Images – Penile pain in the setting of end-stage renal disease: An unusual anatomic location for calciphylaxis

In this report, we present a case of penile calciphylaxis, an extremely rare and serious condition occurring in association with dysregulation of systemic calcium metabolism in the setting of chronic renal impairment. Calciphylaxis can occur at various body sites and is associated with diffuse vascular calcifications in small and medium-sized arteries of the involved tissues. Penile calciphylaxis has a grim prognosis. Calciphylaxis is an important etiologic differential diagnosis for penile necrosis and penile pain in patient’s being treated with dialysis for end-stage kidney disease. Diagnosis of penile calciphylaxis is possible via clinical and radiological evaluations. Medical management may alleviate symptoms; however surgical interventions may be necessary, and histological studies may allow for definitive classification.

Effect of CKD-MBD therapies on the gastrointestinal expression of phosphate transporters

Background: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is prevalent and encompasses biochemical abnormalities, bone alterations, and vascular calcifications. CKD-MBD treatments include phosphate binders and calcimimetics that effectively lower phosphorus and PTH, respectively, but the impact of these treatments on phosphate transporters in the gastrointestinal tract is still unknown. NaPi2B is considered the primary intestinal phosphate transporter. However, NaPi2B inhibition shows limited effectiveness, thus the importance of PIT1 and PIT2 requires further investigation. Methods: We tested the effects phosphate binders (ferric citrate (FC) and calcium gluconate (Ca)) and the calcimimetic KP2326 (KP) in (Cy/+ male rat; CKD) and untreated normal littermates (NL). Treatments lasted 10 weeks until euthanasia at 28 weeks (moderate-to-advanced CKD), where we collected mucosa samples from duodenum, jejunum, and ileum. Blood was collected for biochemistry measurements. Total RNA was isolated, and qPCR performed to assess phosphate transporters expression (NaPi2B, PIT1, PIT2) normalized to b-actin. Results were analyzed via 2-way ANOVA. Results: As expected, CKD had abnormal plasma concentrations of phosphorus, PTH, and FGF23. FC and KP effectively lowered phosphorus. KP and Ca lowered PTH, but Ca increased FGF23. NaPi2B was expressed in the duodenum and jejunum but not in the ileum, and its expression was upregulated with FC compared to NL. PIT1 was expressed in all segments, but the expression was the highest in the ileum, while PIT2 was constitutively expressed in all segments. Ca led to higher PIT1 and PIT2 expression in the duodenum and jejunum compared to NL, CKD, or KP. KP led to higher expression of PIT1 in the ileum compared to CKD, FC, and Ca. Conclusions: CKD-MBD therapies differentially impacted biochemistries and phosphate transporters expression. The effect of Ca on gastrointestinal expression of PIT1 and PIT2 may explain the higher plasma phosphorus and should be further explored.

End-stage renal disease, calcification patterns and clinical outcomes after TAVI

Background Patients with chronic hemodialysis due to end-stage renal disease (ESRD) or severely impaired kidney function (CKD) constitute a relevant share of patients undergoing trans-catheter aortic valve implantation (TAVI). However, data on specific challenges and outcomes remain limited. Aim We aimed to characterize this patient population, evaluate clinical results and assess the significance of calcification patterns. Methods This retrospective single-center analysis evaluated 2,712 TAVI procedures (2012–2019) according to baseline renal function: GFR < 30 ml/min/1.73m2 (CKD; n = 210), chronic hemodialysis (ESRD; n = 119) and control (CTRL; n = 2383). Valvular and vascular calcification patterns were assessed from contrast-enhanced multi-detector computed tomography. Outcomes were evaluated in accordance with the VARC-2 definitions. Results Operative risk was higher in ESRD and CKD vs. CTRL (STS-score 8.4% and 7.6% vs. 3.9%, p < 0.001) and patients with ESRD had more severe vascular calcifications (49.1% vs. 33.9% and 29.0%, p < 0.01). Immediate procedural results were similar but non-procedure-related major/life-threatening bleeding was higher in ESRD and CKD (5.0% and 5.3% vs. 1.6%, p < 0.01). 3-year survival was impaired in patients with ESRD and CKD (33.3% and 35.3% vs. 65.4%, p < 0.001). Multivariable analysis identified ESRD (HR 1.60), CKD (HR 1.79) and vascular calcifications (HR 1.29) as predictors for 3-year and vascular calcifications (HR 1.51) for 30-day mortality. Conclusion Patients with ESRD and CKD constitute a vulnerable patient group with extensive vascular calcifications. Immediate procedural results were largely unaffected by renal impairment, yielding TAVI a particularly valuable treatment option in these high-risk operative patients. Mid-term survival was determined by underlying renal disease, cardiovascular comorbidities, and vascular calcifications as a novel risk marker. Graphical abstract

Matrix-GLA-Protein and Vascular Calcification: Can Diet Influence the Consequences of Matrix GLA Protein Inactivation? A Review

In vascular calcification, as a physiological process, intimal arterial calcification (IAC) associated with increased cardiovascular risk is distinguished from medial arterial calcification (MAC) localized mainly in the lamina elatica interna, which are not only based on different pathophysiological mechanisms. They also lead to different cardiovascular diseases. While intimal arterial calcification involves inflammation and lipid accumulation, a calcification process similar to desmal ossification plays the main role in medial arterial calcification. In this context, the phenotype change of smooth muscle cells from muscular type to synthesizing form in the tunica media is considered to be of great importance, which puts the matrix GLA protein, mainly involved in bone metabolism, in the center of interest. The present review work elucidates the molecular biological basis of interaction of matrix GLA protein subunits in the pathogenesis of vascular calcifications and the influence of diet on the consequences of underactivation of matrix GLA protein.

Breast Arterial Calcifications on Mammography among Patients Attending the Radiology Department in a Tertiary Care Centre: A Descriptive Cross-sectional Study

Introduction: Breast arterial calcifications are common mammographic findings which are associated with coronary artery disease. The aim of this study was to find the prevalence of breast arterial calcifications in women presenting for mammography in a tertiary care centre. Methods: This descriptive cross-sectional study was performed in the Department of Radiology, in a tertiary care hospital after taking ethical clearance, Reference number 352(6-11)E-2, 077/078, data was collected from Syngovia database from March-June 2021 which included 1614 mammograms. Convenience sampling was done and mammograms evaluated for presence of vascular or non-vascular calcification. Further, vascular calcification was graded. Data was entered in Statistical Package for Social Sciences version 25. Point estimate at 95% Confidence Interval was done, and frequency and proportion were calculated. Results: The prevalence of breast arterial calcification was 188 (11.6%) at 95% Confidence Interval (10.03-13.2). The mean age of women included in this study was 48.42±9.55 years with the largest number of patients in the age group 40-49 years, 682 (42.3%), and least in the age group 80-89 years, 3 (0.2%). All patients in the age group 80-89 years, 3 (100%) had vascular calcifications followed by 70-79 years group, 22 (57.5%) and none in patients younger than 30 years. Conclusions: We found an increase in the number and grade of vascular calcifications in breasts with the patient's age. When present breast arterial calcifications must be mentioned in mammogram report. Identification of such calcifications on mammogram should prompt further screening for atherosclerotic disease.

Gut Microbiome, Functional Food, Atherosclerosis, and Vascular Calcifications—Is There a Missing Link?

The gut microbiome is represented by the genome of all microorganisms (symbiotic, potential pathogens, or pathogens) residing in the intestine. These ecological communities are involved in almost all metabolic diseases and cardiovascular diseases are not excluded. Atherosclerosis, with a continuously increasing incidence in recent years, is the leading cause of coronary heart disease and stroke by plaque rupture and intraplaque hemorrhage. Vascular calcification, a process very much alike with osteogenesis, is considered to be a marker of advanced atherosclerosis. New evidence, suggesting the role of dietary intake influence on the diversity of the gut microbiome in the development of vascular calcifications, is highly debated. Gut microbiota can metabolize choline, phosphatidylcholine, and L-carnitine and produce vasculotoxic metabolites, such as trimethylamine-N-oxide (TMAO), a proatherogenic metabolite. This review article aims to discuss the latest research about how probiotics and the correction of diet is impacting the gut microbiota and its metabolites in the atherosclerotic process and vascular calcification. Further studies could create the premises for interventions in the microbiome as future primary tools in the prevention of atherosclerotic plaque and vascular calcifications.

Evaluation of Breast Vascular Calcifications as a Predictor for Coronary Artery Calcification

Background. Cardiovascular diseases are one of the main causes of death among women, and current prevention paradigms may not be sufficient in this group. In this context, it has been suggested that the detection of breast vascular calcifications can improve the screening and assessment of the risk of cardiovascular diseases in apparently healthy women.Objective: to study the role of breast vascular calcifications as a potential predictor for coronary artery calcification. Material and methods. Examinations were made in 123 patients who underwent digital mammography and cardiac computed tomography to estimate a coronary artery calcium score.Results. The use of the Wilcoxon-Mann-Whitney W-test for abnormal distribution showed a relationship between the presence of breast vascular calcifications and calcium score (p< 0.001), and that between aortic wall calcification and calcium score (p< 0.001).Conclusion. Breast vascular calcifications detected by mammography are an indicator of a higher frequency of coronary artery calcification and, apparently, a predictor for the increased risk of cardiovascular disease.