Abnormal Calcium-phosphorus Metabolism Research Articles

Rethinking Mitral Annular Calcification and Its Clinical Significance: From Passive Process to Active Pathology.

Mitral annulus calcification is a chronic degenerative condition affecting the fibrous base of the mitral valve. Historically viewed as an age-related phenomenon, recent studies suggest it is driven by active mechanisms involving systemic inflammation, hemodynamic stress, abnormal calcium-phosphorus metabolism, and lipid accumulation. Despite often being asymptomatic and incidentally detected, its clinical relevance stems from its strong association with increased cardiovascular disease risk, higher cardiovascular mortality, and elevated overall mortality. This article investigates the complexities and controversies surrounding mitral annular calcification as a potential embolic source, focusing on its diagnosis, its relationship with systemic inflammation, and its links to metabolic and chronic disorders. The findings highlight that mitral annular calcification is not merely a passive marker of aging but an active indicator of atherosclerotic burden with significant implications for cardiovascular health. Mitral annulus calcification should be recognized as an important factor in cardiovascular risk assessment, offering insight into systemic inflammatory processes and metabolic dysregulation.

The clinical and genetic spectrum of primary familial brain calcification

Primary familial brain calcification (PFBC), formerly known as Fahr’s disease, is a rare neurodegenerative disease characterized by bilateral progressive calcification of the microvessels of the basal ganglia and other cerebral and cerebellar structures. PFBC is thought to be due to an altered function of the Neurovascular Unit (NVU), where abnormal calcium-phosphorus metabolism, functional and microanatomical alterations of pericytes and mitochondrial alterations cause a dysfunction of the blood–brain barrier (BBB) and the generation of an osteogenic environment with surrounding astrocyte activation and progressive neurodegeneration. Seven causative genes have been discovered so far, of which four with dominant (SLC20A2, PDGFB, PDGFRB, XPR1) and three with recessive inheritance (MYORG, JAM2, CMPK2). Clinical presentation ranges from asymptomatic subjects to movement disorders, cognitive decline and psychiatric disturbances alone or in various combinations. Radiological patterns of calcium deposition are similar in all known genetic forms, but central pontine calcification and cerebellar atrophy are highly suggestive of MYORG mutations and extensive cortical calcification has been associated with JAM2 mutations. Currently, no disease-modifying drugs or calcium-chelating agents are available and only symptomatic treatments can be offered.

Bulky Mitral Annulus Caseous Calcification in an Atypical Location.

Mitral annular calcification (MAC) is a commonly observed chronic and degenerative fibrotic process of the base of the mitral valve, usually deemed as an incidental finding. Although initially, MAC was thought to be a consequence of an age-related degenerative process, recent findings suggest other independent contributive mechanisms, such as atherosclerosis and abnormal calcium-phosphorus metabolism. Caseous calcification of the mitral annulus (cMAC) is a rarely described variant of MAC, characterized by an ovoid, focal mass with internal caseous fluid-like calcifications and debris. Differentiating a cMAC from other cardiac masses attached to the mitral annulus may be challenging. A single imaging modality, such as transthoracic echocardiography, may not be sufficient for a clear diagnosis. Therefore, a multimodal imaging approach is necessary, including cardiac tomography computerized imaging and cardiac magnetic resonance (CMR). MAC and cMAC typically affect the posterior mitral annulus, with very few cases in the literature describing the involvement of the anterior annulus. We present a rare case of an anterior mitral annulus caseous calcification found in a CMR performed to evaluate a left atrial mass identified on a transthoracic echocardiogram.

Chronic Kidney Disease and Cerebrovascular Disease: Consensus and Guidance From a KDIGO Controversies Conference.

The global health burden of chronic kidney disease is rapidly rising, and chronic kidney disease is an important risk factor for cerebrovascular disease. Proposed underlying mechanisms for this relationship include shared traditional risk factors such as hypertension and diabetes, uremia-related nontraditional risk factors, such as oxidative stress and abnormal calcium-phosphorus metabolism, and dialysis-specific factors such as cerebral hypoperfusion and changes in cardiac structure. Chronic kidney disease frequently complicates routine stroke risk prediction, diagnosis, management, and prevention. It is also associated with worse stroke severity, outcomes and a high burden of silent cerebrovascular disease, and vascular cognitive impairment. Here, we present a summary of the epidemiology, pathophysiology, diagnosis, and treatment of cerebrovascular disease in chronic kidney disease from the Kidney Disease: Improving Global Outcomes Controversies Conference on central and peripheral arterial disease with a focus on knowledge gaps, areas of controversy, and priorities for research.

Increased iron deposition of deep cerebral gray matter structures in hemodialysis patients: A longitudinal study using quantitative susceptibility mapping.

The cerebral iron overload in hemodialysis patients has been reported in a previous study, in which the evaluation of the changes in iron content could be affected by the cross-sectional analysis. To investigate the longitudinal changes of iron deposition in hemodialysis patients using quantitative susceptibility mapping (QSM) and correlate these findings with the longitudinal changes of neurocognitive function and clinical factors. Prospective; longitudinal. In all, 34 patients and 30 healthy controls (HCs); the mean follow-up interval was 22 ± 7 months. 3.0T, susceptibility-weighted imaging (SWI). QSM reconstructed from original phase data of SWI was used to measure the susceptibility of gray matter structures including bilateral caudate nucleus (CN), globus pallidus (GP), putmen (PUT), red nucleus (RN), substantia nigra (SN), dentate nucleus (DN), thalamus (THA), pulvinar of thalamus (PT). The Mini-Mental State Examination (MMSE) test and clinical factors were recorded. Analysis of covariance adjusting for age and gender as covariates or a paired t-test for the differences in susceptibility, MMSE scores, and clinical factors among baseline, follow-up patients, and HCs. Correlation and stepwise regression analysis for the relationship between susceptibility, MMSE scores, and clinical factors. The susceptibility of bilateral CN, GP, PUT, RN, SN, DN, THA, PT in follow-up patients was significantly higher than that in baseline between patients and HCs except for left THA (all P < 0.05; Bonferroni corrected). MMSE scores significantly negatively correlated with the susceptibility of bilateral CN, PUT, and RRN in the baseline examination and bilateral CN, PUT, RN, and DN in the follow-up examination (all P < 0.05; false discovery rate [FDR] corrected). The follow-up interval, creatinine, phosphorus, and calcium were independent factors for the increased susceptibility of some nuclei (all P < 0.05). The iron deposition of gray matter nuclei in hemodialysis patients increased over roughly a 2-year period and may be a risk factor for neurocognitive impairment. Creatinine and abnormal calcium-phosphorus metabolism were independent risk factors for abnormal iron deposition. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:786-799.

A case of chorioretinal atrophy due to sclerochoroidal calcification

Editor, Ectopic scleral and choroidal calcification, a rare pathology, can be classified as dystrophic or metastatic (Honavar et al. 2001). The former is associated with senile degeneration, chronic inflammation or trauma and the latter with systemic abnormal calcium–phosphorus metabolism including hyperparathyroidism, pseudohypoparathyroidism, sarcoidosis, hypervitaminosis D and chronic renal failure (Shields & Shields 2002). We report a case with bilateral chorioretinal atrophy secondary to metastatic sclerochoroidal calcification in a patient with chronic renal failure and hyperparathyroidism. A recent advance in computed tomography (CT), that is three-dimensional (3D) orbital reconstruction from thin CT slices, helped establish the diagnosis. A 57-year-old Japanese woman was referred to our department for the evaluation of bilateral eye wall calcifications identified on routine head CT before kidney transplantation. She had a 17-year history of haemodialysis because of chronic renal failure. Blood tests showed elevated levels of parathyroid hormone (74.5 pg/ml) and phosphate (4.6 mg/dl) and borderline serum calcium depletion (8.7 mg/dl); the hyperparathyroidism was secondary to end-stage renal disease. Her best-corrected visual acuity was 1.2 bilaterally, and the intraocular pressure measured by applanation tonometry was 14 mmHg bilaterally. A relative afferent pupillary defect was plus/minus in the left eye. Funduscopy showed a vertical cup-to-disc ratio of 0.5 bilaterally; the inferior rim of the right disc was slightly pale, as was the entire rim of the left disc. Chorioretinal atrophy was present in the mid-peripheral fundus bilaterally (Fig. 1A, 1B). Visual field testing by Goldman perimetry showed a virtually normal right eye (Fig. 1C) and a relative scotoma in the left eye (Fig. 1D). Ultrasound sonography showed dense echogenic areas with acoustic shadowing at the ocular walls bilaterally (not shown). The 3D orbital images reconstructed from thin-sliced (0.67-mm step) axial CT (Brilliance CT 64-Channel, Philips Electronics, Eindhoven, the Netherlands) showed ectopic calcifications around both optic nerves (Fig. 1E, Video clip S1); the extent of the calcification coincided exactly with that of the chorioretinal atrophy bilaterally. The patient was diagnosed with hyperparathyroidism-related metastatic sclerochoroidal calcifications and related chorioretinal atrophy bilaterally. Areas of chorioretinal atrophy (dotted lines) are seen in the mid-peripheral fundus of the right (A) and the left (B) eyes. The visual field in the right eye (C) is normal; the left eye (D) has a relative scotoma. The 3D CT orbital image shows ectopic sclerochoroidal calcification bilaterally (E); the spatial distribution of the calcification matches the chorioretinal atrophy (A, B). Although visual disturbances caused by sclerochoroidal calcification have been reported in cases with posterior segment involvement (Zaman & Spalton 1995) and choroidal neovascularization (Cohen et al. 1998), most sclerochoroidal calcifications are asymptomatic and found incidentally. Sclerochoroidal calcification classically manifests as multiple discrete white or yellow fundus lesions (Honavar et al. 2001); the current patient had only diffuse chorioretinal atrophy, a relative scotoma and subtle changes in the optic nerve heads that were presumably related to antegrade degeneration from the chorioretinal atrophy. Thus, if we did not have her medical history, the chorioretinal atrophy easily could have been interpreted as simple ageing changes or changes owing to unknown aetiology. Zaheen et al. (2000) previously published orbital 3D images of one case of idiopathic sclerochoroidal calcification; however, to our best knowledge, the current case is the first to clearly show the spatial relationships between the extent of the chorioretinal atrophy and ectopic calcification formation. When ophthalmologists observe chorioretinal atrophy, obtaining a medical history of systemic diseases that could alter calcium and phosphorus metabolism is important; if a patient has such a systemic disease, sclerochoroidal calcification must be included in the differential diagnosis. Three-dimensional orbital imaging is useful for recognizing the association between the calcification and the fundus lesions. Video Clip S1. The orbital 3D CT images. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer-reviewed and may be re-organized for online delivery, but are not copy-edited. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

133 POSTER The reproducibility of perfusion parameters obtained from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in liver and lung tumors, and implications for sample size in clinical trials using DCE-MRI

Chronic kidney disease (CKD) is a major risk factor for coronary artery disease (CAD). As well as their high prevalence of traditional CAD risk factors, such as diabetes and hypertension, persons with CKD are also exposed to other nontraditional, uremia-related cardiovascular disease risk factors, including inflammation, oxidative stress, and abnormal calcium-phosphorus metabolism. CKD and end-stage kidney disease not only increase the risk of CAD, but they also modify its clinical presentation and cardinal symptoms. Management of CAD is complicated in CKD patients, due to their likelihood of comorbid conditions and potential for side effects during interventions. This summary of the Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference on CAD and CKD (including end-stage kidney disease and transplant recipients) seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of CAD in CKD and to identify knowledge gaps, areas of controversy, and priorities for research.

140 POSTER Morphologic assessments of tumor size: scan-rescan reproducibility of long- and short-axis measurements using manual and automated 3-dimensional assessments in liver and lung tumors using magnetic resonance imaging (MRI)

Chronic kidney disease (CKD) is a major risk factor for coronary artery disease (CAD). As well as their high prevalence of traditional CAD risk factors, such as diabetes and hypertension, persons with CKD are also exposed to other nontraditional, uremia-related cardiovascular disease risk factors, including inflammation, oxidative stress, and abnormal calcium-phosphorus metabolism. CKD and end-stage kidney disease not only increase the risk of CAD, but they also modify its clinical presentation and cardinal symptoms. Management of CAD is complicated in CKD patients, due to their likelihood of comorbid conditions and potential for side effects during interventions. This summary of the Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference on CAD and CKD (including end-stage kidney disease and transplant recipients) seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of CAD in CKD and to identify knowledge gaps, areas of controversy, and priorities for research.

Cardiovascular disease in children with chronic renal failure

Cardiovascular disease (CVD), including atherosclerosis, hypertension, myocardial infarction, and cerebrovascular accidents, constitutes an important cause of morbidity and mortality in adults with chronic kidney disease (CKD). However, evidence has been accumulating over the past several years that children and young adults with CKD also experience significant cardiovascular complications. Studies in the United States and Europe have shown that CVD is a leading cause of death in young adults diagnosed with CKD in childhood. Risk factors include hypertension, dyslipidemia, anemia, and abnormal calcium–phosphorus metabolism, all of which are present in many children with CKD. Although improved control of uremia and treatment of traditional and nontraditional cardiovascular risk factors have proved to be beneficial in adults with CKD, no such data exist for children. The NIH is currently conducting a large-scale, prospective observational study of children with CKD that should help to elucidate the role of CVD in the progression of CKD in children and what interventions might reduce the risk of cardiovascular complications in these young patients.

Cardiac and Vascular Adaptation in Pediatric Patients with Chronic Kidney Disease

In children, cardiac abnormalities such as increased left ventricular mass (LVM) and diastolic dysfunction develop at the time of mild to moderate chronic renal insufficiency (CRI) and progress as renal function deteriorates. It was hypothesized that in this age group, vascular abnormalities develop early in the course of chronic kidney disease (CKD) in parallel with cardiac abnormalities and become more severe as end-stage disease is reached. Echocardiography and ultrasound of the carotid artery were performed on 44 patients with CKD stages 2 to 4 (CRI group), 16 patients who were on maintenance dialysis, and 35 healthy individuals. Carotid artery intima-media thickness (cIMT) was measured and distensibility and stiffness were calculated to assess carotid artery structure and function. Both the CRI and dialysis groups had greater cIMT, higher LVM index, and poorer diastolic function than the control subjects (P < 0.0001). Children who were on dialysis had greater cIMT and higher LVM index than those with CRI (P < 0.001) and greater arterial stiffness than both CRI patients and control subjects (P < 0.001). Arterial compliance was similar in CRI and control subjects. In all patients with CKD (CRI and dialysis), increased calcium-phosphorus product predicted increased cIMT. Increased serum phosphorus and intact parathyroid hormone predicted increased arterial stiffness. Elevated intact parathyroid hormone was a predictor of increased LVM index and poor diastolic function. In dialysis patients, the cumulative dose of phosphate binders and calcitriol predicted abnormal vascular structure and function. It is concluded that vascular abnormalities are already present in children and adolescents during early stages of CKD; they are more severe in children who are on maintenance dialysis and are related to abnormal calcium-phosphorus metabolism.

Idiopathic sclerochoroidal calcification

Background Idiopathic sclerochoroidal calcification (ISC) is an uncommon condition of calcium deposition at the level of the sclera and choroid of the posterior pole. With normal acuity and visual field, it typically manifests in asymptomatic older males. It can be diagnosed on clinical grounds, appearing as multiple geographic, yellowish, placoid-like lesions in the sclera and choroid, commonly found in the super-otemporal arcade of the midperipheral fundus in both eyes. Ocular ultrasound and fluorescein angiography have classic results. Case Report An 85-year-old white man came to us for routine examination. Best-corrected visual acuity was 20/40 O.D. and O.S. Dilated fundus examination revealed several midperipheral yellowish-white deposits with retinal pigment epithelium hyperpigmentation temporally in each eye. Ocular ultrasound revealed high reflectivity consistent with calcium. The lesions demonstrated mild hyperfluorescence in the late phase of fluorescein angiography. Laboratory testing was void of abnormal calcium or phosphorous metabolism, and a diagnosis of ISC was made. Conclusion Idiopathic sclerochoroidal calcification is a benign lesion of calcium deposition in the posterior pole, often discovered on routine examination. Although it is idiopathic, systemic evaluation is warranted to rule out dystrophic or metastatic calcification by various pathological conditions associated with abnormal calcium-phosphorus metabolism— most notably, hyperparathyroidism. Differential diagnoses include choroidal osteoma, melanoma, and metastatic carcinoma.

Risk factors for cardiovascular disease in children on maintenance dialysis.

Cardiovascular disease mortality is high in children on maintenance dialysis, accounting for about 25% of patient deaths. Cardiovascular-related mortality rates for children on dialysis are higher than for children with successful kidney transplants. Data on the long-term consequences of risk factors for cardiovascular disease are lacking for pediatric end-stage renal disease patients. This article reviews pediatric data pertaining to the following risk factors: anemia, hypertension, hyperlipidemia, left ventricular hypertrophy, abnormal calcium-phosphorus metabolism, and hyperhomocysteinemia. The potential relationship of end-stage renal disease to the etiology of several functional disorders of the cardiovascular system is discussed. Clinical studies are needed to assess the prevalence of cardiovascular disease and of cardiovascular disease risk factors in the pediatric end-stage renal disease population. Possible preventive and therapeutic guidelines need to be developed for at-risk children on maintenance dialysis.

Management of patients with chronic renal insufficiency in the Northeastern United States.

Comorbid conditions that develop during chronic renal insufficiency (CRI) contribute to the high morbidity and mortality among patients with end-stage renal disease (ESRD). Thus, appropriate management during CRI may lead to improved ESRD outcomes. A retrospective cohort study was performed to describe the management of patients with CRI. A total of 602 patients with CRI (creatinine > or =1.5 mg/dl for women and > or =2.0 mg/dl for men) were seen between October 1994 and September 1998 at five nephrology outpatient clinics in the Boston area. The mean (SD) age of the patients was 63 (15.5) yr, and 53% were male. At the first nephrology visit, mean (SD) serum creatinine was 3.2 (1.6) mg/dl, and mean (SD) predicted GFR was 22.3 (8.9) ml/min per 1.73 m(2). Laboratory tests for iron levels were performed in only 18% of patients, serum parathyroid hormone levels were obtained in only 15%, lipid studies were obtained in fewer than half, and among patients with diabetes, only 28% had a glycosylated hemoglobin level measured. A hematocrit <30% was present in 38%, and abnormal calcium-phosphorus metabolism was noted in 55%. Only 59% of patients who had hematocrit <30% received recombinant human erythropoietin. Among patients who received recombinant human erythropoietin, only 47% received iron. Angiotensin-converting enzyme inhibitor use was recorded for only 65% of patients with diabetes (49% of patients overall). Among patients who were known to have progressed to ESRD, only 41% had permanent access placed before initiation of dialysis. There seems to be room for improvement in the management of patients with CRI, which could result in a slower rate of progression of CRI and reduced severity of comorbid conditions.

Sclerochoroidal calcification: clinical manifestations and systemic associations.

Sclerochoroidal calcification is an unusual ocular condition that is believed to be idiopathic in most cases. To describe the clinical manifestations of sclerochoroidal calcification and to investigate its possible systemic associations. This noncomparative consecutive case series included patients diagnosed as having sclerochoroidal calcification based on clinical characteristics and diagnostic test findings. We analyzed the demographic, systemic, and ocular features of 27 such patients. Systemic evaluation included tests for calcium-phosphorus metabolism in 19 patients and renal tubular hypokalemic metabolic alkalosis syndromes (Bartter or Gitelman syndrome) in 13. All the patients were asymptomatic older (mean age, 70 years) white individuals, incidentally noted as having a choroidal lesion on routine examination. Among 38 eyes, the main referral diagnoses were choroidal metastasis in 10 eyes (26%), choroidal melanoma in 8 (21%), and choroidal nevus in 4 (11%). Sixteen patients (59%) had unilateral clinical findings, while 11 (41%) had bilateral. The Snellen visual acuity was 20/50 or better in 37 eyes (97%). Cogan scleral plaque was visible anterior to the insertion of horizontal rectus muscles in 10 eyes (26%). Among 77 foci, there were a mean of 2 foci of sclerochoroidal calcification in each eye, 41 yellow (53%), 32 yellow-white (42%), 2 white (3%), and 2 orange (3%), measuring a mean 2.6 mm in diameter and 1.1 mm in thickness. The most common locations were postequatorial in 45 (58%), along the temporal vascular arcades in 30 (39%), and in the superotemporal quadrant in 43 (56%). A-scan and B-scan ultrasonography revealed dense echoes compatible with calcium, with orbital shadowing. All the lesions remained stable in size and configuration during a mean follow-up of 38 months. One patient developed a choroidal neovascular membrane over the area of sclerochoroidal calcification. Investigations for abnormal calcium-phosphorus metabolism in 19 patients revealed primary hyperparathyroidism in 1 patient (5%). Clinical and biochemical evaluation of 13 patients demonstrated hypomagnesemia in 6 (46%). Four patients (31%) met the criteria for the diagnosis of Gitelman syndrome. Sclerochoroidal calcification usually manifests as multiple discrete yellow placoid lesions in the midperipheral fundus of asymptomatic older white individuals. Although most cases may be idiopathic in nature, some patients may have underlying systemic disorders involving abnormal calcium-phosphorus metabolism or renal tubular hypokalemic metabolic alkalosis syndromes. All patients with sclerochoroidal calcification should be tested for these treatable systemic associations.

The significance of bilateral basal ganglia calcification.

Bilateral basal ganglia calcification was first recognized as a histologic entity in 1855 and described independently in that year by Virchow (1) and Bamberger (2). This phenomenon was encountered postmortem by many authors during the next eighty years but was not reported as a radiographic finding until 1935, when Fritzsche (4) and then Kasanin and Crank (5) described the roentgen appearance of this specific type of intracranial calcification in living patients. Four years later, in 1939, its occurrence in idiopathic hypoparathyroidism was described by Eaton, Camp, and Love (6). Its occurrence in pseudohypoparathyroidism, another disease characterized by abnormal calcium phosphorus metabolism, was first reported in 1945 by Sprague, Haines, and Power (14). Camp re-emphasized the association with hypoparathyroidism in 1947 (18). Anatomical Considerations The basal ganglia (Fig. 1) are masses of gray matter lying in the base of each cerebral hemisphere. They include three major structures—the caudate nucleus, the putamen, and the globus pallidus— and two minor centers—the amygdala and the claustrum. The caudate nucleus is an elongated mass of gray matter composed of a pear-shaped head, which bulges into the anterior horn of the lateral ventricle, and a slender arcuate tail, which is closely related to the atrium and temporal horn of the lateral ventricle. The putamen and globus pallidus form an oval wedge of gray matter, the lenticulate nucleus, which lies lateral to the head of the caudate nucleus. The basal ganglia are major centers of the extrapyramidal nervous system. In diseases of this system, such as parkinsonism or athetosis, they are the site of degenerative histologic lesions. It is interesting that skull films of these patients seldom display basal ganglia calcification and, conversely, only 20 per cent of patients with calcification manifest symptoms of parkinsonism or athetosis. Pathology The pathogenesis of basal ganglia calcification appears to consist in deposition of a colloid material in and around the finer cerebral blood vessels, with subsequent calcification of this colloid (6). Eaton, Camp, and Love presented an excellent description of these histologic changes with photomicrographs. Such calcification, of a degree insufficient to be roentgenographically demonstrable, is evident histologically in about two-thirds of routine postmortem brain examinations (3, 48). In the cases described in this report the range in prominence was from massive calcifications to those that were barely discernible in routine skull films. Roentgen Demonstration of Basal Ganglia Calcification Basal ganglia calcifications appear as a cluster of irregular punctate densities located at a distance of 3 to 5 cm. above the sella turcica in the lateral projection of the skull, and 2 to 4 cm. lateral to the midline in the frontal and occipital projections (Fig. 2). These calcifications are almost invariably bilateral, and are usually symmetrical.