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Autosomal recessive disorders are prevalent in Pakistan, a developing South Asian country where consanguineous marriages are common. This study seeks to determine the prevalence of monogenic causes in children presenting with nephrocalcinosis and nephrolithiasis at a dialysis and transplant center in Karachi, Pakistan. A retrospective analysis was conducted in children aged 1–18 years presenting with nephrocalcinosis, between 2010 and 2019. Demographic information, clinical profile, laboratory parameters and stone analysis were collected, on a pre-designed questionnaire. One hundred and twenty-six children were included, with 11 and 3 diagnosed with renal tubular acidosis and Bartter's syndrome respectively. Next-generation sequencing and Sanger sequencing was performed on 112 children. Eighty-seven patients were diagnosed with primary hyperoxaluria, with mutations in alanine–glyoxylate-aminotransferase gene found in 73, followed by glyoxylate reductase/hydroxy-pyruvate reductase in 13, and 4-hydroxy-2-oxaloglutarate aldolase in 1. Twenty-five patients reported negative for mutations. Sixty-four percent were males, with a statistically significant difference (p < 0.05). History of parental consanguineous marriage was found in 98% of the cohort. Fifty-four and 40 patients presented to the clinic with Chronic Kidney Disease Stage 1 and Stage 5, respectively, with a statistically significant difference p = 0.007. Mutations noted in our cohort are different and more severe than those reported in the developed world. The disease poses a major disease burden in developing world context with the only treatment option of combined liver–kidney transplantation not available in Pakistan. [ABSTRACT FROM AUTHOR]

Amelogenesis Imperfecta (AI) is also called as Hereditary enamel dysplasia, hereditary brown enamel and also as hereditary brown opalescent teeth. It represents a group of hereditary defects of enamel associated with any other generalized defect. A few case reports have been published where AI is seen to be associated with certain syndromes and metabolic disorders. AI, along with nephroclacinosis is an unusual presentation, which becomes more complex when it is presented with multiple unerupted teeth in siblings of adolescence age. Here, we report cases of two siblings with AI and multiple un erupted teeth, which is a rare occurrence. The importance of early detection of nephrocalcinosis in patients with AI is also emphasized. [ABSTRACT FROM AUTHOR]

Objective: Hereditary factors are the main cause of pediatric nephrolithiasis (NL)/nephrocalcinosis (NC). We summarized the genotype–phenotype correlation of hereditary NL/NC in our center, to evaluate the role of genetic testing in early diagnosis. Methods: The clinical data of 32 NL/NC cases, which were suspected to have an inherited basis, were retrospectively analyzed from May 2017 to August 2020. The trio-whole exome sequencing was used as the main approach for genetic testing, variants were confirmed by Sanger sequencing, and pathogenicity analysis according to protein function was predicted with custom-developed software. Results: Causative monogenic mutations were detected in 24 of 32 NL/NC patients, and copy number variation was detected in one patient. A summary of manifestations in patients with inherited diseases revealed a significant degree of growth retardation, increased urinary excretion of the low-molecular weight protein, hypercalciuria, electrolyte imbalances, and young age of onset to be common in heredity disease. In addition, some patients had abnormal renal function (3 ppm 25). The most frequent pathology identified was distal renal tubular acidosis (with inclusion of SLC4A1, ATP6V1B1, and ATP6VOA4 genes), followed by Dent disease (CLCN5 and OCRL1 genes), primary hyperoxaluria (PH) (AGXT and HOGA1 genes) and Kabuki syndrome (KMT2D gene), which was more likely to present as NC or recurrent stone and having a higher correlation with a specific biochemical phenotype and extrarenal phenotype. Conclusion: The etiology of NL/NC is heterogeneous. This study explored in depth the relationship between phenotype and genotype in 32 patients, and confirmed that genetic testing and clinical phenotype evaluation enable the precision medicine approach to treating patients. [ABSTRACT FROM AUTHOR]

Background: Genetic kidney diseases contribute a significant portion of kidney diseases in children and young adults. Nephrogenetics is a rapidly evolving subspecialty; however, in the clinical setting, increased use of genetic testing poses implementation challenges. Consequently, we established a national nephrogenetics clinic to apply a multidisciplinary model. Methods: Patients were referred from different pediatric or adult nephrology units across the country if their primary nephrologist suspected an undiagnosed genetic kidney disease. We determined the diagnostic rate and observed the effect of diagnosis on medical care. We also discuss the requirements of a nephrogenetics clinic in terms of logistics, recommended indications for referral, and building a multidisciplinary team. Results: Over 24 months, genetic evaluation was completed for a total of 74 unrelated probands, with an age range of 10 days to 72 years. The most common phenotypes included congenital anomalies of the kidneys and urinary tract, nephrotic syndrome or unexplained proteinuria, nephrocalcinosis/nephrolithiasis, tubulopathies, and unexplained kidney failure. Over 80% of patients were referred due to clinical suspicion of an undetermined underlying genetic diagnosis. A molecular diagnosis was reached in 42/74 probands, yielding a diagnostic rate of 57%. Of these, over 71% of diagnoses were made via next generation sequencing (gene panel or exome sequencing). Conclusions: We identified a substantial fraction of genetic kidney etiologies among previously undiagnosed individuals which influenced subsequent clinical management. Our results support that nephrogenetics, a rapidly evolving field, may benefit from well-defined multidisciplinary co-management administered by a designated team of nephrologist, geneticist, and bioinformatician. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Mutations in SLC4A4 have been reported to be associated with proximal renal tubular acidosis (RTA), short stature, band keratopathy, cataract, glaucoma, and hypoplastic-type amelogenesis imperfecta. In this study, the authors describe the clinical manifestations, and investigate the molecular etiology, in a patient with RTA. The authors report on a girl with distal RTA who carried a novel homozygous base substitution of 2 consecutive base pair variants (NM_001098484.3:c.808-2A>C and NM_001098484.3:c.808-1G>C) in the SLC4A4 gene. The patient had clinical manifestations of autoimmune thyroiditis and distal RTA, including hypercalciuria, nephrocalcinosis, and nephrolithiasis. In addition to the presence of hypoplastic-type amelogenesis imperfecta, generalized enamel hypomaturation, a feature seen in mice lacking Slc4a4 , was also observed in the patient. The basic defect in this patient appeared to be impaired hydrogen ion secretion, leading to an inability to acidify the urine, resulting in alkaline urine (despite a normal serum anion gap), hypokalemic, and hyperchloremic metabolic acidosis. The pulp stones found in the patient may likely be the consequences of a disrupted acid-base homeostatic environment that precipitated mineral deposits. Even with proper treatments for distal RTA, the patient has had frequent recurrences of band keratopathy, pupillary membrane, and cataract. This is the first report of distal RTA, autoimmune thyroiditis, tooth agenesis, enamel hypomaturation, and pulp stones associated with an SLC4A4 mutation. It is important for dentists to be aware that amelogenesis imperfecta in patients may be a sign of systemic diseases including RTA, nephrocalcinosis, or nephrolithiasis. [ABSTRACT FROM AUTHOR]

Objective: We aimed to present the characteristics, genetic analysis results, long-term prognosis of our patients with distal kidney tubular acidosis, and the relationship between hyperammonemia and distal kidney tubular acidosis. Materials and Methods: Biochemical, clinical, and imaging findings were collected at presentation and the last clinic visit, and results of the genetic analysis were recorded. Results: Our study included 9 patients (3 female, 33%). The median age at diagnosis was 3 months, and the median follow-up period was 111 months. Height standard deviation scores were less than -2 in 4 (44%) patients at presentation and in 3 (33%) at the last clinic visit. The median estimated glomerular filtration rate was 98 mL/min/1.73 m² at presentation and 126 mL/min/1.73 m² at the last clinic visit. We have found 8 different types of mutations of 2 genes, including 6 in the ATP6V0A4 gene, 2 in the SLCA4A1 gene, and 2 of them were novel. At the time of presentation, nephrocalcinosis and hypercalciuria were present in all our patients, but at the last visit, only 1 patient had hypercalciuria. Sensorineural hearing loss was found in 4 of our patients with a mutation in the ATP6V0A4 gene. Serum ammonia levels were found to be high in 3 patients with mutations in the ATP6V0A4 gene. Conclusion: Adequate metabolic control is essential for optimal growth and preserved kidney function in distal kidney tubular acidosis patients. Distal kidney tubular acidosis may be associated with hyperammonemia. We recommend keeping potassium levels at high-normal levels to reduce ammonia levels, especially in the absence of acidosis. [ABSTRACT FROM AUTHOR]

Background: Renal parenchymal disease is commonly encountered on imaging, and an understanding of the spectrum of pathology is vital to making correct diagnoses and recommendations for management. These conditions can be categorized based on the presence of calcifications, cysts, solid masses, patterns of enhancement, and other characteristic non-mass findings, as well as on their spatial distribution (i.e., medullary vs. cortical). Making an accurate diagnosis is often challenging, as there is overlap in the features of various diseases, and many benign entities may mimic pathology. Objective: This review broadly discusses imaging features of renal parenchymal disease and provides a systematic approach to characterize findings and appropriately guide further management. [ABSTRACT FROM AUTHOR]

Introduction The prevalence of chronic kidney disease (CKD) in the general population is 9.1%. Current guidelines recommend a cut-off GFR value of 60 mL/min/1.73 m² for diagnosis of CKD, without considering the physiological decline of GFR with aging, or the association with cardiovascular (CV), cerebrovascular or renal outcomes. There is also an increase in arterial stiffness with aging, which is estimated by pulse wave velocity (PWV). Aim The aim of this study is to show how the ePWV predicts CV incidents independently of SCORE chart and traditional risk factors. Materials and Methods This prospective observational study will include 2058 subjects from the Endemic nephropathy in Croatia – epidemiology, diagnosis and etiopathogenesis scientific research project. Conclusion This will be the first study that could show how the estimated arterial stiffness, independently of CKD contributes to overall CV, cerebrovascular and renal risk. We could also, based on the results, propose an age-independent definition of CKD based on the association with CV disease and mortality. [ABSTRACT FROM AUTHOR]

Nephrocalcinosis refers to the deposits of calcium within the renal parenchyma, usually detected on ultrasonography or computed tomography. The presence of medullary nephrocalcinosis may represent a variety of different etiologies. Early childhood onset of kidney stones and/or nephrocalcinosis often represent an inherited defect more frequently than in adults. The cases reported here highlight three different diseases that were diagnosed based on genetic analysis following presentation as medullary nephrocalcinosis in childhood. [ABSTRACT FROM AUTHOR]

Background: Hypercalciuria is one of the most frequent metabolic disorders associated with nephrolithiasis and/or nephrocalcinosis possibly leading to chronic kidney disease (CKD) and bone complications in adults. Orphan diseases with different underlying primary pathophysiology share inappropriately increased 1,25(OH)2D levels and hypercalciuria, e.g., hypersensitivity to vitamin D and renal phosphate wasting. Their management is challenging, typically based on hyperhydration and dietary advice. The antifungal azoles are known to inhibit the 1α-hydroxylase and therefore decrease 1,25(OH)2D levels; they are commonly used, with well described pharmacokinetic and tolerability data. Fluconazole has been successfully reported to reduce calciuria in patients with CYP24A1 or SLC34A3 mutations, with no safety warnings. Thus, based on these case reports, we hypothesize that fluconazole is effective to decrease and normalize calciuria in patients with hypercalciuria and increased 1,25(OH)2D levels.Methods: The FLUCOLITH trial is a prospective, interventional, randomized in parallel groups (1:1), placebo-controlled, double-blind trial. A total of 60 patients (10-60 years) with nephrolithiasis and/or nephrocalcinosis history, hypercalciuria (> 0.1 mmol/kg/day), increased 1,25(OH)2D levels (> 150 pmol/L), and 25-OH-D levels >20 nmol/L will be included. Inclusions will be performed only from mid-September to the beginning of February to avoid bias due to sunlight-induced vitamin D synthesis. The primary endpoint will be the proportion of patients with normalization of 24-h calciuria between baseline and 16 weeks, or with a relative decrease of at least 30% of 24-h calciuria in patients who still display at W16 a 24-h hypercalciuria.Discussion: The current challenge is to propose an efficient treatment to patients with hypercalciuria and increased 1,25(OH)2D levels in order to prevent later complications and notably CKD that can ultimately lead to end-stage renal disease. Based on improvement of knowledge in phosphate/calcium metabolism, pathophysiology and genetics, the "off-label" use of fluconazole was recently reported to be useful in hypercalciuric patients with increased 1,25(OH)2D levels. Thus, the FLUCOLITH study is a unique opportunity to develop a new indication of a well-known and not expensive drug in orphan renal diseases, the ultimate objective being the secondary prevention of CKD worsening in these patients.Trial Registration: ClinicalTrials.gov NCT04495608 . Registered on July 23, 2020. [ABSTRACT FROM AUTHOR]

Background: Pathologic studies have shown that in patients with critical limb threatening ischaemia (CLTI) medial arterial calcifications are frequently found and may be responsible for aggravating the disease. These extensive calcifitcations are found not only in arteries of the leg but also in the coronary arteries and the aorta. The progression of these calcifications is fast and they stiffen the vessel wall and may thus increase the cardiovascular risk. Reduction of progression of calcification may not only reduce the burden of CLTI but may also reduce the high residual cardiovascular risk. Medial calcifications have been halted by etidronate in other trials. Its potential to reduce the burden from peripheral vascular disease in CLTI and residual cardiovascular risk remains to be established. Methods: This is an investigator-initiated multicenter, double blind, placebo-controlled, randomized trial comparing the effects of etidronate versus placebo in patients with CLTI. Subjects will be randomized to either treatment with etidronate for 12 months (cyclical 20 mg/kg for 2 weeks on and 10 weeks off) orally or placebo for 12 months (in a similar routine). The primary endpoint is the change in arterial calcification as quantified by CT-scan. Secondary endpoints are the number of amputations above and below the ankle, mortality, number of vascular interventions and quality of life. Discussion: Up to now, the inert end stage of vascular disease in patients with CLTI, has been considered calcification of vessel walls. We believe there is reason to reverse causation and hypothesize that calcification causes vascular disease. This reversal can be proven in a clinical trial if halting the calcification process improves the outcome of the patient. Therefore we use etidronate, a bisphosphate that has proven to stop the calcification in several rare monogenetic calcifying diseases. We aim to perform this mechanistic proof-of-concept study hopefully leading to a clinical outcome study later on. [ABSTRACT FROM AUTHOR]

Background: Vitamin D (VitD) supplementation is recommended by the American Academy of Pediatrics (AAP) for preterm infants to improve bone density. Complications of VitD supplementation include hypercalciuria and nephrocalcinosis (NC). NC has been reported in 7–64% infants < 32 weeks gestational age (GA) or < 1500 g birth weight (BW). The relationships between VitD supplementation, serum 25-hydroxy VitD levels, bone density, hypercalciuria and development of NC in preterm infants are not well established. Methods: Prospective, observational cohort study of 56 infants with GA ≤ 32 weeks or BW ≤ 1800 g. Demographics, dietary intakes, serum 25-hydroxy VitD levels and weekly urinalyses were collected until 40 weeks corrected GA or discharge. Bone mineral density (BMD) and content (BMC) were assessed using dual-energy X-ray absorptiometry (DEXA) scan. NC was identified by kidney ultrasound. Results: 56 infants received on average 447 IU/day of VitD with average serum 25-hydoxy VitD level 39.6 ng/mL. DEXA scan showed average BMD 0.13 g/cm2 and BMC 35.8 g. 23/56 (41%) infants were diagnosed with NC. Infants with NC had lower GA (p < 0.01) and BW (p < 0.01) and increased presence of calcium oxalate crystals (78% vs. 36%) (p = 0.002). There were no differences in VitD intake, urine calcium/creatinine ratios or BMD and BMC in infants with versus without NC. Conclusions: VitD supplementation per AAP guidelines resulted in acceptable serum 25-hydroxyVitD levels, but no improvement in BMD or BMC compared to previously reported values. However, infants receiving recommended amounts born at earlier GA and lower BW are at increased risk of NC. VitD supplementation and serum levels should be closely monitored in this high-risk population. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Background: Progression of vascular calcification causes cardiovascular disease, which is the most common cause of death in chronic kidney failure and after kidney transplantation (KT). The prognostic impact of the extent of medial vascular calcification at KT is unknown. Methods: In this prospective cohort study, we investigated the impact of medial calcification compared to a mix of intimal and medial calcification represented by coronary artery calcification (CAC score) and aortic valve calcification in 342 patients starting on kidney failure replacement therapy. The primary outcomes were cardiovascular events (CVE) and death. The median follow‐up time was 6.4 years (interquartile range 3.7–9.6 years). Exposure was CAC score and arteria epigastrica medial calcification scored as none, mild, moderate, or severe by a pathologist at time of KT (n = 200). We divided the patients according to kidney failure replacement therapy during follow‐up, that is, living donor KT, deceased donor KT, or dialysis. Results: Moderate to severe medial calcification in the arteria epigastrica was associated with higher mortality (p = 0.001), and the hazard ratio for CVE was 3.1 (95% confidence interval [CI] 1.12–9.02, p < 0.05) compared to no or mild medial calcification. The hazard ratio for 10‐year mortality in the dialysis group was 33.6 (95% CI, 10.0–113.0, p < 0.001) compared to living donor recipients, independent of Framingham risk score and prevalent CAC. Conclusion: Scoring of medial calcification in the arteria epigastrica identified living donor recipients as having 3.1 times higher risk of CVE, independent of traditional risk factors. The medial calcification score could be a reliable method to identify patients with high and low risk of CVE and mortality following KT. [ABSTRACT FROM AUTHOR]

Summary: The present study was the first prospective cohort evaluated the efficacy and safety of different doses of calcitriol in XLH children. The results suggested that a dose of 40 ng/kg/day calcitriol, compared with 20 ng/kg/day, was more effective in relieving the rickets, with similar safety outcomes. Further investigations were expected to set more dose groups. Introduction: Dose recommended for calcitriol in X-linked hypophosphatemia (XLH) varies in different studies. Therefore, we aimed to compare the efficacy as well as the safety of 20 ng/kg/d and 40 ng/kg/d calcitriol in Chinese XLH pediatrics population. Methods: A 2-year, randomized, open-label, prospective study recruited 68 XLH children, which were randomized to receive either 40 ng/kg/day or 20 ng/kg/day calcitriol. Efficacy endpoints were the total Thacher ricket severity score (RSS) change from baseline to month 12 and 24, the difference in serum TALP level, fasting serum phosphate level, body height Z-score, and frequency of dental abscess. Safety assessments were done using renal ultrasound nephrocalcinosis grades (0–4), fasting serum and 24 h urine calcium level, and the occurrence of hyperparathyroidism. Results: The decrease in the total RSS from baseline was more significant in the high-dose group at 12 (difference 0.87, p = 0.049) and 24 month (difference 1.23, p = 0.011). The serum TALP level was significantly lower in the high-dose group at 6 months. Pi level, height Z-score change, frequency of dental abscess and ratio of de novo nephrocalcinosis were comparable. A lower incidence of secondary hyperparathyroidism was seen in the high-dose group (p < 0.0001). Conclusion: For the first time in this prospective cohort, 40 ng/kg/d calcitriol was shown to be the more effective therapy in XLH children than the 20 ng/kg/d. Moreover, 40 ng/kg/d calcitriol was not associated with increasing adverse events. Trial registration: ClinicalTrials.gov Identifier: NCT 03,820,518. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to develop a novel interpretable artificial intelligence (AI) model algorithm focusing on automatic detection and classification of various patterns of calcification distribution in mammographic images using a unique graph convolution approach. Materials and methods: Images from 292 patients, which showed calcifications according to the mammographic reports and diagnosed breast cancers, were collected. The calcification distributions were classified as diffuse, segmental, regional, grouped, or linear. Excluded were mammograms with (1) breast cancer with multiple lexicons such as mass, asymmetry, or architectural distortion without calcifications; (2) hidden calcifications that were difficult to mark; or (3) incomplete medical records. Results: A graph-convolutional-network-based model was developed. A total of 581 mammographic images from 292 cases of breast cancer were divided based on the calcification distribution pattern: diffuse (n = 67), regional (n = 115), group (n = 337), linear (n = 8), or segmental (n = 54). The classification performances were measured using metrics including precision, recall, F1 score, accuracy, and multi-class area under the receiver operating characteristic curve. The proposed model achieved a precision of 0.522 ± 0.028, sensitivity of 0.643 ± 0.017, specificity of 0.847 ± 0.009, F1 score of 0.559 ± 0.018, accuracy of 64.325 ± 1.694%, and area under the curve of 0.745 ± 0.030; thus, the method was found to be superior compared to all baseline models. The predicted linear and diffuse classifications were highly similar to the ground truth, and the predicted grouped and regional classifications were also superior compared to baseline models. The prediction results are interpretable using visualization methods to highlight the important calcification nodes in graphs. Conclusions: The proposed deep neural network framework is an AI solution that automatically detects and classifies calcification distribution patterns on mammographic images highly suspected of showing breast cancers. Further study of the AI model in an actual clinical setting and additional data collection will improve its performance. [ABSTRACT FROM AUTHOR]

Background: Although the primary cause of death in COVID‐19 infection is respiratory failure, there is evidence that cardiac manifestations may contribute to overall mortality and can even be the primary cause of death. More importantly, it is recognized that COVID‐19 is associated with a high incidence of thrombotic complications. Hypothesis: Evaluate if the coronary artery calcium (CAC) score was useful to predict in‐hospital (in‐H) mortality in patients with COVID‐19. Secondary end‐points were needed for mechanical ventilation and intensive care unit admission. Methods: Two‐hundred eighty‐four patients (63, 25 years, 67% male) with proven severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection who had a noncontrast chest computed tomography were analyzed for CAC score. Clinical and radiological data were retrieved. Results: Patients with CAC had a higher inflammatory burden at admission (d‐dimer, p =.002; C‐reactive protein, p =.002; procalcitonin, p =.016) and a higher high‐sensitive cardiac troponin I (HScTnI, p = <.001) at admission and at peak. While there was no association with presence of lung consolidation and ground‐glass opacities, patients with CAC had higher incidence of bilateral infiltration (p =.043) and higher in‐H mortality (p =.048). On the other side, peak HScTnI >200 ng/dl was a better determinant of all outcomes in both univariate (p = <.001) and multivariate analysis (p = <.001). Conclusion: The main finding of our research is that CAC was positively related to in‐H mortality, but it did not completely identify all the population at risk of events in the setting of COVID‐19 patients. This raises the possibility that other factors, including the presence of soft, unstable plaques, may have a role in adverse outcomes in SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

• This study aims to screen a drug for treating kidney injury and inflammation in patients with nephrocalcinosis. • We constructed anmodel of crystalline nephropathy and used experiments to verify the expression of related factors. • We screened a plant-derived natural product, pectolinarigenin, discovered the inhibitory effect of pectolinarigenin on inflammation and oxidative stress in CaOx nephrocalcinosis. • This study differs from other studies that screen drugs in libraries of synthetic compounds by focusing on herbs. • This study is the first to identify a therapeutic role for pectolinarigenin in nephrocalcinosis, which may provide new ideas on how to cure nephrocalcinosis more effectively. Calcium oxalate (CaOx) crystals are the main constituents of renal crystals in humans and induce tubular lumen damage in renal tubules, leading to renal calcium deposition and kidney stone formation. Oxidative stress and inflammation play important roles in regulating calcium oxalate-induced injury. Here, we evaluated the efficacy in inhibiting oxidation and inflammation of pectinolinarigenin, a biologically active natural metabolite, in CaOx nephrocalcinosis and further explored its targets of action. First, we developed cellular and mouse models of calcium oxalate renal nephrocalcinosis and identified the onset of oxidative stress and inflammation according to experimental data. We found that pectolinarigenin inhibited this onset while reducing renal crystal deposition. Network pharmacology was subsequently utilized to screen for hypoxia-inducible factor-1α (HIF-1α), a regulator involved in the body's release and over-oxidation of inflammatory factors. Finally, molecular docking, cellular thermal shift assay, and other experiments to detect HIF-1α expression showed that pectolinarigenin directly combined with HIF-1α and prevented downstream reactive oxygen species activation and release. Our results indicate that pectolinarigenin can target and inhibit HIF-1α-mediated inflammatory responses and oxidative stress damage and be a novel drug for CaOx nephrocalcinosis treatment. [ABSTRACT FROM AUTHOR]

Warfarin produced a similar proportional increase in progression in ESRD patients, but because of the underlying propensity towards arterial calcification in ESRD, the rate of progression in ESRD patients treated with warfarin was almost 20-fold greater than in women without ESRD not treated with warfarin. One could argue that it could be used in patients with excellent control of their mineral metabolism but our data show that warfarin increases arterial calcification in patients with normal renal function and presumably normal mineral metabolism. Patients with end-stage renal disease (ESRD) often have indications for long-term anticoagulation such as atrial fibrillation, thrombosis of arteriovenous fistulas and grafts, metallic heart valves, and hypercoagulable states. [Extracted from the article]

The peripheral arterial occlusive disease is responsible for a significant amount of morbidity and mortality in patients of endstage renal disease. This disease might not be as common as end-stage renal disease in vascular complications arising after renal transplant. The peripheral arterial occlusive disease is responsible for lower limb amputation in chronic kidney disease. It is important to identify the peripheral arterial occlusive disease as it may lead to septicaemia which in turn can result in multiple organ failure and thus can prove to be a potentially fatal complication of renal disease. Here the authors report a case of a 42-year-old female who had undergone a renal transplant four years back. She presented with breathlessness and bilateral pedal oedema along with autoamputation of toes and ultimately had to be taken for haemodialysis. The patient was intrervene for an arteriovenous fistula for haemodialysis in view of graft rejection. Through this brief case report, the authors highlight the importance of a neglected autoamputation which was a missed warning sign of impending renal graft rejection in the present case. [ABSTRACT FROM AUTHOR]

High coronary artery calcification (CAC) burden is a significant risk factor for adverse cardiovascular and kidney outcomes. However, it is unknown whether changes in the coronary atherosclerotic burden can accompany changes in kidney disease progression. Here, we evaluated the relationship between CAC progression and the risk of kidney failure with replacement therapy (KFRT). We analyzed 1173 participants with chronic kidney disease (CKD) G1 to G5 without kidney replacement therapy from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Participants were categorized into three groups according to the change in the CAC score between enrollment and year 4 (non-progressors, ≤0 AU; moderate progressors, 1–199 AU; and severe progressors, ≥200 AU). The primary outcome was the development of KFRT. During a follow-up period of 4690 person-years (median, 4.2 years), the primary outcome occurred in 230 (19.6 %) participants. The incidence of KFRT was 37.6, 54.3, and 80.9 per 1000 person-years in the non-, moderate, and severe progressors, respectively. In the multivariable cause-specific hazard model, the hazard ratios (HRs) for the moderate and severe progressors were 1.71 (95 % confidence interval [CI], 1.02–2.87) and 2.55 (95 % CI, 1.07–6.06), respectively, compared with non-progressors. A different definition of CAC progression with a threshold of 100 AU yielded similar results in a sensitivity analysis. CAC progression is associated with an increased risk of KFRT in patients with CKD. Our findings suggest that coronary atherosclerosis changes increase the risk of CKD progression. [Display omitted] • Coronary artery calcification (CAC) is common in patients with chronic kidney disease (CKD). • CAC progression was more evident in patients with advanced CKD. • Greater CAC progression was associated with a higher risk for kidney failure with replacement therapy in patients with CKD. • CAC score assessment and follow-up could serve as a valuable tool for risk stratification in patients with CKD. [ABSTRACT FROM AUTHOR]

• Medial vascular calcification (mVC) lacks a cost-effective assessment in clinical practice. • Peripheral pulse wave analysis, alongside traditional factors, predicts mVC effectively. • The model incorporating pulse wave features and risk factors, achieves high accuracy. • Integration of non-invasive pulse wave analysis can aid early detection of mVC. Medial vascular calcification (mVC), particularly prevalent in patients with chronic kidney disease (CKD), is a pathological deposition of minerals in the medial layer of the vessel wall and is associated with an increased risk of cardiovascular disease. Currently, there is no cost–effective and non-invasive procedure of mVC assessment in routine clinical practice. We explored whether in–depth analysis of non-invasively recorded peripheral pulse waves can serve as an effective mVC biomarker. The study included 97 CKD patients with histological assessment of mVC in the epigastric artery and pulse wave measurements in the brachial artery. Pulse waves were analysed in the frequency domain to obtain features, which, together with traditional mVC risk factors (i.e., age, sex, and body mass index), were used to build generalized linear models for mVC prediction. The classifiers with the best scores in terms of balanced accuracy were combined in an ensemble establishing the final model. The final, ensembled model, assessed using a leave-one-out cross-validation process, achieved a balanced accuracy equal to 0.87, an accuracy of 0.93, an AUC ROC of 0.91, and an F-score of 0.96. Apart from the features associated with pulse waves, the selected variables included age, sex, body mass index, heart rate and diastolic blood pressure. Analysis of non-invasively recorded peripheral pulse waveforms combined with traditional risk factors, can help to detect mVC in CKD patients and thus, potentially introduce risk-lowering therapeutic strategies at earlier disease stages in the future. [ABSTRACT FROM AUTHOR]

Background: Despite marked progress in endovascular treatment (EVT) techniques and devices, calcified lesions remain one of the toughest obstacles to EVT success. Moreover, because the common femoral artery (CFA) is known as a "non-stenting zone," endovascular strategies for this area are controversial. Case presentation: Here we describe the technical tips for a novel, less invasive, and effective debulking strategy for severe nodular calcification using an endovascular maneuver. This technique was demonstrated in a 73-year-old man with severe calcified stenosis of the CFA. To complete a stent-less strategy for CFA, we conducted aggressive debulking of the nodular calcification, established a bidirectional approach from the radial artery and the superficial femoral artery (SFA), and inserted a balloon-guiding catheter in the SFA. Under distal protection provided by this catheter, we crushed the nodular calcification 43 times using myocardial biopsy forceps. After achieving a volume reduction of nodular calcification through this maneuver, we completed the procedure by inflating a 6-mm drug-coated balloon catheter. Final angiography demonstrated a reduced filling defect of the contrast medium in the CFA and favorable blood flow as far as the ankle. The puncture site on the SFA was closed with a vascular suture assisted by balloon inflation inside the vessel, which allowed the patient to be ambulatory immediately after the procedure without requiring bed rest. Conclusions: Severely calcified lesions in the CFA are usually difficult to treat using an endovascular strategy, but our novel and less invasive method may become a promising technique for managing these lesions. [ABSTRACT FROM AUTHOR]

Background: Dent disease is an X-linked disorder characterized by low molecular weight proteinuria (LMWP), hypercalciuria, nephrolithiasis and chronic kidney disease (CKD). It is caused by mutations in the chloride voltage-gated channel 5 (CLCN5) gene (Dent disease-1), or in the OCRL gene (Dent disease-2). It is associated with chronic metabolic acidosis; however metabolic alkalosis has rarely been reported.Case Presentation: We present a family with Dent-2 disease and a Bartter-like phenotype. The main clinical problems observed in the proband included a) primary phosphaturia leading to osteomalacia and stunted growth; b) elevated serum calcitriol levels, leading to hypercalcemia, hypercalciuria, nephrolithiasis and nephrocalcinosis; c) severe salt wasting causing hypotension, hyperaldosteronism, hypokalemia and metabolic alkalosis; d) partial nephrogenic diabetes insipidus attributed to hypercalcemia, hypokalemia and nephrocalcinosis; e) albuminuria, LMWP. Phosphorous repletion resulted in abrupt cessation of hypercalciuria and significant improvement of hypophosphatemia, physical stamina and bone histology. Years later, he presented progressive CKD with nephrotic range proteinuria attributed to focal segmental glomerulosclerosis (FSGS). Targeted genetic analysis for several phosphaturic diseases was unsuccessful. Whole Exome Sequencing (WES) revealed a c.1893C > A variant (Asp631Glu) in the OCRL gene which was co-segregated with the disease in male family members.Conclusions: We present the clinical characteristics of the Asp631Glu mutation in the OCRL gene, presenting as Dent-2 disease with Bartter-like features. Phosphorous repletion resulted in significant improvement of all clinical features except for progressive CKD. Angiotensin blockade improved proteinuria and stabilized kidney function for several years. [ABSTRACT FROM AUTHOR]

The clinical presentation of primary hyperoxaluria in children ranges from mildly symptomatic nephrocalcinosis to very early onset end-stage kidney failure with systemic oxalosis, a devastating complication. We review the various manifestations of pediatric hyperoxaluria, treatment options for children with preserved kidney function and appropriate dialysis regimens. Liver or combined liver/kidney transplantation is currently the only definitive treatment for primary hyperoxaluria type 1, but novel RNA interference treatments offer hope for the future. Finally, we address the medical and ethical dilemmas facing pediatricians treating children with hyperoxaluria. [ABSTRACT FROM AUTHOR]

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder that is characterized by renal magnesium wasting, hypercalciuria and eventually kidney failure which mostly affects children and young aged adults. Mutation of genes of claudin-16 and claudin-19 are involved in the pathogenesis of this disorder, which leads to renal magnesium and calcium wasting. A 35-year-old man with end-stage kidney disease (ESKD) was referred to our clinic due to bilateral nephrocalcinosis, detected by ultrasonographic study, for further evaluation. Detailed investigations revealed that his siblings had also similar presentations of hypomagnesemia, hypercalciuria, nephrocalcinosis and chronic kidney disease (CKD). Sanger sequencing showed a novel mutation (c.338G > A: p.C113Y) at the second exon of the CLDN16 gene. The patient underwent kidney transplantation and his siblings received only medical treatment. In young patients with ESKD and concomitant nephrocalcinosis, especially where there is a family history of CKD/ESKD, genetic evaluation is strongly recommended.  DOI: 10.52547/ijkd.6845. [ABSTRACT FROM AUTHOR]

Biallelic loss of function mutations in the CLDN16 gene cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and chronic kidney disease. Here we report two cases of FHHNC with diverse clinical presentations and hypercalcemia in one as a novel finding. Pt#1 initially presented with urinary tract infection and failure to thrive at 5.5 months of age to another center. Bilateral nephrocalcinosis, hypercalcemia (Ca: 12.2 mg/dl), elevated parathyroid hormone (PTH) level, and hypercalciuria were detected. Persistently elevated PTH with high/normal Ca levels led to subtotal-parathyroidectomy at the age of 2.5. However, PTH levels remained elevated with progressive deterioration in renal function. At 9-year-old, she was referred to us for evaluation of hyperparathyroidism and, hypomagnesemia together with hypercalciuria, elevated PTH with normal Ca levels, and medullary nephrocalcinosis were detected. Compound heterozygosity of CLDN16 variants (c.715G>A, p.G239R; and novel c.360C>A, p.C120*) confirmed the diagnosis. Pt#2 was a 10-month-old boy, admitted with irritability and urinary crystals. Hypocalcemia, hypophosphatemia, elevated PTH and ALP, low 25(OH)D levels, and radiographic findings of rickets were detected. However, additional findings of hypercalciuria and bilateral nephrocalcinosis were inconsistent with the nutritional rickets. Low/normal serum Mg levels suggested the diagnosis of FHHNC which was confirmed genetically as a homozygous missense (c.602G > A; p.G201E) variant in CLDN16. Yet, hypocalcemia and hypomagnesemia persisted in spite of treatment. In conclusion, FHHNC may present with diverse clinical features with mild hypomagnesemia leading to secondary hyperparathyroidism with changing Ca levels from low to high. Early and accurate clinical and molecular genetic diagnosis is important for proper management. [ABSTRACT FROM AUTHOR]

Pseudoxanthoma elasticum (PXE; OMIM 264800) is a rare heritable multisystem disorder, characterized by ectopic mineralization affecting elastic fibres in the skin, eyes and the cardiovascular system. Skin findings often lead to early diagnosis of PXE, but currently, no specific treatment exists to counteract the progression of symptoms. PXE belongs to a group of Mendelian calcification disorders linked to pyrophosphate metabolism, which also includes generalized arterial calcification of infancy (GACI) and arterial calcification due to CD73 deficiency (ACDC). Inactivating mutations in ABCC6, ENPP1 and NT5E are the genetic cause of these diseases, respectively, and all of them result in reduced inorganic pyrophosphate (PPi) concentration in the circulation. Although PPi is a strong inhibitor of ectopic calcification, oral supplementation therapy was initially not considered because of its low bioavailability. Our earlier work however demonstrated that orally administered pyrophosphate inhibits ectopic calcification in the animal models of PXE and GACI, and that orally given Na4P2O7 is absorbed in humans. Here, we report that gelatin‐encapsulated Na2H2P2O7 has similar absorption properties in healthy volunteers and people affected by PXE. The sodium‐free K2H2P2O7 form resulted in similar uptake in healthy volunteers and inhibited calcification in Abcc6−/− mice as effectively as its sodium counterpart. Novel pyrophosphate compounds showing higher bioavailability in mice were also identified. Our results provide an important step towards testing oral PPi in clinical trials in PXE, or potentially any condition accompanied by ectopic calcification including diabetes, chronic kidney disease or ageing. [ABSTRACT FROM AUTHOR]

Monogenic causes of paediatric nephrocalcinosis are associated with extensive phenotypic variability. We report a 14-year-old male who presented at 8 years of age with incidentally identified nephrocalcinosis alongside growth impairment and dental anomalies. Extensive genetic investigation confirmed a molecular diagnosis of Bartter syndrome type II. This is exceptional in both late presentation and the presence of amelogenesis imperfecta, a very rare association of inherited tubulopathies. Details of the nephrocalcinosis gene panel analysed and associated phenotypes are presented to highlight the utility of a phenotype-driven genetic panel in resolving an atypical presentation of nephrocalcinosis, allowing precise diagnosis, tailored therapy and prognostication. [ABSTRACT FROM AUTHOR]

Kidney stones (also known as urinary stones or nephrolithiasis) are highly prevalent, affecting approximately 10% of adults worldwide, and the incidence of stone disease is increasing. Kidney stone formation results from an imbalance of inhibitors and promoters of crystallization, and calcium-containing calculi account for over 80% of stones. In most patients, the underlying aetiology is thought to be multifactorial, with environmental, dietary, hormonal and genetic components. The advent of high-throughput sequencing techniques has enabled a monogenic cause of kidney stones to be identified in up to 30% of children and 10% of adults who form stones, with ~35 different genes implicated. In addition, genome-wide association studies have implicated a series of genes involved in renal tubular handling of lithogenic substrates and of inhibitors of crystallization in stone disease in the general population. Such findings will likely lead to the identification of additional treatment targets involving underlying enzymatic or protein defects, including but not limited to those that alter urinary biochemistry. [ABSTRACT FROM AUTHOR]

Background: Nephrocalcinosis is a pathological feature of chronic kidney disease (CKD). Its pathophysiological implications for cats with CKD are unexplored. Objectives: Identify nephrocalcinosis risk factors and evaluate its influence on CKD progression and all‐cause mortality. Animals: Fifty‐one euthyroid client‐owned cats with International Renal Interest Society (IRIS) stages 2‐3 azotemic CKD. Methods: Retrospective cohort study. Histopathological kidney sections were assessed for nephrocalcinosis (von Kossa stain). Nephrocalcinosis severity was determined by image analysis (ImageJ). Ordinal logistic regressions were performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression and mortality risk were assessed using linear mixed model and Cox regression, respectively. Cats were categorized by their owner‐reported time‐averaged phosphate‐restricted diet (PRD) intake, where PRD comprised ≥50%, 10‐50%, or none of food intake. Results: Nephrocalcinosis was rated as mild‐to‐severe in 78.4% and absent‐to‐minimal in 21.6% of cases. Higher baseline plasma total calcium concentration (tCa; odds ratio [OR] = 3.07 per 1 mg/dL; P =.02) and eating a PRD (10%‐50%: OR = 8.35; P =.01; ≥50%: OR = 5.47; P =.01) were independent nephrocalcinosis risk factors. Cats with absent‐to‐minimal nephrocalcinosis had increasing plasma creatinine (0.250 ± 0.074 mg/dL/month; P =.002), urea (5.06 ± 1.82 mg/dL/month; P =.01), and phosphate (0.233 ± 0.115 mg/dL/month; P =.05) concentrations over a 1‐year period, and had shorter median survival times than cats with mild‐to‐severe nephrocalcinosis. Conclusion and Clinical Importance: Higher plasma tCa at CKD diagnosis and PRD intake are independently associated with nephrocalcinosis. However, nephrocalcinosis is not associated with rapid CKD progression in cats. [ABSTRACT FROM AUTHOR]

Keywords: Editorials; coronary atherosclerosis; incidental finding; risk assessment; statins EN Editorials coronary atherosclerosis incidental finding risk assessment statins 715 717 3 03/02/23 20230228 NES 230228 B Article, see p 703 b Statins are a cornerstone of primary prevention but remain underused.[1] Even among adults followed routinely in a clinical setting, <40% of those recommended for a statin for primary prevention are on an appropriate one.[2] Novel approaches are needed to improve statin use in primary prevention. This project echoes previous work showing a large proportion of enrolled patients having no detectable CAC ("CAC zero"), among whom a flexible approach of delaying or avoiding statins may be prudent on the basis of American Heart Association/American College of Cardiology guidelines. In the notification arm, the patients' providers were sent a message notifying them of the existence of previous CAC, with a representative image from previous CT scans and a suggestion to start a statin. [Extracted from the article]

A quiz concerning the unexpected fnding in kidney biopsy of a child with nephrotic proteinuria including renal tubular function tests including urine protein electrophoresis.

Dent disease type 1 is suspected in the presence of a complete phenotype of low molecular weight (LMW) proteinuria, hypercalciuria and at least one of the following: nephrocalcinosis, nephrolithiasis, haematuria, hypophosphatemia or chronic kidney disease (CKD). We present two brothers who presented with CKD alone. In the absence of typical clinical features, further assessment of LMW proteinuria and hypercalciuria was not undertaken. Whole-genome sequencing revealed hemizygous loss of function mutations in chloride voltage-gated channel 5 (CLCN5) consistent with Dent disease. Dent disease should, therefore, be considered in patients with an incomplete phenotype, including unexplained CKD alone. [ABSTRACT FROM AUTHOR]

Background: Hypophosphatasia (HPP) is a rare inherited metabolic disorder caused by mutations in the ALPL gene, which encodes tissue nonspecific alkaline phosphatase. The severity of HPP is widely diverse from the perinatal form to the adult mild form. The former represents the most severe form and was earlier associated with high mortality due to pneumonia which was caused by severe hypomineralization of the bones-such as chest deformity and fractured ribs-and muscle weakness. Enzyme replacement therapy using asfotase alfa (AA) was approved in 2015 in Japan for treating patients with HPP and has improved their pulmonary function and life prognosis. There are several practical and ethical challenges related to using orphan drugs for a rare disorder in a publicly funded healthcare system. Sharing experiences about their application is essential towards formulating guidelines to assist clinicians with decisions about their initiation and withdrawal. We report the details of AA experience in ten cases of pediatric-onset HPP in nine families from January 2015 to November 2019 (median [interquartile range] age 11.0 [7.6-12.5] years; 60% male). This is a study of a single-center cohort describing the clinical course of patients with HPP, mainly consisting of the mild childhood form of HPP, treated with AA in Japan.Results: One case of perinatal form of HPP, two cases of benign prenatal form, and seven cases of childhood form were observed. The most common symptom at onset was pain. All patients had low serum alkaline phosphatase levels as compared to the age-matched reference range before the commencement of AA. All HPP patients seem to have responded to AA treatment, as evidenced by pain alleviation, increased height standard deviation, improvement in respiratory condition and 6-min walk test result improvement, disappearance of kidney calcification, alleviation of fatigue, and/or increases in bone mineralization. There were no serious adverse events, but all patients had an injection site reaction and skin changes at the injection sites. Genetic analysis showed that eight out of ten patients had compound heterozygosity.Conclusions: AA may be effective in patients with mild to severe pediatric-onset forms of HPP. [ABSTRACT FROM AUTHOR]

Background: Cardiac Society of Australia and New Zealand (CSANZ) guidelines recommend elective high-risk percutaneous coronary intervention (PCI) is not performed in sites greater than 1 hour from cardiac surgery.Methods: In hospital outcomes for all patients from Orange Health Service (OHS) from January 2017 to January 2020 who were transferred electively to tertiary centres in Sydney for high risk PCI were examined.Results: One hundred and fourteen (114) patients were identified, with 1,259 PCIs performed at OHS over the same period without transfer. The mean age of these 114 patients was 71 years, with 74.6% male. Receiving hospitals were Royal Prince Alfred Hospital, Sydney, NSW (66.7%), Concord Repatriation General Hospital, Concord, NSW (19.3%) and Strathfield Private Hospital, Strathfield, NSW (14%). The definition of high risk and indication for transfer included at least one of: moderate or greater calcification of the target lesion or proximal segment (34%), single or multiple target lesions that in aggregate jeopardised over 50% of remaining viable myocardium (27%), degenerated saphenous vein grafts (14.8%), chronic total occlusions (7.0%) and severe left ventricular (LV) impairment (3.9%). American Heart Society/American College of Cardiology (AHA/ACC) lesion types were A (1%), B1 (4.2%), B2 (40.2%), and C (54.6%). PCI was performed via the femoral route in 96.2%. The mean procedure duration was 72 minutes, mean combined fluoroscopy time was 19 minutes and mean radiation dose as defined by Reference Air Kerma was 1,630 mGy. Complications occurred in 13 patients and were: acute vessel dissection requiring stenting (4), perforation (2), acute vessel closure (4), puncture site related (1), and life-threatening arrhythmia (2). There were no cases of emergent coronary artery bypass graft (CABG) or death.Conclusion: This contemporary cohort of high-risk patients transferred electively from a regional PCI centre to a tertiary cardiac unit underwent lengthy PCI procedures, with high radiation doses, and a modest rate of peri-procedural complications, but had otherwise excellent procedural and clinical outcomes. [ABSTRACT FROM AUTHOR]

Breast arterial calcification (BAC) is increasingly recognized as a specific marker of medial calcification. The present retrospective observational cohort study aimed to define the prevalence, progression rate, risk factors and clinical implications of BAC in chronic kidney disease (CKD) patients across stages of disease. The presence and extent of BAC were determined on mammograms in 310 females (58.7 ± 10.8 years, Caucasian) with CKD across various stages of disease [CKD G2–5D n  = 132; transplant (Tx) recipients n  = 178]. In a subset of 88 patients, repeat mammography was performed, allowing us to calculate the annualized BAC rate. Overall, BAC was observed in 34.7% of the patients. BAC prevalence (P = 0.02) and BAC score (P = 0.05) increased along the progression of CKD. In the overall cohort, patients with BAC were characterized by older age, more cardiovascular disease, more inflammation, higher pulse pressure and borderline higher prevalence of diabetes and were more often treated with a vitamin K antagonist (VKA). The BAC progression rate was significantly lower in Tx patients as compared with CKD G5D. Progressors were characterized by more inflammation, worse kidney function, higher BAC score and higher serum phosphate level (Tx only) at baseline and were more often treated with a VKA. Major adverse cardiovascular event-free survival was significantly worse in Tx patients with BAC. In conclusion, BAC is common among CKD patients, progresses at a slower pace in Tx patients as compared with CKD 5D and associates with dismal cardiovascular outcomes. BAC score, kidney function, serum phosphate at baseline and VKA usage seem to be important determinants of progression. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular disease represents the leading cause of death in chronic hemodialysis (HD) patients; in this field, abdominal aortic calcifications (AAC) which represent a predictor of cardiovascular events are associated with cardiovascular morbidity and mortality. Objectives: The purpose of our study is to determine the prevalence and factors associated with AAC. Patients and Methods: This cross-sectional study including 40 chronic HD patients for more than six months having benefited from screening for AAC by profile abdominal x-ray without preparation. The AAC were evaluated according to the Kauppila score (ScK). Demographic, biological and radiological data were collected and then analyzed to assess the prevalence of AAC. Patients were divided into two groups according to ScK, highly calcified (ScK ≥12) and slightly or moderately calcified (ScK <12), in order to determine the associated factors to severe AAC. Results: The mean age was 58 ± 16 years, 55% were women, and the median of HD duration is 82 months. The prevalence of AAC was 65% and the median score of AAC was four. Patients with highly AAC (ScK ≥12) represented 27.5% of population and slightly or moderately AAC (ScK <12) represented 72.5%. The factors associated with severe AAC retained in the univariate analysis were age (P = 0.029), phosphoremia (P = 0.027), duration of dialysis (P = 0.047) and calcemia (P = 0.035). Only duration of dialysis (P = 0.042), age (P = 0.018) and phosphoremia (P = 0.044) remained statistically significant in multivariate. Conclusion: AAC are associated with advanced age, long duration of dialysis, and phosphocalcic balance abnormalities. Profile abdominal x-ray without preparation is currently recommended by the KDIGO (kidney disease improving global outcomes) for early detection and follow-up of vascular calcifications on HD, which should be considered for any patient. [ABSTRACT FROM AUTHOR]

Background and Aims: Abdominal aortic calcification (AAC) is common in chronic kidney disease (CKD) patients and associated with increased mortality. Comparative data on the AAC score progression in CKD patients transitioning from conservative treatment to different modalities of renal replacement therapy (RRT) are lacking and were examined. Methods: 150 study patients underwent lateral lumbar radiograph to study AAC in the beginning of the study before commencing RRT (AAC1) and at 3 years of follow-up (AAC2). We examined the associations between repeated laboratory tests taken every 3 months, echocardiographic and clinical variables and AAC increment per year (ΔAAC), and the association between ΔAAC and outcomes during follow-up. Results: At the time of AAC2 measurement, 39 patients were on hemodialysis, 39 on peritoneal dialysis, 39 had a transplant, and 33 were on conservative treatment. Median AAC1 was 4.8 (0.5–9.0) and median AAC2 8.0 (1.5–12.0) (p < 0.0001). ΔAAC was similar across the treatment groups (p = 0.19). ΔAAC was independently associated with mean left ventricular mass index (LVMI) (log LVMI: β = 0.97, p = 0.02) and mean phosphorus through follow-up (log phosphorus: β = 1.19, p = 0.02) in the multivariable model. Time to transplantation was associated with ΔAAC in transplant recipients (per month on the waiting list: β = 0.04, p = 0.001). ΔAAC was associated with mortality (HR 1.427, 95% confidence interval 1.044–1.950, p = 0.03). Conclusion: AAC progresses rapidly in patients with CKD, and ΔAAC is similar across the CKD treatment groups including transplant recipients. The increment rate is associated with mortality and in transplant recipients with the time on the transplant waiting list. [ABSTRACT FROM AUTHOR]

Vascular calcification (VC) causes cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD), particularly those with end-stage kidney disease (ESKD) on maintenance dialysis treatment. Although many mechanisms have been proposed, their detailed effects remain incompletely understood. In this issue of the JCI, Li et al. examined the molecular mechanism of the protective role of SIRT6 in VC in patients with CKD. Using in vitro and animal models of CKD, the authors demonstrated that SIRT6 prevents VC by suppressing the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Mechanistically, SIRT6 bound and deacetylated the runt-related transcription factor 2 (Runx2), a key transcription factor for osteogenic differentiation, promoting its nuclear export for proteasome degradation. These studies provide a pathway in the pathogenesis of VC and justify investigating SIRT6 as a potential target in CKD. [ABSTRACT FROM AUTHOR]

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Vascular calcification is common in chronic kidney disease (CKD) and associated with increased cardiovascular mortality. Aldosterone has been implicated as an augmenting factor in the progression of vascular calcification. The present study further explored putative beneficial effects of aldosterone inhibition by the mineralocorticoid receptor antagonist spironolactone on vascular calcification in CKD. Serum calcification propensity was determined in serum samples from the MiREnDa trial, a prospective, randomized controlled clinical trial to investigate efficacy and safety of spironolactone in maintenance hemodialysis patients. Experiments were conducted in mice with subtotal nephrectomy and cholecalciferol treatment, and in calcifying primary human aortic smooth muscle cells (HAoSMCs). Serum calcification propensity was improved by spironolactone treatment in patients on hemodialysis from the MiREnDa trial. In mouse models and HAoSMCs, spironolactone treatment ameliorated vascular calcification and expression of osteogenic markers. These observations support a putative benefit of spironolactone treatment in CKD-associated vascular calcification. Further research is required to investigate possible improvements in cardiovascular outcomes by spironolactone and whether the benefits outweigh the risks in patients with CKD. • Spironolactone improves calcification propensity (T 50) in hemodialysis patients. • Spironolactone ameliorates vascular calcification in subtotal nephrectomized mice. • Spironolactone reduces cholecalciferol-induced vascular calcification in mice. • Spironolactone blunts high calcium-induced VSMC calcification. [ABSTRACT FROM AUTHOR]

The article discusses the diagnostic possibilities in a child with hypocalcemia and snephrocalcinosis. Topics include differential diagnoses for hypocalcemia with nephrocalcinosis are familial isolated hypoparathyroidism (FIH); and Activating mutations of the CaSR gene cause autosomal dominant hypocalcemia type 1 with normal serum creatinine, confrming hypoparathyroidism.

Chronic kidney disease (CKD)-mineral and bone disorder (CKD-MBD) is a common complication of CKD, often accompanied by extra-skeletal calcification in adult patients. As increased vascular calcification is predicted to increase cardiovascular mortality and morbidity, the revised Kidney Disease: Improving Global Outcomes guidelines recommend avoiding calcium-containing phosphate chelators. However, extra-skeletal calcification is less commonly noticed in pediatric patients. Here, we report our experience of such a complication in pediatric patients receiving maintenance peritoneal dialysis. Extra-skeletal calcification was noticed at the corneas, pelvic cavity, and soft tissues of the lower leg in 4 out of 32 patients on maintenance peritoneal dialysis. These patients experienced the aggravation of extra-skeletal calcifications during peritoneal dialysis, and 2 of them underwent excisional operations. It is required to monitor extra-skeletal calcifications in children on kidney replacement therapy. [ABSTRACT FROM AUTHOR]