RESUMEN
Primary aldosteronism is the most frequent cause of secondary hypertension. Three variants of familial hyperaldosteronism are known today. Early onset hypertension and severe target organ damage are hallmarks of the heritable forms. The underlying gene defect has already been identified in familial hyperaldosteronism type I. In type II and III research is ongoing. A highly variable phenotype often precludes the discovery of the familial appearance of these syndromes. Taking a sound family history is extremely important to discover the Mendelian pattern of inheritance. The identification of affected families is highly rewarding because all variants can potentially be cured or at least specifically treated. Testing the relatives of an index patient sometimes even allows preemptive treatment. However, the availability of specific treatment options necessitates a solid differentiation between the three syndromes to avoid unnecessary medical therapy or surgery.
Asunto(s)
Hiperaldosteronismo/diagnóstico , Algoritmos , Técnicas de Diagnóstico Endocrino , Familia , Pruebas Genéticas , Humanos , Hiperaldosteronismo/clasificación , Hiperaldosteronismo/genética , Hiperaldosteronismo/terapia , Hipertensión/diagnóstico , Hipertensión/etiologíaRESUMEN
INTRODUCTION: the deadly threat of systemic infections with coagulase negative Staphylococcus lugdunensis despite an appropriate antibiotic therapy has only recently been recognized. The predominant infectious focus observed so far is left-sided native heart valve endocarditis, but bone and soft tissue infections, septicaemia and vascular catheter-related bloodstream infections have also been reported. We present a patient with a fatal Staphylococcus lugdunensis septicaemia following zoster bacterial superinfection of the pelvic region. case presentation: a 71-year old male diagnosed with IgG kappa plasmocytoma presented with a conspicuous weight loss, a hypercalcaemic crisis and acute renal failure. After initiation of haemodialysis treatment his condition improved rapidly. However, he developed a varicella-zoster virus infection of the twelfth thoracic dermatome requiring intravenous acyclovir treatment. Four days later the patient presented with a fulminant septicaemia. Despite an early intravenous antibiotic therapy with ciprofloxacin, piperacillin/combactam and vancomycin the patient died within 48 hours, shortly before the infective isolate was identified as Staphylococcus lugdunensis by polymerase chain reaction. CONCLUSION: despite S. lugdunensis belonging to the family of coagulase-negative staphylococci with an usually low virulence, infections with S. lugdunensis may be associated with an aggressive course and high mortality. This is the first report on a Staphylococcus lugdunensis septicaemia following a zoster bacterial superinfection of the pelvic region.
Asunto(s)
Herpes Zóster/complicaciones , Herpesvirus Humano 3 , Sepsis/microbiología , Infecciones Estafilocócicas/complicaciones , Staphylococcus lugdunensis , Anciano , Resultado Fatal , Humanos , Masculino , Pelvis/virología , Sepsis/virología , Sobreinfección/microbiología , Sobreinfección/virologíaRESUMEN
In patients with chronic kidney disease elevated blood pressure is a common finding, but primary hypertension can also damage healthy kidneys. Renal outcome is strictly dependent on blood pressure, no matter whether the kidneys are cause or consequence of hypertension. Furthermore, hypertension and kidney disease are strong cardiovascular risk factors. In every patient diagnosed with hypertension glomerular filtration rate has to be checked. Proteinuria and structural abnormalities of the kidneys should be ruled out. Patients with a decreased glomerular filtration rate, proteinuria or pathologic ultrasound should be seen by a nephrologist. A strict antihypertensive therapy (blood pressure <130/80 mmHg) can substantially improve the prognosis of hypertensive renal patients. In patients with kidney damage, inhibitors of the renin-angiotensin-system are preferred. To avoid adverse events a close monitoring of antihypertensive therapy is warranted.
Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión/diagnóstico , Hipertensión/terapia , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/terapia , Humanos , Hipertensión/complicaciones , Fallo Renal Crónico/etiologíaRESUMEN
An appropriate phosphate homeostasis is absolutely required for correct bone mineralization and remodeling, for diverse signaling pathways as well as cell membrane formation. Its disequilibrium results in serious complications like hypophosphatemia and excessively reduced fractional tubule phosphate reabsorption (TRP). A rare cause of such a disturbed phosphate balance is tumor-induced osteomalacia (TIO)--a phosphate wasting disorder sometimes associated with certain mesenchymal tumors. These primitive tumors secrete so-called phosphatonins--recently identified factors involved in the regulation of phosphate homeostasis such as the secreted frizzled related protein 4 (sFRP-4), the fibroblast growth factors 7 and 23 (FGF-7/-23), or the matrix extracellular phosphoglycoprotein (MEPE). Progressive muscular weakness and spontaneous bone fractures caused by inadequate osteoid mineralization are the characteristic clinical symptoms, which completely resolve after tumor resection. Here we report a new case of TIO caused by tumor secreted FGF-23 and review the literature to facilitate the correct diagnosis of this rare disorder.
Asunto(s)
Hipofosfatemia Familiar/complicaciones , Osteomalacia/etiología , Síndromes Paraneoplásicos/etiología , Fosfatos/orina , Adulto , Biopsia , Diagnóstico Diferencial , Factor-23 de Crecimiento de Fibroblastos , Estudios de Seguimiento , Humanos , Hipofosfatemia Familiar/diagnóstico , Hipofosfatemia Familiar/orina , Imagen por Resonancia Magnética , Masculino , Osteomalacia/diagnóstico , Osteomalacia/orina , Síndromes Paraneoplásicos/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: This study aimed to evaluate the impact of 5 mg of prednisolone/day on HbA1c levels and its association with the development of pre-diabetes and new-onset diabetes mellitus (NODAT) in non-diabetic first renal transplant recipients on long-term follow-up. METHODS: Four hundred patients were analysed on an average of 4.1 ± 3.0 years after successful transplantation: 96 (24%) were steroid-free and 304 (76%) treated with 5 mg of prednisolone/day combined with cyclosporine A (CsA) or tacrolimus (Tac) as part of their immunosuppressive protocol. Pre-diabetes and NODAT were defined based on the HbA1c levels according to the current ADA guidelines. The Mann-Whitney U test and the Chi-square test were used to determine intergroup differences. Multivariate logistic regression analyses (adjusted for steroid-free versus 5 mg of prednisolone per day, body mass index (BMI), number of HLA mismatches, eGFR according to the CKD-EPI formula, sex, negative vs. positive PRA titre, CMV and HCV positivity of the recipient, CsA vs. Tac immunosuppressive medication, dialysis vintage (years), age at the last follow-up and time from transplantation to the last follow-up) were performed to identify an independent effect of low-dose steroids on the evolution of pre-diabetes and NODAT. RESULTS: A small but statistically significant difference in HbA1c levels was observed between the control and the steroid groups (5.56 ± 0.54 vs. 5.67 ± 0.0.45%, p = 0.045). The incidence rates of pre-diabetes and NODAT per 100 patients per year were 9.3 and 3.0, respectively. Regression analysis showed that low-dose steroids (p = 0.026, risk ratio (RR) 1.789, 95%; confidence interval (CI) 1.007-3.040) and age (p = 0.000, RR 1.037/year, 95% CI 1.018-1.057) were associated with pre-diabetes, whereas BMI (p = 0.000, RR 1.190, 95% CI 1.084-1.307), age (p = 0.000, RR 1.087/year, 95% CI 1.047-1.129) and Tac use (p = 0.010, RR 3.300, 95% CI 1.328-8.196) were associated with NODAT. CONCLUSION: Using 5 mg of prednisolone/day was associated with increased HbA1c levels and an increased risk in developing pre-diabetes, but not NODAT, whereas BMI, age and the use of tacrolimus were associated with an increased risk in developing NODAT.
Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Glucocorticoides/administración & dosificación , Hemoglobina Glucada , Trasplante de Riñón , Estado Prediabético/epidemiología , Prednisolona/administración & dosificación , Adulto , Factores de Edad , Anciano , Índice de Masa Corporal , Ciclosporina/uso terapéutico , Diabetes Mellitus Tipo 2/sangre , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Masculino , Persona de Mediana Edad , Estado Prediabético/sangre , Factores de Riesgo , Tacrolimus/uso terapéutico , Factores de Tiempo , Receptores de TrasplantesRESUMEN
Uncontrolled studies suggest the benefits of an add-on antihypertensive therapy with an aldosterone receptor antagonist. However, it still must be clarified whether a PHA screening has a predictive value for the efficacy of a therapy with an aldosterone receptor antagonist. Before generally accepted recommendations can be made, a randomized, controlled study with aldosterone antagonists must prove that such a therapy is safer, tolerable and leads to better long-term blood pressure control as well as lower renal and cardiovascular morbidity and mortality.
Asunto(s)
Antihipertensivos/uso terapéutico , Hiperaldosteronismo/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Neoplasias de la Corteza Suprarrenal/complicaciones , Neoplasias de la Corteza Suprarrenal/diagnóstico , Adenoma Corticosuprarrenal/complicaciones , Adenoma Corticosuprarrenal/diagnóstico , Presión Sanguínea/efectos de los fármacos , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensión/etiología , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
CONTEXT: Primary aldosteronism (PA) is the most common cause of secondary hypertension. Aldosterone excess can cause DNA damage in vitro and in vivo. Single case reports have indicated a coincidence of PA with renal cell carcinoma and other tumors. However, the prevalence of benign and malignant neoplasms in patients with PA has not yet been studied. PATIENTS AND DESIGN: In the multicenter MEPHISTO study, the prevalence of benign and malignant tumors was investigated in 335 patients with confirmed PA. Matched hypertensive subjects from the population-based Study of Health in Pomerania cohort served as controls. RESULTS: Of the 335 PA patients, 119 (35.5%) had been diagnosed with a tumor at any time, and 30 had two or more neoplasms. Lifetime malignancy occurrence was reported in 9.6% of PA patients compared to 6.0% of hypertensive controls (P = .08). PA patients with a history of malignancy had higher baseline aldosterone levels at diagnosis of PA (P = .009), and a strong association between aldosterone levels and the prevalence of malignancies was observed (P = .03). In total, 157 neoplasms were identified in the PA patients; they were benign in 61% and malignant in 25% of the cases (14% of unknown dignity). Renal cell carcinoma was diagnosed in five patients (13% of all malignancies) and was not reported in controls CONCLUSION: Compared to hypertensive controls, the prevalence of malignancies was positively correlated with aldosterone levels, tended to be higher in PA patients, but did not differ significantly.
Asunto(s)
Aldosterona/sangre , Biomarcadores de Tumor/sangre , Hiperaldosteronismo/fisiopatología , Hipertensión/fisiopatología , Neoplasias/epidemiología , Adulto , Anciano , Presión Sanguínea , Estudios de Casos y Controles , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/diagnóstico , Prevalencia , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: The half synthetic Vitamin D analogue dihydrotachysterol (DHT) is widely used for hypocalcaemic hypoparathyroidism following surgical removal of parathyroids. Such treatment generally initiated by surgeons right after surgery has to be continued in clinical practice. Unfortunately, the required careful monitoring of calcium metabolism is often lacking and as demonstrated may lead to life-threatening conditions. PATIENTS AND METHODS: Here we report on five patients referred to our nephrology unit because of unknown impairment of renal function during therapy with DHT. All patients had clinical signs of hypercalcaemia. Since most symptoms are nonspecific they were not perceived by primary care physicians. In fact DHT treatment was continued for 4 - 50 years. In all cases calcium levels were determined after inadequate long intervals ranging from 3.08 to 4.97 mmol/l. Creatinine levels ranged from 277 to 365 micromol/l. All patients suffered from symptoms of severe hypercalcaemia, three of them needing intensive care unit treatment. RESULTS: All patients were treated effectively with a regimen consisting of intravenous saline, a loop diuretic, and application of bisphosphonates. As confirmed by renal biopsy persisting alleviation of renal function was due to calcifications. After discontinuation of DHT therapy patients were safely switched to shorter acting vitamin D derivates maintaining a normal calcium level. CONCLUSIONS: In comparison to short acting vitamin-D derivates hypercalcaemic episodes with DHT appear to last longer and may therefore occur with higher incidence. A future option could be the use of synthetic parathyroid hormone (s-PTH) recently shown to be safe and effective. Nevertheless a customized therapy and careful monitoring is indispensable in any case to prevent irreversible organ damage.
Asunto(s)
Dihidrotaquisterol/efectos adversos , Dihidrotaquisterol/uso terapéutico , Hipoparatiroidismo/tratamiento farmacológico , Insuficiencia Renal/inducido químicamente , Vitamina D/análogos & derivados , Anciano , Monitoreo de Drogas , Femenino , Humanos , Hipercalcemia/inducido químicamente , Hipercalcemia/terapia , Masculino , Insuficiencia Renal/terapia , Vitamina D/efectos adversos , Vitamina D/uso terapéuticoRESUMEN
We report a case of a young man with a history of kidney stones. Occurrence of gross hematuria several months after the extracorporeal shock wave, lithotripsy (ESWL) treatment lead to hospitalization. By ultrasound and abdominal CT scan, the urologist could exclude post-renal causes of the gross hematuria and acute renal failure. After transfer to a department of nephrology hemodialysis was started, an immediate kidney biopsy was performed and prednisolone was administered on the same day. The kidney biopsy revealed an anti-glomerular basement membrane (GBM) disease. The renal function did not recover and the patient remained on hemodialysis. In the literature it has been hypothesized that ESWL-treated patients are prone to develop anti-GBM disease by liberation of glomerular basement antigen through the ESWL high energy shock waves. An additional hypothesis considering the higher susceptibility for anti-GBM disease among certain HLA-tissue types is discussed with regard to our case. Unfortunately, the prolonged track to diagnosis and delayed immunosuppressive treatment could not prevent poor clinical outcome. Although anti-GBM disease is a rather rare disease, it should be included as a differential diagnosis for hematuria--especially months after ESWL treatment. Otherwise early diagnosis may be missed and as in our patient immunosuppressive treatment will remain unsuccessful to recover renal function.
Asunto(s)
Glomerulonefritis/etiología , Hematuria/etiología , Cálculos Renales/terapia , Litotricia/efectos adversos , Adulto , Biopsia , Diagnóstico Diferencial , Glomerulonefritis/diagnóstico , Glomerulonefritis/tratamiento farmacológico , Hematuria/diagnóstico , Humanos , Masculino , Diálisis RenalRESUMEN
UNLABELLED: Adrenal disorders are relative frequent with regard to the incidence of adrenal tumors and the high portion in causes of secondary hypertension. Morphological changes in the adrenal glands can lead to very different functional disorders that may be clinically overt or hard to diagnose. On the other hand, they can already be functionally relevant when structural changes are too small to be picked up by imaging. Adrenal venous sampling serves to determine the source of hormone excess through the analysis of adrenal blood. In this manuscript, we call attention to the clinical backgrounds, critical points in praxis, technical aspects and developments in the the field of adrenal venous sampling. The consideration of these important points in the clincal setting may make adrenal vein sampling studies sucessful and help to select patients that qualify for adrenalectomy. KEY POINTS: ⢠Selective adrenal venous sampling (AVS) currently continues to be the gold standard for localization diagnostics in patients with primary hyperaldosteronism. ⢠Comprehensive standardization of all preceding examinations and AVS is necessary to ensure high success rates. ⢠The method is supported by contrast-enhanced imaging for ensuring proper positioning of the catheter in the adrenal veins and the rapid cortisol assay. ⢠Knowledge of the anatomy and normal variants of the adrenal veins facilitates adrenal venous sampling.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico , Glándulas Suprarrenales/irrigación sanguínea , Recolección de Muestras de Sangre/métodos , Cateterismo/métodos , Radiología Intervencionista , Neoplasias de las Glándulas Suprarrenales/sangre , Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía , Recolección de Muestras de Sangre/instrumentación , Cateterismo/instrumentación , Síndrome de Cushing/sangre , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/cirugía , Diagnóstico Diferencial , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirugía , Hipertensión/sangre , Hipertensión/etiología , Neoplasias Primarias Múltiples/sangre , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/cirugía , Flebografía , Valor Predictivo de las Pruebas , Radiología Intervencionista/instrumentación , Tomografía Computarizada por Rayos XRESUMEN
HISTORY AND ADMISSION FINDINGS: A 38-year-old woman presented with strong headache, abdominal and chest pain. Blood pressure was 240/115 mmHg. In the emergency room lab troponin T was elevated. Further tests showed signs of hemolysis and thrombopenia. In addition kidney failure was present. INVESTIGATIONS: The ECG showed tachycardia, but no other changes. Echocardiography revealed hypertrophy of the left ventricle. In the eye exam hypertensive retinopathy was demonstrated. Kidney biopsy showed signs compatible with malignant hypertension. TREATMENT AND COURSE: Due to chest pain and elevation of troponin T acute coronary syndrome was diagnosed. In combination with thrombopenia and hemolysis a thrombotic microangiopathy was suspected. Because of the hypertensive emergency malignant hypertension became a possible differential diagnosis. Unfortunately antiplatelet treatment precluded kidney biopsy right at the beginning. Thus, plasmapheresis was initiated together with antihypertensive treatment. Kidney biopsy was done after plasma exchange and confirmed the diagnosis of malignant hypertension. CONCLUSION: Diagnosis of malignant hypertension can be difficult because symptoms of thrombotic microangiopathy are frequently present. In many cases only the combination of history, exams of endorgan damage and clinical course is needed to confirm the diagnosis. Prompt and sustained lowering of the blood pressure is pivotal. Even after successful treatment patients keep an elevated cardiovascular risk and need a close follow up.
Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Urgencias Médicas , Hipertensión Maligna/diagnóstico , Trombocitopenia/diagnóstico , Microangiopatías Trombóticas/diagnóstico , Adulto , Antihipertensivos/uso terapéutico , Biopsia , Terapia Combinada , Quimioterapia Combinada , Ecocardiografía , Electrocardiografía , Femenino , Humanos , Hipertensión Maligna/terapia , Hipertensión Renal/diagnóstico , Hipertensión Renal/patología , Riñón/patología , Nefritis/diagnóstico , Nefritis/patología , Nefroesclerosis/diagnóstico , Nefroesclerosis/terapia , Intercambio Plasmático , Plasmaféresis , Recuento de Plaquetas , Insuficiencia Renal/diagnóstico , Terapia de Reemplazo Renal , Trombocitopenia/terapia , Microangiopatías Trombóticas/terapia , Troponina T/sangreRESUMEN
Recent data suggests that chronic renal failure and hyperparathyroidism are associated with sympathetic overactivity. Since peptide hormones are known to modulate norepinephrine (NE) release by activating prejunctional receptors, this study investigates whether parathyroid hormone fragment (1-34) (hPTH(1-34)) increases neuronal NE release in human heart and kidney. Using specific PTH-receptor agonists and antagonists, this study furthermore highlights functional differences between PTH1 and PTH2 receptors. Human atrial and renal tissues were incubated with [(3)H]-NE and superfused. Three electrical stimulations (5Hz, 1min) induced a stable [(3)H]-NE release which was taken as an index of endogenous NE release. RT-PCR with specific primers for PTH1- and PTH2-receptor was performed in heart and kidney. hPTH(1-34) (0.01-0.1µmol/L) and a stable analog of its second messenger cAMP (8-bromo-cAMP) increased [(3)H]-NE release in human atria. This facilitatory effect of PTH was also observed in human renal cortex. The PTH1-receptor antagonist (D-Trp(12), Tyr(34))-pTH-(7-34) (0.5µmol/L) abolished the effect of hPTH(1-34). This data was verified using isolated perfused mouse kidneys. Tuberoinfundibular peptide of 39 residues (TIP-39) (0.1nmol/L-0.1µmol/L) decreased [(3)H]-NE release in atria. PTH1- and PTH2-receptor expressions were demonstrated in human heart and kidney. Moreover, a splice variant of the PTH2-receptor was detected in human kidney. In conclusion, PTH is able to facilitate NE release in human atria and renal cortex by activation of PTH1-receptors. The highly increased PTH levels that can be observed in chronic renal failure might be one contributor for the elevated sympathetic nerve activity and the associated cardiovascular mortality in patients with end stage renal disease.
Asunto(s)
Corazón/metabolismo , Riñón/metabolismo , Neuropéptidos/metabolismo , Norepinefrina/metabolismo , Hormona Paratiroidea/metabolismo , Fragmentos de Péptidos/metabolismo , Receptor de Hormona Paratiroídea Tipo 1/metabolismo , Receptor de Hormona Paratiroídea Tipo 2/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Células Cultivadas , Cocaína/administración & dosificación , Cocaína/farmacología , Corticosterona/administración & dosificación , Corticosterona/farmacología , Humanos , Fallo Renal Crónico/etiología , Ratones , Persona de Mediana Edad , Receptor de Hormona Paratiroídea Tipo 1/agonistas , Receptor de Hormona Paratiroídea Tipo 1/antagonistas & inhibidores , Receptor de Hormona Paratiroídea Tipo 1/genética , Receptor de Hormona Paratiroídea Tipo 2/agonistas , Receptor de Hormona Paratiroídea Tipo 2/antagonistas & inhibidores , Receptor de Hormona Paratiroídea Tipo 2/genética , Transmisión Sináptica/fisiologíaRESUMEN
BACKGROUND AND PURPOSE: ApolipoproteinE-deficient [apoE (-/-)] mice, a model of human atherosclerosis, develop endothelial dysfunction caused by decreased levels of nitric oxide (NO). The endogenous peptide, angiotensin-(1-7) [Ang-(1-7)], acting through its specific GPCR, the Mas receptor, has endothelium-dependent vasodilator properties. Here we have investigated if chronic treatment with Ang-(1-7) improved endothelial dysfunction in apoE (-/-) mice. EXPERIMENTAL APPROACH: ApoE (-/-) mice fed on a lipid-rich Western diet were divided into three groups and treated via osmotic minipumps with either saline, Ang-(1-7) (82 µg·kg(-1) ·h(-1) ) or the same dose of Ang-(1-7) together with D-Ala-Ang-(1-7) (125 µg·kg(-1) ·h(-1) ) for 6 weeks. Renal vascular function was assessed in isolated perfused kidneys. KEY RESULTS: Ang-(1-7)-treated apoE (-/-) mice showed improved renal endothelium-dependent vasorelaxation induced by carbachol and increased renal basal cGMP production, compared with untreated apoE (-/-) mice. Tempol, a reactive oxygen species (ROS) scavenger, improved endothelium-dependent vasorelaxation in kidneys of saline-treated apoE (-/-) mice whereas no effect was observed in Ang-(1-7)-treated mice. Chronic treatment with D-Ala-Ang-(1-7), a specific Mas receptor antagonist, abolished the beneficial effects of Ang-(1-7) on endothelium-dependent vasorelaxation. Renal endothelium-independent vasorelaxation showed no differences between treated and untreated mice. ROS production and expression levels of the NAD(P)H oxidase subunits gp91phox and p47phox were reduced in isolated preglomerular arterioles of Ang-(1-7)-treated mice, compared with untreated mice, whereas eNOS expression was increased. CONCLUSION AND IMPLICATIONS: Chronic infusion of Ang-(1-7) improved renal endothelial function via Mas receptors, in an experimental model of human cardiovascular disease, by increasing levels of endogenous NO.
Asunto(s)
Angiotensina I/uso terapéutico , Antihipertensivos/uso terapéutico , Apolipoproteínas E/deficiencia , Aterosclerosis/prevención & control , Endotelio Vascular/efectos de los fármacos , Riñón/efectos de los fármacos , Fragmentos de Péptidos/uso terapéutico , Angiotensina I/administración & dosificación , Angiotensina I/farmacología , Angiotensina II/administración & dosificación , Angiotensina II/análogos & derivados , Angiotensina II/farmacología , Angiotensina II/uso terapéutico , Animales , Antihipertensivos/administración & dosificación , Antihipertensivos/farmacología , Apolipoproteínas E/genética , Aterosclerosis/metabolismo , Aterosclerosis/fisiopatología , GMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Peróxido de Hidrógeno/metabolismo , Bombas de Infusión Implantables , Riñón/irrigación sanguínea , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Óxido Nítrico/metabolismo , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/farmacología , Perfusión , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Vasodilatación/efectos de los fármacosRESUMEN
BACKGROUND: Patients with hypertension often suffer from obstructive sleep apnea (OSA). In addition to hypertension several other risk factors (hypoxemia, hyperlipidemia, and increased sympathic nerve activity) may contribute to progressive renal dysfunction in OSA patients. The aim of this study was to compare renal function in OSA-patients with and without hypertension. METHODS: 81 consecutive patients (50 males, 31 females) were screened for sleep apnea. Parameters of renal function (serum creatinine, creatinine clearance, microalbuminuria), and of lipid and glucose metabolism were correlated to polysomnographic results. RESULTS: OSA (apnea/hypopnea index [AHI] > or = 5) was found in 57 of 81 patients. Mean AHI was 26.7 +/- 26.1. Hypertension (blood pressure > or = 140/90 mmHg or use of antihypertensive drugs) occurred in 63 of 81 patients. Serum creatinine in OSA patients was significantly higher than in patients without OSA (1.11 +/- 0.15 vs. 0.91 +/- 0.12 mg/dl, p < 0.001). Serum creatinine correlated significantly with AHI. Creatinine clearance was associated with age (r = -0.314; p = 0.014) and presence of OSA (r = 0.265; p = 0.093). No correlation was shown between hypertension and serum creatinine or creatinine clearance. Microalbuminuria was not associated with OSA. CONCLUSION: Our results suggest an independent association between OSA and impaired renal function. Further prospective studies will have to be done to elucidate the pathophysiological mechanisms.
Asunto(s)
Hipertensión/fisiopatología , Riñón/fisiopatología , Apnea Obstructiva del Sueño/fisiopatología , Adulto , Anciano , Albuminuria/diagnóstico , Creatinina/sangre , Creatinina/orina , Femenino , Humanos , Hipertensión/complicaciones , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Polisomnografía , Factores de Riesgo , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/complicacionesRESUMEN
Cleidocranial dysplasia (CCD) is a dominantly inherited disorder characterized by patent fontanelles, wide cranial sutures, hypoplasia of clavicles, short stature, supernumerary teeth, and other skeletal anomalies. We recently demonstrated that mutations in the transcription factor CBFA1, on chromosome 6p21, are associated with CCD. We have now analyzed the CBFA1 gene in 42 unrelated patients with CCD. In 18 patients, mutations were detected in the coding region of the CBFA1 gene, including 8 frameshift, 2 nonsense, and 9 missense mutations, as well as 2 novel polymorphisms. A cluster of missense mutations at arginine 225 (R225) identifies this residue as crucial for CBFA1 function. In vitro green fluorescent protein fusion studies show that R225 mutations interfere with nuclear accumulation of CBFA1 protein. There is no phenotypic difference between patients with deletions or frameshifts and those with other intragenic mutations, suggesting that CCD is generally caused by haploinsufficiency. However, we were able to extend the CCD phenotypic spectrum. A missense mutation identified in one family with supernumerary teeth and a radiologically normal skeleton indicates that mutations in CBFA1 can be associated exclusively with a dental phenotype. In addition, one patient with severe CCD and a frameshift mutation in codon 402 had osteoporosis leading to recurrent bone fractures and scoliosis, providing first evidence that CBFA1 may help maintain adult bone, in addition to its function in bone development.