Renal osteodystrophy: something old, something new, something needed.

PURPOSE OF REVIEW: Renal osteodystrophy (ROD) is a complex disorder of bone metabolism that affects virtually all adults and children with chronic kidney disease (CKD). ROD is associated with adverse clinical outcomes including bone loss, mineralization and turnover abnormalities, skeletal deformities, fractures, cardiovascular events, and death. Despite current therapies, fracture incidence is 2-fold to 100-fold higher in adults and 2-fold to 3-fold higher in children when compared to without CKD. Limited knowledge of ROD pathogenesis, due to the lack of patient-derived large-scale multimodal datasets, impedes development of therapeutics aimed at reducing morbidity and mortality of CKD patients. The purpose of the review is to define the much needed infrastructure for the advancement of RDO treatment. RECENT FINDINGS: Recently, we created a large-scale data and tissue biorepository integrating clinical, bone quality, transcriptomic, and epigenomic data along with stored urine, blood, and bone samples. This database will provide the underpinnings for future research endeavors leading to the elucidation and characterization of the pathogenesis of ROD in CKD patients with and without dialysis. SUMMARY: The availability of an open-access NIH-funded resource that shares bone-tissue-based information obtained from patients with ROD with the broad scientific community represents a critical step in the process of discovering new information regarding unrecognized bone changes that have severe clinical complications. This will facilitate future high-impact hypothesis-driven research to redefine our understanding of ROD pathogenesis and pathophysiology and inform the development of disease-modifying and prevention strategies.

Overview of renal osteodystrophy in Brazil: a cross-sectional study.

INTRODUCTION: The epidemiologic profile of renal osteodystrophy (ROD) is changing over time and cross-sectional studies provide essential information to improve care and health policies. The Brazilian Registry of Bone Biopsy (REBRABO) is a prospective, nationalmulticenter cohort that includes patients with chronic kidney disease (CKD) undergoing bone biopsy. REBRABO aims to provide clinical information on ROD. The main objective of this subanalysis was to describe the profile of ROD, including clinically relevant associations. METHODS: From Aug/2015 to Dec/2021, 511 patients with CKD who performed bone biopsy were included in the REBRABO platform. Patients with no bone biopsy report (N = 40), GFR > 90 mL/min (N = 28), without asigned consent (N = 24), bone fragments inadequate for diagnosis (N = 23), bone biopsy indicated by a specialty other than nephrology (N = 6), and < 18 years old (N = 4) were excluded. Clinical-demographic data (e.g., age, sex, ethnicity, CKD etiology, dialysis vintage, comorbidities, symptoms, and complications related to ROD), laboratory (e.g., serum levels of total calcium, phosphate, parathormone, alkaline phosphatase, 25-hydroxyvitamin D, and hemoglobin), and ROD (e.g., histological diagnosis) were analyzed. RESULTS: Data from 386 individuals were considered in this subanalysis of REBRABO. Mean age was 52 (42-60) years; 198 (51%) were male; 315 (82%) were on hemodialysis. Osteitis fibrosa (OF) [163 (42%)], adynamic bone disease (ABD) [96 (25%)] and mixed uremic osteodystrophy (MUO) [83 (21%)] were the most frequent diagnosis of ROD in our sample; 203 (54%) had the diagnosis of osteoporosis, 82 (56%) vascular calcification; 138 (36%) bone aluminum accumulation, and 137 (36%) iron intoxication; patients with high turnover were prone to present a higher frequency of symptoms. CONCLUSIONS: A high proportion of patients were diagnosed with OF and ABD, as well as osteoporosis, vascular calcification and clinical symptoms.

[Diagnosis and treatment of osteoporosis in patients with chronic kidney disease : Joint guidelines of the Austrian Society for Bone and Mineral Research (ÖGKM), the Austrian Society of Physical and Rehabilitation Medicine (ÖGPMR) and the Austrian Society of Nephrology (ÖGN)]. / Diagnose und Therapie der Osteoporose bei Patienten mit chronischer Niereninsuffizienz : Gemeinsame Leitlinie der Österreichischen Gesellschaft für Knochen- und Mineralstoffwechsel (ÖGKM), der Österreichischen Gesellschaft für Physikalische Medizin und Rehabilitation (ÖGPMR) und der Österreichischen Gesellschaft für Nephrologie (ÖGN).

DEFINITION AND EPIDEMIOLOGY: Chronic kidney disease (CKD): abnormalities of kidney structure or function, present for over 3 months. Staging of CKD is based on GFR and albuminuria (not graded). Osteoporosis: compromised bone strength (low bone mass, disturbance of microarchitecture) predisposing to fracture. By definition, osteoporosis is diagnosed if the bone mineral density T­score is ≤ -2.5. Furthermore, osteoporosis is diagnosed if a low-trauma (inadequate trauma) fracture occurs, irrespective of the measured T­score (not graded). The prevalence of osteoporosis, osteoporotic fractures and CKD is increasing worldwide (not graded). PATHOPHYSIOLOGY, DIAGNOSIS AND TREATMENT OF CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER (CKD-MBD): Definition of CKD-MBD: a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; renal osteodystrophy; vascular calcification (not graded). Increased, normal or decreased bone turnover can be found in renal osteodystrophy (not graded). Depending on CKD stage, routine monitoring of calcium, phosphorus, alkaline phosphatase, PTH and 25-OH-vitamin D is recommended (2C). Recommendations for treatment of CKD-MBD: Avoid hypercalcemia (1C). In cases of hyperphosphatemia, lower phosphorus towards normal range (2C). Keep PTH within or slightly above normal range (2D). Vitamin D deficiency should be avoided and treated when diagnosed (1C). DIAGNOSIS AND RISK STRATIFICATION OF OSTEOPOROSIS IN CKD: Densitometry (using dual X­ray absorptiometry, DXA): low T­score correlates with increased fracture risk across all stages of CKD (not graded). A decrease of the T­score by 1 unit approximately doubles the risk for osteoporotic fracture (not graded). A T-score ≥ -2.5 does not exclude osteoporosis (not graded). Bone mineral density of the lumbar spine measured by DXA can be increased and therefore should not be used for the diagnosis or monitoring of osteoporosis in the presence of aortic calcification, osteophytes or vertebral fracture (not graded). FRAX can be used to aid fracture risk estimation in all stages of CKD (1C). Bone turnover markers can be measured in individual cases to monitor treatment (2D). Bone biopsy may be considered in individual cases, especially in patients with CKD G5 (eGFR < 15 ml/min/1.73 m2) or CKD 5D (dialysis). SPECIFIC TREATMENT OF OSTEOPOROSIS IN PATIENTS WITH CKD: Hypocalcemia should be treated and serum calcium normalized before initiating osteoporosis therapy (1C). CKD G1-G2 (eGFR ≥ 60 ml/min/1.73 m2): treat osteoporosis as recommended for the general population (1A). CKD G3-G5D (eGFR < 60 ml/min/1.73 m2 to dialysis): treat CKD-MBD first before initiating osteoporosis treatment (2C). CKD G3 (eGFR 30-59 ml/min/1.73 m2) with PTH within normal limits and osteoporotic fracture and/or high fracture risk according to FRAX: treat osteoporosis as recommended for the general population (2B). CKD G4-5 (eGFR < 30 ml/min/1.73 m2) with osteoporotic fracture (secondary prevention): Individualized treatment of osteoporosis is recommended (2C). CKD G4-5 (eGFR < 30 ml/min/1.73 m2) and high fracture risk (e.g. FRAX score > 20% for a major osteoporotic fracture or > 5% for hip fracture) but without prevalent osteoporotic fracture (primary prevention): treatment of osteoporosis may be considered and initiated individually (2D). CKD G4-5D (eGFR < 30 ml/min/1.73 m2 to dialysis): Calcium should be measured 1-2 weeks after initiation of antiresorptive therapy (1C). PHYSICAL MEDICINE AND REHABILITATION: Resistance training prioritizing major muscle groups thrice weekly (1B). Aerobic exercise training for 40 min four times per week (1B). Coordination and balance exercises thrice weekly (1B). Flexibility exercise 3-7 times per week (1B).

Investigation on maintenance hemodialysis patients with mineral and bone disorder in Anhui province, China.

BACKGROUND: Chronic kidney disease-mineral bone disorder (CKD-MBD) is a common comorbidity in patients with CKD. The study aims to describe the control rates of serum-corrected calcium (Ca), phosphate (P) and intact parathyroid hormone (iPTH) and its risk factors among maintenance hemodialysis (MHD) patients in Anhui Province of China. METHODS: The study was conducted in 27 hemodialysis centers of Anhui Province between January 1st 2020 and December 31th 2020. Chi-square test was used to compare the control rates of serum-corrected Ca, P and iPTH between the present study and DOPPS 4 or Anhui Province in 2014. Binary logistic regression analysis was used to explore the risk factors of the control rates of serum-corrected Ca, P and iPTH. RESULTS: A total of 3 025 MHD patients were recruited in this study, with a mean age of 54.8 (SD: 12.8) years, and 60.1% were males. According to the Chinese Diagnosis and Treatment Guidelines for CKD-MBD, the control rates of serum-corrected Ca, P and iPTH in the present study were 57.9%, 20.0% and 56.0%, respectively. Based on KDOQI guidelines (2003), the control rates of the above indicators were 43.1%, 35.3% and 22.3%, respectively. The control rates of serum-corrected Ca, P and iPTH in this study were lower than those of DOPPS 4 (P < 0.001). Compared to the results of Anhui Province in 2014, the control rate of corrected Ca was higher (P < 0.001) and the control rate of iPTH was lower (P = 0.005). Age, residential area, BMI, dialysis vintage, albumin and hemoglobin levels were factors of serum-corrected Ca, P and iPTH not within target range. CONCLUSION: The control rates of serum-corrected Ca, P and iPTH in MHD patients in Anhui Province are relatively low. Monitoring and management should be strengthened to improve the prognosis of patients undergoing dialysis.

Bone health as a co-morbidity of chronic kidney disease.

Chronic kidney disease and osteoporosis commonly co-exist in aged patients. Chronic kidney disease affects bone health because of its effect on mineral metabolism in the syndrome, Chronic Kidney Disease Mineral and Bone Disorder, resulting in an increased risk of fractures. Hip fracture risk may be as much as four-fold higher in the worst affected. Tools to estimate fracture risk such as FRAX® and measuring bone density can be used in patients with chronic kidney disease; however, bone density may underestimate fracture risk in this population as it does not give information on bone quality. While osteoporosis treatment in patients with chronic kidney disease stage 1-3 does not differ from the general population, in the absence of Chronic Kidney Disease Mineral and Bone Disorder, patients with disease stage 4-5 require special consideration. It is, however, of the utmost importance that these patients receive pharmacological treatment because of their high risk of fractures.

High prevalence of biochemical disturbances of chronic kidney disease - mineral and bone disorders (CKD-MBD) in a nation-wide peritoneal dialysis cohort: are guideline goals too hard to achieve? / Alta Prevalência de Distúrbios Bioquímicos Minerais e Ósseos na Doença Renal Crônica em uma coorte de diálise peritoneal nacional: as metas das diretrizes são muito difíceis de alcançar?

Abstract Introduction: Chronic kidney disease - mineral and bone disorders (CKD-MBD) are common in dialysis patients. Definition of targets for calcium (Ca), phosphorus (P), parathormone (iPTH), and alkaline phosphatase (ALP) and their treatment recommendations, are provided by international guidelines. There are few studies analyzing CKD-MBD in peritoneal dialysis (PD) patients and the impact of guidelines on mineral metabolism control. The aim of our study was to describe the prevalence of biomarkers for CKD-MBD in a large cohort of PD patients in Brazil. Methods: Data from the nation-wide prospective observational cohort BRAZPD II was used. Incident patients were followed between December 2004 and January 2011. According to KDOQI recommendations, reference ranges for total Ca were 8.4 to 9.5 mg/dL, for P, 3.5 to 5.5 mg/dL, for iPTH, 150-300 pg/mL, and for ALP, 120 U/L. Results: Mean age was 59.8 ± 16 years, 48% were male, and 43% had diabetes. In the beginning, Ca was 8.9 ± 0.9 mg/dL, and 48.3% were on the KODQI target. After 1 year, Ca increased to 9.1 ± 0.9 mg/dL and 50.4% were in the KDOQI preferred range. P at baseline was 5.2 ± 1.6 mg/dL, with 52.8% on target, declining to 4.9 ± 1.5 mg/dL after one year, when 54.7% were on target. Median iPTH at baseline was 238 (P25% 110 - P75% 426 pg/mL) and it remained stable throughout the first year; patients within target ranged from 26 to 28.5%. At the end of the study, 80% was in 3.5 meq/L Ca dialysate concentration, 66.9% of patients was taking any phosphate binder, and 25% was taking activated vitamin D. Conclusions: We observed a significant prevalence of biochemical disorders related to CKD-MBD in this dialysis population.

Resumo Introdução: Os distúrbios minerais e ósseos da doença renal crônica (DMO-DRC) são comuns em pacientes em diálise. A definição de metas para cálcio (Ca), fósforo (P), paratormônio (PTHi) e fosfatase alcalina (FA) e suas recomendações de tratamento são fornecidas por diretrizes internacionais. Há poucos estudos analisando o DMO-DRC em pacientes em diálise peritoneal (DP) e o impacto das diretrizes no controle do metabolismo mineral. O objetivo do nosso estudo foi descrever a prevalência de alterações nos marcadores para DMO-DRC em uma grande coorte de pacientes em DP no Brasil. Métodos: Foram utilizados dados da coorte observacional prospectiva nacional BRAZPD II. Pacientes incidentes foram acompanhados entre Dezembro de 2004 e Janeiro de 2011. De acordo com as recomendações do KDOQI, os intervalos de referência para Ca total foram de 8,4 a 9,5 mg/dL, para P, 3,5 a 5,5 mg/dL, para PTHi, 150-300 pg/mL, e para FA, 120 U/L. Resultados: A idade média foi de 59,8 ± 16 anos, 48% eram homens e 43% tinham diabetes. No início, o Ca era de 8,9 ± 0,9 mg/dL, e 48,3% estavam na meta do KODQI. Após 1 ano, o Ca aumentou para 9,1 ± 0,9 mg/dL e 50,4% estavam na faixa preferida do KDOQI. P basal era 5,2 ± 1,6 mg/dL, com 52,8% na meta, diminuindo para 4,9 ± 1,5 mg/dL após um ano, quando 54,7% estavam na meta. O PTHi basal mediano foi de 238 (P25% 110 - P75% 426 pg/mL) e permaneceu estável durante o primeiro ano; os pacientes dentro da meta variaram de 26 a 28,5%. No final do estudo, 80% estavam na concentração de 3,5 meq/L de Ca dialisato, 66,9% dos pacientes estavam tomando qualquer quelante de fosfato, e 25% estavam tomando vitamina D ativada. Conclusões: Observamos uma prevalência significativa de distúrbios bioquímicos relacionados ao DMO-DRC nesta população em diálise.

Changing Spectrum of Mineral Bone Disorder in Chronic kidney disease stage 3 to 5 D and Its Associated Factors, A Prospective Cross-Sectional Study from Tertiary Care Hospital in Northern India.

INTRODUCTION: Mineral bone disease is an important complication of chronic kidney disease ends up in increased cardiovascular morbidity and mortality in these patients. The aim of present study was to determine the pattern, prevalence and the clinical, biochemical and radiological profile of mineral bone disease in predialysis and dialysis (stage 5D) patients of chronic kidney disease. METHODS: Patients of stage 3, 4, 5 and 5D of chronic kidney disease admitted to the department of nephrology were enrolled in this study. RESULTS: 200 patients of chronic kidney disease (19, 29, 43 and 109 cases of stage 3, 4, 5 and 5D respectively) with mean age of 52.4 ± 16.7 years and male to female ratio of 2.4:1 were enrolled. Diabetic nephropathy (45%), hypertensive nephropathy (33%), and chronic glomerulonephritis (14.5%) were the most common etiologies of chronic kidney disease. Proximal muscle weakness (91.5%) bone pain (59.5%) and pruritus (25.5%) were the common symptoms. Biochemical parameters showed hypercalcemia (19%), hypocalcaemia (55%), hyperphosphatemia (75.5%) and vitamin D deficiency in 84.5% of cases. High turnover bone disease was present in all predialysis and only 7% of dialysis patients. Adynamic bone disease was observed in 92.7% of dialysis patients. On univariate analysis i-PTH was significantly associated with sex, eGFR, serum calcium, and 25(OH) vit-D level and no association was found with age and FGF-23 levels. CONCLUSION: Adynamic bone disease has emerged as the most common form of CKD-MBD in dialysis patients and secondary hyperparathyroidism being common in the predialysis patients of chronic kidney disease. Hyperphosphatemia and vitamin D deficiency were the most common reported biochemical abnormalities.

Osteoporosis and Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD): Back to Basics.

Osteoporosis is defined as a skeletal disorder of compromised bone strength predisposing those affected to an elevated risk of fracture. However, based on bone histology, osteoporosis is only part of a spectrum of skeletal complications that includes osteomalacia and the various forms of renal osteodystrophy of chronic kidney disease-mineral and bone disorder (CKD-MBD). In addition, the label "kidney-induced osteoporosis" has been proposed, even though the changes caused by CKD do not qualify as osteoporosis by the histological diagnosis. It is clear, therefore, that such terminology may not be helpful diagnostically or in making treatment decisions. A new label, "CKD-MBD/osteoporosis" could be a more appropriate term because it brings osteoporosis under the official label of CKD-MBD. Neither laboratory nor noninvasive diagnostic investigations can discriminate osteoporosis from the several forms of renal osteodystrophy. Transiliac crest bone biopsy can make the diagnosis of osteoporosis by exclusion of other kidney-associated bone diseases, but its availability is limited. Recently, a classification of metabolic bone diseases based on bone turnover, from low to high, together with mineralization and bone volume, has been proposed. Therapeutically, no antifracture treatments have been approved by the US Food and Drug Administration for patients with kidney-associated bone disease. Agents that suppress parathyroid hormone (vitamin D analogues and calcimimetics) are used to treat hyperparathyroid bone disease. Antiresorptive and osteoanabolic agents approved for osteoporosis are being used off-label to treat CKD stages 3b-5 in high-risk patients. It has now been suggested that intermittent administration of parathyroid hormone as early as CKD stage 2 could be an effective management strategy. If confirmed in clinical trials, it could mitigate the retention of phosphorus and subsequently the rise in fibroblast growth factor 23 and may be beneficial for coexisting osteoporosis.

High prevalence of biochemical disturbances of chronic kidney disease - mineral and bone disorders (CKD-MBD) in a nation-wide peritoneal dialysis cohort: are guideline goals too hard to achieve?

INTRODUCTION: Chronic kidney disease - mineral and bone disorders (CKD-MBD) are common in dialysis patients. Definition of targets for calcium (Ca), phosphorus (P), parathormone (iPTH), and alkaline phosphatase (ALP) and their treatment recommendations, are provided by international guidelines. There are few studies analyzing CKD-MBD in peritoneal dialysis (PD) patients and the impact of guidelines on mineral metabolism control. The aim of our study was to describe the prevalence of biomarkers for CKD-MBD in a large cohort of PD patients in Brazil. METHODS: Data from the nation-wide prospective observational cohort BRAZPD II was used. Incident patients were followed between December 2004 and January 2011. According to KDOQI recommendations, reference ranges for total Ca were 8.4 to 9.5 mg/dL, for P, 3.5 to 5.5 mg/dL, for iPTH, 150-300 pg/mL, and for ALP, 120 U/L. RESULTS: Mean age was 59.8 ± 16 years, 48% were male, and 43% had diabetes. In the beginning, Ca was 8.9 ± 0.9 mg/dL, and 48.3% were on the KODQI target. After 1 year, Ca increased to 9.1 ± 0.9 mg/dL and 50.4% were in the KDOQI preferred range. P at baseline was 5.2 ± 1.6 mg/dL, with 52.8% on target, declining to 4.9 ± 1.5 mg/dL after one year, when 54.7% were on target. Median iPTH at baseline was 238 (P25% 110 - P75% 426 pg/mL) and it remained stable throughout the first year; patients within target ranged from 26 to 28.5%. At the end of the study, 80% was in 3.5 meq/L Ca dialysate concentration, 66.9% of patients was taking any phosphate binder, and 25% was taking activated vitamin D. CONCLUSIONS: We observed a significant prevalence of biochemical disorders related to CKD-MBD in this dialysis population.

Bone Mineral Density and Aortic Calcification: Evidence for a Bone-vascular Axis After Kidney Transplantation.

BACKGROUND: Chronic kidney disease mineral and bone disorders (CKD-MBD) and vascular calcification are often seen in kidney transplantation recipients (KTR). This study focused on the bone-vascular axis hypothesis, the pathophysiological mechanisms driving both bone loss and vascular calcification, supported by an association between lower bone mineral density (BMD) and higher risk of vascular calcification. METHODS: KTR referred for a dual-energy X-ray absorptiometry procedure within 6 mo after transplantation were included in a cross-sectional study (2004-2014). Areal BMD was measured at the proximal femur, and abdominal aortic calcification (AAC) was quantified (8-points score) from lateral single-energy images of the lumbar spine. Patients were divided into 3 AAC categories (negative-AAC: AAC 0; low-AAC: AAC 1-3; and high-AAC: AAC 4-8). Multivariable-adjusted multinomial logistic regression models were performed to study the association between BMD and AAC. RESULTS: We included 678 KTR (51 ± 13 y old, 58% males), 366 (54%) had BMD disorders, and 266 (39%) had detectable calcification. High-AAC was observed in 9%, 11%, and 25% of KTR with normal BMD, osteopenia, and osteoporosis, respectively (P < 0.001). Higher BMD (T-score, continuous) was associated with a lower risk of high-AAC (odds ratio 0.61, 95% confidence interval 0.42-0.88; P = 0.008), independent of age, sex, body mass index, estimated glomerular filtration rate, and immunosuppressive therapy. KTR with normal BMD were less likely to have high-AAC (odds ratio 0.24, 95% confidence interval 0.08-0.72; P = 0.01). CONCLUSIONS: BMD disorders are highly prevalent in KTR. The independent inverse association between BMD and AAC may provide evidence to point toward the existence, while highlighting the clinical and epidemiological relevance, of a bone-vascular axis after kidney transplantation.

Trabecular bone score may indicate chronic kidney disease-mineral and bone disorder (CKD-MBD) phenotypes in hemodialysis patients: a prospective observational study.

BACKGROUND: In the general population, the trabecular bone score (TBS) represents the bone microarchitecture and predicts fracture risk independent of bone mineral density (BMD). A few studies reported that TBS is significantly reduced in dialysis patients. Chronic kidney disease-mineral and bone disorder (CKD-MBD) are accompanied by increased fracture risk, cardiovascular morbidity, and mortality. We investigated whether TBS is associated with comorbidity related to CKD-MBD or frailty in hemodialysis patients. METHODS: In this prospective observational study, TBS was obtained using the TBS iNsight software program (Med-Imaps) with BMD dual energy x-ray absorptiometry (DXA) images (L1-L4) from prevalent hemodialysis patients. A Tilburg frailty indicator was used to evaluate frailty, and hand grip strength and bio-impedance (InBody) were measured. A patient-generated subjective global assessment (PG-SGA) was used for nutritional assessment. The history of cardiovascular events (CVE) and demographic, clinical, laboratory, and biomarker data were collated. We then followed up patients for the occurrence of CKD-MBD related complications. RESULTS: We enrolled 57 patients in total. The mean age was 56.8 ± 15.9 years (50.9% female). Prevalence of Diabetes mellitus (DM) was 40.4% and CVE was 36.8%. Mean TBS was 1.44 ± 0.10. TBS significantly reduced in the CVE group (1.38 ± 0.08 vs. 1.48 ± 0.10, p <  0.001). Multivariable regression analysis was conducted adjusting for age, sex, dialysis vintage, DM, CVE, albumin, intact parathyroid hormone, fibroblast growth factor 23, handgrip strength, and phosphate binder dose. Age (ß = - 0.030; p = 0.001) and CVE (ß = - 0.055; p = 0.024) were significant predictors of TBS. During the follow up period after TBS measurements (about 20 months), four deaths, seven incident fractures, and six new onset CVE were recorded. Lower TBS was associated with mortality (p = 0.049) or new onset fracture (p = 0.007, by log-rank test). CONCLUSION: Lower TBS was independently associated with increased age and CVE prevalence in hemodialysis patients. Mortality and fracture incidence were significantly higher in patients with lower TBS values. These findings suggest that TBS may indicate a phenotype of frailty and also a CKD-MBD phenotype reciprocal to CVE.

Editorial on the Special Issue "Comorbidities in Chronic Kidney Disease".

With a mean worldwide prevalence of 13 [...].

Should We Consider the Cardiovascular System While Evaluating CKD-MBD?

Cardiovascular (CV) disease is highly prevalent in the population with chronic kidney disease (CKD), where the risk of CV death in early stages far exceeds the risk of progression to dialysis. The presence of chronic kidney disease-mineral and bone disorder (CKD-MBD) has shown a strong correlation with CV events and mortality. As a non-atheromatous process, it could be partially explained why standard CV disease-modifying drugs do not provide such an impact on CV mortality in CKD as observed in the general population. We summarize the potential association of CV comorbidities with the older (parathyroid hormone, phosphate) and newer (FGF23, Klotho, sclerostin) CKD-MBD biomarkers.

Bone turnover markers predict type of bone histomorphometry and bone mineral density in Asian chronic haemodialysis patients.

BACKGROUND: Although the levels of intact parathyroid hormone (iPTH) are well-controlled following the Kidney Disease Outcomes Quality Initiative guideline, the incidence of osteoporosis and fracture are still high in haemodialysis (HD) patients. This study was conducted to investigate the correlation between bone turnover markers, bone mineral density (BMD), and bone histomorphometry in HD patients. METHODS: Twenty-two chronic HD patients were enrolled. Serum levels of bone turnover markers were measured. Double tetracycline-labelled iliac crest bone specimens were evaluated using specialized a computer program (Osteomeasure). The types of bone histomorphometry were classified based on turnover, mineralization and volume. BMD and coronary artery calcification were also determined. RESULTS: Bone histomorphometry revealed osteitis fibrosa (50%), adynamic bone disease (45%) and mixed uremic osteodystrophy (5%). Serum iPTH level predicted high bone turnover with area under the receiver operating characteristic (ROC) of 0.833 (95% CI = 0.665-1.000, P = 0.008). Serum TRAP-5b also had ROC of 0.733 (95% CI = 0.517-0.950, P = 0.065). In addition, when using serum iPTH (cut-off 484.50 ng/mL) or serum TRAP-5b (cut-off 1.91 pg./mL) to predict high turnover, the sensitivity was 0.917. On the other hand, when both iPTH and TRAP-5B were above these cut-off, the specificity was 1.000. Low BMD and severe vascular calcification were commonly identified. However, there were no significant correlations between bone biomarkers and BMD or severe vascular calcification. CONCLUSION: Although iPTH levels were close to the target of Kidney Disease Outcomes Quality Initiative guideline, abnormal bone histomorphometry, BMD, and severe vascular calcification are still common. Bone biopsy is still crucially required as an accurate diagnostic tool in providing optimal guide for the treatment. © 2019 Asian Pacific Society of Nephrology.

Musculoskeletal disorders in hemodialysis patients: different disease clustering according to age and dialysis vintage.

Musculoskeletal disorders remain a major problem in hemodialysis patients. The aim of the study was to estimate the prevalence of musculoskeletal manifestations in hemodialysis patients and identify disease cluster profiles. We performed a cross-sectional study including all adult patients in the hemodialysis unit at Hotel-Dieu de France Hospital. We collected demographic characteristics, musculoskeletal symptoms, biologic parameters, and treatments. Musculoskeletal disorders were classified by a rheumatologist into predefined diagnostic categories. Prevalence was presented, and a cluster analysis was performed. Eighty-nine patients were included, mean age was 67.5 ± 12 years, and 43.8% were female. Dialysis vintage was 5.7 ± 5.37 years. Musculoskeletal symptoms were reported by 76.4% of the patients. Pain was the most frequent symptom (44.9%). The main diagnoses were osteoarthritis (53.9%) and fracture (27%). Musculoskeletal symptoms and disorders were significantly associated with dialysis vintage and age. Cluster analysis identified three patient profiles: younger with low calcium levels, younger but long dialysis vintage with osteoarthritis and carpal tunnel syndrome, and older with long dialysis vintage and fractures. The prevalence of musculoskeletal manifestations is high in the hemodialysis population and increases with dialysis vintage. Musculoskeletal disorders cluster according to age and dialysis vintage. Key Points• Musculoskeletal symptoms are highly prevalent among hemodialysis patients (76.4%).• All musculoskeletal disorders are associated with dialysis vintage and age.• Three clusters are identified among hemodialysis patients: young with low calcium levels, young but long dialysis vintage with osteoarthritis and carpal tunnel syndrome and old with long dialysis vintage with fractures.

Prevalence and pattern of chronic kidney disease-mineral bone disorders among hemodialysis patients in kano, northwest nigeria.

Introduction: Mineral and bone disorders (MBD) are among the important complications of chronic kidney disease (CKD) including end-stage renal disease. In addition to the higher rate of all-cause and cardiovascular-related mortality, MBD is also a cause of significant morbidity in CKD patients. Materials and Methods: This is a cross-sectional study of all consenting patients on hemodialysis at Aminu Kano Teaching Hospital, between December 2011 and June 2012. With the aid of an interviewer-administered questionnaire, the demographic profile and clinical features of the patients were obtained. After a general physical examination, blood sample was taken for the determination of calcium, phosphate, intact parathyroid hormone, 25 hydroxy (25[OH]) Vitamin D3, packed cell volume, serum creatinine, and potassium. Results: Forty-eight patients on maintenance hemodialysis were recruited for the study, 39 (81.3%) were male and 9 (18.8%) were female. The age range was 40-59 years, with a mean of 45.96 ± 13.7 years. Chronic glomerulonephritis was the predominant cause of CKD (25%). Hyperphosphatemia was noted in 19 (39.5%) of the patients, whereas 22 (46%) had hypocalcemia. In 26 (54.1%) of the patients, the calcium-phosphate product was >4.55 mmol2/L2. We found that 58% of the patients had CKD-MBD, of which 15 (31%) had secondary hyperparathyroidism, whereas 13 (27%) had features suggestive of adynamic bone disease. None of the patient had normal serum 25(OH) Vitamin D3(mean: 43.79 ± 21 ng/ml). Conclusion: CKD-MBD is common among patients on hemodialysis in our center. Screening for CKD-MBD and appropriate use of phosphate binder and Vitamin D when indicated are highly recommended.

RésuméIntroduction: Les maladies minérales et osseuses comptent parmi les complications importantes de la néphropathie chronique, notamment: phase terminale de la maladie rénale. Outre le taux plus élevé de mortalité toutes causes confondues et liée à la cardiopathie, la MBD est également une cause de morbidité chez les patients atteints d'IRC. Matériels et Méthodes: Ceci est une étude transversale de tous les patients consentants sous hémodialyse à Aminu Hôpital universitaire de Kano, entre décembre 2011 et juin 2012. À l'aide d'un questionnaire administré par un intervieweur, le le profil et les caractéristiques cliniques des patients ont été obtenus. Après un examen physique général, un échantillon de sang a été prélevé pour la determination de calcium, de phosphate, d'hormone parathyroïde intacte, de 25 hydroxy (25 [OH]) vitamine D3, de volume de globules rouges, de créatinine sérique et de potassium. Résultats: Quarante-huit patients sous hémodialyse d'entretien ont été recrutés pour l'étude, 39 (81,3%) étaient des hommes et 9 (18,8%) des femmes. La tranche d'âge était comprise entre 40 et 59 ans, avec une moyenne de 45,96 ± 13,7 ans. La glomérulonéphrite chronique était la principale cause de néphropathie chronique (25%). Une hyperphosphatémie a été notée chez 19 (39,5%) des patients, alors que 22 (46%) présentaient une hypocalcémie. Dans 26 (54,1%) des patients, le le produit de phosphate de calcium était> 4,55 mmol2 / L2. Nous avons constaté que 58% des patients étaient atteints de MRC, dont 15 (31%) avaient une atteinte secondaire. hyperparathyroïdie, alors que 13 (27%) présentaient des signes évocateurs d'une maladie osseuse adynamique. Aucun patient ne présentait un taux sérique normal de 25 (OH) Vitamine D3 (moyenne: 43,79 ± 21 ng / ml). Conclusion: La MPC est fréquente chez les patients hémodialysés de notre centre. Dépistage de CKD-MBD et l'utilisation appropriée du liant de phosphate et de la vitamine D lorsque cela est indiqué sont fortement recommandés.

Chronic kidney disease-mineral bone disorder.

Chronic kidney disease-mineral bone disorder is typically seen in patients with advanced chronic kidney disease. It is managed primarily by renal physicians, but non-renal physicians are also likely to encounter patients undergoing treatment for this condition in both inpatient and outpatient settings so a basic understanding of the principles may be helpful. This article covers the fundamentals of the pathophysiology, diagnosis and treatment of chronic kidney disease-mineral bone disorder.

Effect of extended hours dialysis on markers of chronic kidney disease-mineral and bone disorder in the ACTIVE Dialysis study.

BACKGROUND: Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) is a significant cause of morbidity among haemodialysis patients and is associated with pathological changes in phosphate, calcium and parathyroid hormone (PTH). In the ACTIVE Dialysis study, extended hours dialysis reduced serum phosphate but did not cause important changes in PTH or serum calcium. This secondary analysis aimed to determine if changes in associated therapies may have influenced these findings and to identify differences between patient subgroups. METHODS: The ACTIVE Dialysis study randomised 200 participants to extended hours haemodialysis (≥24 h/week) or conventional haemodialysis (≤18 h/week) for 12 months. Mean differences between treatment arms in serum phosphate, calcium and PTH; and among key subgroups (high vs. low baseline phosphate/PTH, region, time on dialysis, dialysis setting and frequency) were examined using mixed linear regression. RESULTS: Phosphate binder use was reduced with extended hours (- 0.83 tablets per day [95% CI -1.61, - 0.04; p = 0.04]), but no differences in type of phosphate binder, use of vitamin D, dose of cinacalcet or dialysate calcium were observed. In adjusted analysis, extended hours were associated with lower phosphate (- 0.219 mmol/L [- 0.314, - 0.124; P < 0.001]), higher calcium (0.046 mmol/L [0.007, 0.086; P = 0.021]) and no change in PTH (0.025 pmol/L [- 0.107, 0.157; P = 0.713]). The reduction in phosphate with extended hours was greater in those with higher baseline PTH and dialysing at home. CONCLUSION: Extended hours haemodialysis independently reduced serum phosphate levels with minimal change in serum calcium and PTH levels. With a few exceptions, these results were consistent across patient subgroups. TRIAL REGISTRATION: Clinicaltrials.gov NCT00649298 . Registered 1 April 2008.

Racial-ethnic differences in chronic kidney disease-mineral bone disorder in youth on dialysis.

BACKGROUND: Studies in healthy pediatric populations and adults treated with dialysis demonstrate higher parathyroid hormone (PTH) and lower 25-hydroxyvitamin D levels in African-Americans. Despite these findings, African-Americans on dialysis demonstrate greater bone strength and a decreased risk of fracture compared to the Caucasian dialysis population. The presence of such differences in children and young adult dialysis patients is unknown. METHODS: Differences in the markers of mineral and bone metabolism (MBM) were assessed in 661 incident dialysis patients (aged 1 month to < 21 years). Racial-ethnic differences in PTH, calcium, phosphate, and total alkaline phosphatase (AP) activity were analyzed over the first year of dialysis using multivariate linear mixed models. RESULTS: African-American race predicted 23% higher serum PTH (95% CI, 4.7-41.3%) when compared to Caucasian patients, while Hispanic ethnicity predicted 17.5% higher PTH (95% CI, 2.3-38%). Upon gender stratification, the differences in PTH were magnified in African-American and Hispanic females: 38% (95% CI, 14.8-69.8%) and 28.8% (95% CI, 4.7-54.9%) higher PTH compared to Caucasian females. Despite higher PTH values, African-American females persistently demonstrated up to 10.9% lower serum AP activity (95% CI, - 20.6-- 0.7%). CONCLUSIONS: There are racial-ethnic differences in the markers of MBM. Higher PTH is seen in African-American and Hispanic children and young adults on dialysis with a magnification of this difference amongst the female population. There is a need to consider how factors like race, ethnicity, and gender impact the goal-targeted treatment of MBM disorders.