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Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. Among CKD patients, adynamic bone disease or low bone turnover is the most common type of renal osteodystrophy. The consequences of CKD-MBD include increased fracture risk, greater morbidity, and mortality. Thus, the goal is to prevent the occurrences of fractures by means of alleviating CKD-induced MBD and treating subsequent osteoporosis. Changes in mineral and humoral metabolism as well as bone structure develop early in the course of CKD. CKD-MBD includes abnormalities of calcium, phosphorus, PTH, and/or vitamin D; abnormalities in bone turnover, mineralization, volume, linear growth, or strength; and/or vascular or other soft tissue calcification. In patients with CKD-MBD, using either DXA or FRAX to screen fracture risk should be considered. Biomarkers such as bALP and iPTH may assist to assess bone turnover. Before initiating an antiresorptive or anabolic agent to treat osteoporosis in CKD patients, lifestyle modifications, such as exercise, calcium, and vitamin D supplementation, smoking cessation, and avoidance of excessive alcohol intake are important. Managing hyperphosphatemia and SHPT are also crucial. Understanding the complex pathogenesis of CKD-MBD is crucial in improving one’s short- and long-term outcomes. Treatment strategies for CKD-associated osteoporosis should be patient-centered to determine the type of renal osteodystrophy. This review focuses on the mechanism, evaluation and management of patients with CKD-MBD. However, further studies are needed to explore more details regarding the underlying pathophysiology and to assess the safety and efficacy of agents for treating CKD-MBD.

Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is a systemic disorder that leads to vascular calcification and accelerated atherosclerosis. Uric acid has been shown to associate with vascular calcification and with carotid intima-media thickness (CIMT) and to suppress the 1 α-hydroxylase enzyme leading to lower 1,25-dihydroxyvitamin D (1,25(OH)2D) and higher intact parathyroid hormone (iPTH) levels. We hypothesized that lowering serum uric acid would reduce CIMT, calcification propensity, and circulating markers of CKD-MBD in CKD. This is a post-hoc analysis of a randomized, double-blind study of 80 patients with stage 3 CKD and hyperuricemia who received allopurinol or placebo for 12 weeks. CIMT and T50 were measured as markers of vascular disease and serum calcification propensity, respectively. The following markers of CKD-MBD were measured: serum calcium, phosphorus, vitamin D metabolites, iPTH, and fibroblast growth factor-23 (FGF-23). Expression of extra-renal 1α-hydroxylase was evaluated in endothelial cells of study participants. Allopurinol successfully lowered serum uric acid levels compared to placebo with an estimate of -3.3 mg/dL (95% C.I. -4.1,-2.5; p < 0.0001). After 12 weeks, however, we found no significant change in CIMT or serum T50. There was not a significant change in vitamin D metabolites, iPTH, FGF-23, or the expression of endothelial 1α-hydroxylase. These data suggest that factors other than uric acid may play a more important role in the regulation of CKD- MBD including vascular calcification and vitamin D metabolism in patients with CKD.

The guidelines proposed by the Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that intact parathyroid hormone (iPTH) should be maintained in a target range between 150 and 300 pg ml−1 for patients with stage 5 chronic kidney disease. Our study sought to verify the effectiveness of that range in preventing bone remodeling problems in hemodialysis patients. We measured serum ionized calcium and phosphorus while iPTH was measured by a second-generation assay. Transiliac bone biopsies were performed at the onset of the study and after completing 1 year follow-up. The PTH levels decreased within the target range in about one-fourth of the patients at baseline and at the end of the study. The bone biopsies of two-thirds of the patients were classified as showing low turnover and a one-fourth showed high turnover, the remainder having normal turnover. In the group achieving the target levels of iPTH 88% had low turnover. Intact PTH levels less than 150 pg ml−1 for identifying low turnover and greater than 300 pg ml−1 for high turnover presented a positive predictive value of 83 and 62%, respectively. Our study suggests that the iPTH target recommended by the K/DOQI guidelines was associated with a high incidence of low-turnover bone disease, suggesting that other biochemical markers may be required to accurately measure bone-remodeling status in hemodialysis patients.

In children with chronic kidney disease (CKD), optimal control of bone and mineral homeostasis is essential, not only for the prevention of debilitating skeletal complications and achieving adequate growth but also for preventing vascular calcification and cardiovascular disease. Complications of mineral bone disease (MBD) are common and contribute to the high morbidity and mortality seen in children with CKD. Although several studies describe the prevalence of abnormal calcium, phosphate, parathyroid hormone, and vitamin D levels as well as associated clinical and radiological complications and their medical management, little is known about the dietary requirements and management of calcium (Ca) and phosphate (P) in children with CKD. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists, who develop clinical practice recommendations (CPRs) for the nutritional management of various aspects of renal disease management in children. We present CPRs for the dietary intake of Ca and P in children with CKD stages 2–5 and on dialysis (CKD2-5D), describing the common Ca- and P-containing foods, the assessment of dietary Ca and P intake, requirements for Ca and P in healthy children and necessary modifications for children with CKD2-5D, and dietary management of hypo- and hypercalcemia and hyperphosphatemia. The statements have been graded, and statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs based on the clinical judgment of the treating physician and dietitian. These CPRs will be regularly audited and updated by the PRNT.

Background Chronic kidney disease associated mineral bone disorder (CKD-MBD) is one of the major causes of excess morbidity and mortality in hemodialysis patients. The purpose of this study was to investigate whether education about dietary intakes and specific food processing methods affect serum calcium and PTH concentrations in hemodialysis patients. Methods Forty-seven hemodialysis patients were randomly divided into a control and an intervention group. All participants were on individualized phosphate binder therapy. Both groups received education on dietary intake by a trained dietitian. The intervention group received additional education on specific preparation methods of different foodstuffs and consumed two hospital meals prepared according to these methods during hemodialysis. Serum calcium and PTH levels, and vitamin D analog therapy dosage were periodically monitored during the 1-year study period. Results At the baseline of the study, there were no differences between control and intervention groups in serum calcium ( p  = 0.078), serum PTH ( p  = 0.670), and vitamin D analog therapy dosage ( p  = 0.184). At the end of the study, serum calcium was better regulated in the intervention group, resulting in a significant difference between the study groups ( p  = 0.013). This was also confirmed by serum PTH levels in the intervention group, which remained stable until the end of the study ( p  = 0.110). Discussion Additional education on specific food processing techniques may result in improved management of serum calcium and PTH levels, which could ultimately provide better control of secondary hyperparathyroidism in hemodialysis patients. Graphical abstract

A distinct form of chronic kidney disease of unknown etiology (CKDu) has emerged in tropical regions of Sri Lanka, predominantly affecting individuals aged 30–60 years in the North Central Province. Unlike conventional chronic kidney disease (CKD), CKDu occurs independently of diabetes or hypertension and is characterized by tubulointerstitial damage, including tubular atrophy, interstitial inflammation, and fibrosis. Epidemiological studies showed familial clustering, suggesting an underlying genetic predisposition. This study aimed to identify genetic variants associated with CKDu in Sri Lankan populations using whole-exome sequencing (WES). Eighty-six individuals (47 CKDu patients and 39 controls) were recruited from endemic and non-endemic regions. Physiological, biochemical, and geographic parameters were recorded. DNA extracted from blood was subjected to WES to identify variants associated with CKDu. Results: A total of 171 unique variants across 121 genes were identified. Among the most prevalent genes were ATXN3, LFNG, PNLDC1, LINC02456, and HLA-DRB1. In the case–control comparison, only LFNG showed statistically significant enrichment in affected individuals, whereas signals in ATXN3, PNLDC1, and LINC02456 were not statistically significant, but have an association with renal dysfunction, and thus are included as hypothesis-generating variant observations. HLA-DRB1 variants showed trends toward a protective haplotype. LFNG showed the greatest prevalence in affected individuals (71.7%), followed by PNLDC1 (63%), ATXN3 (56%), FIP1L1 (41%), and HLA-DRB1 (32%). Conclusion: Findings suggest genetic variants in combination with environmental factors may contribute to CKDu susceptibility in the Sri Lankan population. We underscore the multi-factorial nature of CKDu and highlight the need for integrative genomic and environmental research to elucidate disease mechanisms and inform targeted prevention strategies.

BackgroundInfants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce.MethodsPICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2 years of age with CKD stages 2–5 or on dialysis. Clinical practice points (CPPs) were developed and leveled using the American Academy of Pediatrics grading matrix. A Delphi consensus approach was followed.ResultsWe present 34 CPPs for diagnosis and management of CKD-MBD in infants, including dietary control of calcium and phosphate, and medications to prevent and treat CKD-MBD (native and active vitamin D, calcium supplementation, phosphate binders).ConclusionAs there are few high-quality studies in this field, the strength of most statements is weak to moderate, and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested.

Phosphate is a key uremic toxin associated with adverse outcomes. As chronic kidney disease (CKD) progresses, the kidney capacity to excrete excess dietary phosphate decreases, triggering compensatory endocrine responses that drive CKD-mineral and bone disorder (CKD-MBD). Eventually, hyperphosphatemia develops, and low phosphate diet and phosphate binders are prescribed. Recent data have identified a potential role of the gut microbiota in mineral bone disorders. Thus, parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched in the Th17 cell-inducing taxa segmented filamentous bacteria. Furthermore, the microbiota was required for PTH to stimulate bone formation and increase bone mass, and this was dependent on bacterial production of the short-chain fatty acid butyrate. We review current knowledge on the relationship between phosphate, microbiota and CKD-MBD. Topics include microbial bioactive compounds of special interest in CKD, the impact of dietary phosphate and phosphate binders on the gut microbiota, the modulation of CKD-MBD by the microbiota and the potential therapeutic use of microbiota to treat CKD-MBD through the clinical translation of concepts from other fields of science such as the optimization of phosphorus utilization and the use of phosphate-accumulating organisms.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is associated with secondary hyperparathyroidism (HPT) and serum elevations in the phosphaturic hormone FGF23, which may be maladaptive and lead to increased morbidity and mortality. To determine the role of FGF23 in the pathogenesis of CKD-MBD and development of secondary HPT, we developed a monoclonal FGF23 antibody to evaluate the impact of chronic FGF23 neutralization on CKD-MBD, secondary HPT, and associated comorbidities in a rat model of CKD-MBD. CKD-MBD rats fed a high-phosphate diet were treated with low or high doses of FGF23-Ab or an isotype control antibody. Neutralization of FGF23 led to sustained reductions in secondary HPT, including decreased parathyroid hormone, increased vitamin D, increased serum calcium, and normalization of bone markers such as cancellous bone volume, trabecular number, osteoblast surface, osteoid surface, and bone-formation rate. In addition, we observed dose-dependent increases in serum phosphate and aortic calcification associated with increased risk of mortality in CKD-MBD rats treated with FGF23-Ab. Thus, mineral disturbances caused by neutralization of FGF23 limited the efficacy of FGF23-Ab and likely contributed to the increased mortality observed in this CKD-MBD rat model.

Uremic pruritus or chronic kidney disease-associated pruritus (CKD-aP) remains a frequent and compromising symptom in patients with advanced or end-stage renal disease, strongly reducing the patient’s quality of life. More than 40% of patients undergoing hemodialysis suffer from chronic pruritus; half of them complain about generalized pruritus. The pathogenesis of CKD-aP remains obscure. Parathormone and histamine as well as calcium and magnesium salts have been suspected as pathogenetic factors. Newer hypotheses are focusing on opioid-receptor derangements and microinflammation as possible causes of CKD-aP, although until now this could not be proven. Pruritus may be extremely difficult to control, as therapeutic options are limited. The most consequential approaches to treatment are: topical treatment with or without anti-inflammatory compounds or systemic treatment with (a) gabapentin, (b) μ-opioid receptor antagonists and κ-agonists, (c) drugs with an anti-inflammatory action, (d) phototherapy, or (e) acupuncture. A stepwise approach is suggested starting with emollients and gabapentin or phototherapy as first-line treatments. In refractory cases, more experimental options as μ-opioid-receptor—antagonists (i.e., naltrexone) or κ-opioid-receptor agonist (nalfurafine) may be chosen. In desperate cases, patients suitable for transplantation might be set on ‘high urgency’-status, as successful kidney transplantation will relieve patients from CKD-aP.