CKD-MBD Research Articles

The impact of metformin in chronic kidney disease-mineral and bone disorder

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a disorder of mineral and bone metabolism due to chronic kidney disease (CKD). Bone disease and mortality are more common in patients with CKD. In addition of antidiabetic properties of metformin (MET), it possesses anti-inflammatory, anti-fibrotic properties and increases the markers of osteogenic effects. Therefore, it improves bone quality and decreases the risk of fractures in patients with type 2 diabetes. Metformin can also inhibit arterial calcification, maintain calcium-phosphorus balance, decrease cellular infiltration, fibrosis, and inflammation in kidney. Based on evidence, the prevalence of lactic acidosis due to metformin in patients with type 2 diabetes (T2D) and renal dysfunction is lower compared to other oral antidiabetic agents. Metformin decreases all-cause mortality in patients with diabetic nephropathy. The administration of metformin showed no difference in the prevalence of lactic acidosis in patients with T2D who had normal, mild, moderate, or severe renal dysfunction. Therefore, metformin can be used in patients with significant CKD to inhibit CKD-MBD due to its osteogenic effects.

Potential Biomarkers of the Turnover, Mineralization, and Volume Classification: Results Using NMR Metabolomics in Hemodialysis Patients

ABSTRACTBone biopsy is still the gold standard to assess bone turnover (T), mineralization (M), and volume (V) in CKD patients, and serum biomarkers are not able to replace histomorphometry. Recently, metabolomics has emerged as a new technique that could allow for the identification of new biomarkers useful for disease diagnosis or for the understanding of pathophysiologic mechanisms, but it has never been assessed in the chronic kidney disease–mineral and bone disorder (CKD–MBD) scenario. In this study, we investigated the association between serum metabolites and the bone TMV classification in patients with end‐stage renal disease by using serum NMR spectroscopy and bone biopsy of 49 hemodialysis patients from a single center in Brazil. High T was identified in 21 patients and was associated with higher levels of dimethylsulfone, glycine, citrate, and N‐acetylornithine. The receiver‐operating characteristic curve for the combination of PTH and these metabolites provided an area under the receiver‐operating characteristic curve (AUC) of 0.86 (0.76 to 0.97). Abnormal M was identified in 30 patients and was associated with lower ethanol. The AUC for age, diabetes mellitus, and ethanol was 0.83 (0.71 to 0.96). Low V was identified in 17 patients and was associated with lower carnitine. The association of age, phosphate, and carnitine provided an AUC of 0.83 (0.70 to 0.96). Although differences among the curves by adding selected metabolites to traditional models were not statistically significant, the accuracy of the diagnosis according to the TMV classification seemed to be improved. This is the first study to evaluate the TMV classification system in relation to the serum metabolome assessed by NMR spectroscopy, showing that selected metabolites may help in the evaluation of bone phenotypes in CKD–MBD. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Cinacalcet studies in pediatric subjects with secondary hyperparathyroidism receiving dialysis

BackgroundSecondary hyperparathyroidism (sHPT), a complication of chronic kidney disease (CKD) characterized by persistently elevated parathyroid hormone (PTH), alterations in calcium-phosphorus homeostasis, and vitamin D metabolism, affects 50% of children receiving dialysis. A significant proportion of these children develop CKD-mineral and bone disorder (CKD-MBD), associated with an increased risk of fractures and vascular calcification. The standard of care for sHPT in children includes vitamin D sterols, calcium supplementation, and phosphate binders. Several agents are approved for sHPT treatment in adults undergoing dialysis, including vitamin D analogs and calcimimetics, with limited information on their safety and efficacy in children. The calcimimetic cinacalcet is approved for use in adults with sHPT on dialysis, but is not approved for pediatric use outside Europe.MethodsThis review provides dosing, safety, and efficacy information from Amgen-sponsored cinacalcet pediatric trials and data from non-Amgen sponsored clinical studies.ResultsThe Amgen cinacalcet pediatric clinical development program consisted of two Phase 3 randomized studies, one Phase 3 single arm extension study, one open-label Phase 2 study, and two open-label Phase 1 studies. Effects of cinacalcet on PTH varied across studies. Overall, 7.4 to 57.1% of subjects who received cinacalcet in an Amgen clinical trial attained PTH levels within recommended target ranges and 22.2 to 70.6% observed a ≥ 30% reduction in PTH. In addition, significant reductions in PTH were demonstrated in all non-Amgen-supported studies.ConclusionsTo help inform the pediatric nephrology community, this manuscript contains the most comprehensive review of cinacalcet usage in pediatric CKD patients to date.

Dietary Protein Intake and Bone Across Stages of Chronic Kidney Disease.

This review aims to summarize the current evidence on the effect of very-low-, low-, and high-protein diets on outcomes related to chronic kidney disease-mineral and bone disorder (CKD-MBD) and bone health in patients with CKD. Dietary protein restriction in the form of low- and very-low-protein diets have been used to slow down the progression of CKD. These diets can be supplemented with alpha-keto acid (KA) analogues of amino acids. Observational and randomized controlled trials have shown improvements in biochemical markers of CKD-MBD, including reductions in phosphorus, parathyroid hormone, and fibroblast growth factor-23. However, few studies have assessed changes in bone quantity and quality. Furthermore, studies assessing the effects of high-protein diets on CKD-MBD are scarce. Importantly, very-low- and low-protein diets supplemented with KA provide supplemental calcium in amounts that surpass current dietary recommendations, but to date there are no studies on calcium balance with KA. Current evidence suggests that dietary protein restriction in CKD may slow disease progression, which may subsequently benefit CKD-MBD and bone health outcomes. However, prospective randomized controlled trials assessing the effects of modulating dietary protein and supplementing with KA on all aspects of CKD-MBD and particularly bone health are needed.

Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)

Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)

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

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. 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. 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). 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.

Adverse Effects of Autoclaved Diets on the Progression of Chronic Kidney Disease and Chronic Kidney Disease-Mineral Bone Disorder in Rats

Background: Autoclaving rodent diets is common in laboratory animals, but autoclaving increases the formation of dietary advanced glycation end-products (AGE). We studied the effect of autoclaved (AC) diet alone or in combination with a diet high in bioavailable phosphorus on biochemistries of chronic kidney disease-mineral and bone disorder (CKD-MBD), intestinal gene expression, and oxidative stress. Methods: Male CKD rats (Cy/+) and normal littermates were fed 1 of 3 diets: AC 0.7% phosphorus grain-based diet for 28 weeks (AC); AC diet for 17 weeks followed by non-autoclaved (Non-AC) 0.7% phosphorus casein diet until 28 weeks (AC + Casein); or Non-AC diet for 16 weeks followed by a Non-AC purified diet until 30 weeks (Non-AC + Casein). Results: AC diets contained ~3× higher AGEs and levels varied depending on the location within the autoclave. Rats fed the AC and AC + Casein diets had higher total AGEs and oxidative stress, irrespective of kidney function. Kidney function was more severely compromised in CKD rats fed AC or AC + Casein compared to Non-AC + Casein. There was a disease-by-diet interaction for plasma phosphorus, parathyroid hormone, and c-terminal fibroblast growth factor-23, driven by high values in the CKD rats fed the AC + Casein diet. Compared to Non-AC + Casein, AC and AC + Casein-fed groups had increased expression of receptor of AGEs and intestinal NADPH oxidase dual oxidase-2, independent of kidney function. Conclusions: Autoclaving rodent diets impacts the progression of CKD and CKD-MBD, highlighting the critical importance of standardizing diets in experiments.

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.

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.

Intervention on Osteoporosis and CKD-MBD

Intervention on Osteoporosis and CKD-MBD

The relationship between urinary kidney injury molecule-1 and blood bone metabolism markers in patients with chronic kidney disease .

The aim of this study was to evaluate the changes of urinary kidney injury molecule-1(uKIM-1) in chronic kidney disease (CKD) at different stages, and to determine the relationships between uKIM-1 and circulating bone metabolism markers. This cross-sectional study included CKD patients (n = 121) and controls (n = 65). CKD stages were assigned to each individual according to their estimated glomerular filtration rate (eGFR), which was calculated with the modification of diet in renal disease (MDRD) equation. We evaluated the relationships of bone metabolism markers (including calcium, phosphorus, intact parathyroid hormone (iPTH), 25 hydroxy vitamin D (25(OH)D), alkaline phosphatase (ALP), fibroblast growth factor 23 (FGF23), and α-Klotho), uKIM-1, and eGFR. We also compared the levels of bone metabolism markers and uKIM-1 at different CKD stages. The uKIM-1 level was standardized with urine creatinine (uCr). Compared with healthy controls, CKD patients had higher levels of uKIM-1/uCr, serum creatinine, urea, phosphorus, iPTH, and plasma FGF23, whereas they had lower levels of serum calcium, α-Klotho, and plasma 25(OH)D. In CKD patients, eGFR was positively correlated with levels of serum calcium, α-Klotho, and plasma 25(OH)D, whereas it was negatively correlated with serum phosphorus, iPTH, plasma FGF23, and uKIM-1/uCr. Serum calcium and α-Klotho were significantly decreased in patients with stage 5 CKD compared to those with stage 1 CKD. Serum phosphorus, iPTH, and plasma FGF23 were significantly elevated in patients with stage 4 CKD when compared to those with stage 1 CKD. UKIM-1/uCr was significantly elevated in patients with stage 5 CKD when compared to those with stage 1 CKD. In CKD patients, uKIM-1/uCr levels were positively correlated with levels of serum phosphorus and plasma FGF23, whereas they were negatively correlated with serum calcium and plasma 25(OH)D. UKIM-1/uCr levels are increased with the deterioration of CKD stage and are correlated with the development of CKD-mineral and bone disorder (CKD-MBD).

Effect of CKD-MBD phenotype on health-related quality of life in patients receiving maintenance hemodialysis: A cross-sectional study.

ObjectiveThis study aimed to investigate the factors influencing health-related quality of life (HRQoL) in patients with different chronic kidney disease–mineral and bone disorder (CKD–MBD) phenotypes.MethodsPatients undergoing maintenance hemodialysis (MHD) at our center from 1 July to 31 August 2017 were enrolled. Patients who received hemodialysis for less than 3 months or displayed poor compliance, or those with incomplete clinical data were excluded. QoL was evaluated using the Kidney Disease Quality of Life–Short Form (KDQOL-SF™) 1.3 scale. The influential factors were stratified based on different CKB–MBD phenotypes.ResultsThere were 296 patients enrolled. The serum intact parathyroid hormone (iPTH) concentration was 436.40 ± 490.99 pg/mL, serum calcium (Ca) concentration was 2.14 ±0.27 mmol/L, serum phosphorus (P) concentration was 1.81 ± 0.56 mmol/L, the kidney disease and dialysis-related QoL (KDTA) score was 57.07 ± 10.40, and the SF-36 score was 51.45 ± 17.62. Among patients with different CKD–MBD phenotypes, HRQoL was highest in the group with an iPTH concentration of 150 to 300 pg/mL, serum Ca concentration of <2.10 mmol/L, and serum P concentration of >1.78 mmol/L.ConclusionsCKD−MBD phenotypes significantly affected HRQoL. Comprehensive management of serum iPTH, Ca, and P levels is important to improve QoL in patients receiving hemodialysis.

Evidence in chronic kidney disease-mineral and bone disorder guidelines: is it time to treat or time to wait?

Chronic kidney disease–mineral and bone disorder (CKD–MBD) is one of the many important complications associated with CKD and may at least partially explain the extremely high morbidity and mortality among CKD patients. The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline document was based on the best information available at that time and was designed not only to provide information but also to assist in decision-making. In addition to the international KDIGO Work Group, which included worldwide experts, an independent Evidence Review Team was assembled to ensure rigorous review and grading of the existing evidence. Based on the evidence from new clinical trials, an updated Clinical Practice Guideline was published in 2017. In this review, we focus on the conceptual and practical evolution of clinical guidelines (from eMinence-based medicine to eVidence-based medicine and ‘living’ guidelines), highlight some of the current important CKD–MBD-related changes, and underline the poor or extremely poor level of evidence present in those guidelines (as well as in other areas of nephrology). Finally, we emphasize the importance of individualization of treatments and shared decision-making (based on important ethical considerations and the ‘best available evidence’), which may prove useful in the face of the uncertainty over the decision whether ‘to treat’ or ‘to wait’.

Canadian Society of Nephrology Commentary on the Kidney Disease Improving Global Outcomes 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder.

Purpose of review:(1) To provide commentary on the 2017 update to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD); (2) to apply the evidence-based guideline update for implementation within the Canadian health care system; (3) to provide comment on the care of children with chronic kidney disease (CKD); and (4) to identify research priorities for Canadian patients.Sources of information:The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD.Methods:The commentary committee co-chairs selected potential members based on their knowledge of the Canadian kidney community, aiming for wide representation from relevant disciplines, academic and community centers, and different geographical regions.Key findings:We agreed with many of the recommendations in the clinical practice guideline on the diagnosis, evaluation, prevention, and treatment of CKD-MBD. However, based on the uncommon occurrence of abnormalities in calcium and phosphate and the low likelihood of severe abnormalities in parathyroid hormone (PTH), we recommend against screening and monitoring levels of calcium, phosphate, PTH, and alkaline phosphatase in adults with CKD G3. We suggest and recommend monitoring these parameters in adults with CKD G4 and G5, respectively. In children, we agree that monitoring for CKD-MBD should begin in CKD G2, but we suggest measuring ionized calcium, rather than total calcium or calcium adjusted for albumin. With regard to vitamin D, we suggest against routine screening for vitamin D deficiency in adults with CKD G3-G5 and G1T-G5T and suggest following population health recommendations for adequate vitamin D intake. We recommend that the measurement and management of bone mineral density (BMD) be according to general population guidelines in CKD G3 and G3T, but we suggest against routine BMD testing in CKD G4-G5, CKD G4T-5T, and in children with CKD. Based on insufficient data, we also recommend against routine bone biopsy in clinical practice for adults with CKD or CKD-T, or in children with CKD, although we consider it an important research tool.Limitations:The committee relied on the evidence summaries produced by KDIGO. The CSN committee did not replicate or update the systematic reviews.

KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention and Prevention of Chronic Kidney Disease-Mineral and Bone Disorder (CKDMBD): Indian Commentary.

KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention and Prevention of Chronic Kidney Disease-Mineral and Bone Disorder (CKDMBD): Indian Commentary.

Sclerostin - a potential new marker of exercise influence on vascular calcification and mineral and bone disorder in hemodialysed adults

Chronic Kidney Disease (CKD) is defined as abnormalities of kidney structure or function, present for &gt;3 months, with implications for health. Amongst CKD complications the most fatal is cardiovascular disease, which together with Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) share a possible origin in Wnt signaling pathway disturbances. Sclerostin, a potent Wnt signaling inhibitor may possibly be used as a potential new marker of exercise influence on vascular calcification and mineral and bone disorder in hemodialysed adults.

Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD): Current Perspectives.

Despite the availability of global and regional guidelines to curtail the adverse clinical outcomes associated with chronic kidney disease–mineral and bone disorder (CKD-MBD), most CKD patients are still affected by the consequences of abnormalities of CKD-MBD. This important clinical complication of CKD continues to be studied, in order to improve the understanding and management of CKD-MBD. Some notable discoveries include the role of fibroblast growth factor 23 (FGF23) in the pathogenesis of CKD-MBD, leading to a shift from the previous well-established classic trade-off hypothesis to the updated trade-off hypothesis. More recently, there has been a shift from the treatment of CKD-MBD based on a single level of biomarkers to serial measurements of calcium, phosphate and parathyroid hormone (PTH). Furthermore, some clinical trials have emerged after the 2009 Kidney Disease-Improving Global Outcomes (KDIGO) Guidelines, leading to the 2017 KDIGO updated recommendations. Hence, this review gives an overview of the rapidly evolving trends in CKD-MBD, linking the past and current concepts of CKD-MBD.

Bone alkaline phosphatase: An important biomarker in chronic kidney disease – mineral and bone disorder

Increased cardiovascular morbidity and mortality in chronic kidney disease (CKD) represents an emerging major health problem. Indeed, disturbances in mineral and bone metabolism occur frequently in CKD and are termed chronic kidney disease – mineral and bone disorder (CKD-MBD). These can lead to cardiovascular pathology, resulting in an increased cardiovascular risk. Bone alkaline phosphatase (BALP) is essential for biomineralization. Recent findings demonstrate a crucial role for BALP in the pathogenesis of vascular calcification and identified it as a promising predictor of mortality in CKD. In conjunction with parathyroid hormone (PTH), serum BALP has been suggested as a biomarker of bone turnover in CKD-MBD. In contrast to PTH, serum BALP demonstrates a lower variability and may thus be better suited for the diagnosis and longitudinal follow-up of bone turnover. The linear association with mortality, compared to the U-shaped curve for PTH, is an additional advantage, making BALP more suitable than PTH as a treatment target in CKD. Here we review the main characteristics of alkaline phosphatase isozymes/isoforms and the various assays currently used in clinical routine laboratories. We also discuss the role of BALP in both physiological and pathological mineralization, and the clinical benefit of BALP determination in CKD.

Combinations of mineral and bone disorder markers and risk of death and hospitalizations in the international Dialysis Outcomes and Practice Patterns Study.

BackgroundPrior studies have developed a chronic kidney disease–mineral and bone disorder (CKD-MBD) composite score based on combinations of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) that have been shown to be associated with an increased risk of clinical outcomes in the USA. We examined this association in a contemporary, international cohort of hemodialysis patients.MethodsWe studied 19 313 patients surviving ≥12 months in the Dialysis Outcomes and Practice Patterns Study Phases 3–5 (2005–15) from Europe, Canada and the USA. The CKD-MBD composite score was defined as the number of markers above target levels (P, 3.5–5.5 mg/dL; Ca, 8.4–10.2 mg/dL; PTH, 150–600 pg/mL). Using Cox models, we estimated hazard ratios (HRs) for death and a composite event (death or hospitalization), contrasting MBD 2/3 (2–3 parameters above target) with MBD 0 (all in target), adjusted for a disease risk score (DRS).ResultsMBD 2/3 above target was observed in 10–14% of patients across regions and was associated with greater DRS-adjusted mortality {HR 1.41 [95% confidence interval (CI) 1.10–1.82]} and composite events [HR 1.23 (95% CI 1.10–1.38)] in the USA compared with MBD 0; the mortality association was stronger for patients ≥ 65 years of age [HR 1.82 (95% CI 1.28–2.58)] compared with patients <65 years of age [HR 1.11 (95% CI 0.80–1.55)]. HRs observed in Canada and Europe were generally consistent but weaker. Estimates for MBD 2/3 outside target (above or below) were slightly lower in all regions.ConclusionsSimultaneous consideration of Ca, P and PTH may help in identifying patients on dialysis with a higher risk of major clinical outcomes related to CKD-MBD.

Treatment of hyperphosphatemia: the dangers of high PTH levels.

The control of secondary hyperparathyroidism (SHPT) in pediatric chronic kidney disease is of utmost importance. Even though parathyroid hormone (PTH) is an important biomarker of mineral and bone disorders associated to CKD (CKD-MBD), calcium, phosphate, alkaline phosphatase, and vitamin D are also crucial and should be assessed together. In pediatric dialysis, high PTH levels have been associated with impaired longitudinal growth, bone disease, cardiovascular comorbidities, left ventricular hypertrophy, anemia, and even mortality (when PTH levels were above 500 pg/mL, i.e., 8.3-fold the upper normal limit (UNL)). As such, high PTH levels are for sure deleterious, but too low PTH levels have also been shown to impair growth and to promote vascular calcifications because of the underlying adynamic bone. This manuscript is part of a pros and cons debate for keeping PTH levels within the normal range in pediatric CKD, focusing on the pros. High bone turnover lesions can occur at lower PTH levels than "current" guidelines would suggest; thus, PTH alone is not a good predictor of the underlying osteodystrophy. PTH results can vary locally depending on the assay. Existing guidelines for PTH targets are conflicting and based on a very little evidence. However, the 120-180 pg/mL (2- to 3-fold the UNL) range is common to most of the guidelines; it seems to be a reasonable target in children undergoing dialysis, even though it does not correspond to "normal" PTH levels. As always, the philosophy of PTH levels in pediatric dialysis may be balanced, i.e., "not too low, not too high, and keep phosphate under control."