bluuebunny/crossref_metadata_2025 huggingface dataset:
MO572BONE BIOPSY AND MINERAL METABOLISM, CARDIOVASCULAR DISEASE AND PATIENT SURVIVAL IN END-STAGE RENAL PATIENTS
Authors: Ferreira Ana Carina , Cotovio Patrícia , Aires Inês , Mendes Marco , Navarro David , Silva Cecília , Caeiro Fernando , Salvador Rute , Correia Bruna , Cabral Guadalupe , Nolasco Fernando , Ferreira Manuel Anibal A
Published: May 2021

Background and Aims

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is frequent in end-stage renal disease (ESRD) patients, increasing morbid-mortality. The aim of this study was to determine the prevalence and phenotype of bone disease before transplantation; and to correlate FGF23, klotho and sclerostin serum levels with bone histomorphometric parameters and CV disease. The secondary aim was to correlate bone biopsies data with other bone related parameters, as PTH, bone alkaline phosphatase, 25-hidroxivitamin D3, calcitonin, calcium, phosphorus, and magnesium.

Method

We performed a prospective cohort study of a sample of ESRD patients listed for renal transplant. All patients were submitted to renal transplant and were followed for 12 months. Patient and graft survival were recorded. At inclusion, demographic and clinical data were collected, laboratorial evaluation; bone biopsy and X-ray of the pelvis and hands (Adragão score) were performed. Continuous variables are presented as medians and categorical variables as frequencies. Associations between variables were performed using Wilcoxon rank sum test, Fisher and Kruskal Wallis test. Multivariate analysis was performed using logistic regression. STATA software was used and p < 0.05 was considered statistically significant.

Results

We included 84 patients. Median age 53.5 (IQ range: 40.5 – 61.5) years, 59 men (70.2%), 65 caucasian (77.4%). The median left ventricular mass index was 108.5 (92 – 129) g/m2, with 32 patients presenting left ventricular hypertrophy and 19 valve calcifications. Median Adragão score was 1 (0 – 2). We diagnosed adynamic bone disease in 15 patients; hyperparathyroid bone disease in 19 patients; osteomalacia in 1 patient and mixed renal osteodystrophy in 3 patients. At the end of 12 months, 4 patients died, 5 had graft failure (non-primary function) and 4 had a cardiovascular event. Sclerostin was found to be a risk factor for low bone volume; whereas low phosphorus, low FGF23 and high bAP risk factors for abnormal mineralization. High turnover was mainly present in patients with high bAP and phosphorus and low sclerostin levels. The presence of valve calcifications was associated with low volume and with low or high turnover disorder. FGF23 appears as an important independent factor for vascular calcifications [as well age (p=0.009), BMI (p=0.02), presence of diabetes (p=0.01)], and for cardiovascular events. Sclerostin emerged as a risk factor for vascular calcifications and lower levels of sclerostin were associated with patient survival at the end of 12 months.

Conclusion

From the bone-derived hormones, sclerostin and FGF23 seem to act as risk factors for vascular calcifications and worse outcomes.
MO573CNI AND MTORI-BASED REGIMENS ON FIVE-YEAR COURSE OF BONE MINERAL DENSITY SCORES AFTER RENAL TRANSPLANTATION
Authors: Korucu Berfu , Yeter Hasan Haci , GÜZ Galip
Published: May 2021

Background and Aims

Since glucocorticoids are used in low maintenance doses today, the relationship between calcineurin inhibitors (CNI) and osteoporosis after solid organ transplantation has gained clinical significance. In contrast, (mammalian target of rapamycin inhibitors) mTORi agents are shown to have an antiresorptive effect on bone by reducing osteoclastic activity in vitro and in vivo. We investigated the bone mineral density (BMD) changes on an extremely selective group of incident renal transplant recipients under CNI or mTORi-based maintenance treatment regimens during the first five-year posttransplant course.

Method

This study consists of renal allograft recipients with a dialysis history of less than one year. Patients older than 50 years old, using CNI - mTORi combinations, patients with a history of a prior renal transplant, acute rejection, CNI – mTORi switch after posttransplantation first three months, bisphosphonate treatment, parathyroidectomy, diuretic use, and malignancy excluded to eliminate all confounding factors for bone mineral loss. First and fifth-year BMD scores and simultaneous laboratory parameters were evaluated.

Results

CNI (n=21) and mTORi (n=17) groups had similar demographics, dialysis vintages, cumulative steroid doses, first and fifth-year parathormone, calcium, phosphate, magnesium, alkaline phosphatase, and 25-OH-vitamin D levels. The femur neck scores of the CNI group decreased from -0.82(±0.96) to -1.52(±0.92) (p=0.020). We observed a significant decrease in the CNI group compared to the mTORi group [-0.70(±0.68) and 0.30(±0.36), respectively; p<0.01] when BMD score changes evaluated among years. The mean femur neck score of the mTORi group insignificantly increased from -1.13(±0.65) to -0.82(±0.56) at the fifth-year DXA scan (p=0.230). Although statistically insignificant, similar trends were also observed in L1-4 scores.

Conclusion

Our study suggests that CNI-based treatment is associated with decreased femur neck and L1-4 BMD scores, and mTORi-based treatment tends to be beneficial presumably due to their antiresorptive effects in the posttransplant five-year follow-up. Our findings may shed light on long-term maintenance therapy management in renal transplant patients with bone disease if supported by future studies.
MO575SEX DISPARITY IN THE ASSOCIATION BETWEEN DIETARY SODIUM INTAKE AND THE RISK OF INCIPIENT OSTEOPOROSIS
Authors: Yu Mi-yeon , Choi Jong Wook , Han Sang-Woong , Lee Chang Hwa , Park Joon-Sung
Published: May 2021

Background and Aims

Rationale & Objective: Dietary nutrition is closely related with bone health, but there is wide controversy on the association of dietary sodium intake with bone densitometry (BMD) and risk of incipient osteoporosis.

Method

Study Design: Community-based retrospective cohort study

Measurement: We used Tanaka method for estimating 24-h urinary sodium excretion (e24hUNaETanaka) as candidate indicator of dietary sodium intake.

Setting & Participants: Using long-term follow-up cohort data from the Korean Genome Epidemiology Study, we identified 4310 participants without osteoporosis and classified them into quartile according to their e24hUNaETanaka.

Outcome: Participants were followed up for 12 years of less for a new diagnosis of osteoporosis.

Analytical Approach: Multiple Cox-proportional hazard model was performed to estimate hazard ratio (HR) of osteoporosis and survival curve analysis was utilized to compare cumulative survivals.

Results

Decreased dietary sodium intake was deeply related with low BMD parameters. Multiple Cox-proportional hazard model, adjusted for various conventional risk factors of decreased BMD, demonstrated that e24hUNaETanaka had inverse association with the risk of osteoporosis (adjusted HR = 0.868, 95% CI = 0.768-0.981). Interestingly, our RCS analysis revealed that there was wide variation in the relation between dietary sodium intake and the risk of incipient osteoporosis according to sex and female hormone status: negative curvilinear relationship in male participants; positive linear relationship in premenopausal female participants; and negative linear relationship in postmenopausal female participants.

Conclusion

Our findings suggest that decreased sodium intake was a significant predictor of osteoporosis progression and there was some sex disparity in the relation dietary sodium intake and the risk of incipient osteoporosis.
MO579POST-TRANSPLANT HYPERCALCEMIA AND VITAMIN D SUPPLEMENTATION
Authors: Vatazin Andrey , Parshina Ekaterina , Kantaria Rusudana , Stepanov Vadim , Zulkarnaev Aleksei
Published: May 2021

Background and Aims

Post-transplant hypercalcemia is common after successful kidney transplantation in patients with chronic kidney disease (CKD) and can be partially explained by the side effects of concomitant therapy. We aimed to evaluate the prevalence of hypercalcemia among recipients of kidney transplant and its relationship with vitamin D supplementation.

Method

We performed a cross-sectional study of 236 patients underwent successful kidney transplantation in our clinic. Median age was 49 [Q1-Q3: 39; 58] years, mean estimated glomerular filtration rate (eGFR) was 51,1±21,8 ml/min/1,73 m2. Most of the patients received hemo- or peritoneal dialysis treatment, pre-emptive transplantation was performed in 6% cases. For those previously received dialysis, median duration of any type of dialysis was 21 [Q1-Q3: 11; 36] months. Median time after transplantation reached 42 [Q1-Q3: 19; 75] months. Target range for total serum Ca was defined according to National guidelines on CKD-MBD as 2,1 - 2,5 mmol/l.

Results

In our cohort median serum total Ca level was 2,41 [Q1-Q3: 2,36; 2,56] mmol/l. Hypercalcemia was encountered in 21% (7 of 33) cases during the first year after transplantation and in 30% (61 of 203) – after first year. Serum total Ca weakly correlated with iPTH (ρ= 0,282 [95%CI: 0,15; 0,4], р<0,0001), alkaline phosphatase (ρ=0,181 [95%CI: 0,05; 0,31], р=0,006) and total duration of renal replacement therapy (dialysis + transplantation) - ρ=0,2 [95%CI: 0,07; 0,32], р=0,002. We did not observe statistically significant correlations between serum total Ca and eGFR (p=0,132), total Ca level and time after transplantation (p=0,06). Total Ca levels did not differ in groups with different eGFR (p=0,04 in Kruskall-Wallis test, but no statistically significant differences after correction for multiply comparisons). Data on concomitant therapy were available for 230 patients. 173 of 230 recipients received any therapy of CKD-MBD. Of them, 123 patients took only active vitamin D (alfacalcidol), 33 patients received monotherapy with inactive vitamin D (cholecalciferol). 57 patients not taking any medications were the control group. Serum total Ca level varied significantly between groups (p=0,0006, Kruskall-Wallis test), being higher in patients supplemented with cholecalciferol - fig.1. Meanwhile, iPHT (p=0,171), serum phosphorus (p=0,563) and alkaline phosphatase levels did not differ in these three groups. Fraction of patients with normocalcemia was the lowest in cholecalciferol group (χ2, р=0,0018) - fig. 2.

Conclusion

We observed a high prevalence of hypercalcemia in kidney transplant patients, that was not associated with transplant function or time after transplantation. Our data suggest usage of active vitamin D to be safer than cholecalciferol to prevent hypercalcemia development in renal allograft recipients.
MO580HYPOPROTEIC DIET SUPPLEMENTED WITH KETOANALOGUES IN PATIENTS WITH ADVANCED DIABETIC KIDNEY DISEASE – EFFECTS ON MINERAL BONE DISORDERS
Authors: Garneata Liliana , Mocanu Carmen-Antonia , Simionescu Tudor Petrisor , Mocanu Andreea Elena , Mircescu Gabriel
Published: May 2021

Background and Aims

Dietary protein restriction is rediscussed as mainstay approach in advanced Chronic Kidney Disease (CKD), both in diabetics and non-diabetics to defer renal replacement therapy (RRT), mainly by better metabolic control; improvements in mineral bone disorders (MBD) were also suggested, but less studied in Diabetic Kidney Disease (DKD).

An unicentric prospective interventional trial aimed to assess the effects of ketoanalogue-supplemented low protein diet (sLPD) on proteinuria and CKD progression (data already presented). The parameters of MBD were also evaluated.

Method

Adult diabetic patients (452) with stable CKD stage 4+, proteinuria>3g/g creatininuria and SGA A were enrolled in a run-in phase (3 mo), with LPD (0.6g/kg dry ideal bw). Those who proved adherent (92, 64% males, median age 55.7 yrs, 65% on insulin) received sLPD (Ketosteril®, 1 tablet/10kg) for 12mo. Monitoring and treatment followed the Best Practice Guidelines.

The primary endpoint was proteinuria during intervention as compared to pre-enrolment. Serum levels of calcium, phosphates and iPTH were considered to assess MBD. Nutrition, inflammation (SGA, BMI, serum albumin, CRP) and compliance were safety parameters.

Results

In patients with advanced DKD and severe proteinuria, sLPD was associated with a 69 (63; 82) % reduction in proteinuria (data presented).

Significant amelioration in MBD was noted: serum levels of calcium and phosphates were significantly ameliorated at the end of the study as compared to enrolment - 4.3 (4.2-4.9) vs 3.2 (3.1-3.5) mg/dL and 5.4 (4.9-6.1) vs 8.2 (7.8-8.9) mg/dL, respectively. Serum iPTH significantly decreased: 185 (168-212) vs 375 (354-585) pg/mL. The need for calcium supplementation decreased: 6.5 (6.0-6.7) vs 7.0 (6.8-7.3) g/day. Vitamin D was required by only 35% vs 65% of patients.

Nutritional status was preserved and dietary compliance was very good throughout the study.

Conclusion

In patients with advanced DKD ketoanalogue supplemented low protein diet seems to be effective and safe as part of MBD management.
MO564CHRONIC EXPOSURE TO INDOXYL SULFATE CHANGES BONE PROPERTIES AND EXPRESSION OF SIRT2, SIRT3, AND SIRT7 GENES*
Authors: Karbowska Malgorzata , Sieklucka Beata , Domaniewski Tomasz , Galazyn-Sidorczuk Malgorzata , Pawlak Krystyna , Pawlak Dariusz
Published: May 2021

Background and Aims

Chronic kidney disease (CKD) is connected with accumulation of uremic toxins that leads to dysfunction of many systems including skeletal system. Indoxyl sulfate (IS) is one of the most potent protein-bound uremic toxin. However, its impact on bone and mineral disorders remains unclear. Sirtuins (SIRT) are members of the class III type nicotinamide adenine dinucleotide-dependent histone deacetylases. Their roles are commonly linked to aging, metabolism, and antioxidant defense. However, SIRT1, SIRT3 and SIRT7 maintain also bone formation. In turn, reduction of SIRT2 has a protective role due to reduced activation of osteoclasts-mediated bone resorption. Thus, the aim of this work was to evaluate IS impact on bone metabolism and bone properties, and SIRT genes expression.

Method

Male Wistar rats weighting 180 – 210 g were divided into 2 groups: experimental receiving IS in the dose of 200 mg/kg of b.w. for four weeks (200IS), and control receiving pure water (CON). After four weeks the femurs and tibiae were collected, and geometrical parameters (CI – cortical index, CSA – cortical sectional area, CSMI – cross sectional moment of inertia, MRWT – mean relative wall thickness) were measured. The IS bone (cortical and trabecular), plasma and urine levels were determined by high-performance liquid chromatography (HPLC). The concentrations of Ca, Mg, Zn, Fe, Mn, and Cu in bone tissue were determined by the flame atomic absorption spectrometry. Bone turnover markers (alkaline phosphatase – ALP, and tartrate-resistant acid phosphatase - TRAP) were determined in homogenates from trabecular and cortical left femurs. The expression of ALP, TRAP, SIRT1, SIRT2, SIRT3 and SIRT7 gene was assessed by QRT-PCR in right femurs.

Results

Plasma, urine, cortical and trabecular bone IS concentrations were increased in 200IS compared to CON. Geometrical properties of femur (CI, CSA, CSMI and MRWT) were significantly reduced in 200IS. There were no differences in relative femur weight and length between studied groups. The activity of ALP and TRAP in bone tissue were significantly lower in 200IS compared to CON. In turn, the expression of TRAP gene was increased in 200IS. There were no difference in concentrations of Ca, Mg, Fe, Mn, and Cu in bone tissue. Only Zn concentration in cortical bone was reduced in 200IS. The expressions of SIRT3 and SIRT7 were decreased in 200IS, whereas SIRT2 was increased in 200IS. Chronic exposure to IS did not affect expression of SIRT1.

Conclusion

Obtained results suggest that IS affects bone properties and bone metabolism, and has impact on expression of SIRT2, SIRT3, and SIRT7 genes. Our findings may help to better understand mechanisms leading to dysfunction of skeletal system during CKD.

This work was supported by Polish National Science Centre (Grant No. 2017/27/N/NZ4/00033).
MO582LONGITUDINAL STUDY TO FIND THE ASSOCIATION OF SERUM PHOSPHORUS LEVEL WITH FGF 23 IN THREE DIFFERENT HYPERPHOSPHATEMIA MANAGEMENTS GROUPS OF STAGE 3 AND 4 CHRONIC KIDNEY DISEASE (CKD) PATIENTS
Authors: Kaur Navjot , Mahapatra Himansu , Sharma Neera , Pursnani Lalit , B Muthukumar , Inamdar Neeraj , Singh Mansi , Arora Tannu
Published: May 2021

Background and Aims

There were paucity of clinical evidence on target serum phosphorus levelsin early CKD. Present longitudinal study finds target phosphorus level and its association with FGF 23 in three different hyperphosphatemia managements groups.

Method

This one year, prospective, randomised controlled, open labelled study was conducted among three equally allocated treatment groups in 120 screened early CKD patients.Group1 Dietary phosphorus modificationn40; Group2 calcium-based phosphate bindersn40 and Group3 non calcium-based phosphate bindersn40.Three monthly dietary assessment, MDRD e-GFR, phosphorus, calcium, iPTH, Alkaline phosphatise and six monthly FGF23, 2D Echocardiography, X ray of chest and abdomen were performed. Association of three categories of phosphorus level up to 3.9 mg/dl, 4 to 5mg/dl and >5mg/dl, rate of progression of all parameters and correlation with FGF 23among all three groups were studied.

Results

At baseline, all clinical and biochemical parameters were equally distributed with a controlled nutritional phosphate among all groups. There was no significant difference of FGF23 in all the three categories of phosphorus level among all groups. Association of serum phosphorus at the level of 5 mg/dl was there with iPTH and e-GFR at one year. Over one year there were significant decline in serum phosphorus levels in Group1 p 0.02, Group2 p 0.00,Group3p 0.05;FGF23 was declined significantly only in group3p 0.00.Correlation of FGF23 was positive and negative with iPTH r 0.19,p 0.03 and e-GFR r-0.30, p 0.00respectively but not with phosphorus p0.13

Conclusion

Serum phosphorus levels up to 5mg/dl has no effect on FGF 23 at early CKD stages. Although different treatment groups have significant phosphorus reduction, non-calcium phosphate binder has major impact on FGF23 reduction.
MO584TRABECULAR BONE SCORE AND BONE MICROARCHITECTURE IN HEMODIALYSIS PATIENTS. ITS POTENTIAL RELATIONSHIP WITH PTH-RESISTANCE : A PILOT STUDY
Authors: De paola Luciano , Ciaccio Chiara , Saturno Laura , Mascaro Maria antonietta , Ruotolo Giovanni , Vatrano Marco , Puntieri Paolo , De paola Federica
Published: May 2021

Background and Aims

To explore:i)differences in predictive variables between TrabecularBoneScore(TBS)-derived and LumbarT-score derived bone types.ii)the relationship difference of TBS and LumbarT-score with various ranges of PTH levels in order to identify the levels of PTH that overcome PTH resistance iii) to conform normal upper limit of PTHi levels in hemodialysis patients recommended by K-DIGO guidelines.

Method

In twenty-five hemodialysis patients,following variables were recorded:biochemical variables,DXA derived variables(including TBS),FRAX-tool derived HRs.The relationship of variables with TBS-derived and LumbarTscore-derived bone types was tested by univariate analysis. The association of TBS,LumbarTscore and fracture HRs with PTHi was tested by univariate analysis and regression curve fitting(maximizing R²).

Results

Using univariate analysis,the predictive variables of lumbarT-score derived and TBS-derived bone types are different.By curve fitting regression TBS vs PTHi had a sinusoidal pattern with higher values,correlating to PTHi values in the 4th quartile(462 pg/ml (341 -696)corresponding to the normal levels recommended by K-DIGO guidelines.In the same range of values,LumbarT-score vs PTHi for BMD-derived bone type has a progressively increasing trend for osteopenia and osteoporosis,with a statistically significant difference(P0.008).

Conclusion

The predictive variables of TBs-derived and LumbarT-score derived bone types are different.Bone microarchitecture(MA),measured by TBS,correlates oppositely than LumbarT-score with higher PTHi values in the normal range of PTHi levels recommended by the K-DIGO-CKD-MBD2009-2017 guidelines.Within this range,PTHi values overcome PTH-resistance and improve the bone mineral metabolism. Results must not be extended to higher or lower levels of PTHi compared to those considered in the study for which there is a clear evidence of increase in the relative risk of mortality.
MO585EFFECTS OF LANTHANUM CARBONATE AND CALCIUM CARBONATE ON CARDIOVASCULAR CALCIFICATION IN HEMODIALYSIS PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Yang Junlan , Zhang Xiao liang , Wang Lina
Published: May 2021

Background and Aims

Commonly used phosphorus-lowering drugs include calcium-containing phosphate-binding agents and non-calcium-containing phosphate-binding agents, the latter mainly including lanthanum carbonate (LC). In recent years, some studies have explored the effect of lanthanum carbonate compared with calcium carbonate on serum calcium. However, the results are different. Therefore, we conducted this review to systematically review and meta-analyze evidence on the efficacy of lanthanum carbonate and calcium carbonate (CC) and the risk of cardiovascular calcification in hemodialysis (HD) patients, and to provide reference for phosphorus-lowering drugs in HD patients.

Method

The Cochrane library, PubMed, Web of Science, Chinese journal full-text database (CNKI), WANGFANG DATA and Sino Med were searched between January 1946 and December 2020. The literatures with respect to the randomized controlled clinical trial comparing lanthanum carbonate and calcium carbonate in HD patients were selected. The two evaluators independently collected the data according to the retrieval strategy, screened the literatures according to the inclusion criteria and exclusion criteria, and summarized the literatures that met the criteria. The risk ratio (RR) and 95% confidence interval (CI) were used to represent the counting data. The standard deviation from mean (SMD) and 95%CI were used to represent the continuous variables. Forest plots, sensitivity analysis, Egger regression test and TSA were used to summarized the test performance characteristics.

Results

Of 388 original titles screened, data was extracted from 9 studies included 625 participants (Table 1). There was moderate-certainty evidence from 9 trials (625 participants) that LC can significantly reduce the progression of coronary artery calcification than CC (SMD= -0.59, 95%CI -0.94 to -0.25, P< 0.01) (Figure 2). The serum phosphorus level in the LC group was significantly lower than that in the CC group (SMD= -1.35, 95%CI: -2.33 to -0.36, P< 0.01), and the serum calcium level was significantly reduced (SMD= -1.03, 95% CI: -1.83 to -0.23, P= 0.012). The fibroblast growth factor 23 (FGF-23) level in the LC group was significantly lower than that in the CC group (SMD= -4.80, 95%CI: -7.96 to -1.64, P= 0.003). The Egger regression test of coronary artery calcification score (CACS) showed no potential publication bias (P= 0.72).

Conclusion

In this systematic review, compared with calcium carbonate, lanthanum carbonate can significantly delay the process of coronary artery calcification, and at the same time reduce the patient's serum phosphate, serum calcium and FGF-23. Therefore, we recommend LC as phosphorus-lowering drugs for HD patients.
MO586RISK OF OSTEOPOROSIS IN OBESE PATIENTS WITH TYPE 2 DIABETES: A SYSTEMIC REVIEW AND META-ANALYSIS
Authors: Lin Yen-Chung
Published: May 2021

Background and Aims

The aim of this study is to evaluate the alterations in bone marrow density and other surrogate markers for osteoporosis in obese patients with type 2 diabetes mellitus (T2DM) who received Roux-en-Y gastric bypass (RYGB) versus medical treatment as control.

Method

We searched four electronic databases and reference lists of relevant studies for eligible research published before December, 2019. After quality assessment, eligible studies were synthesized for relevant outcomes, including lumbar spine bone mineral density (L-spine BMD) change, total hip BMD change, osteocalcin level, C-terminal telopeptide (CTX) level and parathyroid hormone (PTH) level.

Results

Three randomized clinical trials and two observational studies concerning 307 total obese T2DM patients were included. Follow-up ranged from 12 to 60 months. Patients underwent RYGB surgery were associated with both higher L-spine BMD loss (mean difference: -2.90, 95% CI: -2.99∼-2.81, p<0.00001 )and total hip BMD loss (mean difference: -5.81, 95% CI: -9.22∼-2.40, p=0.0008). As to biochemical markers of bone metabolism, we found signifcantly higher osteocalcin level in medical treatment (control) group compared with RYGB group (mean difference: 11.16, 95% CI: 8.57∼13.75, p<0.00001). However, higher CTX level and PTH level were noted in medical treatment group (control) compared with RYGB group (mean difference: 0.29, 95% CI: 0.11∼0.48, p=0.002; mean difference: 1.56, 95% CI: 0.84∼2.27, p<0.0001).

Conclusion

RYGB surgery is associated with negative impact on bone metabolism and increase the risk of osteoporosis in obese patients with T2DM. We suggest that clinicians acknowledge the adverse effects of surgery and keep monitoring bone mineral components in post-RYGB populations. Further studies regarding the optimal amount of peri-operative and post-surgical supplementation should be evaluated.
MO566THE BONE EXPRESSION OF WNT INHIBITORS IN THE EXPERIMENTAL MODEL OF EARLY CHRONIC KIDNEY DISEASE
Authors: Bogdanova Evdokia , Semenova Natalia , Galkina Olga , Zubina Irina , Beresneva Olga , Ivanova Galina , Parastaeva Marina , Dobronravov Vladimir
Published: May 2021

Background and Aims

Molecular mechanisms implicated in the initial stages of inorganic phosphate (Pi) imbalance in chronic kidney disease (CKD) remain poorly understood.The aim of the study was to evaluate whether canonical Wnt pathway inhibitors (iWnt) involved in early response to Pi retention in CKD.

Methods

Mild CKD was induced by 3/4 nephrectomy (NE) in spontaneously hypertensive rats (SHR) fed rat chow diet containing 0.6 % phosphate. Controls were sham operated SHR (SO). Duration of experimental exposure (NE or SO) was 2 and 6 months. Serum levels of creatinine (Cr), inorganic phosphate (Pi), fractional Pi excretion (FEPi), intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), alfa-Klotho (KL), sclerostin (SOST) and Dickkopf-1 (DKK1) were measured. The following morphological characteristics by light microscopy of bone metaphysis and kidney tissues: the area of renal interstitial fibrosis (RF) (Masson's trichrome), bone matrix volume (MV), the active osteoblasts to trabecular cells number ratio (aOB/cells), eroded surface to bone surface ratio (ES/BS) (hematoxylin & eosin), and bone SOST and DKK1 proteins expression (by IHC) were analyzed and calculated quantitatively. Statistical comparisons among groups were performed using Mann–Whitney U-test and Kruskal-Wallis H-test.

Results

Serum Cr, RF and indices of Pi exchange in the experimental model corresponded to early CKD (Table). Pi elevated in NE6 suggestive for its renal retention. KL level decreased (Table) in all experimental groups vs control. No differences were observed in serum levels FGF23 (p=0.62) and PTH (p=0.63). Serum SOST and DKK1 levels were significantly higher in NE6 group compared to SO6 (Table). The bone SOST and DKK1 expression increased in NE6 compared to SO6 (Figure). aOB/cells were lower in NE2, SO6 and NE6 vs SO2 (all p-values<=0.041). ES/BS increased in NE2 (vs SO2) while being lowest in NE6 and SO6 animals (Table). SOST and DKK1 metaphyseal expression increased in NE6 compared to SO2, SO6, NE2 (Figure). Osteocyte SOST expression increased in SO6 compared to SO2 and NE2 without differences in later groups. Osteoblast SOST expression was also higher in SO6 vs SO2 (Figure).

Conclusion

Increased serum levels of sclerostin and Dickkopf-1 and their bone expression are apparent in early stages of experimental CKD associating with hyperphosphatemia. Alterations of bone resorption and osteoblast depopulation occurred before the increase of serum Pi likely reflecting incipient stages of renal Pi retention. These molecular and cellular events seem to be independent of systemic FGF23 and PTH response.
MO568STATIC PARAMETERS OF HISTOMORPHOMETRY FOR THE EVALUATION OF BONE TURNOVER IN RENAL OSTEODYSTROPHY
Authors: Jørgensen Hanne Skou , Behets Geert , D'Haese Patrick , Evenepoel Pieter
Published: May 2021

Background and Aims

A full histomorphometric analysis of a transiliac bone biopsy with prior tetracycline labeling remains the gold standard to diagnose renal osteodystrophy. Bone turnover is primarly evaluated by the dynamic parameter bone formation rate, calculated from the incorporation of tetracycline in bone. In cases of failed tetracycline labels, however, an evaluation of bone turnover based on static parameters is warranted. This study investigates the diagnostic accuracy of static histomorphometric parameters for the diagnosis of high and low bone turnover.

Method

Bone biopsies with prior tetracycline labeling of sufficient quality for a full histomorpometric analysis were included (n = 205). Mean age of participants was 56±13 years, 67% were men, and 22% had diabetes mellitus. Diagnostic accuracy of static histomorphometric parameters for bone turnover was evaluated by area under the receiver operator characteristics curve (AUC) statistics, against the full set of static and dynamic histomorphometric parameters. The cohort was randomly split to allow calculation of optimal diagnostic cutoffs in an exploration cohort (n=105), with subsequent validation in a separate subset of patients (n=100).

Results

All histomorphometric parameters were significantly different across categories of low (24%), normal (60%), and high (16%) bone turnover (p < 0.01), and all were significant predictors of both high and low bone turnover (Figure 1). Calculated optimal cutoffs and their sensitivities and specificities in the validation cohort are shown in Table 1.

Diagnostic accuracy was very good for high turnover, as the combination of presence of fibrosis with ObPm>5.4%, OcPm>1.5%, and OAr>2.4% provided a correct diagnosis in 94% of patients, with positive (PPV) and negative (NPV) predictive values of 80% and 96%, respectively. Using the same predefined combination, an accuracy of 80% was achieved for low turnover (no fibrosis, ObPm≤1.9% OcPm≤0.9% and OAr≤1.6%), with a PPV of 71% and a NPV of 82%.

Conclusion

Static histomorphometric parameters provide an acceptable alternative for the diagnosis of high and low bone turnover. In the absence of successful tetracycline labeling, the proposed cutoffs may provide a suitable alternative for the evaluation of bone turnover in renal osteodystrophy.
MO569MACROPHAGE PROMOTE VASCULAR CALCIFICATION VIA THE MIGRASOMES/ INTEGRIN Α5Β1 PATHWAY IN CKD
Authors: Zhu Xiaodong , Liu Yuqiu , Yang Xin , Fang Yaping , Zhang Xiao liang
Published: May 2021

Background and Aims

Patients with chronic kidney disease (CKD) have a predisposition to develop vascular calcification due to dysregulated homeostatic mechanisms. Macrophages can promote vascular calcification by releasing diverse extracellular vehicles including the newly found migrasomes (M-mig). Our previous research had found that M-mig provide nucleating foci for calcific mineral formation and initiating bone mineralization process. However, the specific mechanism by which M-mig influence the formation of vascular calcification remains incompletely understood.

Method

To study calcifying M-mig, we exposed M-mig to high Ca/P (Ca/P=3 mmol/L calcium/2 mmol/L phosphate) and/or with LPS for 1, 3, 5,7 days. The expression of M-mig surface integrin α5β1 was determined by fluorescence staining. To block the M-mig-integrin α5β1 mediated calcification, we modulated the expression of integrin α5 using siRNAs to produce M-migintegrin α5- or using 20 nM ATN-161 (small peptide antagonist of integrin α5β1) or integrin α5 antibody under high Ca/P stimulation. The stray mice artery co-cultivate with M-mig integrin α5- under high level Ca/P. Then the calcifying M-mig were assessed by TEM, Fluo-3 staining and calcium content assay.

Results

We discovered that Ca/P-stimulated macrophages released M-mig capable of mineralization. Amorphous calcium phosphate mineral deposit the surface or internal of M-mig. The M-mig exhibited increased Ca/P mineral content, implying aggregate larger calcifying M-mig that develop over time. Significantly, following a 7 days incubation with high level Ca/P, fiber tube and vesicle structure of M-mig showed rupture or fragmentation and the expression of M-mig surface integrin α5β1 increased. Pre-treatment with integrin α5β1 antagonist or block by integrin α5 antibody significantly reduced the calcifying M-mig formation. Further investigation showed that M-mig induced stray mice artery microcalcification while M-migintegrin α5- exhibited a reduce microcalcification.

Conclusion

Our finding revealed an association between microcalcification and integrin α5β1 signalling in the fiber tube and vesicle structure of M-mig and provide a new insight into vascular calcification in CKD.
MO493PATTERNS OF HYPERKALEMIA AND ASSOCIATED ADVERSE HEALTH OUTCOMES IN PERSONS WITH CHRONIC KIDNEY DISEASE
Authors: Trevisan Marco , Clase Catherine M , Evans Marie , Ludvigsson Jonas , Sjolander Arvid , Carrero Juan Jesus
Published: May 2021

Background and Aims

Patients with CKD are often described as having chronic hyperkalemia, but earlier studies have relied on a single potassium measurement. Whether the hyperkalemia in CKD is chronic or transient, and whether temporal patterns have different outcome implications, is unknown.

Method

Observational study from the Stockholm Creatinine Measurements (SCREAM) project of patients with confirmed CKD G3-5. We extracted all data on potassium measured during routine outpatient care and estimated its longitudinal trajectories. At each month, we created a rolling assessment of the proportion of time in which potassium was abnormal during the previous year, defining patterns of normokalemia (100% of time with potassium 3.5-5.0 mmol/L), transient (<50% of time with potassium >5.0 mmol/L) and chronic hyperkalemia (≥50% of time with potassium >5.0 mmol/L). We described the presence of chronic and transient hyperkalemia throughout the spectrum of CKD G3-5 and identified clinical predictors by logistic regression. Through time-dependent Cox models we examined whether previous hyperkalemia patterns offer prognostic gain beyond that of the current potassium value.

Results

We included 36,511 participants (56% women) with confirmed CKD G3-5, median age 81 years, and eGFR 46 ml/min/1.73 m2. During 3-year-median follow-up, patterns of transient and chronic hyperkalemia were observed in 15% and 4% of patients with CKD G3a, increasing to 50% and 17% of patients with CKD G5. Factors associated with chronic hyperkalemia were younger age, male sex, more severe CKD category, presence of diabetes or heart failure, use of renin-angiotensin system inhibitors, and use of potassium binders. Major cardiovascular events (MACE) occurred in 13,104 (36%) patients and 13,570 (37%) died. In time-dependent models, independent of identified confounders and of time-updated potassium values, compared with the normokalemic pattern, patients with transient (HR 1.37, 95% CI 1.29-1.46) or chronic (HR 1.17, 95% CI 1.04-1.32) hyperkalemia patterns were at higher risk of MACE. Transient hyperkalemia pattern (HR 1.43, 95% CI 1.35-1.52) and time-updated elevated potassium, but not a state of chronic hyperkalemia (HR 1.07, 95% CI 0.95-1.20), predicted the risk of death.

Conclusion

Chronic hyperkalemia occurs in 4-17% of patients with CKD G3-5. We did not observe a clear dose-response for the association between hyperkalemia pattern (normal, transient, chronic) with either MACE or death. There was modest incremental information in the previous potassium pattern, beyond potassium measured at a single time point.
MO482URINE METABOLITE LEVELS OF CKD PATIENTS ARE ASSOCIATED WITH ADVERSE KIDNEY OUTCOMES AND MORTALITY*
Authors: Steinbrenner Inga , Schultheiß Ulla T , Kotsis Fruzsina Kinga , Schlosser Pascal , Stockmann Helena , Mohney Robert P , Schmid Matthias , Oefner Peter , Eckardt Kai-Uwe , Köttgen Anna , Sekula Peggy
Published: May 2021

Background and Aims

Chronic kidney disease (CKD) affects >10% of the adult population worldwide and is associated with increased risk of kidney failure (KF) and mortality. Mechanisms underlying the variable course of disease progression are incompletely understood. This study aimed at identifying novel metabolite biomarkers of adverse kidney outcomes and overall mortality, which may offer insights into pathophysiological mechanisms.

Method

Using measurements of 1,487 metabolites in urine of 5,087 CKD patients enrolled in the German Chronic Kidney Disease study, we evaluated the association of urine metabolite levels with adverse events. Main endpoints include KF, a combined endpoint of KF and acute kidney injury (KF+AKI), and overall mortality. Statistical analysis was based on a discovery-replication design (ratio 2:1) and multivariable adjusted Cox regression models. We performed cause-specific hazard regression as well as subdistribution hazard analyses with death of other causes as a competing event for the endpoints KF and KF+AKI. Statistical significance was defined using a Bonferroni correction for the number of tested metabolites per stage. An association was considered replicated if effect estimates from both stages were significant and direction-consistent.

Results

Median follow-up time was 4 years. At time of analysis, 362 patients died, 241 experienced KF, and 382 KF+AKI. Overall, we identified 55 urine metabolites whose levels were significantly and reproducibly associated with adverse kidney outcomes and/or mortality. Cause-specific and subdistribution hazard analyses showed almost identical results. Higher levels of the amino acid C-glycosyltryptophan in urine were associated with higher risk for all three endpoints (KF: hazard ratio 1.43, 95% confidence interval [1.27;1.61], KF+AKI: 1.40 [1.27;1.55], mortality: 1.47 [1.33;1.63]). The cumulative incidence function of KF was higher for each quartile of urine C-glycosyltryptophan levels and the effect were most pronounced in the highest quartile (see Figure). The replicated metabolites belong to different biochemical classes, and those belonging to the phosphatidylcholines pathway showed enrichment. Members of this pathway contributed to the improvement of the prediction performance for KF observed when multiple metabolites were added to the well-established kidney failure risk equation by Tangri.

Conclusion

This comprehensive screen of the association between urine metabolite levels and adverse kidney outcomes and mortality identified and replicated 55 urine metabolites associated with adverse kidney events, potentially providing new insights into the mechanisms of kidney disease progression. The study represents a valuable resource for future experimental studies of biomarkers of CKD progression.
MO502EGFR TRAJECTORY AND RISKS OF CARDIOVASCULAR EVENTS AND ENDSTAGING KIDNEY DISEASE IN CKD PATIENTS
Authors: Kokubu Maiko , Uemura Takayuki , Matsui Masaru
Published: May 2021

Background and Aims

Growing evidence has shown the eGFR level is an established predictor of cardiovascular events, but the association of eGFR trajectory with cardiovascular and renal events remained limited.

Method

We conducted a retrospective cohort study on 276 CKD patients in whom at least two measurements of eGFR levels to calculate eGFR slope were confirmed. Patients were divided into two groups according to the below and above cut-off values of eGFR slopes for outcomes using ROC curve. Outcomes are cardiovascular events defined as heart failure requiring hospitalization, revascularization for IHD and PAD, stroke or sudden death, and renal events defined as ESRD or baseline eGFR decline of > 30%.

Results

In total, the median (IQR) age of participants was 68 (56∼77) years and 176 (64%) were male. The median (IQR) levels of baseline eGFR were 33 (20∼48) mL/min/1.73m2 with the median eGFR slope of -5.2(-0.85∼-9.5) mL/min/1.73m2/yr. During the study period, 92 cardiovascular events and 89 renal events occurred. Crude Kaplan-Meier analysis showed participants with lower eGFR slopes had higher probabilities of cardiovascular and renal events with statistical significances (p<0.001 and p<0.001, respectively). In the fully adjusted model, having lower eGFR slopes were associated with HRs (95%CIs) for cardiovascular and renal events of 1.71 [1.08-2.70] and 1.79 [1.09-2.93], respectively.

Conclusion

These data suggest not only current eGFR but also eGFR trajectory is an independent risk factor for cardiovascular and renal events in CKD patients.
MO508HEMATOCRIT, UREA AND GENDER (HUGE) EQUATION AND CARDIOVASCULAR EVENTS: A PROSPECTIVE STUDY IN SPANISH POPULATION
Authors: Cancho Castellano Bárbara , Robles Perez-Monteoliva Nicolas-Roberto , Felix Redondo Francisco Javier , Lozano Luis , Fernandez-Berges Daniel
Published: May 2021

Background and Aims

To evaluate the relationship between chronic kidney disease (CKD) diagnosed by the hematocrit, urea and gender (HUGE) equation and the incidence of major adverse cardiovascular events and cardiovascular mortality in a sample of Spanish general population.

Method

The sample consisted of 2,668 subjects (mean age, 50.6±14.5 years; 54.6% were female). Of them, 55 patients have a HUGE score > 0. The median follow-up was 81 (75-89) months. Serum creatinine, urea and haematocrit were analyzed after overnight fast.  The HUGE formula score was calculated for all subjects. 

Results

Event-free survival was 98.4 % at three years and 97.1% at five years of follow-up for patients with a HUGE score < 0. For patients with a estimated HUGE score higher than 0 survival was 88.9% at three years and 87.0 at five years of follow-up. (p<0.0001). Cardiovascular death survival was 94.4 % at three and 88.0 at five years of follow-up for patients with a HUGE score higher than 0. For patients with a estimated HUGE. score lower than 0 survival was 99.3% at three years, and 99.0% at five years of follow-up. (p<0.001).

Conclusion

A significantly increased cardiovascular risk was associated to the diagnosis of CKD through HUGE formula. This effect on survival could be detected despite of a very small sample of CKD patients. This relationship was close to those obtained using MDRD estimated GFR in a bigger sample of patients. HUGE formula may be a useful tool for diagnosing CKD and to evaluate the cardiovascular risk of these patients.
MO483CHA2DS2-VASC SCORE IN PATIENTS WITH EGFR<30 ML/MIN/1.73 M2 AND ATRIAL FIBRILLATION*
Authors: Freese Ballegaard Ellen Linnea , Bjerring Olesen Jonas , Kamper Anne Lise , Feldt-Rasmussen Bo , Gislason Gunnar , Torp-Pedersen Christian , Carlson Nicholas
Published: May 2021

Background and Aims

CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex) is a validated tool for evaluation of risk of stroke and systemic emboli in patients with atrial fibrillation without nephropathy. The validity of risk determination based on the CHA2DS2-VASc score in patients with severe nephropathy is untested. We investigate the validity of the CHA2DS2-VASc score in patients with eGFR<30 ml/min/1.73m2 (including dialysis treated patients) and atrial fibrillation without anticoagulation treatment.

Method

In a retrospective cohort study, all patients with atrial fibrillation and eGFR<30 ml/min/1.73 m2 were identified in nationwide Danish registers between 2008 and 2018 with subsequent exclusion of patients initiating anticoagulation treatment based on redeemed prescriptions. Cumulative incidences of stroke stratified on CHA2DS2-VASc score were computed using the Aalen-Johansen estimator, and one-year risk of stroke was calculated with comparison of CHA2DS2-VASc score based on Cox regression models adjusted for age, sex and dialysis status with G-computation of one-year risk standardized to the distribution of risk factors in the sample.

Results

From 2,452 patients with eGFR <30 ml/min/1.73 m2 and de novo atrial fibrillation, a total of 1,575 patients (64.2%) without anticoagulation treatment were included. Mean age was 78.0 years (standard deviation ±12.2), 53.3% were male, and 25.5% were on dialysis. The distribution of patients into CHA2DS2-VASc score categories of 0-1, 2, 3, 4 and ≥5 was 8.7%, 14.5%, 24.6%, 24.7% and 27.5%, respectively.

Cumulative incidence of stroke in non-dialysis dependent and dialysis-dependent patients are shown in the figure.

Overall, standardized one-year risk of stroke was 3.3% (95%CI 1.3-6.4%), 2.5% (95%CI 1.0-4.1%), 5.9% (95%CI 3.9-8.2%), 5.1% (95%CI 3.6-7.0%), and 7.3% (95%CI 5.2-10.2%) for CHA2DS2-VASc score categories of 0-1, 2, 3, 4 and ≥5, respectively. Comparably, standardized one-year risk of stroke was 2.5% (95%CI 0.3-5.7%), 1.9% (95%CI 0.0-4.7%), 7.4% (95%CI 3.2-11.5%), 4.7% (95%CI 1.0-8.3%), and 16.5% (95%CI 7.9-27.2%) for CHA2DS2-VASc score categories of 0-1, 2, 3, 4 and ≥5, respectively, in dialysis-treated patients, and 4.3% (95%CI 1.0-10.3%), 2.9% (95%CI 1.1-4.9%), 5.5% (95%CI 3.5-8.1%), 5.1% (95%CI 3.4-7.1%), and 5.9% (95%CI 3.8-8.5%) for CHA2DS2-VASc score categories of 0-1, 2, 3, 4 and ≥5, respectively, in non-dialysis-dependent patients.

Conclusion

Overall, CHA2DS2-VASc score was associated with a progressive increase in one-year risk of stroke. Although the association was most obvious in non-dialysis dependent patients, discrepancy was evident with regard to risk in patients with CHA2DS2-VASc score ≤1 in both subgroups, albeit less so in adjusted analyses.
MO515CONSTIPATION IN CHRONIC KIDNEY DISEASE: PREVALENCE AND RISK FACTORS
Authors: Sharma Sourabh , Sharma Neha , Sharma Kailash
Published: May 2021

Background and Aims

Among various gastrointestinal disorders, constipation is one of the most common symptom in chronic kidney disease (CKD). However it is often neglected by nephrologists as self-limiting condition. Constipation impacts quality of life in multiple ways and increases socio-psychological burden. Constipation and associated risk factors have been poorly studied and most studies are retrospective.

Method

We enrolled CKD stage 3 to 5 patients on regular follow-up with nephrologist from June 2018 to June 2020, at a tertiary care centre in North India. Constipation was defined using Rome IV criteria (Functional constipation) which is composed of six constipation related symptoms, and diagnosis of constipation is established by presence of two or more symptoms for at least 3 months. Patients were also asked to maintain a 7 day prospective stool diary. It consisted of seven day written prospective chart of stool form and frequency. Patients were instructed to record when each bowel movement happened and to mark stool form type for each movement as described in words and pictures on Bristol Stool Form Scale (BSFS). Opioid induced constipation was defined as per Rome IV criteria. The diagnostic criteria is similar to functional constipation, but with requisite that new or worsening symptoms occurred when initiating, changing or increasing opioid therapy.

Results

Two hundred twenty five patients were studied out of which 59 (26.2%) patients were in CKD stage3, eighty one (36%) patients were in CKD stage4 and 85 (37.8%) patients were in stage5. Out of 85 CKD stage5 patients, 23 (27%) were on dialysis. Mean age of patients was 49.1 years. Out of 225 patients, 135 (60%) were male. Constipation symptoms and diagnosis reported in each stage has been depicted in Table 1. Clinical correlates of constipation has been depicted in Table 2.

Conclusion

Constipation measured using Rome IV criteria affects around two-third of CKD stage 3-5 patients. Diabetes, hypertension and opioid use has been found to be significantly associated with constipation.