

2020 ◽

Author(s):

Ursula Thiem ◽

Ina Soellradl ◽

Bernhard Robl ◽

Ewa Watorek ◽

Sabine Blum ◽

...

Keyword(s):

Phosphate Binder ◽

Protocol Analysis ◽

Major Adverse Cardiovascular Event ◽

Serum Phosphate ◽

High Dose ◽

Chronic Haemodialysis ◽

Open Label ◽

Adverse Cardiovascular Event ◽

Randomized Controlled ◽

Secondary Intention

Abstract Background Calcification propensity is associated with the risk for cardiovascular events and death in end-stage renal disease patients. Here we investigated the effect of lowering serum phosphate with oral phosphate binder therapy on calcification propensity. Methods We performed an open-label, randomized, controlled, crossover study in chronic haemodialysis patients with hyperphosphataemia. Patients (n = 39) were randomized in a 1:1 ratio to either low-dose (250 mg/day) sucroferric oxyhydroxide (SO) followed by high-dose (2000 mg/day) SO or vice versa, with washout phases before and after SO treatment. The primary endpoint was changed in calcification propensity as measured by calciprotein particle formation time (T50 test) between washout and high-dose SO treatment in patients with ≥85% adherence to the prescribed SO dose (per-protocol analysis). Results In the primary per-protocol analysis (n = 28), 2000 mg/day SO treatment resulted in a mean increase in T50 of 66 min (95% CI 49–84 min, P < 0.0001), from 243 ± 63 to 309 ± 74 min compared with phosphate binder washout. Serum phosphate decreased from 2.28 ± 0.5 to 1.63 ± 0.43 mmol/L (P < 0.0001). SO at 250 mg/day did not influence T50 (P = 0.4) or serum phosphate concentrations (P = 0.9) compared with phosphate binder washout. The secondary intention-to-treat analysis (n = 39) showed similar results: an increase in T50 of 52 min (95% CI 31–74 min, P < 0.0001) and a decrease in serum phosphate from 2.18 ± 0.5 to 1.64 ± 0.46 mmol/L. No major adverse cardiovascular event, case of calciphylaxis or death occurred during the study. Conclusion Phosphate binder treatment with SO improves serum calcification propensity of haemodialysis patients and might lead to improved outcomes.

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MO752EVALUATION AND ANALYSIS OF CHRONIC PAIN IN HEMODIALYSIS PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab097.0032 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Sanae Ezzaki ◽

Imane Failal ◽

Rania Elafifi ◽

Salma siham Elkhayat ◽

Ghizlane Medkouri ◽

...

Keyword(s):

Chronic Pain ◽

Cross Sectional Study ◽

Hemodialysis Patients ◽

Chronic Hemodialysis ◽

Advanced Age ◽

Dialysis Patients ◽

Cross Sectional ◽

High Prevalence ◽

Significant Intensity

Abstract Background and Aims Despite progress these recent years in support the hemodialysis, chronic pain remains a problem concern that ultimately affect the quality of life and psycho-emotional state, even among dialysis patients already psychologically fragile. However, it is often overlooked and its characteristics in chronic hemodialysis (HDC) are poorly understood. The purpose of this study was to evaluate the prevalence, features, impact and treatment of pain in our population of chronic hemodialysis patients and to determine the factors associated with it. Method cross-sectional study conducted in January 2020 including 71 chronic hemodialysis patients from the nephrology department of the CHU ibn rochd CASABLANCA. They were subjected to a questionnaire on socio-demographic characteristics, the characteristics of the pain, its impact on daily life, the various treatments performed. The pain is chronic if it persists for more than 3 months. The intensity was assessed using a visual analog scale. Results Of the 71 patients, 64.4% report chronic pain, the average age of our patients was 46.5 years, ranging from 16 to 93 years, with a sex ratio M/F 1.1, seniority hemodialysis was 17.3 years. The pain is continuous, frequent, intermittent and rare in respectively 55.5%, 27.5%, 13.7%, 3.44% of cases, it is a weak, moderate, severe, very severe in respectively: 13.7%, 58.6%, 17.24%, 10.3%, causing musculoskeletal was predominant in 75.8% of cases, the most common sites are: shoulders (47,23%), knees (34.5%), the head (41.2%) and the back (19.65%). It resounded on the patient's daily activity in 55.17%, and sleep in 41.3%, the treatment was essentially based analgesics in 58.6% of cases, these analgesics were level 1 in 47.1% cases and level 2 in 52.9% of cases. This is taken daily in 28.5% of patients, common in 42.8% and 28.5% rare among of them, the disappearance of pain was achieved in 65.51% of cases. In perdialyse, the intensity of the pain does not change in 79.4% of patients. Pain was favored by advanced age and age dialysis (advanced age (p = 0.043) and age dialysis (p = 0.01).) Conclusion Chronic pain is a major problem in hemodialysis by its high prevalence, its significant intensity and its impact on life daily patient. However its management remains inadequate. Regular assessment of pain using a well-codified questionnaire is necessary to improve the care of dialysis patients.

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Arteriosclerosis in Dialysis Patients

The International Journal of Artificial Organs ◽

10.1177/039139889601901104 ◽

1996 ◽

Vol 19 (11) ◽

pp. 638-644 ◽

Cited By ~ 25

Author(s):

J. Bommer ◽

E. Strohbeck ◽

J. Goerich ◽

M. Bahner ◽

I. Zuna

Keyword(s):

Calcium Phosphate ◽

Hdl Cholesterol ◽

Cross Sectional Study ◽

Hemodialysis Patients ◽

Chronic Hemodialysis ◽

Maintenance Hemodialysis ◽

Time Interval ◽

Dialysis Patients ◽

Cross Sectional ◽

Vldl Cholesterol

Arteriosclerosis is a constant problem in long-term hemodialysis patients. Computer tomography of the abdominal aorta allows a well-defined and reproducible evaluation of aortosclerosis. In the cross-sectional study, aortosclerosis was significantly accelerated in 84 chronic hemodialysis patients and was comparable to the results found in 20-year older control patients without renal disease. The increase of aortosclerosis correlated significantly with age of the patient, smoking, and duration of dialysis therapy. Furthermore, increased VLDL cholesterol and decreased HDL cholesterol seem to enhance aortosclerosis in our dialysis patients. In the longitudinal study (two CT scans with a time interval of 87 ± 62.7 months) in 36 dialysis patients, progressed aortosclerosis correlated significantly with the long duration of hypertriglyceridemia, VLDL cholesterol, uric acid, and calcium phosphate products. Progression of aortosclerosis was reduced in parathyroidectomized patients. The study suggests that premature aortosclerosis is found in dialysis patients. In addition to the common risk factor of aortosclerosis, disturbed calcium phosphate and parathyroid hormone metabolism seem to enhance aortosclerosis in patients under maintenance hemodialysis.

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P1406A CASE-CONTROL STUDY ON RISK FACTORS OF CALCIPHYLAXIS: DATA FROM CHINESE HEMODIALYSIS PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1406 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Yuqiu Liu ◽

Xiaotong Xie ◽

Canlin Yang ◽

Xin Yang ◽

Xiao liang Zhang

Keyword(s):

Risk Factors ◽

Serum Albumin ◽

Chinese Population ◽

Warfarin Therapy ◽

Hemodialysis Patients ◽

Serum Phosphate ◽

Serum Phosphate Level ◽

Dialysis Patients ◽

Increased Risk ◽

Significant Difference

Abstract Background and Aims Calciphylaxis (CUA) is a rare but potentially fatal disease that is commonly occurred in dialysis patients. Since there is no data based on Chinese population, the study is aimed to investigate risk factors of CUA in Chinese hemodialysis patients. Method We retrospectively evaluated medical records of 20 hemodialysis patients who were newly diagnosed with CUA by skin biopsy admitted to Zhongda Hospital Southeast University from Oct.2017 to Dec.2018. Non-CUA dialysis patients with the same age and duration of dialysis were randomly selected as controls (Ratio=1:2). Results Most of CUA patients were male (80%) and elderly (55%), while 50% had a body mass index higher than 24. The mean time interval since start of dialysis to CUA diagnosis was 114.65±81.32 months, and the median time from appearance of skin lesion to diagnosis was 6 (2, 15) months. The incidence of hyperparathyroidism was higher in patients with CUA (80% vs 62.5%), but the differences of duration of elevated serum intact parathyroid hormone (iPTH) and its highest value were not significant compared with the controls. Warfarin therapy had no significant difference between two groups (15% vs 5%). Univariate logistic regression analysis indicated that male (OR 3.619, 95%CI 1.027-12.748), each 1 point increase in score of use of vitamin D and its analogues (OR 1.505, 1.029-2.201), each 1 mmol/L increase in corrected serum calcium level (OR 24.486, 1.570-381.873), each 1 mmol/L increase in serum phosphate level (OR 5.382, 1.767-16.389), each 1 pg/mL increase in iPTH level (OR 1.002, 1.000-1.003), each 1 g/L decline in serum albumin level (OR 1.181, 1.041-1.340), each 1 IU/L increase in serum alkaline phosphatase (ALP) level (OR 1.005, 1.000-1.009) and each 1 mg/L increase in hypersensitive c-reactive protein level (OR 1.029, 1.000-1.059) were significantly associated with CUA. Serum phosphate, albumin and ALP were still significant risk factors after multivariate analysis. Conclusion This is the first report of risk factors of CUA based on Chinese population. The results show that high levels of serum phosphate and ALP, low level of serum albumin are independent risk factors of CUA in Chinese hemodialysis patients. Unlike previous research from western countries, warfarin therapy didn’t show an increased risk in this study, propably because of the low exposure rate of it in China.

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