Chronic Kidney Disease-mineral Bone Research Articles

Lymphocyte and monocyte vitamin D receptor expression during paricalcitol or calcitriol treatments in patients with stage 5 chronic kidney disease.

In this study, we aimed to investigate the effect of paricalcitol and calcitriol usage on vitamin D receptor (VDR) contents of CD8+ , CD4+ lymphocytes and monocytes in stage 5d chronic kidney disease (CKD) patients. Thirty-six hemodialysis patients older than 18years of age and 19 healthy controls (group HC) without any known acute or chronic diseases were included in the study. The group of patients undergoing scheduled hemodialysis comprised three subgroups: group CL: patients on calcitriol (n: 10), group PC: patients on paricalcitol (n: 13), and group NT: patients not taking any vitamin D or VDR activating medications (n: 13). CD8+/VDR, CD4+/VDR and MONO/VDR values were representing the ratio of VDR representing cells among related cell group. On the other hand, values of CD8+/MFI, CD4+/MFI and MONO/MFI have shown the total amount of cellular VDR content per cell which has been given as of mean fluorescence intensity in the flow cytometric process. Main CKD mineral bone disorder parameters such as a hemogram, serum BUN, creatinine, albumin, Ca, iP, iPTH, 25(OH)D3 levels were also measured. Average VDR contents in CD8+, CD4+and monocytes were not different among three patient groups on hemodialysis. But in all hemodialysis subgroups, CD8+/VDR, CD4+/VDR, MONO/VDR, CD8+/MFI, CD4+/MFI and MONO/MFI levels were found to be higher compared with the healthy control subjects (p < 0.001). Among hemodialysis groups, no significant CD8+/VDR, CD4+/VDR, and MONO/VDR content differences were found with regard to the type of VDR activator agent used. There was no difference in serum levels of 25(OH)D3 and CRP among groups participating in the study. There was no difference between CD8+/VDR, CD4+/VDR, and MONO/VDR levels in hemodialysis patients using calcitriol or paricalcitol, suggesting that both treatment agents may have a similar effect on VDR contents in lymphocytes and monocytes in that patient population. But in all hemodialysis subgroups, CD8+/VDR, CD4+/VDR, and MONO/VDR levels were found to be higher compared with the healthy control subjects, suggesting an overexpression of VDR through a non CRP and/or 25(OH)D3 dependent mechanism.

Diagnosis and Management of Chronic Kidney Disease-Mineral Bone Disease in Children

Diagnosis and Management of Chronic Kidney Disease-Mineral Bone Disease in Children

Hormonal and Mineral Imbalance Effect on Bone Resorption in Predialysis Iraqi Patients with Chronic Kidney Disease

Introduction: Chronic kidney disease mineral bone disorder is a metabolic bone disease present in almost all uremic patients. The aim of this research to indicate the stage of chronic kidney disease (CKD) that affect the bone metabolism that leading to the mineral and hormonal imbalance by studying the relationship among osteocalcin , glomerular filtration rate (GFR), parathyroid hormone, calcium and phosphorus levels in the blood. Method: The study included 52 patients with predialysis chronic kidney disease stage 3-5 and 40 apparently healthy relatives accompanying the patients. Glomerular filtration rate (GFR) was calculated for each patient. Renal function tests, including serum levels of urea, creatinine, a biochemical marker of bone metabolism: osteocalcin (OSN), calcium, phosphorus, and parathyroid hormone (PTH), were measured for each participant. Results: Serum urea and creatinine levels were significantly higher in CKD patients Than that of apparently healthy control. There is significantly higher serum parathyroid hormone, serum phosphorus, serum osteocalcin (P&lt;0.01, P&lt;0.01, P&lt;0.01 respectively) in CKD patients than that of the healthy control group. While low serum calcium level in CKD patients as compared to the corresponding group (P&lt;0.01). Conclusion: Hyperphosphatemia and hypocalcemia in the end stage of predialysis CKD patients lead to increase parathyroid hormone secretion, which causes high bone turnover characterized by significantly high serum osteocalcin in these patients. Parathyroid hormone and osteocalcin were used as a biomarker for the development of bone and mineral disorders in predialysis CKD patients.

EOS789, a novel pan-phosphate transporter inhibitor, is effective for the treatment of chronic kidney disease–mineral bone disorder

Chronic kidney disease is characterized as impaired renal function along with the imbalance and dysregulation of mineral metabolism; recognized as chronic kidney disease-mineral and bone disorder. Hyperphosphatemia, characterized by altered phosphate homeostasis along with elevated fibroblast growth factor-23 and intact parathyroid hormone, is such an alteration of mineral metabolism. We discovered a novel inhibitor, EOS789, that interacts with several sodium-dependent phosphate transporters (NaPi-IIb, PiT-1, and PiT-2) known to contribute to intestinal phosphate absorption. This inhibitor dose-dependently increased the fecal phosphorus excretion rate and inversely decreased the urinary phosphorus excretion rate in normal rats, suggesting inhibition of intestinal phosphorus absorption. In rats with adenine-induced hyperphosphatemia, EOS789 markedly decreased the serum phosphate, fibroblast growth factor-23, and intact parathyroid hormone below values found in normal control rats. Notably, this pan-phosphate transporter inhibitor exhibited a more potent effect on serum phosphate than a NaPi-IIb-selective inhibitor in rats with hyperphosphatemia indicating that PiT-1 and PiT-2 play important roles in intestinal phosphate absorption. Moreover, in a long-term study, EOS789 sustained the suppression of serum phosphorus in parallel with fibroblast growth factor-23 and intact parathyroid hormone and ameliorated ectopic calcification of the thoracic aorta. Additionally, EOS789 treatment also ameliorated kidney deterioration in rats with progressive kidney injury, probably due to the strict phosphate control. Thus, EOS789 has potent efficacy against hyperphosphatemia and its complications and could provide a significant benefit to patients who are ineffectively treated with phosphate binders.

Study of The Polymorphism BsmI and TaqI in Vitamin D Receptor Gene in Egyptian Patients With Chronic Kidney Disease

Abstract Background Chronic kidney disease (CKD) is a major public health problem and a leading cause of morbidity and mortality worldwide. Chronic kidney disease mineral and bone disorders (CKD-MBD) is a common complication of CKD and an important cause of morbidity and decreased quality of life. Serum levels of 25-hydroxy vitamin D and parathyroid hormone (PTH) provide an accurate picture of bone turnover and mineralization states therefore they could be used with other serum bone biomarkers as non-invasive sensitive bone markers to help management of MBD in CKD. Due to the complex role played by vitamin D in kidney disease, the genotyping for vitamin D receptor (VDR) variants in CKD patients has been regarded as a way for improving the management of the disease. Objective The aim of the present work was to study the association of vitamin D receptor gene polymorphisms BsmI and TaqI with the chronic kidney disease and to assess its relationship with development and progression of chronic kidney disease-mineral bone disease. Subjects and Methods The study was conducted on 60 CKD-MBD patients in addition to 30 age- and sex- matched subjects serving as a healthy control group. Patients were subdivided into two subgroups according to the stage of CKD: subgroup 1a; 30 patients with CKD-MBD under conservative management (stages: 3 and 4 CKD) and subgroup 1b; 30 CKD-MBD patients with end-stage CKD on regular hemodialysis. Determination of BsmI (rs1544410, A&amp;gt;G) and TaqI (rs731236, C&amp;gt;T) polymorphisms of VDR gene was carried out using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Results The result of the present study revealed that VDR BsmI (rs1544410) gene polymorphism and alleles (Bb, bb) were not associated with susceptibility to the CKD or development and progression of CKD-MBD in the studied CKD-MBD patients. However, having the gene variants of VDR TaqI (rs731236) tt homotypic genotype increased the susceptibility to CKD-MBD compared to having the gene variant TT wild genotype and Tt heterotypic genotype. Moreover, VDR polymorphisms were associated with the mineral status in CKD-MBD Egyptian patients. The VDR BsmI wild (BB) genotypes and the VDR TaqI homotypic (tt) variant were found to be associated with development of severe secondary hyperparathyroidism, hypocalcemia and vitamin D deficiency in the studied Egyptian patients with CKD-MBD. Conclusion VDR BsmI gene polymorphism failed to prove any association with susceptibility to the CKD or development and progression of CKD-MBD. However, VDR TaqI tt homotypic genotype increased the susceptibility to CKD-MBD and progression toward severe secondary hyperparathyroidism, hypocalcemia and vitamin D deficiency.

New scenarios in secondary hyperparathyroidism: etelcalcetide. Position paper of working group on CKD-MBD of the Italian Society of Nephrology

Bone mineral abnormalities (defined as Chronic Kidney Disease Mineral Bone Disorder; CKD-MBD) are prevalent and associated with a substantial risk burden and poor prognosis in CKD population. Several lines of evidence support the notion that a large proportion of patients receiving maintenance dialysis experience a suboptimal biochemical control of CKD-MBD. Although no study has ever demonstrated conclusively that CKD-MBD control is associated with improved survival, an expanding therapeutic armamentarium is available to correct bone mineral abnormalities. In this position paper of Lombardy Nephrologists, a summary of the state of art of CKD-MBD as well as a summary of the unmet clinical needs will be provided. Furthermore, this position paper will focus on the potential and drawbacks of a new injectable calcimimetic, etelcalcetide, a drug available in Italy since few months ago.

Spectrum of mineral bone disorder in patients with CKD stage 3-5 from eastern India

Introduction:&#x0D; Chronic kidney disease mineral bone disorder (CKD-MBD) is a major determinant of CKD associated morbidity and morbidity. We sought to find the spectrum of CKD-MBD in Eastern India.&#x0D; Methodology:&#x0D; This cross-sectional study was conducted at the Department of Nephrology Institute of Postgraduate Medical Sciences and Research Seth Sukhlal Karnani Memorial hospital Kolkata India from June 2013 and July 2014. The patients with newly diagnosed stage 3-5 CKD were evaluated for bone mineral abnormalities. Patients already on some form of phosphate binders or vitamin D analogs were excluded.&#x0D; Results:&#x0D; Total of 242 patients was included. Male to female ratio was 2.1:1. 52.1% had Diabetic nephropathy. Mean eGFR was 26.51±12.33 ml/min/1.73m2. 36.8% had CKD stage 3, 46.7% CKD stage 4 and 16.5 % had CKD stage 5. 56% had hyperphosphatemia (Phosphate&gt;4.0mg/dl). 30% had hypocalcaemia (corrected calcium &lt;8.5mg/dl). 53.4% had Vit D deficiency (25-OH Vit D &lt; 20ng/ml) and 64.9% had hyperparathyroidism (iPTH&gt;65pg/ml). There was a significant negative correlation of eGFR with Phosphate, iPTH and ALP. The distribution of phosphate, ALP and iPTH across CKD stage 3-5 was significantly different; p-&lt;0.001. 21.3% of patients with iPTH more than twice the upper limit of normal had normal ALP. There was no significant difference in serum calcium and 25-OH Vit D levels across CKD stage 3-5.&#x0D; Conclusions:&#x0D; CKD-MBD has a high prevalence. Secondary hyperparathyroidism is the most common type of CKD-MBD. 25-OH Vit D and serum calcium are determined predominantly by diet and exposure to sunlight. ALP can’t serve as a surrogate marker for iPTH.

Cinacalcet for secondary hyperparathyroidism in end-stage renal disease patients below age 5 years .

Management of chronic kidney disease mineral bone disorder (CKD-MBD) in pediatric patients with end-stage renal disease (ESRD) is challenging. While the use of calcimimetics is well-studied in adults on dialysis, few studies have been performed in pediatrics. Little is known about the use of cinacalcet in young children with ESRD. The aim of this study was to report the efficacy and safety of cinacalcet for treatment of secondary hyperparathyroidism in chronic dialysis patients younger than 5 years. We included children aged < 5 years on chronic dialysis, either hemodialysis (HD) or peritoneal dialysis (PD), who were prescribed cinacalcet for more than 1 month. Retrospective chart review was performed to gather demographics, dialysis prescription, relevant mineral imbalance laboratory parameters, and medications. Data was collected for 6 consecutive months. 18 patients (9 male), mean age at initiation of cinacalcet was 2.3 years; 13 PD and 5 HD. Average starting dose of cinacalcet: 6.2 mg daily, 0.55 mg/kg/day. Average time on dialysis was 14.4 months. Parathyroid hormone significantly decreased over the 1st month following initiation of cinacalcet from 929 (IQR 572 - 1,056) to 427 (IQR 256 - 778) pg/mL, p = 0.009. Three patients developed asymptomatic hypocalcemia (Ca < 9.4 mg/dL). Serum phosphorous decreased after initiation, and this was persistent at 6 months. Significant improvement in linear growth was observed while on cinacalcet and growth hormone (GH). Cinacalcet can be effectively used in young children on dialysis with minimal side effects. Good linear growth was seen in patients on cinacalcet and GH therapy. Long-term large scale data is necessary to confirm. Institution-based management algorithm incorporating cinacalcet would be helpful to maintain uniformity in role of cinacalcet for management of CKD-MBD.

Kidney Disease Progression Does Not Decrease Intestinal Phosphorus Absorption in a Rat Model of Chronic Kidney Disease-Mineral Bone Disorder.

The Cy/+ rat has been characterized as a progressive model of chronic kidney disease-mineral bone disorder (CKD-MBD). We aimed to determine the effect of kidney disease progression on intestinal phosphorus absorption and whole-body phosphorus balance in this model. A total of 48 Cy/+ (CKD) and 48 normal littermates (NL) rats were studied at two ages: 20 weeks and 30 weeks, to model progressive kidney function decline at approximately 50% and 20% of normal kidney function. Sodium-dependent and sodium-independent intestinal phosphorus absorption efficiency were measured by the in situ jejunal ligated loop method using 33 P radioisotope. Our results show that CKD rats had slightly higher sodium-dependent phosphorus absorption compared to NL rats, and absorption decreased from 20 to 30 weeks. These results are in contrast to plasma 1,25OH2 D, which was lower in CKD rats. Gene expression of the major intestinal phosphorus transporter, NaPi-2b, was not different between CKD and NL rats in the jejunum but was lower in CKD rats versus NL rats in the duodenum. Jejunal ligated loop phosphorus absorption results are consistent with percent net phosphorus absorption results obtained from metabolic balance: higher net percent phosphorus absorption values in CKD rats compared with NL, and lower values in 30-week-olds compared with 20-week-olds. Phosphorus balance was negative (below zero) in CKD rats, significantly lower in 30-week-old rats compared with 20-week-old rats, and lower in CKD rats compared with NL rats at both ages. These results demonstrate no reduction in intestinal phosphorus absorption with progression of CKD despite lower 1,25OH2 D status when assessed by an in situ ligated loop test, which is in contrast to the majority of in vitro studies, and if confirmed in further studies, could challenge the physiological relevance of in vitro findings. © 2019 American Society for Bone and Mineral Research.

Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular Calcification

IntroductionPatients with end-stage kidney disease (ESKD) exhibit anemia, chronic kidney disease‒mineral bone disorder (CKD–MBD), and cardiovascular disease. The REN-001 and REN-002 phase II, multicenter, randomized studies examined safety, tolerability, and effects of sotatercept, an ActRIIA-IgG1 fusion protein trap, on hemoglobin concentration; REN-001 also explored effects on bone mineral density (BMD) and abdominal aortic vascular calcification.MethodsForty-three patients were treated in REN-001 (dose range: sotatercept 0.3‒0.7 mg/kg or placebo subcutaneously [s.c.] for 200 days) and 50 in REN-002 (dose range: 0.1‒0.4 mg/kg i.v. and 0.13‒0.5 mg/kg s.c. for 99 days).ResultsIn REN-001, frequency of achieving target hemoglobin response (>10 g/dl [6.21 mmol/l]) with sotatercept was dose-related and greater than placebo (0.3 mg/kg: 33.3%; 0.5 mg/kg: 62.5%; 0.7 mg/kg: 77.8%; 0.7 mg/kg [doses 1 and 2]/0.4 mg/kg [doses 3‒15]: 33.3%; placebo: 27.3%). REN-002 hemoglobin findings were similar (i.v.: 16.7%−57.1%; s.c.: 11.1%‒42.9%). Dose-related achievement of ≥2% increase in femoral neck cortical BMD was seen among only REN-001 patients receiving sotatercept (0.3‒0.7 mg/kg: 20.0%‒57.1%; placebo: 0.0%). Abdominal aortic vascular calcification was slowed in a dose-related manner, with a ≤15% increase in Agatston score achieved by more REN-001 sotatercept versus placebo patients (60%‒100% vs. 16.7%). The most common adverse events during treatment were hypertension, muscle spasm, headache, arteriovenous fistula site complication, and influenza observed in both treatment and placebo groups.ConclusionIn patients with ESKD, sotatercept exhibited a favorable safety profile and was associated with trends in dose-related slowing of vascular calcification. Less-consistent trends in improved hemoglobin concentration and BMD were observed.

Long-term outcomes and management considerations after parathyroidectomy in the dialysis patient.

Parathyroidectomy (PTX) remains an important intervention for dialysis patients with poorly controlled secondary hyperparathyroidism (SHPT), though there are only retrospective and observational data that show a mortality benefit to this procedure. Potential consequences that we seek to avoid after PTX include persistent or recurrent hyperparathyroidism, and parathyroid insufficiency. There is considerable subjectivity in defining and diagnosing these conditions, given that we poorly understand the optimal PTH targets (particularly post PTX) needed to maintain bone and vascular health. While lowering PTH after PTX decreases bone turnover, long-term changes in bone activity have been poorly explored. High turnover bone disease, usually present at the time a PTX is considered, often swings to a state of low turnover in the setting of sufficiently low PTH levels. It remains unclear if all low bone turnover equate with disease. However, such changes in bone turnover appear to predispose to vascular calcification, with positive calcium balance after PTX being a potential contributor. We know little of how the post-PTX state resets calcium balance, how calcium and VDRA requirements change or what kind of adjustments are needed to avoid calcium loading. The current consensus cautions against excessive reduction of PTH although there is insufficient evidence-based guidance regarding the management of chronic kidney disease - mineral bone disease (CKD-MBD) parameters in the post-PTX state. This article aims to compile existing research, provide an overview of current practice with regard to PTX and post-PTX chronic management. It highlights gaps and controversies and aims to re-orient the focus to clinically relevant contemporary priorities in CKD-MBD management after PTX.

The role of uric acid in mineral bone disorders in chronic kidney disease.

Increasing survival in the chronic kidney disease (CKD) population exposes the bone to the cumulative detrimental sequelae of CKD, now defined physiologically and histopathologically as chronic kidney disease mineral bone disorder (CKD-BMD). This disorder is increasingly recognized as a "nontraditional" driver of morbidity and mortality and presents an opportunity to improve CKD outcomes via research. However, recent advances in the literature on this topic have not yet been collected into a single review. Therefore, this report aims to discuss the disordered renal-bone axis in CKD-BMD, molecular and hormonal drivers, novel treatment strategies, and forthcoming research in a clinician-directed format. A key novel topic will be the unique impact of uric acid on CKD-BMD, which is poised to apply extensive existing research in the uric acid domain to benefit the CKD-BMD population.

Exercise Alleviates Osteoporosis in Rats with Mild Chronic Kidney Disease by Decreasing Sclerostin Production

Chronic kidney disease–mineral bone disorder (CKD–MBD), comprising mineral, hormonal, and bone metabolic imbalance, is a major CKD-related issue; it causes osteoporosis prevalence in CKD patients. Osteocyte-derived sclerostin inhibits the osteogenic Wnt/β-catenin signaling pathway; its levels rise when kidney function declines. Exercise modulates the physiological functions of osteocytes, potentially altering sclerostin production. It may aid bone and mineral electrolyte homeostasis in CKD. Mild CKD was induced in rats by partial nephrectomy. They were divided into: sham (no CKD), CKD, and CKD + exercise (8 weeks of treadmill running) groups. Micro-CT scanning demonstrated that the CKD + exercise-group rats had a higher bone mineral density (BMD) of the spine and femoral metaphysis and higher femoral trabecular bone volume than the CKD-group rats. Bone formation rates were not significantly different. The CKD + exercise-group rats had lower serum sclerostin (157.1 ± 21.1 vs 309 ± 38.1 pg/mL, p < 0.05) and CTX-1 (bone resorption marker) levels. Immunohistochemistry revealed higher tibial β-catenin concentrations in the CKD + exercise-group rats. Serum FGF-23, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, and phosphate levels showed no significant differences between these groups. Thus, exercise improves BMD and bone microstructure in mild CKD by inhibiting sclerostin production, but does not alter serum minerals.

Risk Factors Associated With Altered Circulating Micro RNA -125b andTheir Influences on Uremic Vascular Calcification Among PatientsWith End-Stage Renal Disease.

BackgroundMicroRNA‐125b (miR‐125b) has been shown to regulate vascular calcification (VC), and serum miR‐125b levels are a potential biomarker for estimating the risk of uremic VC status. However, it is unknown whether clinical features, including chronic kidney disease–mineral bone disorder molecules, affect serum miR‐125b levels.Methods and ResultsPatients receiving chronic dialysis for ≥3 months were recruited from different institutes. Serum miR‐125b and chronic kidney disease–mineral bone disorder effectors, including intact parathyroid hormone, 25‐OH‐D, fibroblast growth factor‐23, osteoprotegerin, and fetuin‐A, were quantified. We used multivariate regression analyses to identify factors associated with low serum miR‐125b levels and an area under receiver operating characteristic curve curve to derive optimal cutoffs for factors exhibiting close associations. Further regression analyses evaluated the influence of miR‐125b on VC risk. Among 223 patients receiving chronic dialysis (mean age, 67.3 years; mean years of dialysis, 5.2), 54 (24.2%) had high serum miR‐125b levels. Osteoprotegerin (P=0.013), fibroblast growth factor‐23 (P=0.006), and fetuin‐A (P=0.036) were linearly associated with serum miR‐125b levels. High osteoprotegerin levels independently correlated with high serum miR‐125 levels. Adding serum miR‐125b levels and serum osteoprotegerin levels (≥400 pg/mL) into models estimating the risk of uremic VC increased the area under receiver operating characteristic curve values (for models without miR‐125b/osteoprotegerin, with miR‐125b, and both: 0.74, 0.79, and 0.81, respectively).ConclusionsSerum osteoprotegerin levels ≥400 pg/mL and serum miR‐125b levels synergistically increased the accuracy of estimating VC risk among patients receiving chronic dialysis. Taking miR‐125b and osteoprotegerin levels into consideration when estimating VC risk may be recommended.

Correlation of serum intact parathyroid hormone and alkaline phosphatase in diabetic chronic kidney disease stage 3 to 5 patients with mineral bone disorders

Introduction: Chronic kidney disease (CKD) amongst diabetic patients is a worldwide public health problem. It is associated with cardiovascular disease and CKD mineral bone disorder (CKD-MBD). Cardiovascular and MBD are important contributors of morbidity and mortality in CKD patients. Serum intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) are two important markers to identify and mange CKD-MBD. This study was designed to evaluate the relationship between serum iPTH and alkaline phosphatase in diabetic CKD stages 3-5 patients with MBD.&#x0D; Methods: This cross-sectional study was conducted in BIRDEM General Hospital, Dhaka, Bangladesh from January 2013 to December 2014. Diabetic patients suffering from stage 3-5 CKD with MBD and not on dialysis, were consecutively and purposively included in this study. Along with base-line characteristics, clinical and laboratory data including serum alkaline phosphatase and iPTH levels were recorded for all patients. Data were analyzed by using SPSS version 20.0 and Pearson’s correlation test was applied to evaluate the relationship between iPTH and serum ALP.&#x0D; Results: Total patients were 306, of which 166 (54.2%) were males and 140 females (45.8%). Mean age of the study population was 56.5±11.3 years. Mean duration of diabetes mellitus (DM) and CKD were 12.8±7.6 and 2.9±1.7 years respectively. Among the study population, 49 (16.0%) were in CKD stage 3, 90 (29.4%) in stage 4 and rest 167 (54.6%) in stage 5. The mean HbA1c level did not differ significantly (p&gt;0.05 by ANOVA) amongst CKD-MBD stage 3, 4 and 5 cases. Mean±SE values of glycated haemoglobin (HbAlc %), serum creatinine (mg/dl), urea (mg/dl), calcium (mg/dl), phosphate (mg/dl), ALP (U/L) and iPTH (pg/ml) of total study population were 7.77±0.12, 6.8±0.17, 141.1±4.33, 8.1±0.07, 5.2±0.11, 164.1±7.74 and 229.7±8.64 respectively. Out of total cases, serum ALP was raised in only 53.9% CKD-MBD cases compared to 76.8% for iPTH. Serum iPTH level was found elevated in 79.6%, 83.3% and 72.5% CKD-MBD stage 3, 4 and 5 cases respectively while in comparison, serum ALP was found raised in 44.8%, 54.4% and 56.2% cases respectively. On correlation analysis between serum iPTH and ALP, the r values observed were 0.074, 0.231 and 0.046 for stage 3, 4 and 5 CKD-MBD cases respectively.&#x0D; Conclusion: The results of current study showed that most diabetic stage 3-5 pre-dialysis CKD-MBD patients had raised serum iPTH. In comparison, significantly low number of cases had raised serum ALP.&#x0D; IMC J Med Sci 2018; 12(2): 80-85

Hemodialysis versus peritoneal dialysis: a comparative study Menoufia Medical Journal

Objective To compare between dialysis modalities and their effect on anemia control, chronic kidney disease mineral bone disease (CKD-MBD) control, dialysis adequacy, and dialysis complication on end-stage renal disease (ESRD) patients. Background Hemodialysis (HD) and peritoneal dialysis (PD) are dialysis modalities for ESRD patients that have its own effect on patients. Many publications studied the modality effect on ESRD patients, but in Egypt few data was reported about these items. Patients and methods This cross-sectional study was carried out in January 2017 on 82 patients with ESRD maintained on HD and 21 patients with ESRD on PD. HD patients were collected randomly from a pool of HD patients attending regular HD in the Nephrology and Dialysis Department of Damanhour Medical National Institute. The PD patients were collected from the Nephrology and Dialysis Department of Damanhour Medical National Institute (16 patients) and Nephrology and Dialysis Department of New Mansura General Hospital (International) (five patients). A comparison between the two groups regarding anemia control, CKD-MBD, dialysis adequacy, and dialysis complication was performed. Results The PD group was better regarding the target levels of intact parathyroid hormone than HD (61 and 34%, respectively) (P = 0.038) and in the achievement of target Kt/V (90 and 48%, respectively) (P = 0.001). There was no significant difference regarding anemia control or complications. Conclusion PD has a better effect on CKD-MBD and it is easy for the PD patients to achieve adequacy than the HD patients. PD should have more chance as an RRT for the ESRD patients in Egypt.

Osteopontin Levels in Patients With Chronic Kidney Disease Stage 5 on Hemodialysis Directly Correlate With Intact Parathyroid Hormone and Alkaline Phosphatase.

Chronic kidney disease stage 5 (CKD5) marks the fifth stage of renal failure, frequently causing dysregulation of bone and mineral metabolism. Challenges exist in evaluating and managing chronic kidney disease–mineral bone disorder (CKD-MBD) with the standard panel of biomarkers. Our objective was to profile osteopontin (OPN) in patients with CKD5 on maintenance hemodialysis (CKD5-HD) and elucidate its relationship to phosphorus (P), calcium (Ca2+), alkaline phosphatase (AP), and intact parathyroid hormone (iPTH) to improve understanding of the present model of CKD-MBD. Elevation of plasma OPN was seen in the CKD5-HD cohort (n = 92; median: 240.25 ng/mL, interquartile range [IQR]: 169.85 ng/mL) compared to a normal group (n = 49; median: 63.30 ng/mL, IQR: 19.20 ng/mL; p < .0001). Spearman correlation tests revealed significant positive correlations of OPN with iPTH (p < .0001; r = 0.561, 95% confidence interval = 0.397-0.690) and OPN with AP (p < .0001; r = 0.444, 95% confidence interval = 0.245-0.590) in CKD5-HD patients. Ultimately, OPN may play an integral role in the MBD axis, suggesting that it may be important to actively monitor OPN when managing CKD5-HD.

Role of sclerostin, fibroblast growth factor-23, and Klotho in hemodialysis patients

Introduction Chronic kidney disease–mineral bone disorder leads to decreasing bone health. Sclerostin is produced by osteocytes similar to fibroblast growth factor-23 (FGF-23) and might upregulate the FGF-23 production by the osteocyte. FGF-23 may act as a mineralization inhibitor. Klotho serves as an obligate coreceptor for the FGF-23 and represents a marker of chronic kidney disease–mineral bone disorder. Aim We examined the association between serum sclerostin, FGF-23, Klotho, parathyroid hormone, high-sensitivity C-reactive protein (hsCRP), and phosphorus levels in hemodialysis (HD) patients. Patients and methods A total of 63 HD patients in the National Institute of Urology and Nephrology and 20 controls were enrolled in the study. Serum sclerostin, FGF-23, Klotho, parathyroid hormone, hsCRP, and phosphorus levels were assayed. Results We found that serum sclerostin, FGF-23, Klotho, and hsCRP levels of the HD patients were higher than controls [median and interquartile range are 1.379 (0.217–11.680) ng/ml, 61.71 (9.821–565.5) pg/ml, 201.74 (90.53–402.73) pg/ml, and 25.79 (12.10–41.92) mg/l vs. 0.535 (0.169–0.830) ng/ml, 33.077 (10.45–67.342) pg/ml, 349.49 (201.23–721.5) pg/ml, and 4.375 (2.27–6.21), respectively; P Conclusion There is an association between serum levels of sclerostin, phosphorus, and FGF-23 in HD patients, and Klotho may represent an early marker of renal damage.

Cardiotoxicity of Uremic Toxins: A Driver of Cardiorenal Syndrome.

Cardiovascular disease (CVD) is highly prevalent in the setting of chronic kidney disease (CKD). Such coexistence of CVD and CKD—the so-called “cardiorenal or renocardiac syndrome”—contributes to exponentially increased risk of cardiovascular (CV) mortality. Uremic cardiomyopathy is a characteristic cardiac pathology commonly found in CKD. CKD patients are also predisposed to heart rhythm disorders especially atrial fibrillation. Traditional CV risk factors as well as known CKD-associated CV risk factors such as anemia are insufficient to explain CV complications in the CKD population. Accumulation of uremic retention solutes is a hallmark of impaired renal excretory function. Many of them have been considered inert solutes until their biological toxicity is unraveled and they become accepted as “uremic toxins”. Direct cardiotoxicity of uremic toxins has been increasingly demonstrated in recent years. This review offers a mechanistic insight into the pathological cardiac remodeling and dysfunction contributed by uremic toxins with a main focus on fibroblastic growth factor-23, an emerging toxin playing a central role in the chronic kidney disease–mineral bone disorder, and the two most investigated non-dialyzable protein-bound uremic toxins, indoxyl sulfate and p-cresyl sulfate. Potential therapeutic strategies that could address these toxins and their relevant mediated pathways since pre-dialysis stages are also discussed.

Detecting high-risk chronic kidney disease-mineral bone disorder phenotypes among patients on dialysis: a historical cohort study.

The clinical management of chronic kidney disease-mineral bone disorder (CKD-MBD) remains extremely challenging, partially due to difficulties in defining high-risk phenotypes based on serum biomarkers. We evaluated the prevalence and outcomes of 27 mutually exclusive CKD-MBD phenotypes in a large, multi-national cohort of chronic dialysis patients over a 5-year follow-up study. In this historical cohort study, we enrolled all haemodialysis patients registered in EuCliD® on 1 July 2011 across 28 Europe, the Middle East and Africa (EMEA) and South American countries. We created 27 mutually exclusive phenotypes based on combinations of serum parathyroid hormone (PTH), phosphorus (P) and calcium (Ca) 6-month averages (L, low; T, target; H, high). We tested the association between CKD-MBD phenotypes and 5-year mortality and hospitalization risk by outcome risk score-adjusted proportional hazard regression. We enrolled 35 721 eligible patients. Eastern European and South American countries generally achieved poorer CKD-MBD control when compared with Western European countries (prevalence ratio: 0.79; P < 0.001). There were 15 795 deaths [126.7 deaths/1000 person-years; 95% confidence interval (CI) 124.7-128.7]; 18014 had at least one hospitalization (203.9 hospitalizations/1000 person-years; 95% CI 201.0-206.9); the incidence of the composite endpoint was 280.0 events/1000 person-years (95% CI 276.6-283.5). In the fully adjusted model, relative mortality risk ranged from hazard ratio (HR) = 1.07 (PTH/Ca/P: TLT) to HR = 1.59 (PTH/Ca/P: LTL), whereas the relative composite endpoint risk ranged from HR = 1.07 (PTH/Ca/P: TTH) to HR = 1.36 (PTH/Ca/P: LTL). We identified several CKD-MBD phenotypes associated with reduced hospitalization-free survival and increased mortality. Ranking of relative risk estimates or excess events concurs in informing healthcare priority setting.