Placental Growth Factor in Patients with Decreased Renal Function

Background: Patients with decreased renal function are characterized by high cardiovascular morbidity and mortality due to complications of premature atherosclerosis. Placental growth factor (PlGF) is a proatherogenic cytokine and new biomarker of cardiovascular events. The aim of this study was to determine PlGF levels and describe their relationship to renal function and risk factors of atherogenesis in patients with decreased renal function. Methods: The study group consisted of 114 subjects: 45 patients with various degrees of decreased renal function (CHRI), 31 long-term hemodialysis (HD) patients, and 38 age-matched healthy control subjects. PlGF was assessed immunochemically (enzyme-linked immunosorbent assay) and routine biochemical parameters were measured using standard laboratory methods. Results: PlGF levels were significantly increased in CHRI and HD patients compared to controls (10.5 ± 3.3 pg/mL in CHRI patients and 11.5 ± 3.4 pg/mL HD patients vs. 8.1 ± 1.8 pg/mL in controls, both p < 0.0001). In CHRI patients, PlGF was detectable in the urine, and its urine concentration correlated with its serum levels. In HD patients, PlGF correlated with low-density lipoproteins (r?=?0.36, p < 0.05), but was not related to C-reactive protein levels. Higher levels of PlGF were found in CHRI patients with cardiovascular disease, compared with those free of such complication. Conclusions: PlGF levels are increased in patients with decreased kidney function. PlGF is detectable in the urine, and serum and urine levels of PlGF are significantly interrelated. It is higher in CHRI patients with cardiovascular disease. Further studies are required to demonstrate the usefulness and significance of PlGF in patients with chronic kidney disease.     

Beta2-Microglobulin and Alpha1-Microglobulin as Markers of Balkan Endemic Nephropathy,a Worldwide Disease

Background:?Urine beta2-microglobulin (beta2-MG) was mainly used as a tubular marker of Balkan endemic nephropathy (BEN) but recently alpha1-microglobulin (alpha1-MG) was proposed for the diagnosis of BEN. In this study, the potential of urine beta2-MG, alpha1-MG, albumin, and total protein in the differentiation of BEN from healthy persons and patients with glomerulonephritis (GN) and nephrosclerosis (NS) was examined.?Methods:?This study involved 47 patients with BEN, 36 with GN, 11 with NS, 30 healthy subjects from BEN families, and 46 healthy subjects from non-BEN families.?Results:?In BEN patients area under the curve (AUC) for urine beta2-MG (0.828) and alpha1-MG (0.782) was higher than for urine albumin (0.740), but in GN patients AUC for urine protein (0.854) and albumin (0.872) was significantly higher than for the two low molecular weight proteins. AUC for all four urinary markers in NS patients was significantly lower than in BEN patients, ranging between 500 and 595. Median urine beta2-MG excretion in BEN patients was 17.5 times higher than in GN patients and 18.3 times higher than in controls; median alpha1-MG excretion was higher only 3.0 and 2.25 times, respectively. In the differentiation of BEN from healthy controls, beta2-MG had higher sensitivity and specificity at the cutoff levels (p < 0.001) than alpha1-MG (p < 0.05). In the differentiation of BEN from GN, beta2-MG was the best marker.?Conclusion:?All four urinary markers can be used for the differential diagnosis of BEN, beta2-MG being the best. Like in aristolochic acid nephropathy, beta2-MG seems to be an early marker of tubular damage in BEN.     

Evaluation of Criteria for the Diagnosis of Balkan Endemic Nephropathy

Background. The diagnosis of Balkan endemic nephropathy (BEN) is often made using Danilovic's criteria. The aim of this study was to determine the prevalence, sensitivity, specificity, and predictive value of Danilovic's criteria and several additional indices. Methods. The study included 19 BEN patients, 23 BEN-suspected patients, 34 patients with other kidney diseases, and 23 healthy controls. The sensitivity and specificity of Danilovic's criteria was calculated, and these criteria, in addition to age, sex, blood pressure, creatinine clearance, glucosuria, urine osmolality, alkaline phosphatase, alpha 1-microglobulin, fractional sodium excretion, tubular phosphate reabsorption, kidney length, and volume, were combined in a logistic regression. Results. All examined persons were from a BEN-affected village (criterion 1), and all BEN, BEN-suspected patients, and 12/23 healthy controls were from BEN families (criterion 2). None of the remaining Danilovic's criteria was found in the healthy controls. The prevalence of proteinuria, low specific gravity, and anemia (criteria 3–5) differed insignificantly among the patient groups. Azotemia and shrunken kidney (criteria 6 and 7) were significantly more frequent in BEN than in other patients. Only proteinuria showed high sensitivity and specificity in differentiating BEN and BEN-suspected patients from healthy persons, but no criteria differentiated BEN or BEN-suspected from other kidney diseases. Proteinuria is a significant predictor of both BEN and BEN-suspected vs. healthy persons, and alpha 1-microglobulinuria is a significant predictor of BEN vs. other kidney diseases. Conclusion. Danilovic's criteria enabled a diagnosis of BEN only in chronic renal failure and differential diagnosis between BEN and healthy persons but not between BEN and other kidney diseases. Out of the examined indices of proximal tubular disorders, only alpha 1-microglobulinuria significantly discriminated BEN from other kidney diseases.     

Cytokines and adhesion molecules in renal vasculitis and lupus nephritis

Background: Plasma levels of some pro-inflammatory cytokines and soluble adhesion molecules have been suggested to be useful parameters to assess the activity of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis and lupus nephritis. We hypothesized that the renal activity of these diseases is better reflected by the urinary excretion and fractional excretion of these molecules. Methods: Plasma levels and urinary excretion of tumour necrosis factor-&agr; (TNF-&agr;), interleukin (IL)-6, IL-8, and the soluble cell adhesion molecules sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 15 patients with ANCA-positive renal vasculitis (eight active, ANCA-A; six in remission, ANCA-R), six patients with active lupus nephritis (LN), 15 patients with IgA nephropathy (IgAN) and nine healthy subjects. Fractional excretion of selected cytokines and adhesion molecules was also calculated. Results: Patients with ANCA-A had increased urinary excretion and fractional excretion of TNF-&agr; (9.27±3.19% vs 0.58±0.02%, P<0.01), IL-6 (120.79±65.83% vs 1.89±0.34%, P<0.01) and increased fractional excretion of IL-8 (23.34±6.38% vs 2.56±1.07%, P<0.01) and sVCAM-1 (0.81±0.33% vs 0.03±0.02%, P<0.01) compared with controls. Urinary excretion of TNF-&agr; and IL-6 and fractional excretion of TNF-&agr;, IL-6 and IL-8 were higher in ANCA-A than in ANCA-R. Patients with LN had increased plasma TNF-&agr; (20.52±2.01 pg/ml vs 12.33±0.23 pg/ml, P<0.05) and sVCAM-1 (1537.88±276.36 ng/ml vs 692.26±44.42 ng/ml, P<0.05) and increased urinary excretion of TNF-&agr; (2.81±0.51 &mgr;g/mol creat vs 0.98±0.05 &mgr;g/mol creat, P<0.01), IL-8 (35.78±14.03 &mgr;g/mol creat vs 12.46±5.19 &mgr;g/mol creat, P<0.05) and sVCAM-1 (48.98±20.20 &mgr;g/mol creat vs 2.92±1.35 &mgr;g/mol creat, P<0.01) compared with controls. Patients with IgAN had, in comparison with controls only increased plasma TNF-&agr; (18.10±0.57 pg/ml vs 12.33±0.23 pg/ml, P<0.05). Conclusions: Urinary excretion and fractional excretion, but not plasma levels of selected proinflammatory cytokines (TNF-&agr;, IL-6 and IL-8) were increased in patients with active ANCA-positive renal vasculitis, but not in ANCA positive vasculitis in remission. These parameters may be useful to monitor the activity of this disease.     

Renal tubular dysfunction in fetal alcohol syndrome

Renal function was evaluated in six patients with fetal alcohol syndrome (FAS) and eight control subjects before and after fluid restriction and acute acid loading. Baseline serum electrolytes, creatinine clearance, fractional sodium excretion, tubular reabsorption of phosphate, urine and blood pH and osmolalities, plasma renin activity, and plasma aldosterone level were normal in all subjects, but fractional potassium excretion (FE_K) was lower in FAS patients than in control subjects (P<0.001). Despita equivalent plasma osmolalities (295±3 vs 293±2 mosmol/kg,P=0.2), the maximum urinary osmolality after 12 h of water deprivation in patients with FAS was significantly lower compared with controls (560±107 vs 965±77 mosmol/kg;P<0.001) and increased to only 578±101 mosmol/kg after vasopressin administration. After ammonium chloride loading, minimum urine pH was significantly higher in patients than in controls (5.7±0.17 vs 4.81±0.19;P<0.001). Net acid excretion and FE_K were also lower in patients than in controls (102±11 vs 139.6±11.3 Eq/min per 1.73 m² and 23.5±1.3 vs 29±1.6%, respectively;P<0.001). The data indicate a subclinical renal tubular defect in urine concentration and acidification in patients with FAS.     

Urinary excretion of endothelin-1 in children with absorptive idiopathic hypercalciuria

Urinary excretion of endothelin-1 (ET-1) and plasma ET-1 were measured in 21 children with absorptive idiopathic hypercalciuria (AIH) and 22 controls. The absorptive type of idiopathic hypercalciuria was determined by a calcium loading test. Daily urinary excretion of ET-1 and urinary ET-1/creatinine ratio were significantly increased (P=0.005 and P=0.007, respectively) in patients with AIH (9,274±6,444 pg/24 h and 14.04±9.52 pg/mg, respectively) compared with controls (4,699±2,120 pg/24 h and 7.36±4.71 pg/mg, respectively). Plasma ET-1 levels were significantly lower in patients with AIH (0.84±0.64 pg/ml) than in controls (1.54±0.54 pg/ml, P=0.0001). In conclusion, patients with AIH had increased urinary ET-1 excretion and decreased plasma ET-1 levels. This is most likely due to the decreased reabsorption of ET-1 in the renal tubule and increased renal production.     

Role of B-type natriuretic peptide as a marker of mortality in acute kidney injury patients treated with continuous renal replacement therapy

Abstract

Objectives: Acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) is associated with poor outcome. Plasma B-type natriuretic peptide (BNP) is a biomarker related to fluid volume overload, and is elevated in AKI patients. The purpose of the study was to assess whether BNP levels at the time of starting CRRT could be used as a predictor of mortality in patients with AKI receiving CRRT. Methods: We conducted a prospective observational cohort study enrolling 149 patients with AKI receiving CRRT. The primary outcome was mortality during CRRT. Results: The median BNP level of 84 (56.3%) patients who expired was significantly higher than that of those who survived (1812.5 vs. 475.0?pg/mL; p?=?0.01). Receiver operating characteristic curves demonstrated BNP levels as a predictor of mortality during CRRT with an area under the curve of 0.77 (p?=?0.000), and the optimal threshold for BNP was 1054?pg/mL. Patients with BNP levels above 1054?pg/mL had a significantly higher mortality (76.6 vs. 34.7%; p?=?0.01). Conclusion: Elevated BNP level is associated with mortality in patients with AKI receiving CRRT.     

Fibroblast growth factor-23 is a strong predictor of insulin resistance among chronic kidney disease patients

Insulin resistance (IR) is very common among chronic kidney disease (CKD) patients. Disturbance in mineral and bone metabolism (MBD) seems to play a role in the pathogenesis of insulin resistance. Fibroblast growth factor-23 (FGF23) is evolving as the most important link between MBD and many pathologic sequences of CKD. The aim was to evaluate IR in pre-dialysis CKD patients looking for a possible association to mineral metabolism among CKD patients. A total of 100 stage 3–5 CKD patients were selected beside 20 normal control subjects. Homeostatic model assessment of insulin resistance (HOMA-IR) was used to assess IR in selected cases. Both groups were compared for fasting blood glucose (FBG), fasting blood insulin (FBI), HOMA-IR, estimated glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), 25 hydroxy vitamin D (25 OH vit D), parathormone (PTH), and uric acid (UA). Correlation study between HOMA_IR and different studied parameters was performed. HOMA-IR is significantly higher in CKD (8.87?±?3.48 vs. 3.97?±?0.34 in CKD vs. control, respectively, p?p?p?p?p?p?p?相似文献   

Decreased nocturnal urinary antidiuretic hormone excretion in enuresis is increased by imipramine

OBJECTIVE: To assess the role of integrated nocturnal antidiuretic hormone (ADH) secretion in children with enuresis, and possible modifications induced by treatment with imipramine. PATIENTS AND METHODS: The morning plasma ADH and nocturnal urinary ADH integrated concentrations were measured in 18 consecutive enuretic children (patients) and 21 age- and sex-matched controls admitted for minor treatment. Diurnal and nocturnal urine production, and plasma and urinary osmolality were also determined; lumbosacral radiography and uroflowmetry were undertaken in the patients. The assessments were repeated after 14 days of treatment with imipramine hydrochloride (orally, 20 mg/night). RESULTS: Half the patients had occult spinal malformations but the uroflowmetry results were all within the normal range. The median (95% confidence interval, CI) urinary ADH integrated concentrations were markedly lower in patients, at 29.7 (22.1-37.3) vs 63.0 (35.1-90.8) pg/mL/h (P = 0.03) than in controls. Plasma ADH levels were significantly increased by imipramine (0.64 to 1.47 pg/mL, 95% CI, 0.40-0.89 vs -0.26-3.2; P < 0.001), as were nocturnal urinary ADH integrated concentrations, at 29.7 (22.1-37.3) vs 59.0 (37.3-80.6) pg/mL/h (P < 0.001), and morning plasma osmolality decreased, from 298.5 (294.5-302.5) to 294.9 (292.4-297.3) mosmol/kg (P = 0.003), as was the 24-h fluid intake, from 983 (721-1245) to 666 (435-897) mL (P = 0.004). CONCLUSIONS: We conclude that enuretic children have a lower nocturnal ADH excretion; imipramine restores nocturnal ADH excretion, increases morning plasma ADH levels, and causes consistent changes in other biochemical variables.     

The prevalence of metabolic syndrome is increased in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Purpose

Cardiovascular disease is one of the major causes of mortality in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Metabolic syndrome (MetS) is associated with increased cardiovascular risk in the normal population. However, MetS in AAV has not been adequately investigated. We aimed to determine MetS prevalence and associated factors in AAV patients.

Methods

Thirty-seven AAV patients and 42 healthy controls were enrolled. MetS was determined by International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria. The relationship between clinical features of AAV and MetS was also investigated.

Results

MetS was significantly higher in AAV patients than controls by NCEP-ATPIII (51.4% vs. 26.2%, p 0.022) and IDF (62.2% vs. 35.7%, p 0.020). When AAV patients with MetS were compared to those without, there were significant differences in age, CRP, GFR and NT-pro-BNP. Age [58 (13) vs. 50 (8) years p: 0.028], CRP [4.0 (3.6) vs. 3.2 (1.0) mg/l, p 0.021] and NT-pro-BNP [173.5 (343.7) vs. 106.0 (103.0) pg/ml, p 0.013] were significantly higher in AAV patients with MetS than those without; GFR was significantly lower [38 (46) vs. 83 (51) ml/min/1.73 m², p 0.004]. ROC curve analysis showed NT-pro-BNP?>?58.0 ng/ml predicted MetS with 87.1% sensitivity and 46.7% specificity (Area under curve: 0.71, CI 0.536–0.902, p 0.041). Multivariate analysis revealed age [OR (95% CI): 1.180 (1.010–1.370), p 0.039] and NT-pro-BNP?>?58 pg/ml [OR (95% CI): 5.5 (1.02–30.1) p 0.047] were independent predictors of MetS in AAV patients.

Conclusion

MetS is significantly higher in AAV patients than controls and is associated with age and NT-pro-BNP. Screening and treating MetS may improve prognosis in AAV patients.

     

Bacteremia in solid organ transplant recipients as compared to immunocompetent patients: Acute phase cytokines and outcomes in a prospective,matched cohort study

We undertook a prospective, matched cohort study of patients with Staphylococcus aureus bacteremia (SAB) and gram-negative bacteremia (GNB) to compare the characteristics, outcomes, and chemokine and cytokine response in transplant recipients to immunocompetent, nontransplant recipients. Fifty-five transplant recipients (GNB n = 29; SAB n = 26) and 225 nontransplant recipients (GNB n = 114; SAB n = 111) were included for clinical analysis. Transplant GNB had a significantly lower incidence of septic shock than nontransplant GNB (10.3% vs 30.7%, p = .03). Thirty-day mortality did not differ significantly between transplant and nontransplant recipients with GNB (10.3% vs 15.8%, p = .57) or SAB (0.0% vs 11.7%, p = .13). Next, transplant patients were matched 1:1 with nontransplant patients for the chemokine and cytokine analysis. Five cytokines and chemokines were significantly lower in transplant GNB vs nontransplant GNB: IL-2 (median [IQR]: 7.1 pg/ml [7.1, 7.1] vs 32.6 pg/ml [7.1, 88.0]; p = .001), MIP-1β (30.7 pg/ml [30.7, 30.7] vs 243.3 pg/ml [30.7, 344.4]; p = .001), IL-8 (32.0 pg/ml [5.6, 53.1] vs 59.1 pg/ml [39.2, 119.4]; p = .003), IL-15 (12.0 pg/ml [12.0, 12.0] vs 12.0 pg/ml [12.0, 126.7]; p = .03), and IFN-α (5.1 pg/mL [5.1, 5.1] vs 5.1 pg/ml [5.1, 26.3]; p = .04). Regulated upon Activation, Normal T Cell Expressed and Secreted (RANTES) was higher in transplant SAB vs nontransplant SAB (mean [SD]: 750.2 pg/ml [194.6] vs 656.5 pg/ml [147.6]; p = .046).     

Cardiac function and aminoterminal pro-brain natriuretic peptide levels in liver-transplanted cirrhotic patients

Bernal V, Pascual I, Lanas A, Esquivias P, Piazuelo E, Garcia‐Gil FA, Lacambra I, Simon MA. Cardiac function and aminoterminal pro‐brain natriuretic peptide levels in liver‐transplanted cirrhotic patients.
Clin Transplant 2012: 26: 111–116.
© 2011 John Wiley & Sons A/S. Abstract: Background: Cirrhosis is associated with structural and functional abnormalities of the heart. We examined the evolution of these abnormalities after liver transplantation (LT). Methods: Sixty cirrhotic patients, without cardiovascular disease, were included. Clinical data, echocardiography, and aminoterminal pro‐brain natriuretic peptide (NT‐proBNP) levels were analyzed before and after transplantation. Healthy controls (n = 25) were included for reference. Results: Before transplantation, cirrhotic patients had higher left atrium diameter, left ventricular (LV) mass index, and ejection fraction than controls. After transplantation, LV mass index increased (105 ± 31 vs. 119 ± 35 g/m²; p < 0.05), diastolic cardiac function deteriorated, expressed as a reduction in E/A wave ratio (1.105 ± 0.295 vs. 0.798 ± 0.248; p < 0.001), and NT‐proBNP levels decreased significantly in patients compared to pre‐transplantation values (1759 ± 1154 vs. 1117 ± 600 pg/mL; p < 0.001), although they were still above levels found in controls (1117 ± 600 vs. 856 ± 123 pg/mL; p < 0.05). NT‐proBNP levels above 2000 pg/mL before transplantation were significantly associated with risk for cardiovascular events after procedure (37% vs. 9%, p = 0.008). Conclusions: In cirrhotic patients, diastolic function and cardiac structure deteriorate after LT. Compared to controls, NT‐proBNP levels tend to be higher before and after transplantation. The mechanisms and consequences of these results require further study.     

Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm

Non-dipping circadian blood pressure (BP) is a common finding in preeclampsia, accompanied by adverse outcomes. Melatonin plays pivotal role in biological circadian rhythms. This study investigated the relationship between melatonin secretion and circadian BP rhythm in preeclampsia. Cases were women with preeclampsia treated between January 2006 and June 2007 in the University Hospital of Larissa. Volunteers with normal pregnancy, matched for chronological and gestational age, served as controls. Twenty-four hour ambulatory BP monitoring was applied. Serum melatonin and urine 6-sulfatoxymelatonin levels were determined in day and night time samples by enzyme-linked immunoassays. Measurements were repeated 2 months after delivery. Thirty-one women with preeclampsia and 20 controls were included. Twenty-one of the 31 women with preeclampsia were non-dippers. Compared to normal pregnancy, in preeclampsia there were significantly lower night time melatonin (48.4?±?24.7 vs. 85.4?±?26.9?pg/mL, p?0.001) levels. Adjustment for circadian BP rhythm status ascribed this finding exclusively to non-dippers (p?0.01). Two months after delivery, in 11 of the 21 non-dippers both circadian BP and melatonin secretion rhythm reappeared. In contrast, in cases with retained non-dipping status (n?=?10) melatonin secretion rhythm remained impaired: daytime versus night time melatonin (33.5?±?13.0 vs. 28.0?±?13.8?pg/mL, p?=?0.386). Urinary 6-sulfatoxymelatonin levels were, overall, similar to serum melatonin. Circadian BP and melatonin secretion rhythm follow parallel course in preeclampsia, both during pregnancy and, at least 2 months after delivery. Our findings may be not sufficient to implicate a putative therapeutic effect of melatonin, however, they clearly emphasize that its involvement in the pathogenesis of a non-dipping BP in preeclampsia needs intensive further investigation.     

胎盘生长因子在冠状动脉血运重建中的意义

目的 探讨胎盘生长因子(placental growth factor, PlGF)在冠状动脉血运重建中的意义.方法 2006年5月-2007年3月,对61例以胸痛为主要表现的患者行冠状动脉造影检查,记录Gensini冠脉病变积分.其中男53例,女8例;平均年龄61岁.对冠脉病变严重的26例患者行经皮经腔冠状动脉成型术(percutaneous transluminal coronary angioplasty, PTCA)及支架置入术,术后观察不良心血管事件发生情况.另取28例健康志愿者作为对照组,所有观察对象均抽静脉血测定血浆PlGF水平.结果 根据冠状动脉造影结果,胸痛患者可分为冠心病组(n=45)与非冠心病组(n=16).冠心病组血浆PlGF水平为(10.70±0.49)ng/L,明显高于非冠心病组(4.53±0.64)ng/L和对照组(3.64±0.36)ng/L,且差异均有统计学意义(P<0.001),非冠心病组与对照组间差异无统计学意义(P>0.05).相关分析显示,血浆PlGF水平与Gensini冠状动脉病变积分成强正相关(r=0.918,P<0.01).PTCA及支架置入患者术后30d随访,4例发生不良心血管事件,其PlGF水平为(13.98±3.39)ng/L,明显高于未发生心血管事件的患者(7.25±2.96)ng/L,且差异有统计学意义(P<0.01).结论 检测血浆PlGF水平在不明原因胸痛的鉴别诊断中具有一定意义,有助于冠心病的早期诊断;血浆PlGF水平越高,提示冠状动脉病变程度越严重;血浆PlGF水平对冠状动脉血运重建术后不良心血管事件的发生有潜在预测价值.     

Low prevalence of vitamin D deficiency among adolescents with anorexia nervosa

Summary Fifty adolescents with AN and 200 healthy girls underwent vitamin D screening. Girls with AN reported exceptional compliance with vitamin D supplementation and PTH concentrations were lower. Vitamin D deficiency was less common in the group with AN, but when race was considered, the trend was no longer significant. Introduction The objective of this study was to determine whether patients with anorexia nervosa (AN) are more compliant with supplementation and have a lower prevalence of vitamin D deficiency than healthy controls. Methods Fifty adolescents with AN and 200 controls were compared using anthropometric and lifestyle data, serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations, and prevalence of vitamin D deficiency. Results The prevalence of deficiency (<20 ng/mL) was 2% in the AN group vs. 24% among controls (p = 0.003). 25OHD was similar among white participants with AN and white controls (39.5 vs. 36.0 ng/mL, p = 0.20), but higher than in non-white controls (20.6 ng/mL). Significantly more girls with AN reported vitamin D supplementation (86%) than the full control (14%) or white subgroup (27%) (p < 0.001). Participants with AN had lower PTH concentrations than controls, (27.8 vs. 47.4 pg/mL, p = 0.009), a trend that lost significance after age and race adjustment (41.7 pg/mL, p = 0.12). Conclusions Compared to healthy controls, adolescents with AN had a lower prevalence of vitamin D deficiency and PTH concentration. However, 25OHD and PTH concentrations were similar after adjustment for race and age. The trend of lower PTH levels in adolescents with AN, accompanied by exceptional compliance with supplementation, may have bone health implications for these patients. Research Support: Funded by NIH Grants RO1 HD043869 and MO1-RR-2172 to the Children’s Hospital General Clinical Research Center; Department of Defense (US Army, Bone Health and Military Readiness); and Project S-T71-MC-0000-10-S1-R0 from the Maternal and Child Health Bureau.     

Patients with sclerosteosis and disease carriers: Human models of the effect of sclerostin on bone turnover

Sclerosteosis is a rare bone sclerosing dysplasia, caused by loss‐of‐function mutations in the SOST gene, encoding sclerostin, a negative regulator of bone formation. The purpose of this study was to determine how the lack of sclerostin affects bone turnover in patients with sclerosteosis and to assess whether sclerostin synthesis is decreased in carriers of the SOST mutation and, if so, to what extent this would affect their phenotype and bone formation. We measured sclerostin, procollagen type 1 amino‐terminal propeptide (P1NP), and cross‐linked C‐telopeptide (CTX) in serum of 19 patients with sclerosteosis, 26 heterozygous carriers of the C69T SOST mutation, and 77 healthy controls. Chips of compact bone discarded during routine surgery were also examined from 6 patients and 4 controls. Sclerostin was undetectable in serum of patients but was measurable in all carriers (mean 15.5 pg/mL; 95% confidence interval [CI] 13.7 to 17.2 pg/mL), in whom it was significantly lower than in healthy controls (mean 40.0 pg/mL; 95% CI 36.9 to 42.7 pg/mL; p < 0.001). P1NP levels were highest in patients (mean 153.7 ng/mL; 95% CI 100.5 to 206.9 ng/mL; p = 0.01 versus carriers, p = 0.002 versus controls), but carriers also had significantly higher P1NP levels (mean 58.3 ng/mL; 95% CI 47.0 to 69.6 ng/mL) than controls (mean 37.8 ng/mL; 95% CI 34.9 to 42.0 ng/mL; p = 0.006). In patients and carriers, P1NP levels declined with age, reaching a plateau after the age of 20 years. Serum sclerostin and P1NP were negatively correlated in carriers and age‐ and gender‐matched controls (r = 0.40, p = 0.008). Mean CTX levels were well within the normal range and did not differ between patients and disease carriers after adjusting for age (p = 0.22). Our results provide in vivo evidence of increased bone formation caused by the absence or decreased synthesis of sclerostin in humans. They also suggest that inhibition of sclerostin can be titrated because the decreased sclerostin levels in disease carriers did not lead to any of the symptoms or complications of the disease but had a positive effect on bone mass. Further studies are needed to clarify the role of sclerostin on bone resorption. © 2011 American Society for Bone and Mineral Research     

Scoliose idiopathique de l'adolescence : la mélatonine est-elle en cause ?

Background. Although the cause of adolescent idiopathic scoliosis remains unclear, pinealectomy is followed by the development of scoliosis in chickens. Melatonin is the only hormone secreted by pineal gland. Objective. To assess serum melatonin levels in adolescents with idiopathic scoliosis. Methods. Serum melatonin was assayed once, at 12:00 AM, in each of 20 adolescents with idiopathic scoliosis and 10 age-matched siblings. In the patient group, mean age was 14.3 years and the mean Cobb angle was 54.5° (range 20°–110°). Mean age in the control group was 14 years. Results. Serum melatonin was significantly lower in the patients (mean, 7.7 pg/mL; range, 4 to 13 pg/mL) than in the controls (mean, 29.9 pg/mL; range, 19.3 to 46 pg/mL) (P<0.00001). The 12 surgically treated patients had a mean melatonin level of 8.1 pg/ml, versus 7.2 pg/mL in the eight other patients (nonsignificant P and regression coefficient values). Serum melatonin was not significantly correlated with the Cobb's angle (regression coefficient, 0.18; P<0.44). Conclusion. Our data suggest that serum melatonin levels may contribute to the pathogenesis of idiopathic scoliosis.     

Urinary transforming growth factor-{beta}1 in membranous glomerulonephritis

Background: Human idiopathic membranous glomerulonephritis (MGN) has a highly variable clinical course and factors determining its outcome are poorly known. Since transforming growth factor-{beta}1 (TGF-{beta}1) has an essential role in renal fibrogenesis, we studied the possibility to use urinary excretion of TGF-{beta}1 in the assessment of progression of the disease in patients with MGN. Methods: Urinary TGF-{beta}1 was determined in 41 patients with MGN, 25 healthy subjects, six non-proteinuric renal transplant patients, 10 patients with IgA glomerulonephritis, and seven proteinuric patients (with non-progressive diseases) using a novel, double antibody enzyme immunoassay. The results were compared with renal morphology and clinical indices of activity of MGN over 12 months. Results: The median urinary TGF-{beta}1 excretion (pg/mg creatinine) was significantly higher (1730; range 60-16970) in MGN patients than in the healthy controls (300; 30-1330; P <0.0001). In renal allograft recipients the excretion was 840 (250-3440; P <0.0001 vs healthy controls), in IgA GN it was 1130 (30-4910; P=0.039), and in proteinuric patients it was 39 (29-165; P=NS). In MGN but not in the proteinuric controls or renal allograft recipients, urinary TGF-{beta}1 correlated with urinary albumin excretion (r=0.86, P <0.0001) but no correlation with renal function or the duration of the disease was found. Urinary TGF-{beta}1 at renal biopsy correlated with interstitial cellular inflammation and its excretion 1 year before the biopsy correlated with indices of sclerosis/fibrosis. Immunosuppressive therapy significantly decreased urinary TGF-{beta}1 from 2800 (1610-16960) to 840 (170-1600) pg/mg creatinine (P=0.028). Patients with persistent nephrotic syndrome and/or declining renal function had a higher initial TGF-{beta}1 excretion (median 3680; 1830-7420 pg/mg creatinine) than those entering partial or complete remission (1060; 60-1960; P=0.003) within 12 months from sampling. Conclusions: Urinary TGF-{beta}1 excretion was increased in patients with MGN, and high excretion indicted intrarenal sclerosing/fibrosing processes and progressive clinical course. Measuring urinary TGF-{beta}1 may be useful in the assessment of the progression of disease and the effects of treatment in MGN.     

Van Buchem disease: Clinical,biochemical, and densitometric features of patients and disease carriers

Van Buchem disease (VBD) is a rare bone sclerosing dysplasia caused by the lack of a regulatory element of the SOST gene, which encodes for sclerostin, an osteocyte‐derived negative regulator of bone formation. We studied the demographic, clinical, biochemical, and densitometric features of 15 patients with VBD (12 adults and 3 children) and 28 related carriers of the gene mutation. The most common clinical findings in patients were facial palsy (100%) and various degrees of hearing impairment (93%); raised intracranial pressure had been documented in 20%. The clinical course of the disease appeared to stabilize in adulthood, with the majority of patients reporting no progression of symptoms or development of complications with time. Carriers of the disease had none of the clinical features or complications of the disease. Sclerostin could be detected in the serum in all but 1 VBD patients (mean 8.0 pg/mL; 95% confidence interval [CI], 4.9–11.0 pg/mL), and were lower than those of carriers (mean 28.7 pg/mL; 95% CI, 24.5–32.9 pg/mL; p < 0.001) and healthy controls (mean 40.0 pg/mL; 95% CI, 34.5–41.0 pg/mL; p < 0.). Serum procollagen type 1 amino‐terminal propeptide (P1NP) levels were also significantly higher in adult patients (mean 96.0; 95% CI, 54.6–137.4 ng/mL versus mean 47.8; 95% CI, 39.4–56.2 ng/mL, p = 0.003 in carriers and mean 37.8; 95% CI, 34.5–41.0 ng/mL, p = 0.028 in healthy controls) and declined with age. Bone mineral density (BMD) was markedly increased in all patients (mean Z‐score 8.7 ± 2.1 and 9.5 ± 1.9 at the femoral neck and spine, respectively); BMD of carriers was significantly lower than that of patients but varied widely (mean Z‐scores 0.9 ± 1.0 and 1.3 ± 1.5 at the femoral neck and spine, respectively). Serum sclerostin levels were inversely correlated with serum P1NP levels (r = –0.39, p = 0.018) and BMD values (femoral neck r = –0.69, p < 0.001; lumbar spine r = –0.78, p < 0.001). Our results show that there is a gene‐dose effect of the VBD deletion on circulating sclerostin and provide further in vivo evidence of the role of sclerostin in bone formation in humans. The small amounts of sclerostin produced by patients with VBD may explain their milder phenotype compared to that of patients with sclerosteosis, in whom serum sclerostin is undetectable. © 2013 American Society for Bone and Mineral Research.