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JCEM Case Reports Jan 2024We report a case of severe symptomatic hypercalcemia that resolved after a short course of therapy of exclusively fluids and furosemide. An extensive workup for...
We report a case of severe symptomatic hypercalcemia that resolved after a short course of therapy of exclusively fluids and furosemide. An extensive workup for metabolic, neoplastic, and drug-induced causes did not provide a possible etiology of the hypercalcemia. After calcium level returned to baseline, the patient was discharged, only to return a week later with multiple embolic strokes of unknown source. The comparison of cardiac imaging obtained during the hospitalization periods established a possible mechanism for both phenomena; the interior caseous cavity of a calcified mitral annulus (CMAC), which was demonstrated on echocardiography during the first hospitalization, disappeared in a subsequent study in the second hospitalization, probably reflecting a fistulization of the structure into the left ventricle. The spill of contents into the bloodstream, over several days presumably, explains the transient increase in calcium, and the embolic events that followed. We hereby demonstrate a clear relationship between the fistulization of a CMAC and hypercalcemia, emphasizing the risks of this valvular pathology, and introducing a rare mechanism for transient and potentially severe hypercalcemia.
PubMed: 38178955
DOI: 10.1210/jcemcr/luad169 -
Renal Failure Dec 2024Calciphylaxis (CP) is a serious, potentially life-threatening disease that presents with medial calcification of small-sized vessels and painful ischemic ulcerations....
Calciphylaxis (CP) is a serious, potentially life-threatening disease that presents with medial calcification of small-sized vessels and painful ischemic ulcerations. Although calciphylaxis is frequently seen in patients with end-stage kidney disease on dialysis (calcific uremic arteriolopathy, CUA), there are reported cases of nonuremic calciphylaxis (NUC), which often remain undiagnosed. We conducted a retrospective chart review at our dermatological hospital and evaluated data concerning the epidemiology, comorbidities, medication, laboratory abnormalities, and therapeutic approaches of 60 patients diagnosed with calciphylaxis between 01/2012 and 12/2022. We identified 21 patients diagnosed with NUC and 39 with kidney disease. The predilection sites of skin lesions were the lower legs in 88% ( = 53), followed by the thigh and gluteal regions in 7% ( = 4). Significant differences were identified in comorbidities, such as atrial fibrillation ( and hyperparathyroidism ( accounting for CUA patients. Medication with vitamin K antagonists (, phosphate binders (), and loop diuretics () was found to be associated with the onset of calciphylaxis. Hyperphosphatemia (), increased parathyroid hormone () and triglyceride levels (, hypoalbuminemia ( and decreased hemoglobin values ( in the CUA cohort were significantly different from those in the NUC group. All patients with CUA received systemic medication. In contrast, only 38% ( = 8) of patients with NUC received systemic treatment. Striking discrepancies in the treatment of both cohorts were detected. In particular, NUC remains a disease pattern that is still poorly understood and differs from CUA in several important parameters.
Topics: Humans; Calciphylaxis; Retrospective Studies; Kidney Failure, Chronic; Renal Dialysis; Anticoagulants
PubMed: 38178572
DOI: 10.1080/0886022X.2023.2297566 -
European Journal of Nutrition Apr 2024The consumption of highly processed food is often associated with a high intake of inorganic phosphate. Hyperphosphatemia is accompanied by an inflammatory status in...
PURPOSE
The consumption of highly processed food is often associated with a high intake of inorganic phosphate. Hyperphosphatemia is accompanied by an inflammatory status in patients with chronic kidney disease. However, the immune response to high phosphorus intake in healthy individuals is largely unknown. Therefore, the aim of the present study was to evaluate the effect of a single phosphate-enriched meal on inflammasome activity and plasma levels of inflammatory markers.
METHODS
The analysis included 28 participants who received a single dose of either 700 mg phosphorus or a placebo with a test meal. At baseline, 4 and 8 h post-meal, plasma interleukin (IL)-6, IL-1β, IL-10, c-reactive protein (CRP), soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (sgp130) levels were determined. At baseline and 4 h post-meal, peripheral blood mononuclear cells were isolated to assess inflammasome activity. Subsequently, the effect of phosphate with or without glucose on IL-6 and IL-1β gene expression and secretion in U937 monocytes was examined.
RESULTS
While both groups showed a marked postprandial increase in IL-6 plasma levels, neither plasma levels of IL-6, IL-1β, CRP, IL-10, sIL-6R, and sgp130 nor inflammasome activity were affected by phosphate compared to placebo. In U937 cells, there was also no effect of phosphate on IL-6 expression, but the addition of glucose increased it. Phosphate, however, reduced the IL-1β secretion of these cells.
CONCLUSION
Postprandial inflammatory markers were not affected by dietary phosphate. However, IL-6 plasma levels were markedly increased post-meal, which appears to be a metabolic rather than a pro-inflammatory phenomenon.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov, NCT03771924, date of registration: 11th December 2018, retrospectively registered.
Topics: Humans; Interleukin-6; Interleukin-10; Inflammasomes; Cytokine Receptor gp130; Leukocytes, Mononuclear; Healthy Volunteers; C-Reactive Protein; Glucose; Phosphates; Postprandial Period
PubMed: 38175251
DOI: 10.1007/s00394-023-03306-6 -
Theranostics 2024Vascular calcification (VC) is a life-threatening complication in patients with chronic kidney disease (CKD) caused mainly by hyperphosphatemia. However, the regulation...
Vascular calcification (VC) is a life-threatening complication in patients with chronic kidney disease (CKD) caused mainly by hyperphosphatemia. However, the regulation of VC remains unclear despite extensive research. Although serum- and glucocorticoid-induced kinase 3 (SGK3) regulate the sodium-dependent phosphate cotransporters in the intestine and kidney, its effect on VC in CKD remains unknown. Additionally, type III sodium-dependent phosphate cotransporter-1 (Pit-1) plays a significant role in VC development induced by high phosphate in vascular smooth muscle cells (VSMCs). However, it remains unclear whether SGK3 regulates Pit-1 and how exactly SGK3 promotes VC in CKD via Pit-1 at the molecular level. Thus, we investigated the role of SGK3 in the certified outflow vein of arteriovenous fistulas (AVF) and aortas of uremic mice. In our study, using uremic mice, we observed a significant upregulation of SGK3 and calcium deposition in certified outflow veins of the AVF and aortas, and the increase expression of SGK3 was positively correlated with calcium deposition in uremic aortas. , the downregulation of SGK3 reversed VSMCs calcification and phenotype switching induced by high phosphate. Mechanistically, SGK3 activation enhanced the mRNA transcription of Pit-1 through NF-κB, downregulated the ubiquitin-proteasome mediated degradation of Pit-1 via inhibiting the activity of neural precursor cells expressing developmentally downregulated protein 4 subtype 2 (Nedd4-2), an E3 ubiquitin ligase. Moreover, under high phosphate stimulation, the enhanced phosphate uptake induced by SGK3 activation was independent of the increased protein expression of Pit-1. Our co-immunoprecipitation and kinase assays confirmed that SGK3 interacts with Pit-1 through Thr468 in loop7, leading to enhanced phosphate uptake. Thus, it is justifiable to conclude that SGK3 promotes VC in CKD by enhancing the expression and activities of Pit-1, which indicate that SGK3 could be a therapeutic target for VC in CKD.
Topics: Animals; Humans; Mice; Calcium; Glucocorticoids; Myocytes, Smooth Muscle; Neural Stem Cells; Phosphates; Protein Serine-Threonine Kinases; Renal Insufficiency, Chronic; Sodium; Transcription Factors; Vascular Calcification
PubMed: 38169564
DOI: 10.7150/thno.87317 -
Journal of Clinical Medicine Dec 2023Data suggest that non-calcium-based binders, and specifically sevelamer, may lead to lower rates of death when compared with calcium-based binders in end-stage renal...
Data suggest that non-calcium-based binders, and specifically sevelamer, may lead to lower rates of death when compared with calcium-based binders in end-stage renal disease (ESRD) patients. However, the association between sevelamer use and mortality for those with non-dialysis-dependent chronic kidney disease (NDD-CKD) patients has been uncertain. Our research is presented in a prospective cohort study. A total of 966 participants with NDD-CKD stages 4-5 were enrolled in the PECERA study from 12 centers in Spain. The participants were treated with sevelamer. This study yielded all-cause and cardiovascular mortality outcomes. We conducted an association analysis between mortality and sevelamer use with time-dependent Cox proportional hazards models. After a median follow-up of 29 months (IQR: 13-36 months), death occurred in 181 participants (19%), with cardiovascular ( = 95, 53%) being the leading cause of death. In a multivariable model, the adjusted hazard ratios (HRs) for patients under sevelamer treatment were 0.44 (95% CI, 0.22 to 0.88) and 0.37 (95% CI, 0.18 to 0.75) for all-cause and cardiovascular mortality, respectively, compared with those of untreated patients. Some limitations include potential confusion via indication bias; causal statements about these associations cannot be made due to the observational nature of this study. : In this prospective NDD-CKD cohort study, the administration of sevelamer was independently associated with lower all-cause and cardiovascular mortality, suggesting that non-calcium-based phosphate binders might be the first-line therapy for phosphate lowering in this population. Further interventional studies clarifying the risks and benefits of phosphate binders in NDD-CKD are warranted.
PubMed: 38137700
DOI: 10.3390/jcm12247631 -
JBMR Plus Dec 2023Although the eyes are the main site of metastatic calcification in patients with chronic kidney disease (CKD), corneal and conjunctival calcification (CCC) is poorly...
Although the eyes are the main site of metastatic calcification in patients with chronic kidney disease (CKD), corneal and conjunctival calcification (CCC) is poorly evaluated in this population. Whether CCC correlates with coronary artery calcification remains unknown since studies so far have relied on methods with low sensitivity. Our objective was to test the relationship between CCC and coronary calcification based on tomography. This was a cross-sectional study that included patients on maintenance dialysis. Clinical, demographic, and biochemical data (calcium, phosphorus, parathormone, alkaline phosphatase, and 25(OH)-vitamin D) were recorded. Hyperparathyroidism was defined as parathyroid hormone (PTH) > 300 pg/mL. CCC was evaluated by anterior segment optical coherence tomography (AS-OCT), and coronary calcium scores (Agatston method) were assessed by computed tomography. We compared no/mild with moderate/severe CCC. Twenty-nine patients were included (49.6 ± 15.0 years, 62.1% female, on hemodialysis for 5.7 [2.7-9.4] years, 17.2% with diabetes mellitus, 75.9% with hyperparathyroidism). CCC was found in 82.7% of patients, with median scores of 9 (3, 14.5), ranging from 0 to 16. CCC was classified as absent/mild, moderate, and severe in 27.6%, 20.7%, and 51.7%, respectively. Coronary calcification was found in 44.8% of patients, with median scores of 11 (0, 464), varying from 0 and 6456. We found no significant correlation between coronary calcium scores and CCC ( = 0.203, = 0.282). Hyperphosphatemia was more frequent in patients with moderate/severe CCC than in those with absent/mild CCC. We concluded that CCC was frequent in patients with CKD on dialysis and did not correlate with coronary calcium scores. Hyperphosphatemia appears to contribute to CCC. © 2023 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PubMed: 38130747
DOI: 10.1002/jbm4.10823 -
Physiological Reports Dec 2023In-depth understanding of intra- and postdialytic phosphate kinetics is important to adjust treatment regimens in hemodialysis. We aimed to modify and validate a...
In-depth understanding of intra- and postdialytic phosphate kinetics is important to adjust treatment regimens in hemodialysis. We aimed to modify and validate a three-compartment phosphate kinetic model to individual patient data and assess the temporal robustness. Intradialytic phosphate samples were collected from the plasma and dialysate of 12 patients during two treatments (HD1 and HD2). 2-h postdialytic plasma samples were collected in four of the patients. First, the model was fitted to HD1 samples from each patient to estimate the mass transfer coefficients. Second, the best fitted model in each patient case was validated on HD2 samples. The best model fits were determined from the coefficient of determination (R ) values. When fitted to intradialytic samples only, the median (interquartile range) R values were 0.985 (0.959-0.997) and 0.992 (0.984-0.994) for HD1 and HD2, respectively. When fitted to both intra- and postdialytic samples, the results were 0.882 (0.838-0.929) and 0.963 (0.951-0.976) for HD1 and HD2, respectively. Eight patients demonstrated a higher R value for HD2 than for HD1. The model seems promising to predict individual plasma phosphate in hemodialysis patients. The results also show good temporal robustness of the model. Further modifications and validation on a larger sample are needed.
Topics: Humans; Phosphates; Renal Dialysis; Kinetics
PubMed: 38129113
DOI: 10.14814/phy2.15899 -
Kidney International Reports Dec 2023
PubMed: 38106599
DOI: 10.1016/j.ekir.2023.09.032 -
American Journal of Nephrology 2024Sucroferric oxyhydroxide (SO), a non-calcium, chewable, iron-based phosphate binder (PB), effectively lowers serum phosphorus (sP) concentrations while reducing pill...
INTRODUCTION
Sucroferric oxyhydroxide (SO), a non-calcium, chewable, iron-based phosphate binder (PB), effectively lowers serum phosphorus (sP) concentrations while reducing pill burden relative to other PBs. To date, SO studies have largely examined treatment-experienced, prevalent hemodialysis populations. We aimed to explore the role of first-line SO initiated during the first year of dialysis.
METHODS
We retrospectively analyzed deidentified data from adults receiving in-center hemodialysis who were prescribed SO monotherapy within the first year of hemodialysis as part of routine clinical care. All patients continuing SO monotherapy for 12 months were included. Changes from baseline in sP, achievement of sP ≤5.5 and ≤4.5 mg/dL, and other laboratory parameters were analyzed quarterly for 1 year.
RESULTS
The overall cohort included 596 patients, 286 of whom had a dialysis vintage ≤3 months. In the 3 months preceding SO initiation, sP rapidly increased (mean increases of 1.02 and 1.65 mg/dL in the overall cohort and incident cohort, respectively). SO treatment was associated with significant decreases in quarterly sP (mean decreases of 0.26-0.36; p < 0.0001 for each quarter and overall). While receiving SO, 55-60% of patients achieved sP ≤5.5 mg/dL and 21-24% achieved sP ≤4.5 mg/dL (p < 0.0001 for each quarter and overall vs. baseline). Daily PB pill burden was approximately 4 pills. Serum calcium concentrations increased and intact parathyroid hormone concentrations decreased during SO treatment (p < 0.0001 vs. baseline).
CONCLUSIONS
Among patients on hemodialysis, initiating SO as a first-line PB resulted in significant reductions in sP while maintaining a relatively low PB pill burden.
Topics: Adult; Humans; Phosphorus; Hyperphosphatemia; Retrospective Studies; Renal Dialysis; Ferric Compounds; Sucrose; Phosphates; Drug Combinations
PubMed: 38091973
DOI: 10.1159/000535754 -
Jornal Brasileiro de Nefrologia 2024The Brazilian Dialysis Survey (BDS) is an annual national survey about patients on chronic dialysis that contributes to health policies.
INTRODUCTION
The Brazilian Dialysis Survey (BDS) is an annual national survey about patients on chronic dialysis that contributes to health policies.
OBJECTIVE
To report the 2022 epidemiological data from the BDS of the Brazilian Society of Nephrology (BSN).
METHODS
A survey was carried out in Brazilian chronic dialysis centers using an online questionnaire that included clinical and epidemiological aspects of patients on chronic dialysis, dialysis therapy data, and dialysis center characteristics.
RESULTS
Overall, 28% (n = 243) of the centers answered the questionnaire. In July 2022, the estimated total number of patients on dialysis was 153,831. The estimated prevalence and incidence rates of patients per million population (pmp) were 758 and 214, respectively. Of the prevalent patients, 95.3% were on hemodialysis (HD, 4.6% of these on hemodiafiltration) and 4.7% on peritoneal dialysis (PD). Only 1.3% of patients were not vaccinated against COVID-19. The prevalence of anemia (Hb < 10g/dL) was 27% and hyperphosphatemia (P > 5.5mg/dL) reached 30%. The estimated overall crude annual mortality rate was 17.1%.
CONCLUSIONS
The absolute number and prevalence rate of patients on chronic dialysis continue to increase. A growing number of patients were receiving hemodiafiltration. The mortality rate decreased, probably due to the end of COVID-19 pandemic. The conclusions were drawn in the context of relatively low voluntary participation, which imposed methodological limitations on our estimates.
Topics: Humans; Renal Dialysis; Brazil; Pandemics; Surveys and Questionnaires; Peritoneal Dialysis; Kidney Failure, Chronic
PubMed: 38078834
DOI: 10.1590/2175-8239-JBN-2023-0062en