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1.
J Clin Endocrinol Metab ; 109(2): e488-e494, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-37843399

RESUMO

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.


Assuntos
Doenças Cardiovasculares , Raquitismo Hipofosfatêmico Familiar , Hipertensão , Hipofosfatemia , Adulto , Humanos , Raquitismo Hipofosfatêmico Familiar/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Análise de Onda de Pulso , Fatores de Risco , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Fatores de Risco de Doenças Cardíacas , Sódio , Fatores de Crescimento de Fibroblastos , Fosfatos
3.
Expert Rev Hematol ; 14(11): 1027-1040, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34747320

RESUMO

INTRODUCTION: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune blood disorder, which presents with microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis and is caused by severe deficiency of ADAMTS13. iTTP may result in both acute and chronic complications and is rapidly fatal without expedient treatment. Life-time risk of relapse is approximately 40%. AREAS COVERED: A number of predictors of relapse has been described in the literature. The most well-studied predictor of relapse is persistent ADAMTS13 deficiency; however, it is not a perfect marker. Relapse can be prevented by treatment with immunosuppressive medications, with rituximab being the most studied. EXPERT OPINION: Patients who recover from iTTP should be regularly assessed, including with ADAMTS13 activity testing. The optimal frequency of assessments has not been established, but every 3 months is recommended. Considering the potential for significant organ damage and mortality associated with iTTP relapse, patients in remission and with persistent ADAMTS13 activity of 10-20% should be prophylactically treated with immunosuppression. Additional markers to precisely identify patients at higher risk of relapse are needed.


Assuntos
Púrpura Trombocitopênica Trombótica , Trombose , Proteína ADAMTS13/metabolismo , Humanos , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/prevenção & controle , Recidiva , Rituximab/uso terapêutico , Trombose/tratamento farmacológico
4.
Blood Adv ; 5(20): 4211-4218, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34521110

RESUMO

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder of systemic microthrombosis and organ ischemia. The etiology of chronic cerebrovascular outcomes in iTTP survivors is largely unknown. In this pilot study, we measured blood-brain barrier (BBB) permeability in patients with iTTP at the start of remission and 6 months later. This prospective pilot study included 7 adult patients with incident iTTP. Eligibility criteria included ADAMTS13 activity < 10% and detectable inhibitor at diagnosis. Patients were recruited from London Health Sciences Centre in Canada (2017-2019) within 3 days of hospital admission and followed for 6 months after remission (defined as normalization of platelet count and lactate dehydrogenase with no clinical signs or symptoms of microvascular injury for more than 30 days after the last plasma exchange). All patients had cerebral computed tomography perfusion scans with BBB permeability surface product measurements. Patients (5 women, 2 men) had a mean age of 48 years (range, 21-77 years). At diagnosis, patients had a mean platelet count of 22 (standard deviation [SD], 25) × 109/L. At the start of remission, mean BBB permeability surface product was 0.91 (0.30) mL/min/100 g. Six months later, the mean permeability surface product was 0.56 (0.22) mL/min/100 g, with a mean difference of -0.312 mL/min/100 g (95% confidence interval: -0.4729 to -0.1510; P = .0032). In this pilot study of patients with iTTP, pathologically increased BBB permeability was evident, and although there was some improvement, this persisted 6 months after remission. Future work will explore the chronicity of these findings and their clinical implications.


Assuntos
Púrpura Trombocitopênica Idiopática , Púrpura Trombocitopênica Trombótica , Adulto , Idoso , Barreira Hematoencefálica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Permeabilidade , Projetos Piloto , Estudos Prospectivos , Sobreviventes , Adulto Jovem
7.
Pediatr Nephrol ; 32(6): 917-919, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28197886

RESUMO

In a recent article in Pediatric Nephrology, EM Yang and colleagues (Pediatr Nephrol 2017: doi: 10.1007/s00467-016-3587-6 ) published a retrospective cross-sectional study involving a cohort of 442 children with an mean estimated glomerular filtration rate of >60 mL/min/1.73 m2. The authors measured 24-h urine protein excretion (24-h UProt) alongside the morning spot urine protein to creatinine ratio (Prot/Cr) in this group of patients. While the Prot/Cr may be the only feasible way to routinely estimate the daily protein excretion of a young child, inter-individual variability in childrens' urinary creatinine excretion (UCr) may heavily influence the result. The authors sought to determine which equation was the most accurate in predicting UCr. Not only did they discover that the adult Cockcroft-Gault equation worked best, they also found that multiplying the Prot/Cr by the estimated UCr significantly improved the accuracy of the 24-h UProt estimate. In this editorial we discuss both the strengths and limitations of the study by EM Yang and colleagues. We also highlight the importance of adhering to internationally agreed upon reporting guidelines such as the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement.


Assuntos
Creatinina , Adulto , Criança , Estudos Transversais , Humanos , Testes de Função Renal , Proteinúria , Estudos Retrospectivos
8.
Pediatr Transplant ; 20(1): 34-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26589470

RESUMO

Although de novo DSA are associated with inferior graft survival, there are no effective strategies to prevent their formation. Underexposure to MPA (prodrug: MMF) also contributes to rejection rates early after transplantation, but the effect of this phenomenon on the formation of DSA long-term post-transplantation is unknown. Data are expressed as mean (standard deviation). All available data from 32 renal transplant recipients (age at transplantation 7.5 [4.5] yr) on tacrolimus and MPA immunosuppression with an average follow-up of 9.4 (s.d. 4.6) yr were analyzed. DSA were measured using the Luminex assay (>500 MFI was considered DSA-positive). Tacrolimus and MPA levels were measured with the Abbot Tacro II and EMIT assay, respectively. Among 1964 MPA and 3462 tacrolimus trough levels, the average MPA trough level was 3.2 (1.5) mg/L and the average tacrolimus level was 6.7 (2.8) ng/mL. At last follow-up, only 5/32 patients had undetectable DSA, with 5/32 having no class I antibodies and 6/32 having no class II antibodies. DSA formation was associated with a lower minimum MPA trough level (0.27 [0.23] vs. 0.47 [0.18] mg) and cystatin C eGFR (48 [21] vs. 70 [23] mL/min/1.73 m(2)) for class I DSA formers. The average eGFR of patients without class I DSA was 70 (23) mL/min/1.73 m(2), whereas the average eGFR of patients with class I DSA was 48 (21) mL/min/1.73 m(2) (p = 0.0071). MPA trough levels <1.3 mg/L long-term post-transplantation are associated with the formation of DSA. The association between the formation of DSA and minimum MPA exposure may support a strategy for preventing the formation of DSA.


Assuntos
Formação de Anticorpos , Ácido Micofenólico/sangue , Ácido Micofenólico/uso terapêutico , Insuficiência Renal/sangue , Insuficiência Renal/cirurgia , Antropometria , Anticorpos/imunologia , Área Sob a Curva , Criança , Estudos de Coortes , Cistatina C/sangue , Monitoramento de Medicamentos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Transplante de Rim , Masculino , Insuficiência Renal/imunologia , Tacrolimo/sangue , Tacrolimo/uso terapêutico , Doadores de Tecidos , Transplantados , Resultado do Tratamento
9.
Pediatr Transplant ; 18(4): E109-13, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24646330

RESUMO

Management of late humoral rejection remains challenging, and DSA may persist. A case report illustrates how individual DSA titers using solid-phase-based assays may help to assess for accommodation. A male cystinosis patient received a cadaveric renal transplant at the age of 12 yr with a daclizumab, tacrolimus, MMF, and steroids-based immunosuppression. After three acute rejection episodes over the first eight months, interstitial fibrosis/tubular atrophy (IF/TA) was diagnosed on biopsy, while the immunosuppression was left unchanged with a high target exposure for both tacrolimus and MPA. One yr later, AMR type III (C4d and DSA positive) was treated with daily plasmapheresis, IVIG 100 mg/kg and pulse steroids 5 mg/kg. DSA (DR 53, DQ4, and DQ 2) were not responding until the plasma volume was increased to 2.5 plasma volumes. A second rise of creatinine confirmed worse humoral rejection; daily plasma exchange was resumed, and two doses of rituximab (375 mg/m(2)) were given. Subsequently, all DSA dropped, but only DR53 DSA remained unchanged, whereas the DQ antibodies rebounded to very strong titers. With a follow-up of over 120 days after recovery of the CD19 count, off all additional treatment and on identical immunosuppression with tacrolimus and MMF and prednisone, the patient's creatinine remained stable between 45 and 50 um while DQ DSA remain strong to very strong. We conclude that the patient is in a state of accommodation. DSA titers should be monitored when managing late humoral rejection.


Assuntos
Rejeição de Enxerto/diagnóstico , Isoanticorpos/sangue , Transplante de Rim , Adolescente , Biomarcadores/sangue , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Humanos , Masculino
10.
Clin Biochem ; 47(1-2): 129-31, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24161477

RESUMO

OBJECTIVE: To assess the relationship between angiotensin-converting enzyme (ACE) levels and cystatin C in a patient with the presumed diagnosis of sarcoidosis. DESIGN AND METHODS: Case report with correlation analysis between ACE levels and cystatin C concentrations while considering gold-standard nuclear medicine glomerular filtration rate (GFR) methods for the measurement of renal function. RESULTS: We observed a strong correlation between ACE levels and cystatin C concentration in 12-year old with the presumed diagnosis of sarcoidosis in the absence of renal pathology and abnormal renal function. CONCLUSION: Elevated ACE levels may cause non-specific cystatin C elevation irrespective of GFR.


Assuntos
Cistatina C/sangue , Peptidil Dipeptidase A/metabolismo , Criança , Humanos , Masculino
14.
Pediatr Nephrol ; 26(10): 1759-62, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21533869

RESUMO

The management of steroid-dependent nephrotic syndrome, especially in patients who have failed to respond to cytotoxic drugs, such as cyclophosphamide, remains challenging. Rituximab represents a new (off-label) therapeutic option. In a significant portion of patients, it has a short serum half-life following the recovery of CD20-positive cells. The addition of mycophenolate mofetil (MMF) as a maintenance therapy is also an attractive option, but one which requires testing in a prospective randomized clinical trial with therapeutic drug monitoring and mechanistic ancillary studies.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Síndrome Nefrótica/tratamento farmacológico , Feminino , Humanos , Masculino , Ácido Micofenólico/uso terapêutico , Rituximab
15.
Clin Biochem ; 44(5-6): 435-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21291879

RESUMO

OBJECTIVES: It is unclear whether fibroblast growth factor-23 (FGF-23) increases in response to phosphate accumulation or to decrease clearance in chronic kidney disease (CKD) as is the case with other low molecular weight proteins such as cystatin C (CysC). DESIGN AND METHODS: This cross-sectional study measured serum FGF-23, CysC, and other serum markers of bone metabolism in 69 patients, aged 18 months-24 years, with various stages of CKD (eGFR=11-214mL/min). RESULTS: FGF-23 levels were significantly correlated with CysC and parathyroid hormone levels (PTH) on univariate non-linear regression analysis. In multivariate linear regression analysis, log (CysC) (ß=0.660, p<0.0001), log (PTH) (ß=0.038, p=0.37), and phosphate (ß=0.222, p=0.028) explained 69.1% of the variance of FGF-23. CONCLUSIONS: CysC had the largest unique contribution to FGF-23 variance in this model, supporting the hypothesis that renal clearance may be the most responsible factor for elevated FGF-23 levels in early stages of CKD.


Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Taxa de Filtração Glomerular , Falência Renal Crônica/fisiopatologia , Estudos Transversais , Fator de Crescimento de Fibroblastos 23 , Humanos , Falência Renal Crônica/sangue
17.
Clin J Sport Med ; 16(1): 27-33, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16377972

RESUMO

OBJECTIVE: To learn more about the prevalence of dietary supplement and medication use by Canadian athletes in the Olympic Games in Atlanta 1996 and Sydney 2000. SETTING AND PARTICIPANTS: Data were collected from personal interviews with Canadian athletes who participated at the 1996 Atlanta and 2000 Sydney Olympic Games. The athletes were interviewed by Canadian physicians regarding the use of vitamins, minerals, nutritional supplements, and prescribed and over-the-counter medications. Of the 271 Canadian athletes who participated at the Atlanta Olympics, 257 athletes were interviewed; at the Sydney Olympics, 300 of 304 Canadian athletes were interviewed. MAIN OUTCOME MEASUREMENT: A quantitative and qualitative description of the use of dietary supplements by Canadian athletes at the Atlanta and Sydney Olympics. RESULTS: At the Atlanta Games, 69% of the athletes used some form of dietary supplements, whereas 74% of the athletes used dietary supplements at the Sydney Games. Vitamins were taken by 59% of men and 66% of women in Atlanta, and 65% of men and 58% women in Sydney. Mineral supplements were used by 16% of men and 45% of women in Atlanta, and 30% of men and 21% of women in Sydney. Nutritional supplements were used by 35% of men and 43% of women in Atlanta, and 43% of men and 51% of women in Sydney. The most popular vitamins were multivitamins in both Olympics. The most popular mineral supplements were iron supplements. The most commonly used nutritional supplement in Atlanta was creatine (14%), but amino acids (15%) were the most commonly used nutritional supplement in Sydney. In Atlanta, 61% of the athletes were using some form of medication, 54% of the athletes were using medications in Sydney. Nonsteroidal antiinflammatory drugs (NSAIDS) were the most commonly used medications at both Olympic Games. Among all sports, the highest prevalence of vitamin use occurred in boxing (91%) in Atlanta and swimming (76%) in Sydney. Rowers (56%) and cyclists (73%) demonstrated the highest use of mineral supplements. Nutritional supplement use occurred most often in swimming (56%) and cycling (100%). The use of NSAIDs was highest in softball (60%) in Atlanta and gymnastics (100%) in Sydney. CONCLUSION: This review demonstrates that dietary supplement use was common among Canadian athletes at both the Atlanta and Sydney Olympic Games. There was a slight increase in total dietary supplement use at the Sydney Games. Widespread use of supplements, combined with an absence of evidence of their efficacy and a concern for the possibility of "inadvertent" doping, underscore the need for appropriately focused educational initiatives in this area.


Assuntos
Suplementos Nutricionais/estatística & dados numéricos , Dopagem Esportivo/estatística & dados numéricos , Esportes , Adulto , Canadá , Coleta de Dados , Feminino , Humanos , Cooperação Internacional , Masculino , Prevalência , Estudos Retrospectivos
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