RESUMEN
Copeptin is a 39-amino-acid long glycosylated peptide with a leucine-rich core segment in the C-terminal part of pre-pro-vasopressin. It exhibits a rapid response comparable to arginine vasopressin (AVP) in response to osmotic, hemodynamic, and nonspecific stress-related stimuli. This similarity can be attributed to equimolar production of copeptin alongside AVP. However, there are markedly different decay kinetics for both peptides, with an estimated initial half-life of copeptin being approximately two times longer than that of AVP. Like AVP, copeptin correlates strongly over a wide osmolality range in healthy individuals, making it a useful alternative to AVP measurement. While copeptin does not appear to be significantly affected by food intake, small amounts of oral fluid intake may result in a significant decrease in copeptin levels. Compared to AVP, copeptin is considerably more stable in vitro. An automated immunofluorescent assay is now available and has been used in recent landmark trials. However, separate validation studies are required before copeptin thresholds from these studies are applied to other assays. The biological variation of copeptin in presumably healthy subjects has been recently reported, which could assist in defining analytical performance specifications for this measurand. An established diagnostic utility of copeptin is in the investigation of polyuria-polydipsia syndrome and copeptin-based testing protocols have been explored in recent years. A single baseline plasma copeptin >21.4 pmol/L differentiates AVP resistance (formerly known as nephrogenic diabetes insipidus) from other causes with 100% sensitivity and specificity, rendering water deprivation testing unnecessary in such cases. In a recent study among adult patients with polyuria-polydipsia syndrome, AVP deficiency (formerly known as central diabetes insipidus) was more accurately diagnosed with hypertonic saline-stimulated copeptin than with arginine-stimulated copeptin. Glucagon-stimulated copeptin has been proposed as a potentially safe and precise test in the investigation of polyuria-polydipsia syndrome. Furthermore, copeptin could reliably identify those with AVP deficiency among patients with severe hypernatremia, though its diagnostic utility is reportedly limited in the differential diagnosis of profound hyponatremia. Copeptin measurement may be a useful tool for early goal-directed management of post-operative AVP deficiency. Additionally, the potential prognostic utility of copeptin has been explored in other diseases. There is an interest in examining the role of the AVP system (with copeptin as a marker) in the pathogenesis of insulin resistance and diabetes mellitus. Copeptin has been found to be independently associated with an increased risk of incident stroke and cardiovascular disease mortality in men with diabetes mellitus. Increased levels of copeptin have been reported to be independently predictive of a decline in estimated glomerular filtration rate and a greater risk of new-onset chronic kidney disease. Furthermore, copeptin is associated with disease severity in patients with autosomal dominant polycystic kidney disease. Copeptin predicts the development of coronary artery disease and cardiovascular mortality in the older population. Moreover, the predictive value of copeptin was found to be comparable with that of N-terminal pro-brain natriuretic peptide for all-cause mortality in patients with heart failure. Whether the measurement of copeptin in these conditions alters clinical management remains to be demonstrated in future studies.
RESUMEN
Monoclonal gammopathy (MG) is a spectrum of diseases ranging from the benign asymptomatic monoclonal gammopathy of undetermined significance to the malignant multiple myeloma. Clinical guidelines and laboratory recommendations have been developed to inform best practices in the diagnosis, monitoring, and management of MG. In this review, the pathophysiology, relevant laboratory testing recommended in clinical practice guidelines and laboratory recommendations related to MG testing and reporting are examined. The clinical guidelines recommend serum protein electrophoresis, serum immunofixation and serum free light chain measurement as initial screening. The laboratory recommendations omit serum immunofixation as it offers limited additional diagnostic value. The laboratory recommendations offer guidance on reporting findings beyond monoclonal protein, which was not required by the clinical guidelines. The clinical guidelines suggested monitoring total IgA concentration by turbidimetry or nephelometry method if the monoclonal protein migrates in the non-gamma region, whereas the laboratory recommendations make allowance for involved IgM and IgG. Additionally, several external quality assurance programs for MG protein electrophoresis and free light chain testing are also appraised. The external quality assurance programs show varied assessment criteria for protein electrophoresis reporting and unit of measurement. There is also significant disparity in reported monoclonal protein concentrations with wide inter-method analytical variation noted for both monoclonal protein quantification and serum free light chain measurement, however this variation appears smaller when the same method was used. Greater harmonization among laboratory recommendations and reporting format may improve clinical interpretation of MG testing.
Asunto(s)
Gammopatía Monoclonal de Relevancia Indeterminada , Paraproteinemias , Humanos , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Paraproteinemias/diagnóstico , Laboratorios , Cadenas Ligeras de InmunoglobulinaRESUMEN
OBJECTIVES: The ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate (TmP/GFR) is used to evaluate renal phosphate transport. TmP/GFR is most probably calculated using the formula described by Kenny and Glen or obtained from the nomogram described by Walton and Bijvoet. Even though the calculation itself is well described, no attention has been given to its measurement uncertainty (MU). The aim of this study is to provide a procedure for evaluating the MU of the Kenny and Glen formula; a procedure which is based on the Evaluation of measurement data - Guide to the expression of uncertainty in measurement (GUM). METHODS: TmP/GFR is a quantity value calculated from the input of measured values for serum (plasma) phosphate and creatinine, plus measured values of urine phosphate and creatinine. Given the measurement uncertainty associated with these input quantities, the GUM describes the mathematical procedures required to determine the uncertainty of the calculated TmP/GFR. From a medical laboratory perspective, these input uncertainties are the standard deviations of the respective internal quality control estimates for serum and urine phosphate, plus serum and urine creatinine. RESULTS: Based on representative measurements for the input quantities and their associated standard uncertainties, the expanded relative uncertainty for a calculated TmP/GFR is approximately 3.0-4.5â¯%. CONCLUSIONS: With the continued relevance of the TmP/GFR procedure and the use of creatinine clearance as an estimate of GFR, the addition of an uncertainty estimate is important as an adjunct to this diagnostic procedure.
Asunto(s)
Túbulos Renales , Fosfatos , Humanos , Creatinina , Incertidumbre , Tasa de Filtración GlomerularRESUMEN
BACKGROUND: Early recognition of severe COVID-19 is essential for timely patient triage. AIMS: To report clinical and laboratory findings and patient outcomes at a tertiary hospital in Melbourne, Australia. METHODS: This is a retrospective study of adult inpatients with COVID-19 admitted to Northern Health from March to September 2020. Data were extracted from electronic medical records. RESULTS: Key admission data were available for 182 patients (median age 67.0 years (interquartile range, 47.9-83.1); 51.1% female). Fifty-six (30.8%) were from residential care. One hundred and seventeen (64.3%) patients were assigned Goals of Patient Care (GOPC) A or B and 65 (35.7%) GOPC C or D. Comorbidities were present in 135 patients (74.2%). 63.2% of patients received antibiotics, 6.6% had antivirals, 45.6% received systemic glucocorticoid and 3.3% had tocilizumab. Fifty-six (30.8%) developed clinical deterioration (24 requiring ventilation, 21 receiving critical care, 34 died). Overall, inhospital clinical deterioration was significantly associated with older age (P < 0.001), history of diabetes (P = 0.038), lower lymphocyte count (P = 0.002) and platelet count (P = 0.004), higher neutrophil-to-lymphocyte ratio (P = 0.002), elevated fibrinogen (P = 0.004), higher serum ferritin (P = 0.027) and C-reactive protein (CRP; P = 0.002). The accuracy of the 4C Deterioration model was moderate, with an area under the curve (AUC) of 0.79 (95% confidence interval (CI), 0.68-0.90) compared with an AUC of 0.77 (95% CI, 0.76-0.78) in the original validation cohort. CONCLUSIONS: In the present study, high neutrophil-to-lymphocyte ratio, abnormal d-dimer, high serum CRP and ferritin appear to be useful prognostic markers.
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COVID-19 , Deterioro Clínico , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Proteína C-Reactiva/metabolismo , Femenino , Ferritinas , Mortalidad Hospitalaria , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2 , Centros de Atención TerciariaRESUMEN
OBJECTIVE: Current Endocrine Society Clinical Practice Guidelines use a specific aldosterone/renin ratio (ARR) threshold to screen for primary aldosteronism (a treatable disease causing up to 15% of hypertension in primary care) in all patients. We sought to characterize demographic variations in the ARR, hypothesizing a need for age- and sex-specific reference ranges to improve the accuracy of the test. DESIGN: Retrospective cross-sectional analysis of ARR measurements at a single tertiary hospital from December 2016 to June 2018. PATIENTS: A total of 442 patients with clinically indicated ARR were included, after excluding those who were on spironolactone or the oral contraceptive pill, were pregnant or had an existing adrenal condition. MEASUREMENTS: Aldosterone, renin and the ARR. RESULTS: Among those aged 20-39 years (n = 74), females had significantly higher median aldosterone (369 vs 244 pmol/L, P = .028), lower median renin (17.0 vs 27.6 mIU/L, P = .034) and higher median ARR (20.7 vs 10.3 (pmol/L)/(mIU/L), P = .001) than males, despite having lower systolic (135 vs 145 mmHg, P = .021) and diastolic (89 vs 96.5 mmHg, P = .007) blood pressure. The ≥ 60-year age group (n = 157) also had significant sex differences in the ARR. With increasing age (20-39 vs ≥ 60 years), there was a significant fall in plasma aldosterone in females (369 pmol/L vs 264 pmol/L, P = .005), with no change observed in males. CONCLUSIONS: For those 20-39 years old, aldosterone and the ARR are significantly higher in females despite a lower systolic and diastolic BP, highlighting the potential for false-positive results. Our findings indicate the need for prospective studies with a control population to define age- and sex-specific ARR reference ranges.
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Hiperaldosteronismo , Hipertensión , Aldosterona , Estudios Transversales , Femenino , Humanos , Hiperaldosteronismo/diagnóstico , Recién Nacido , Masculino , Estudios Prospectivos , Valores de Referencia , Renina , Estudios RetrospectivosRESUMEN
BACKGROUND: Adrenal vein sampling (AVS) is crucial for accurate lateralization of aldosterone excess but it is technically challenging due to the difficulty of adrenal vein cannulation. The use of adrenocorticotropic hormone (ACTH) to improve cannulation success is controversial and can lead to discordant lateralization outcomes. OBJECTIVE: To evaluate the utility of ACTH in two centres with different levels of AVS expertise and formulate a strategy for interpreting discordant results. DESIGN: A retrospective cross-sectional analysis of AVS results and postoperative patient outcomes. SETTING: Two large tertiary hospitals with harmonized AVS protocols where adrenal venous samples are collected both before and after ACTH stimulation. MEASUREMENTS: Cannulation success (measured by selectivity index, SI), lateralization (measured by lateralization index, LI) and postoperative biochemical cure. RESULTS: Number of AVS procedures judged to have successful bilateral adrenal vein cannulation increased from 53% pre- to 73% post-ACTH. The increase in cannulation success was significantly higher in centre where AVS was performed by multiple radiologists with a lower basal success rate. In both centres, the proportion of cases deemed to display lateralization significantly decreased with the use of ACTH (70% pre- to 52% post-ACTH). Based on postoperative outcomes of patients with discordant results who underwent unilateral adrenalectomy, the combination of LI >3 pre-ACTH and LI >2 post-ACTH was predictive of a biochemical cure. CONCLUSION: Adrenocorticotropic hormone can increase the rate of cannulation success during AVS at the expense of reduced lateralization. The criteria for lateralization should be carefully determined based on local data when ACTH is used.
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Hormona Adrenocorticotrópica , Hiperaldosteronismo , Glándulas Suprarrenales , Aldosterona , Estudios Transversales , Humanos , Estudios RetrospectivosRESUMEN
Gonadal hormones impact bone health and higher values of sex hormone-binding globulin (SHBG) have been independently associated with fracture risk in men without chronic kidney disease. People with chronic kidney disease have a greatly increased fracture risk, and gonadal dysfunction is common in men receiving dialysis treatment. Nevertheless, in these men the effect of gonadal steroids and SHBG on bone mineral density (BMD) and fracture risk is unknown. Here we investigate relationships between gonadal steroids, SHBG, BMD and fracture in men on long-term dialysis therapy, awaiting kidney or simultaneous pancreas kidney transplantation. Results of serum biochemistry, SHBG, gonadal steroids (total testosterone, calculated free testosterone and estradiol), BMD by dual-energy X-ray absorptiometry and thoracolumbar X-rays were obtained. Multivariable regression models were used to examine associations between SHBG, gonadal steroids, BMD and fracture of 321 men with a mean age of 47 years. Diabetes mellitus was present in 45% and their median dialysis vintage was 24 months. Prior fractures occurred in 42%, 18% had vertebral fracture on lateral spine X-ray, 17% had non-vertebral fragility fracture within 10 years and 7% had both. After adjustment for age, body mass index and dialysis vintage, higher SHBG levels were significantly associated with nonvertebral fractures [odds ratio 1.81 (1.30-2.53)] and remained significant after adjustment for BMD. Calculated free testosterone and estradiol values were not associated with fracture. Prevalent fracture rates were high in relatively young men on dialysis awaiting transplantation. Thus, SHBG is a novel biomarker associated with fracture, which warrants investigation in prospective studies.
Asunto(s)
Fracturas Óseas/diagnóstico , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/terapia , Globulina de Unión a Hormona Sexual/análisis , Absorciometría de Fotón , Adulto , Factores de Edad , Biomarcadores/sangre , Densidad Ósea , Estudios de Cohortes , Fracturas Óseas/sangre , Fracturas Óseas/epidemiología , Hormonas Esteroides Gonadales/sangre , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Insuficiencia Renal Crónica/sangreRESUMEN
BACKGROUND: The saline suppression test (SST) serves to confirm the diagnosis of primary aldosteronism (PA) whilst adrenal vein sampling (AVS) is used to determine whether the aldosterone hypersecretion is unilateral or bilateral. An accurate prediction of bilateral PA based on SST results could reduce the need for AVS. AIM: We sought to identify SST parameters that reliably predict bilateral PA. METHODS: The results from 121 patients undergoing SSTs at Monash Health from January 2010 to January 2018 including screening blood tests, imaging, AVS and histopathology results were evaluated. Patients were subtyped into unilateral or bilateral PA based on AVS and surgical outcomes. RESULTS: Of 113 patients with confirmed PA, 33 had unilateral disease whilst 42 had bilateral disease. In those with bilateral disease, plasma aldosterone concentration (PAC) was significantly lower post-SST, together with a significant fall in the aldosterone-renin ratio (ARR). The combination of PAC < 300 pmol/L and a reduction in ARR post-SST provided 96.8% specificity in predicting bilateral disease. Eighteen of 39 patients (49%) with bilateral PA could have avoided AVS using these criteria. CONCLUSION: A combination of PAC < 300 pmol/L and a lower ARR post-SST could reliably predict bilateral PA. An independent cohort will be needed to validate these findings.
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Hiperaldosteronismo/sangre , Solución Salina/uso terapéutico , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/patología , Adulto , Aldosterona/sangre , Recolección de Muestras de Sangre , Femenino , Humanos , Hiperaldosteronismo/terapia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Renina/sangreAsunto(s)
Aplicaciones Móviles , Poliuria , Humanos , Poliuria/diagnóstico , Polidipsia/diagnóstico , Diagnóstico Diferencial , SíndromeRESUMEN
PURPOSE: Increased fracture rates are observed in renal transplant recipients (RTRs) compared with the general population. Risk factors include age, diabetes, dialysis vintage, immunosuppression and mineral and bone disorders.1 Low serum phosphorus levels occur post-transplantation; however, its relationship with fracture risk has not been evaluated. The purpose of this study was to evaluate risk factors for fracture in RTRs at a single tertiary referral centre. METHODS: A retrospective cross-sectional analysis of 146 patients (75 M, 71 F) who had been referred for dual energy X-ray densitometry (DXA) post-renal transplantation was performed. Aetiology of end stage kidney disease (ESKD), duration of dialysis, parathyroidectomy history, immunosuppression regimen, bone mineral density (BMD), biochemistry and fractures were documented. Statistical analyses included univariable and multivariable regression. RESULTS: The mean age of patients was 54 years and mean time post-transplantation 6.7 years. A total of 79 fractures occurred in 52 patients (35%), with 40 fractures occurring post-transplantation. Ankle/foot fractures were most common (48%). Lower serum phosphorus levels and declining femoral neck (FN) T-score and were associated with fractures in both univariable and multivariable regression analyses after adjusting for age, gender, weight, estimated glomerular filtration rate and pre-transplant history of fracture (P=.011 and P=.042 respectively). The relationship between serum phosphorus and fracture remained significant independent of FN T-score, parathyroid hormone levels, parathyroidectomy status and prednisolone use. CONCLUSION: Fracture was common post-renal transplantation. Lower serum phosphorus levels and declining FN T-scores were associated with fractures. The mechanism of this previously unreported observation requires further evaluation in prospective studies.
Asunto(s)
Fracturas Óseas/etiología , Trasplante de Riñón/efectos adversos , Fósforo/sangre , Adulto , Anciano , Estudios Transversales , Femenino , Cuello Femoral/patología , Traumatismos de los Pies , Humanos , Masculino , Menopausia , Persona de Mediana Edad , Fracturas Osteoporóticas , Estudios Retrospectivos , Factores de RiesgoAsunto(s)
Hiperaldosteronismo , Hipertensión , Diagnóstico Precoz , Humanos , Hiperaldosteronismo/diagnósticoRESUMEN
BACKGROUND: Plasma copeptin measurement is useful for the differential diagnoses of polyuria-polydipsia syndrome. It has also been proposed as a prognostic marker for cardiovascular diseases. However, limited information is available about the within- (CVI) and between-subject (CVG) biological variation (BV). This study presents BV estimates for copeptin in healthy individuals. METHODS: Samples were collected weekly from 41 healthy subjects over 5 weeks and analyzed using the BRAHMS Copeptin proAVP KRYPTOR assay after at least 8â h of food and fluid abstinence. Outlier detection, variance homogeneity, and trend analysis were performed followed by CV-ANOVA for BV and analytical variation (CVA) estimation with 95% confidence intervals. Reference change values (RCVs), index of individuality (II), and analytical performance specification (APS) were also calculated. RESULTS: The analysis included 178 results from 20 males and 202 values from 21 females. Copeptin concentrations were significantly higher in males than in females (mean 8.5 vs 5.2â pmol/L, P < 0.0001). CVI estimates were 18.0% (95% CI, 15.4%-21.6%) and 19.0% (95% CI, 16.4%-22.6%), for males and females, respectively; RCVs were -35% (decreasing value) and 54% (increasing value). There was marked individuality for copeptin. No result exceeded the diagnostic threshold (>21.4â pmol/L) for arginine vasopressin resistance. CONCLUSIONS: The availability of BV data allows for refined APS and associated II, and RCVs applicable as aids in the serial monitoring of patients with specific diseases such as heart failure. The BV estimates are only applicable in subjects who abstained from oral intake due to the rapid and marked effects of fluids on copeptin physiology.