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2.
Artículo en Inglés | MEDLINE | ID: mdl-38688870

RESUMEN

RATIONALE & OBJECTIVE: The concept of residual kidney function (RKF) is exclusively based upon urine volume and small solute clearance, making RKF challenging to assess in clinical practice. The aim of this study was to test the technical feasibility of obtaining useable 23Na-MRI kidney images in hemodialysis (HD) participants. STUDY DESIGN: We conducted an exploratory prospective study to quantify the cortico-medullary sodium gradient in healthy and HD participants. Participants fasted for eight hours prior to their study visit. Urine samples were collected to measure urinary osmolarity, before MRI. Proton and sodium pictures were merged; ROIs were delineated for the medulla and cortex when feasible. In cases where cortex could not be identified, we considered the cortico to medulla gradient (CMG) to be no longer present, resulting in a medulla-to-cortex ratio of 1. SETTING & PARTICIPANTS: 17 healthy volunteers and 21 HD participants. FINDINGS: Median (IQR) fasting medulla to cortex ratio was significantly higher 1.56 [1.5-1.61] in healthy volunteers compared to HD patients 1.22 [1.13-1.3], p < 0.0001. Medulla to cortex ratio and median urinary osmolarity were correlated (r = 0.87, p < 0.0001) in the whole population. We found a significant association between HD vintage and medulla to cortex ratio whereas we did not find any association with urine volume. Sodium signal intensity distribution within healthy kidney describes two different peaks- relating to well defined cortex and medulla; whereas HD participants displays only a single peak indicative of the markedly lower sodium concentration. LIMITATIONS: This study is only an exploratory study with a modest number of patients. CONCLUSIONS: the application of kidney sodium MRI to the study of RKF in patients receiving maintenance HD is practical and provides a previously unavailable ability to interrogate the function of remnant tubular function.

4.
J Am Soc Nephrol ; 35(5): 653-664, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38273436

RESUMEN

Hemodialysis is a life-saving treatment for patients with kidney failure. However, patients requiring hemodialysis have a 10-20 times higher risk of cardiovascular morbidity and mortality than that of the general population. Patients encounter complications such as episodic intradialytic hypotension, abnormal perfusion to critical organs (heart, brain, liver, and kidney), and damage to vulnerable vascular beds. Recurrent conventional hemodialysis exposes patients to multiple episodes of circulatory stress, exacerbating and being aggravated by microvascular endothelial dysfunction. This promulgates progressive injury that leads to irreversible multiorgan injury and the well-documented higher incidence of cardiovascular disease and premature death. This review aims to examine the underlying pathophysiology of hemodialysis-related vascular injury and consider a range of therapeutic approaches to improving outcomes set within this evolved rubric.‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬.


Asunto(s)
Isquemia , Diálisis Renal , Humanos , Encéfalo/irrigación sanguínea , Isquemia Encefálica/etiología , Isquemia/etiología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Diálisis Renal/efectos adversos
5.
J Clin Endocrinol Metab ; 109(2): e488-e494, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-37843399

RESUMEN

CONTEXT: X-linked hypophosphatemia (XLH) is a rare genetic disorder that results in increased plasma levels of fibroblast growth factor 23 (FGF23). Several studies have demonstrated a direct association between FGF23 and cardiovascular mortality in cohorts of patients with chronic renal failure. However, in patients with XLH, studies on the cardiovascular impact of the disease are rare, with contradictory results. OBJECTIVE: The aim was to assess whether the disease led to an increased cardiovascular risk. METHODS: We conducted a single-center retrospective observational study on a local cohort of adult patients with XLH. The primary endpoint was a composite endpoint of the frequency of left ventricular hypertrophy (LVH) or presence of high blood pressure. Our secondary objectives were to assess echocardiographic, pulse wave velocity, and central blood pressure data as other markers of CV health. Independently of this cohort, tissue sodium content with magnetic resonance imaging was studied in 2 patients with XLH before and after burosumab. RESULTS: Twenty-two patients were included. Median serum phosphate was 0.57 (0.47-0.72) mmol/L and FGF23 94 pg/L (58-2226). Median blood pressure was 124 (115-130)/68 (65-80) mm Hg, with only 9% of patients being hypertensive. A majority of patients (69%) had no LVH, only 1 had a left ventricular mass >100 g/m² and 25% of patients had left ventricular remodeling. Pulse wave velocity was normal in all patients. No differences in skin and muscle sodium content were observed before and after burosumab in the 2 patients who underwent sodium magnetic resonance imaging. CONCLUSION: We found no elevated risk of developing hypertension or LVH in patients with XLH.


Asunto(s)
Enfermedades Cardiovasculares , Raquitismo Hipofosfatémico Familiar , Hipertensión , Hipofosfatemia , Adulto , Humanos , Raquitismo Hipofosfatémico Familiar/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Análisis de la Onda del Pulso , Factores de Riesgo , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/etiología , Hipertensión/complicaciones , Hipertensión/epidemiología , Factores de Riesgo de Enfermedad Cardiaca , Sodio , Factores de Crecimiento de Fibroblastos , Fosfatos
6.
Sci Rep ; 13(1): 21210, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-38040779

RESUMEN

Acute and chronic kidney disease continues to confer significant morbidity and mortality in the clinical setting. Despite high prevalence of these conditions, few validated biomarkers exist to predict kidney dysfunction. In this study, we utilized a novel kidney multiplex panel to measure 21 proteins in plasma and urine to characterize the spectrum of biomarker profiles in kidney disease. Blood and urine samples were obtained from age-/sex-matched healthy control subjects (HC), critically-ill COVID-19 patients with acute kidney injury (AKI), and patients with chronic or end-stage kidney disease (CKD/ESKD). Biomarkers were measured with a kidney multiplex panel, and results analyzed with conventional statistics and machine learning. Correlations were examined between biomarkers and patient clinical and laboratory variables. Median AKI subject age was 65.5 (IQR 58.5-73.0) and median CKD/ESKD age was 65.0 (IQR 50.0-71.5). Of the CKD/ESKD patients, 76.1% were on hemodialysis, 14.3% of patients had kidney transplant, and 9.5% had CKD without kidney replacement therapy. In plasma, 19 proteins were significantly different in titer between the HC versus AKI versus CKD/ESKD groups, while NAG and RBP4 were unchanged. TIMP-1 (PPV 1.0, NPV 1.0), best distinguished AKI from HC, and TFF3 (PPV 0.99, NPV 0.89) best distinguished CKD/ESKD from HC. In urine, 18 proteins were significantly different between groups except Calbindin, Osteopontin and TIMP-1. Osteoactivin (PPV 0.95, NPV 0.95) best distinguished AKI from HC, and ß2-microglobulin (PPV 0.96, NPV 0.78) best distinguished CKD/ESKD from HC. A variety of correlations were noted between patient variables and either plasma or urine biomarkers. Using a novel kidney multiplex biomarker panel, together with conventional statistics and machine learning, we identified unique biomarker profiles in the plasma and urine of patients with AKI and CKD/ESKD. We demonstrated correlations between biomarker profiles and patient clinical variables. Our exploratory study provides biomarker data for future hypothesis driven research on kidney disease.


Asunto(s)
Lesión Renal Aguda , Fallo Renal Crónico , Insuficiencia Renal Crónica , Humanos , Inhibidor Tisular de Metaloproteinasa-1 , Fallo Renal Crónico/terapia , Biomarcadores , Proteínas Plasmáticas de Unión al Retinol
7.
Clin Nephrol ; 100(6): 259-268, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37870263

RESUMEN

BACKGROUND: Telemedicine use increased during the COVID-19 pandemic. We compared both adolescent/caregiver attitudes towards telemedicine pre- and intra-pandemic. MATERIALS AND METHODS: In a tertiary care setting with a large remote catchment area, we conducted qualitative analysis of structured interviews with dyads of 11 to 18-year-old patients and their caregivers using NVivo during the pandemic and compared the findings to our previous research [1]. RESULTS: We enrolled 14 dyads (35 ± 27 in-person visits and 4 ± 3 telemedicine visits per participant) and compared these with 11 dyads before the pandemic. Adolescents' mean age was 15.2 ± 2.1 years (range 11.2 - 18.2). The median distance to our medical center was 184.8 km (range 3.9 - 1,214 km, 6 dyads > 100 km). While the preferred ratio of telemedicine to in-person visits was 2 : 1 in caregivers (like pre-pandemic), many emphasized telemedicine as the safer option. Interestingly, adolescents preferred more in-person visits during the pandemic (1 : 1 ratio) compared to pre-pandemic (2 : 1 ratio). Qualitative analysis identified two main themes: consultation-specific factors and contextual factors. Consultation-specific factors were more valued during in-person visits, especially by adolescents. Consultation-specific factors remained the same pre- and post-pandemic, however, adolescents more often emphasized comfort, communication, and personal connection for in-person visits during the pandemic. Contextual factors were valued for telemedicine by adolescents and caregivers, and telemedicine was identified as the norm during the pandemic. Interestingly, the two main contextual themes pre-pandemic: frustration with technological aspects of telemedicine and adolescents not taking telemedicine seriously, disappeared during the pandemic. No disadvantages for telemedicine in the contextual factors were identified during the pandemic. CONCLUSION: The COVID-19 pandemic changed the user-expressed attitudes (especially among adolescents) on the transfer to telemedicine for chronic care.


Asunto(s)
COVID-19 , Cuidadores , Telemedicina , Adolescente , Niño , Humanos , Comunicación , COVID-19/epidemiología , Pandemias , Actitud hacia los Computadores
8.
Front Nephrol ; 3: 1124130, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37675381

RESUMEN

Introduction: The life-sustaining treatment of hemodialysis (HD) induces recurrent and cumulative systemic circulatory stress resulting in cardiovascular injury. These recurrent insults compound preexisting cardiovascular sequalae leading to the development of myocardial injury and resulting in extremely high morbidity/mortality. This is largely a consequence of challenged microcirculatory flow within the myocardium (evidenced by detailed imaging-based studies). Currently, monitoring during HD is performed at the macrovascular level. Non-invasive monitoring of organ perfusion would allow the detection and therapeutic amelioration of this pathophysiological response to HD. Non-invasive percutaneous perfusion monitoring of the skin (using photoplethysmography-PPG) has been shown to be predictive of HD-induced myocardial stunning (a consequence of segmental ischemia). In this study, we extended these observations to include a dynamic assessment of skin perfusion during HD compared with directly measured myocardial perfusion during dialysis and cardiac contractile function. Methods: We evaluated the intradialytic microcirculatory response in 12 patients receiving conventional HD treatments using continuous percutaneous perfusion monitoring throughout HD. Cardiac echocardiography was performed prior to the initiation of HD, and again at peak-HD stress, to assess the development of regional wall motion abnormalities (RWMAs). Myocardial perfusion imaging was obtained at the same timepoints (pre-HD and peak-HD stress), utilizing intravenous administered contrast and a computerized tomography (CT)-based method. Intradialytic changes in pulse strength (derived from PPG) were compared with the development of HD-induced RWMAs (indicative of myocardial stunning) and changes in myocardial perfusion. Results: We found an association between the lowest pulse strength reduction (PPG) and the development of RWMAs (p = 0.03) and also with changes in global myocardial perfusion (CT) (p = 0.05). Ultrafiltration rate (mL/kg/hour) was a significant driver of HD-induced circulatory stress [(associated with the greatest pulse strength reduction (p = 0.01), a reduction in global myocardial perfusion (p = 0.001), and the development of RWMAs (p = 0.03)]. Discussion: Percutaneous perfusion monitoring using PPG is a useful method of assessing intradialytic hemodynamic stability and HD-induced circulatory stress. The information generated at the microcirculatory level of the skin is reflective of direct measures of myocardial perfusion and the development of HD-induced myocardial stunning. This approach for the detection and management of HD-induced cardiac injury warrants additional evaluation.

9.
J Clin Med ; 12(13)2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37445416

RESUMEN

Sodium imbalance is a hallmark of chronic kidney disease (CKD). Excess tissue sodium in CKD is associated with hypertension, inflammation, and cardiorenal disease. Sodium magnetic resonance imaging (23Na MRI) has been increasingly utilized in CKD clinical trials especially in the past few years. These studies have demonstrated the association of excess sodium tissue accumulation with declining renal function across whole CKD spectrum (early- to end-stage), biomarkers of systemic inflammation, and cardiovascular dysfunction. In this article, we review recent advances of 23Na MRI in CKD and discuss its future role with a focus on the skin, the heart, and the kidney itself.

11.
J Am Soc Nephrol ; 34(6): 1090-1104, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36890644

RESUMEN

SIGNIFICANCE STATEMENT: Hemodialysis (HD) results in reduced brain blood flow, and HD-related circulatory stress and regional ischemia are associated with brain injury over time. However, studies to date have not provided definitive direct evidence of acute brain injury during a HD treatment session. Using intradialytic magnetic resonance imaging (MRI) and spectroscopy to examine HD-associated changes in brain structure and neurochemistry, the authors found that multiple white (WM) tracts had diffusion imaging changes characteristic of cytotoxic edema, a consequence of ischemic insult and a precursor to fixed structural WM injury. Spectroscopy showed decreases in prefrontal N -acetyl aspartate (NAA) and choline concentrations consistent with energy deficit and perfusion anomaly. This suggests that one HD session can cause brain injury and that studies of interventions that mitigate this treatment's effects on the brain are warranted. BACKGROUND: Hemodialysis (HD) treatment-related hemodynamic stress results in recurrent ischemic injury to organs such as the heart and brain. Short-term reduction in brain blood flow and long-term white matter changes have been reported, but the basis of HD-induced brain injury is neither well-recognized nor understood, although progressive cognitive impairment is common. METHODS: We used neurocognitive assessments, intradialytic anatomical magnetic resonance imaging, diffusion tensor imaging, and proton magnetic resonance spectroscopy to examine the nature of acute HD-associated brain injury and associated changes in brain structure and neurochemistry relevant to ischemia. Data acquired before HD and during the last 60 minutes of HD (during maximal circulatory stress) were analyzed to assess the acute effects of HD on the brain. RESULTS: We studied 17 patients (mean age 63±13 years; 58.8% were male, 76.5% were White, 17.6% were Black, and 5.9% were of Indigenous ethnicity). We found intradialytic changes, including the development of multiple regions of white matter exhibiting increased fractional anisotropy with associated decreases in mean diffusivity and radial diffusivity-characteristic features of cytotoxic edema (with increase in global brain volumes). We also observed decreases in proton magnetic resonance spectroscopy-measured N -acetyl aspartate and choline concentrations during HD, indicative of regional ischemia. CONCLUSIONS: This study demonstrates for the first time that significant intradialytic changes in brain tissue volume, diffusion metrics, and brain metabolite concentrations consistent with ischemic injury occur in a single dialysis session. These findings raise the possibility that HD might have long-term neurological consequences. Further study is needed to establish an association between intradialytic magnetic resonance imaging findings of brain injury and cognitive impairment and to understand the chronic effects of HD-induced brain injury. CLINICAL TRIALS INFORMATION: NCT03342183 .


Asunto(s)
Lesiones Encefálicas , Sustancia Blanca , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Imagen de Difusión Tensora/métodos , Ácido Aspártico/metabolismo , Imagen por Resonancia Magnética , Lesiones Encefálicas/etiología , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Sustancia Blanca/diagnóstico por imagen , Diálisis Renal/efectos adversos , Análisis Espectral , Colina/metabolismo
12.
Pediatr Nephrol ; 38(2): 499-507, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35655040

RESUMEN

BACKGROUND: Sodium-23 magnetic resonance imaging (23Na MRI) allows non-invasive assessment of tissue sodium concentration ([Na+]). Age and chronic kidney disease (CKD) are associated with increased tissue [Na+] in adults, but limited information is available pertaining to children and adolescents. We hypothesized that pediatric CKD is associated with altered tissue [Na+] compared to healthy controls. METHODS: This was a case-control exploratory study on healthy children and adults and pediatric CKD patients. Study participants underwent an investigational visit, blood/urine biochemistry, and leg 23Na MRI for tissue [Na+] quantification (whole leg, skin, soleus muscle). CKD was stratified by etiology and patients' tissue [Na+] was compared against healthy controls by computing individual Z-scores. An absolute Z-score > 1.96 was deemed to deviate significantly from the mean of healthy controls. Pearson correlation was used to compute the associations between tissue [Na+] and kidney function. RESULTS: A total of 36 pediatric participants (17 healthy, 19 CKD) and 19 healthy adults completed the study. Healthy adults had significantly higher tissue [Na+] compared with pediatric groups; conversely, no significant differences were found between healthy children/adolescents and CKD patients. Four patients with glomerular disease and one kidney transplant recipient due to atypical hemolytic-uremic syndrome had elevated whole-leg [Na+] Z-scores. Reduced whole-leg [Na+] Z-scores were found in two patients with tubular disorders (Fanconi syndrome, proximal-distal renal tubular acidosis). All tissue [Na+] measures were significantly associated with proteinuria and hypoalbuminemia. CONCLUSIONS: Depending on etiology, pediatric CKD was associated with either increased (glomerular disease) or reduced (tubular disorders) tissue [Na+] compared with healthy controls. A higher resolution version of the Graphical abstract is available as Supplementary information.


Asunto(s)
Acidosis Tubular Renal , Insuficiencia Renal Crónica , Adulto , Adolescente , Humanos , Niño , Sodio , Proyectos Piloto , Causalidad , Factores de Riesgo
13.
J Vasc Access ; 24(5): 1078-1083, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34991397

RESUMEN

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in patients with end-stage kidney disease. Arterio-venous fistulas (AVF), the gold standard for hemodialysis vascular access, are known to alter cardiac morphology and circulatory hemodynamics. We present a prospective case series of patients after creation of an AVF, explore the timeline for changes in their cardiac morphology, and detail considerations for clinicians. METHODS: Patients were recruited in 2010 at multiple centers immediately prior to the creation of an upper-arm AVF and the initiation of hemodialysis. Cardiovascular magnetic resonance images were taken at intake before the creation of the AVF, 6-month follow-up, and 12-month follow-up. Image segmentation was used to measure left ventricular volume and mass, left atrial volume, and ejection fraction. RESULTS: Eight patients met eligibility criteria. All eight patients had a net increase in left ventricular mass over enrollment, with a mean increase of 9.16 g (+2.96 to +42.66 g). Five participants had a net decrease in ejection fraction, with a mean change in ejection fraction of -5.4% (-21% to +5%). Upon visual inspection the patients with the largest ejection fraction decrease had noticeably hypertrophic and dilated ventricles. Left atrial volume change was varied, decreasing in five participants, while increasing in three participants. Changes in morphology were present at 6-month follow-up, even in patients who did not maintain AVF patency for the entirety of the 6-month period. CONCLUSION: All patients included in this prospective case series had increases in left ventricular mass, with variability in the effects on the ejection fraction and left atrial volume. As left ventricular mass is an independent predictor of morbidity and mortality, further research to determine appropriate vascular access management in both end-stage kidney disease and kidney transplant populations is warranted.


Asunto(s)
Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Fallo Renal Crónico , Humanos , Estudios Retrospectivos , Diálisis Renal
14.
Sci Rep ; 12(1): 20236, 2022 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-36424380

RESUMEN

Severe COVID-19 infection results in significant immune dysregulation resulting from excessive recruitment and activation of neutrophils. The aim of this study was to confirm feasibility, initial safety and detect signal of efficacy of a non-propriety device delivered using an intermittent extra-corporeal system (LMOD) allowing leucocytes modulation in the setting of Severe COVID-19 infection. Twelve patients were recruited. Inclusion criteria were > 18 years age, confirmed COVID-19, acute respiratory distress syndrome requiring mechanical support and hypotension requiring vasopressor support. Primary end point was vasopressor requirements (expressed as epinephrine dose equivalents) and principle secondary endpoints related to safety, ability to deliver the therapy and markers of inflammation assessed over five days after treatment initiation. LMOD treatment appeared safe, defined by hemodynamic stability and no evidence of white cell number depletion from blood. We demonstrated a significant decrease in vasopressor doses (-37%, p = 0.02) in patients receiving LMOD therapy (despite these patients having to tolerate an additional extracorporeal intermittent therapy). Vasopressor requirements unchanged/increasing in control group (+ 10%, p = 0.48). Although much about the use of this therapy in the setting of severe COVID-19 infection remains to be defined (e.g. optimal dose and duration), this preliminary study supports the further evaluation of this novel extracorporeal approach.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Humanos , Enfermedad Crítica , Oxigenación por Membrana Extracorpórea/métodos , Inmunomodulación , Vasoconstrictores/uso terapéutico
15.
Curr Opin Nephrol Hypertens ; 31(6): 553-559, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36172854

RESUMEN

PURPOSE OF REVIEW: Patients with chronic kidney disease characteristically exhibit microcirculatory dysfunction, in combination with vascular damage. Hemodialysis superimposes additional circulatory stress to the microvasculature (repetitive ischemic insults/cumulative damage) resulting in high mortality. Intradialytic monitoring and hemodialysis delivery is currently limited to macrovascular/systemic assessment and detection of intradialytic systemic hypotension. Monitoring of the microcirculation has the potential to provide valuable information on hemodialysis-induced circulatory stress likely to result in end-organ ischemia (with/without systemic hypotension) generating an opportunity to intervene before tissue injury occurs. RECENT FINDINGS: Various noninvasive technologies have been used assessing the microcirculation in hemodialysis patients at rest. Some technologies have also been applied during hemodialysis studying the effects of treatment on the microcirculation. Despite the approach used, results are consistent. Hemodialysis patients have impaired microcirculations with treatment adding additional stress to inadequately regulated vascular beds. Utility/practicality/clinical relevance vary significantly between methodologies. SUMMARY: Intradialytic monitoring of the microcirculation can provide additional insights into a patient's individual response to treatment. However, this valuable perspective has not been adopted into clinical practice. A microcirculatory view could provide a window of opportunity to enable a precision medicine approach to treatment delivery improving current woefully poor subjective and objective clinical outcomes.


Asunto(s)
Hipotensión , Insuficiencia Renal Crónica , Humanos , Hipotensión/diagnóstico , Hipotensión/etiología , Microcirculación , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia
16.
Bone Rep ; 16: 101591, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35663378

RESUMEN

Background: Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) (SLC34A3 gene, OMIM 241530) is an autosomal recessive disorder that results in a loss of function of the sodium-phosphate NPT2c channel at the proximal tubule. Phosphate supplementation rarely improves serum phosphate, hypercalciuria, nephrocalcinosis, 1,25(OH)2 vitamin D (1,25(OH)2D) levels or short stature. Methods: We describe 23Na MRI and the successful use of recombinant human growth hormone (rhGH) and Fluconazole to improve growth (possibly confounded by puberty) and hypercalciuria in a now 12-year-old male with HHRH (novel homozygous SLC34A3 mutation, c.835_846 + 10del.T). Results: The patient had chronic bone pain, hypophosphatemia (0.65 mmol/L[reference interval 1.1-1.9]), pathological fractures and medullary nephrocalcinosis/hypercalciuria (urinary calcium/creatinine ratio 1.66 mol/mmol[<0.6]). TmP/GFR was 0.65 mmol/L[0.97-1.64]; 1,25(OH)2D was >480 pmol/L[60-208]. Rickets Severity Score was 4. Treatment with 65 mg/kg/day of sodium phosphate and potassium citrate 10 mmol TID failed to correct the abnormalities.Adding rhGH at 0.35 mg/kg/week to the phosphate therapy, improved bone pain, height z-score from -2.09 to -1.42 over 6 months, without a sustained effect on TmP/GFR. Fluconazole was titrated to 100 mg once daily, resulting for the first time in a reduction of the 1,25(OH)2D to 462 and 426 pmol/L; serum phosphate 0.87 mmol/L, and calcium/creatinine ratio of 0.73.23Na MRI showed normal skin (z-score + 0.68) and triceps surae muscle (z-score + 1.5) Na+ levels; despite a defect in a sodium transporter, hence providing a rationale for a low sodium diet to improve hypercalciuria. Conclusions: The addition of rhGH, Fluconazole and salt restriction to phosphate/potassium supplementation improved the conventional therapy. Larger studies are needed to confirm our findings.

18.
Clin Kidney J ; 15(6): 1129-1136, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35664280

RESUMEN

Background: Sodium-23 magnetic resonance imaging (23Na MRI) allows the measurement of skin sodium concentration ([Na+]). In patients requiring dialysis, no data are available relating to the clinical outcomes associated with skin sodium accumulation or the determinants of increasing deposition. Methods: This was an exploratory, observational study of adult hemodialysis (HD) and peritoneal dialysis (PD) patients. Participants underwent skin [Na+] quantification with leg 23Na MRI at the study's beginning. Outcomes of interest were all-cause mortality and composite all-cause mortality plus major adverse cardiovascular events. Cumulative total and event-free survival were assessed using the Kaplan-Meier survival function after stratification into skin [Na+] quartiles. Cox proportional hazards regression was used to model the association between skin [Na+] and outcomes of interest. Multiple linear regression was used to model the predictors of skin [Na+]. Results: A total of 52 participants (42 HD and 10 PD) underwent the study procedures. The median follow-up was 529 days (interquartile range: 353-602). Increasing skin [Na+] quartiles were associated with significantly shorter overall and event-free survival (log-rank χ2(1) = 3.926, log-rank χ2(1) = 5.685; P for trend <0.05 in both instances). Skin [Na+] was associated with all-cause mortality {hazard ratio (HR) 4.013, [95% confidence interval (95% CI) 1.988-8.101]; P < 0.001} and composite events [HR 2.332 (95% CI 1.378-3.945); P < 0.01], independently of age, sex, serum [Na+] and albumin. In multiple regression models, dialysate [Na+], serum albumin and congestive heart failure were significantly associated with skin [Na+] in HD patients (R2 adj = 0.62). Conclusions: Higher skin [Na+] was associated with worse clinical outcomes in dialysis patients and may represent a direct therapeutic target.

19.
Front Neurol ; 13: 719208, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35370903

RESUMEN

Background: Abnormalities in cognitive function are almost universal in patients receiving hemodialysis (HD) and are associated with worse quality of life, impaired decision making, increased healthcare utilization and mortality. While cognitive impairment in the HD population is increasingly recognized, it is unclear how quickly it develops after starting HD. Methods: This was a cross-sectional study of a cohort of low dialysis vintage HD patients (<12 months). We used the validated Cambridge Brain Science (CBS) battery of web-based tests to evaluate cognition compared to age- and sex matched controls across three cognitive domains: verbal processing, reasoning and short-term memory. Results: Forty-nine HD patients were included in this study; 43 completed the full battery of tests. The average scores for HD patients were consistently below the age and sex-matched controls. Fifty-five percent of HD patients had cognitive impairment in verbal skills, 43% in reasoning and 18% in short-term memory. Conclusions: There is a high prevalence of CI evident early after starting HD, with the largest deficits seen in reasoning and verbal processing. These deficits may be attributable to the HD treatment itself. Further studies are needed to characterize the natural history of CI in this patient population and to test interventions aimed at preventing or slowing its progression.

20.
Radiology ; 303(2): 384-389, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35133199

RESUMEN

Background To the knowledge of the authors, urinary osmolarity is the only tool currently available to assess kidney corticomedullary gradient (CMG). Comparisons between CMG and urinary osmolarity and the use of modalities such as sodium MRI to evaluate renal disease in humans are lacking. Purpose To investigate the ability of sodium MRI to measure CMG dynamics compared with urinary osmolarity after water load in healthy volunteers and CMG in participants with kidney disease. Materials and Methods A prospective study was conducted from July 2020 to January 2021 in fasting healthy volunteers undergoing water load and participants with chronic kidney disease (CKD) from cardiorenal syndrome included in a clinical trial. In both groups, CMG was estimated by measuring the medulla-to-cortex signal ratio from sodium MRI at 3.0 T. A custom-built two-loop (diameter, 18 cm) butterfly radiofrequency surface coil, tuned for sodium frequency (33.786 MHz), was used to acquire renal sodium images. Two independent observers measured all sodium MRI cortical and medullary values for each region of interest to compute the intraclass correlation coefficient. Pearson correlation was performed between urinary osmolarity and CMG. Results Five participants with CKD (mean age, 77 years ± 12 [standard deviation]; all men) and 10 healthy volunteers (mean age, 42 years ± 15; six men, four women) were evaluated. A reduction was observed between baseline and peak urinary dilution time for both mean medulla-to-cortex ratios (1.55 ± 0.11 to 1.31 ± 0.09, respectively; P < .001) and mean urinary osmolarity (756 mOsm/L ± 157 to 73 mOsm/L ± 14, respectively; P < .001) in healthy volunteers. Medulla-to-cortex and corresponding urinary osmolarity were correlated in both groups (r2 = 0.22; P < .001). Kidney sodium tissue content was successfully acquired in all five participants with CKD. The intraclass correlation coefficient measurement was 0.99 (P < .001). Conclusion Functional sodium MRI accurately depicted corticomedullary gradient (CMG) dynamic changes in healthy volunteers and demonstrated feasibility of CMG measurement in participants with reduced kidney function. Clinical trial registration no. NCT04170855. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Laustsen and Bøgh in this issue.


Asunto(s)
Insuficiencia Renal Crónica , Sodio , Adulto , Anciano , Femenino , Humanos , Riñón/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Masculino , Estudios Prospectivos , Insuficiencia Renal Crónica/diagnóstico por imagen , Agua
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