Daily urine iodine excretion while consuming a low-iodine diet in preparation for radioactive iodine therapy in a high iodine intake area

Objective Recommended durations of low‐iodine diet (LID) in preparation for radioactive iodine therapy (RAIT) vary among major guidelines and are important for patients in areas where iodine intake is high. The aim of this study was to investigate daily changes in urine iodine excretion after starting a LID. Design The daily iodine/creatinine (I/Cr) ratios and simple iodine concentration (simple I) of morning spot urine from 19 patients with differentiated thyroid carcinoma were measured for 2 weeks from the start of LID for RAIT preparation. We set the cut‐off of I/Cr and simple I for poor LID preparation at >66·2 μg/gCr and >150 μg/l, respectively. The day when daily I/Cr or simple I became equal to or below the cut‐off both by 95% CI and 90th percentile was defined as the end‐point for the appropriate duration of LID for RAIT. Results On day 6 of LID, the I/Cr ratio decreased below the cut‐off (≤66·2 μg/gCr) both by 95% CI (0–60·8) and by 90th percentile (51·9). Simple I reached the cut‐off (≤150 μg/l) on day 3 by both parameters (95%CI: 2·3–90·5; 90th percentile: 126·5). The morning spot‐urine I/Cr and simple I on day 7 and day 14 were significantly lower than on day 0 (P < 0·05). Conclusions One week of a strict LID is enough to decrease the level of urine iodine excretion in preparation for RAIT even in high iodine intake areas. These results provide essential data for future outcome studies regarding LID preparation for RAIT.     

Reevaluation of stringent low iodine diet in outpatient preparation for radioiodine examination and therapy

To decrease total body iodine is a key point in preparation for radioiodine study and therapy. We introduced a stringent self-managed low iodine diet (LID) and compared the outcome to that of the conventional restricted iodine diet (RID) for outpatients. We measured urine iodine to creatinine ratios (I/Cr) in patients prepared with RID for one week, LID for one week, or LID for two weeks. Mean urinary iodine excretion after RID for one week (n = 210) was 182.2 microg/gCr (range, 13-986 microg/gCr; standard deviation (SD) = 158.5) not reaching below the recommended level (I/Cr<100 microg/gCr). Urinary iodine excretion after LID for one week (n = 15) showed a lower mean urinary iodine level (I/Cr 119.4 microg/gCr; range, 23-218 microg/gCr; SD = 55.9) than RID for one-week, and two-week LID (n = 17) showed an even lower mean level (I/Cr 63.1 microg/gCr; range, 7-134 microg/gCr; SD = 38.7). The one-week LID period adequately (recommended level of I/Cr being less than 100 microg/gCr) prepared 26% of the patients, while two-weeks on the diet adequately prepared 70% of the patients. Furthermore, none of the two-week LID patients had I/Cr>150 microg/gCr, although a significantly greater number of one-week LID patients (19%) did. Our self-managed, outpatient LID successfully induced iodine deficiency, and two-week LID may be recommended for preparation in radioiodine study and therapy for thyroid cancer.     

Two-week low iodine diet is necessary for adequate outpatient preparation for radioiodine rhTSH scanning in patients taking levothyroxine.

We evaluated a self-managed, outpatient, low iodine diet (LID) (<50 microg/day) designed to decrease total body iodine (TBI) in preparation for radioiodine (131I) scans. However, levothyroxine (LT4) ingestion is a significant source of dietary iodine in recombinant human TSH (rhTSH)-stimulated studies. Measuring urine iodine to creatinine ratios (I/Cr), a reflection of TBI, we evaluated the LID for 7-day and 14-day periods to determine the efficacy of our LID to deplete TBI, with and without LT4. Patients following the LID for 14 days (n = 28) without LT4 attained the goal of an iodine deficient state (I/Cr <50 microg/g) in 78% of cases, establishing the diet's efficacy in significantly reducing TBI. In patients taking LT4, 7 days of the LID was insufficient to attain this goal of true iodine deficiency. However, a 14 day LID while taking LT4 resulted in 21% of patients being iodine deficient. For diagnostic purposes, a 7 day LID period (n = 21) suboptimally but adequately (I/Cr <100 microg/g) prepared 41% of the patients, whereas 14 days on the diet (n = 24) adequately prepared 71% of the patients taking LT4. Our simple, self-managed, outpatient, LID effectively makes patients iodine deficient. Though less efficacious when taking LT4, this LID adequately reduces TBI for rhTSH-stimulated 131I uptake scans when followed for 14 days.     

Indicators of iodine status among adults. Dutch Nutrition Surveillance System.

To evaluate the iodine status of Dutch adults we used three different iodine status indicators, namely urinary 24-hour iodide excretion (I/24 h), iodide/creatinine ratio in 24-hour urine samples (I/Cr) and 24-hour iodide excretion per kilogram body weight (I/kg). Additionally, the habitual daily iodine intake was calculated. Men had higher mean I/24 h and mean iodine intake than women. No differences between men and women were found for mean I/Cr and mean I/kg. Relatively high (greater than or equal to 18%) prevalences of low values for the different iodine status indicators were found, especially for I/24 h. The intraindividual variance for all three indicators was high. Risk assessment regarding iodine supply, based on urinary iodide excretion, depends on the indicator used, and therefore caution is called for when drawing conclusions. Our results do not argue against the usage of I/24 h as iodine status indicator. More research is needed to solve the question whether iodine requirement depends on such factors as body size, body composition and physical activity.     

The protein–creatinine ratio in spot morning urine samples and 24-h urinary protein excretion in patients with systemic lupus erythematosus

A 24-h urinary protein is a standard way to diagnose lupus nephritis. Assessment of protein–creatinine (Pr–Cr) ratio in morning spot urine is a valuable method in diabetic patients but not use in systemic lupus erythematous (SLE) patients routinely. In this study Pr–Cr ratio in spot urine was compare with 24-h urine protein; if they have valuable correlation we can use this test instead of 24-h urinary protein. The aim of this study was to evaluate the correlation of spot urine Pr–Cr ratio for prediction of significant proteinuria (≥300 mg/24 h) in patients with SLE. A cross-section study was conducted in 74 hospitalized women with SLE. The correlation between Pr–Cr in first morning urine specimens and urinary protein excretion in 24-h collections were analyzed. Correlation between Pr–Cr ratio in spot morning urine specimens and urinary protein excretion in 24-h collections was significant (P < 0.0001, r = 0.83). A high correlation and precision of agreement were demonstrated between the two methods of assessment proteinuria in lupus patients. The difference between the two methods was less than the biological variability in the protein excretion and its measurement, enabling the methods to be used interchangeably creatinine ratio in spot morning urine samples is a precise indicator of proteinuria in patients with lupus nephritis and represents a simple and inexpensive procedure in establishing severity of proteinuria in patients with SLE.     

Colostrum iodine and perchlorate concentrations in Boston-area women: a cross-sectional study

Objective To measure levels of colostrum iodine, which has not been previously measured, and perchlorate and cotinine (a surrogate for thiocyanate derived from cigarette smoke) in women up to 60 h postpartum. Perchlorate and thiocyanate are environmental inhibitors of iodide transport into the thyroid and lactating breast. Design Cross‐sectional. Patients Ninety seven postpartum women in Boston, Massachusetts, USA. Measurements Colostrum iodine and perchlorate, and spot urine iodine, perchlorate, cotinine and creatinine concentrations were measured. Results Sufficient colostrum was obtained to measure iodine in 61 samples and perchlorate in 46 samples. Median colostrum iodine content was 51·4 µmol/l (range 21·3–304·2 µg/l). Perchlorate was detectable in 43 of 46 colostrum samples (median 2·5 µmol/l; range, < 0·05–188·9 µmol/l). Median urine iodine in 97 samples was 82·2 µmol/l (range, 10·3–417·1 µmol/l). Perchlorate was detectable in all 97 urine samples (median 2·6 µmol/l; range, 0·2–160·6 µmol/l). Colostrum iodine content was not significantly correlated with levels of colostrum perchlorate or concentrations per litre of urinary iodine, perchlorate, or cotinine. Colostrum perchlorate concentrations were not significantly associated with urinary iodine, perchlorate, or cotinine levels. Urinary cotinine levels were not significantly associated with urinary iodine or perchlorate levels. There was no association between maternal urinary iodine and urinary perchlorate levels. Conclusions Iodine is present in human colostrum and thus available for breastfeeding infants immediately after birth. Perchlorate was also present in 93% of samples measured, but the concentrations did not correlate with colostrum iodine concentrations.     

Low iodine diet in differentiated thyroid cancer: a review

Radioactive iodine (RAI) ablation is a beneficial, adjuvant therapy for the management of differentiated thyroid cancer (DTC) after thyroidectomy. The goal of RAI is to destroy remnant thyroid and microscopic cancerous tissue. Radioactive iodine uptake is enhanced by elevating TSH levels and initiating a low iodine diet (LID) prior to ablation. An ideal LID should preferably not exceed 50 mcg/day of dietary iodine for 1–2 weeks, although the duration may be shortened to a week with a structured patient education programme. A pre‐ablation spot urinary iodine concentration (UIC) of <100 mcg/l and/or a urinary iodine to creatinine ratio (UICR) of <100 mcg/gCr would support an adequate LID preparation. Hyponatraemia, most likely due to iatrogenic hypothyroidism, is a potential side effect associated with LID and occurs during and a few days after the LID. Although the overall incidence of hyponatraemia is low, patients at high risk (older age, female sex, use of thiazide diuretics) may benefit from serum sodium monitoring. The existing evidence on the impact of LID on RAI ablation has been largely inconsistent due to retrospective study designs and the lack of an objective measurement of urinary iodine levels. Future large prospective randomized control trials are needed to elucidate and confirm the crucial role of LID in achieving successful RAI ablation and greater disease‐free survival in DTC.     

Low urinary iodine postpartum is associated with hypothyroid postpartum thyroid dysfunction and predicts long-term hypothyroidism

Background Postpartum thyroid dysfunction (PPTD) is characterized by an early hyperthyroid phase followed, with peak prevalence at 6 months, by a hypothyroid phase which carries a risk of long‐term hypothyroidism. Iodine has a major effect on thyroid function. Western Australia has previously been shown to be iodine replete. Objective To examine the iodine status of women with and without PPTD and the relationship of iodine status postpartum with long‐term hypothyroidism. Design Case–control with follow‐up. Patients A total of 149 women at 6 months postpartum (74 PPTD, 75 controls) with 98 (46 PPTD, 52 controls) followed up at 12 years. Measurements Urinary iodine concentration (UIC) and thyroid function at 6 months postpartum; thyroid function at 12‐year follow‐up. Results At 6 months postpartum, median UIC (quartiles) for observed TSH ranges were: for TSH < 0·4 mU/l 130·0 μg/l (82·0, 170·0); for TSH 0·4–4·0 mU/l 123·0 μg/l (80·5, 168·0); for TSH > 4·0 mU/l 85·0 μg/l (40·0, 141·5), P = 0·018. The odds ratio (OR) of hypothyroid PPTD with each unit of decreasing log iodine was 2·54, (95%CI: 1·47, 4·35), and with UIC < 50 μg/l, OR 4·22, (95%CI: 1·54, 11·55). In the long term, decreased log UIC significantly predicted hypothyroidism at 12‐year follow‐up (P = 0·002); as did UIC < 100 μg/l (P = 0·03) and UIC < 50 μg/l (P = 0·02). The association was independent of antibody status. Conclusion Low UIC measured at 6 months postpartum is associated with hypothyroid PPTD and independently predicts long‐term hypothyroidism. We believe that it results from more severe preceding destructive thyroiditis, with discharge of thyroidal iodine, and thereby predicts a greater risk of long‐term hypothyroidism.     

Development of a Model to Estimate 24‐Hour Urinary Creatinine Excretion

The accuracy of the spot urine analyte/creatinine ratio in estimating 24‐hour excretion of the analyte is compromised because it is not adjusted for 24‐hour creatinine excretion. The authors developed a model for conveniently estimating 24‐hour creatinine excretion. The model was derived from 24‐hour urine collections using multiple linear regression, including sex, weight, race, and age. The model was then evaluated in a validation cohort, assessing the correlation between estimated and measured 24‐hour creatinine excretion and by comparing their correlation with muscle mass. Estimated creatinine excretion correlated strongly with measured creatinine excretion (r=0.80 in the entire cohort and 0.93 after eliminating patients with incomplete collections), and correlated at least as strongly as measured creatinine excretion with lean muscle mass (r=0.94 vs r=0.82, respectively). Adjusting spot urine analyte/creatinine ratios using the estimated 24‐hour creatinine excretion by this convenient method can improve the accuracy of estimating 24‐hour excretion of albumin, sodium, and other analytes.     

A cautious iodization programme bringing iodine intake to a low recommended level is associated with an increase in the prevalence of thyroid autoantibodies in the population

Autoantibodies against the thyroid gland with thyroid peroxidase antibody (TPO‐Ab) and thyroglobulin antibody (Tg‐Ab) as the most common can often be demonstrated in serum. The effect of public iodization programmes on antibody prevalence is uncertain. Aim To measure the concentrations of thyroid autoantibodies in the Danish population before and after mandatory iodization of salt. Methods Two identical cross‐sectional population studies were performed before (Cohort 1 (C1), year 1997–1998, n = 4649, median urinary iodine 61 μg/l) and 4–5 years after (Cohort 2 (C2), year 2004–2005, n = 3570, median urinary iodine 101 μg/l) mandatory iodine fortification of salt was implemented in Denmark. Blood tests were analysed for TPO‐Ab and Tg‐Ab using sensitive assays. Results Antibodies were more frequent in C2 than in C1: TPO‐Ab > 30 U/ml, C1 vs C2: 14·3 vs 23·8% (P < 0·001) and Tg‐Ab > 20 U/ml, C1 vs C2: 13·7 vs 19·9% (P < 0·001). The C2 vs C1 effect was confirmed in multivariate regression models (C1 reference): TPO‐Ab: OR (95% CI): 1·80 (1·59–2·04) and Tg‐Ab: 1·49 (1·31–1·69). The increase in the frequency of thyroid antibodies was most pronounced in young women and especially observed at low concentrations of antibodies. Conclusion The prevalence of both TPO‐Ab and Tg‐Ab was higher 4–5 years after a cautious iodine fortification of salt was introduced in Denmark. The increase was most pronounced in young women and in the low concentrations of antibody. Further studies are needed to evaluate the long‐term effects of increased iodine intake on thyroid autoimmunity in the population.     

Adipokines in type 1 diabetes after successful pancreas transplantation: normal visfatin and retinol‐binding‐protein‐4, but increased total adiponectin fasting concentrations

Objective In type 1 diabetes mellitus (T1DM), the release of many hormones, not only from beta‐cells, but also from adipocytes (adipokines) may be altered. After successful pancreas–kidney‐transplantation (PKTx), T1DM patients can revert to a nondiabetic metabolism, but it is unclear whether alterations of adipokines are still present after PKTx. Design, patients and measurements Concentrations of adipokines [visfatin, retinol‐binding protein‐4 (RBP‐4), adiponectin, high molecular weight (HMW) adiponectin] were measured at fasting in 10 PKTx and in 19 T1DM. Nondiabetic healthy controls (CON, n = 9) and six nondiabetic patients after kidney transplantation (KTx) were examined as control groups. In PKTx, KTx and CON, indices of insulin sensitivity (OGIS) and beta cell function (adaptation index, AI) were calculated from 75 g oral glucose tolerance test (OGTT) data. Results Fasting serum visfatin (T1DM: 56 ± 4 μg/l, PKTx: 42 ± 6 μg/l, KTx: 39 ± 3 μg/l, CON: 40 ± 3 μg/l) and RBP‐4 (T1DM: 490 ± 26 μg/l, PKTx: 346 ± 39 μg/l, KTx: 401 ± 13 μg/l, CON: 359 ± 36 μg/l) was increased by 40% and 36%, respectively (each P < 0·03) in T1DM only. Levels were positively correlated with HbA1c in all subjects (visfatin: r = 0·43, P < 0·004; RBP‐4: r = 0·46, P < 0·03). Fasting plasma adiponectin was 80% higher in T1DM and in PKTx (T1DM: 18 ± 2 mg/l, PKTx: 18 ± 3 mg/l, KTx: 12 ± 3 mg/l, CON: 10 ± 1 mg/l; P < 0·04) and was positively correlated with diabetes duration (r = 0·37, P < 0·02). HMW/total adiponectin ratio was increased in T1DM (P < 0·02). PKTx displayed a normoglycaemic metabolism as insulin sensitive as CON, but AI was lower than in CON and KT (P < 0·01). Conclusions T1DM after successful PKTx show normal fasting visfatin and RBP‐4 levels and HMW‐adiponectin/adiponectin‐ratio, which are elevated in T1DM, whereas total adiponectin levels are similarly increased in T1DM and PKTx patients.     

Influence of iodine on the reference interval of TSH and the optimal interval of TSH: results of a follow-up study in areas with different iodine intakes

Objective The aim of the present study was to evaluate whether the status of iodine nutrition influences the TSH concentration in a selected Chinese reference population according to the criteria proposed by National Academy of Clinical Biochemistry (NACB) and regular thyroid ultrasonography, to establish a new reference interval of TSH based on the wide variation of iodine nutrition in populations, and to identify an optimal interval of TSH by following up the cohort with normal TSH concentrations at baseline. Design The study was conducted in Panshan, Zhangwu and Huanghua, the regions with mildly deficient, more than adequate and excessive iodine intake, respectively. Of the 3761 unselected subjects who were enrolled at baseline, 2237 met the criteria for a reference population. Of 3048 subjects with normal serum TSH at baseline, 2727 (80·0%) participated in the 5‐year follow‐up study. TSH and thyroid autoantibodies in serum and iodine in urine were measured, and B‐mode ultrasonography of the thyroid was performed. Results In the reference population, there was a urinary iodine‐related increment of serum TSH levels (r = 0·21, P = 0·000), and the mean levels of TSH in Panshan, Zhangwu and Huanghua were 1·15, 1·28 and 1·93 mIU/l, respectively (P = 0·000), corresponding to the rising regional iodine intake. Based on the overall data, we obtained a reference interval of 0·3–4·8 mIU/l. TSH concentrations obtained in the follow‐up study correlated well with those at baseline (r = 0·58, P = 0·000). A baseline serum TSH > 1·9 mIU/l was associated with an increased incidence of development of supranormal TSH and a baseline serum TSH < 1·0 mIU/l was associated with an increased incidence of subnormal TSH development. Conclusions Iodine nutrition is an important factor associated with TSH concentration even in the rigorously selected reference population. Baseline TSH of 1·0–1·9 mIU/l is an optimal interval with the lowest incidence of abnormal TSH in 5 years.     

Urine protein-to-creatinine ratio in an untimed urine collection is a reliable measure of proteinuria in lupus nephritis

OBJECTIVE: To evaluate the accuracy of urine protein-to-creatinine (P/C) ratio in an untimed urine specimen as compared with 24 h total protein excretion for measurement of proteinuria in patients with lupus nephritis. METHODS: Proteinuria in patients with lupus nephritis was assessed by 24 h total protein excretion and spot urine P/C ratio. Correlation and limits of agreement between the two methods were evaluated. The discriminant cutoff values for spot urine P/C ratio in predicting 24 h protein 'threshold' excretion of > or =0.3, > or =0.5, > or =1.0 and > or =3.5 g/day were determined using receiver operating characteristic curves. RESULTS: A total of 165 samples were available for assessment with 21.8% excluded due to inadequate collection. A strong correlation (r = 0.91, P < 0.0001) was found between spot urine P/C ratio and 24 h urine protein excretion. Bland-Altman plot showed the two tests had acceptable limits of agreement in low level of protein excretion (-0.86 to +0.92 g/day when protein excretion was <2.0 g/day). The limits became wider as the protein excretion increased. The spot urine P/C ratios of 0.45 (sensitivity 0.92; specificity 0.88), 0.7 (0.92; 0.89) and 1.84 (1.0; 0.86) mg/mg reliably predicted 24 h urine total protein equivalent 'thresholds' at > or =0.5, 1.0 and 3.5 g/day. CONCLUSION: This study supports the recommendation of using spot urine P/C ratio in screening and monitoring proteinuria in patients with lupus nephritis. However, in assessing the exact amount of proteinuria, the urine P/C ratio may have unacceptably wide limits of agreement in high protein excretion range.     

Therapeutic efficacy of platelet components treated with amotosalen and ultraviolet A pathogen inactivation method: results of a meta‐analysis of randomized controlled trials

Background and Objectives There are conflicting data regarding the therapeutic efficacy of platelets inactivated using amotosalen and ultraviolet A light. We have performed a meta‐analysis to summarize the results of different randomized controlled trials (RCT). Materials and Methods Five RCTs reported through March 2011 met the criteria for meta‐analysis. Weighted mean difference (WMD) in corrected count increment (CCI) at 1 h, CCI‐24 h, and transfusion interval (days) and summary odds ratio (OR) of bleeding in inactivated platelet (I‐P) group vs. noninactivated platelet (C‐P) group were calculated across studies. Results Randomized controlled trials were statistically homogeneous when we analysed CCI‐24 h, and the transfusion of C‐P was associated with a higher CCI‐24 h when compared with the transfusion of I‐P (WMD, 3 × 10³; 95% CI, 2·32 × 10³–3·69 × 10³; P < 0·00001). RCTs were statistically heterogeneous when we analysed CCI‐1 h, transfusion interval and OR of bleeding. Regarding the OR of bleeding in the I‐P and C‐P groups, it varied by as much as a multiple of four among the trials, from 0·66 to 2·66. When we combined double‐blinded and high methodologic quality score RCTs, the use of I‐P was not statistically associated with an increase in the OR of bleeding when compared with the use of C‐P (OR, 0·97; 95% CI, 0·75–1·27; P = 0·84). Conclusion Although the transfusion of I‐P was associated with lower CCI‐24 h when compared with the transfusion of C‐P, this was not associated with differences in the OR of bleeding between I‐P and C‐P.     

The effect of spironolactone upon corticosteroid hormone metabolism in patients with early stage chronic kidney disease

Context Aldosterone has emerged as an important mediator of disease progression and mortality in patients with chronic heart and kidney disease (CKD). Despite the increasing use of mineralocorticoid receptor antagonists in these patients, little is known about the effects on corticosteroid hormone secretion and metabolism. Objective To assess corticosteroid hormone secretion and metabolism in patients with early stage CKD before and after spironolactone (Spiro). Design Randomized, double‐blind, placebo‐controlled interventional study. Setting Single tertiary referral centre. Patients A total of 112 patients with stable stage 2/3 CKD. Interventions Patients were randomized to receive either Spiro 25 mg once daily or placebo for 36 weeks. Main outcome measures Plasma renin activity (PRA), angiotensin II (AngII) and steroid hormones were analysed by standard assays; urinary corticosteroid hormone metabolites (5α+5β‐tetrahydro‐cortisol (5α+5β‐THF), TH–cortisone (THE), 3α5β‐TH‐aldosterone (TH‐Aldo), 5α+5β‐TH‐deoxycorticosterone (5α+5β‐TH‐DOC), TH‐11‐desoxycortisol (THS)) were analysed by gas chromatography/mass spectrometry. Results Plasma aldosterone concentration (PAC) was inversely correlated with eGFR (r = ?0·331, P < 0·001). Urinary 24‐h excretion of TH‐Aldo was correlated with PAC (r = 0·214, P < 0·05) and diastolic blood pressure (BP) (r = 0·212, P = <0·05), whereas total 24‐h urinary cortisol metabolite excretion was correlated with systolic BP (r = 0·316, P < 0·01). In addition, 11β‐hydroxysteroid dehydrogenase (11β‐HSD) type 1 activity (urinary 5α+5β‐THF)/THE) ratio) was correlated with PRA (r = 0·277, P < 0·01). Spiro treatment significantly reduced BP (123 ± 11/76 ± 7 vs 119 ± 11/73 ± 8 mmHg, P < 0·01) despite renin–angiotensin–aldosterone system induction, reflected by increased urinary 24‐h TH‐Aldo excretion (17·6 (12, 86) vs 26 (18, 80) μg/24 h, P < 0·05). By contrast, Spiro had no effect on total urinary cortisol metabolite excretion, 11β‐hydroxylase, 11β‐HSD type 1 and 2 activity. Conclusions Aldo and cortisol are positively associated with BP suggesting that adrenal hyperactivity may in part explain the increased cardiovascular risk in patients with early end‐stage CKD. Addition of Spiro had no effect on glucocorticoid metabolism or total 24‐h corticosteroid production.     

Long‐Term Antiproteinuric Effect of Dual Renin–Angiotensin System Blockade

We evaluated the long‐term changes on overt proteinuria induced by dual blockade of the renin–angiotensin system (RAS). Dual blockade was produced by adding an angiotensin II receptor blocker (ARB) to treatment with maximal recommended doses of an angiotensin converting enzyme (ACE) inhibitor in proteinuric patients. A total of 28 patients (19 men and 9 women) with proteinuria higher than 1 g/24 h were enrolled in this trial of treatment with the ARB candesartan (from 4 up to 32 mg daily) added to existing treatment with an ACE inhibitor. At 6, 12, 24, and 36 months, we evaluated proteinuria in 24‐h urinary collections, office blood pressure (BP), plasmatic creatinine (Cr), serum potassium (K), and 24 h urine collection creatinine clearance (CrC). During monoblockade of the RAS by ACE inhibitor treatment, albuminuria was 2.94 ± 1.92 mg/24 h; BP was 137/76 mmHg; K+ was 4.8 ± 0.5 mmol/l, Cr was 1.76 ± 0.67 mg/dL, and CrC was 62 ± 31.9 mL/min. After 6 months, dual blockade of the RAS albuminuria was 2.18 ± 2.29 mg/24 h (P < 0.01 vs. baseline) and BP was 133/75 mmHg (not significant). At 36 months, albuminuria was 2.21 ± 2.20 mg/24 h (P < 0.05 vs. baseline); BP was 133/73 mmHg (not significant). CrC was not changed along the follow up. A small increment of Cr was detected at 24 months (2.11 ± 1.06 mg/mL, P < 0.05). The antiproteinuric effect of dual renin–angiotensin system blockade combining candesartan and ACE inhibitors remain after 36 months without losing its initial effect. Blood pressure changes seem not to explain this long‐term antiproteinuric effect.     

The relation of serum T4 and TSH with the urinary iodine excretion

The urinary iodine excretion, expressed as the iodine/creatinine (I/Cr) ratio, was correlated with the serum T4 and TSH levels in persons with a relatively constant iodine intake for at least 6 months. It was found that the group with an I/Cr ratio of 151-200 micrograms/g had on average the lowest serum TSH and the highest serum T4 level. The differences in serum TSH from the other groups were statistically significant, whereas the differences in serum T4 were not. It is concluded that an I/Cr ratio of 151-200, corresponding to an iodine intake of about 200 micrograms/day, is associated with the lowest TSH stimulation of the thyroid gland in man and probably represents the optimal conditions for its function.     

In vivo reversal of the anticoagulant effect of rivaroxaban with four‐factor prothrombin complex concentrate

Four‐factor prothrombin complex concentrate (PCC) 50 iu/kg is able to swiftly restore haemostatic parameters in healthy subjects on rivaroxaban. We hypothesized that lower dosages of PCC may be sufficient to restore normal haemostasis. In this double‐blind, crossover, placebo‐controlled study, we compared the effects of PCC 37·5 iu/kg, PCC 25 iu/kg, and placebo on thrombin generation (endogenous thrombin potential, ETP) and prothrombin time in six healthy subjects receiving twice‐daily rivaroxaban 15 mg for 2·5 days. Fifteen min after infusion of PCC 37·5 iu/kg, ETP increased from 47 ± 16% to 64 ± 22% (P = 0·03; pre‐rivaroxaban ETP: 92 ± 14%) and remained higher than after placebo over 24 h (P = 0·001). PCC 25 iu/kg did not modify ETP within 15 min (53 ± 11% to 59 ± 12%; P = 0·14) and was not different from placebo over 24 h (P = 0·31). ETP reached pre‐rivaroxaban levels within 6 h after PCC 37·5 iu/kg infusion and within 12–24 h after PCC 25 iu/kg infusion. Both dosages restored rivaroxaban‐induced prothrombin time prolongation after 15 min (P < 0·001). Placebo did not have an effect on coagulation parameters. 37·5 iu/kg of PCC leads to partial restoration of thrombin generation, whereas 25 iu/kg does not. PCC 37·5 iu/kg may be insufficient for immediate full reversal of peak therapeutic rivaroxaban levels.     

Estimation of 24-Hour Sodium Excretion from Spot Urine Samples

J Clin Hypertens (Greenwich). 2010;12:174–180. ^©2010 Wiley Periodicals, Inc. Despite the effects of sodium intake on blood pressure and on response to antihypertensive medication, sodium intake is rarely monitored in clinical practice. The current method, the 24-hour urine collection for sodium excretion, is cumbersome, often incorrectly performed, and not commonly ordered. Further, its results have limited meaning because of the substantial day-to-day variation in sodium intake. A spot urine test to enable convenient, inexpensive, and serial monitoring of sodium excretion would be desirable. In this study, the accuracy of predicting 24-hour sodium excretion from a spot urine sample was assessed. The urine sodium/creatinine ratio was determined from the following urine samples: an “AM sample,” submitted at the beginning of the 24-hour urine collection; a “PM sample” collected in the later afternoon/early evening before dinner, at roughly the midpoint of the collection; and a “random sample,” collected after its completion. The ratio was then corrected for 24-hour creatinine excretion. The strongest correlation between predicted and actual 24-hour sodium excretion was observed with the PM sample collected near the midpoint (r=0.86, P<.001). This sample also identified persons with sodium excretion <100 mEq/d with a sensitivity of 100% and specificity of 82%. The sodium/creatinine ratio from a spot urine sample collected in the late afternoon/early evening at roughly the midpoint of the 24-hour collection, and adjusted for 24-hour creatinine excretion, strongly correlated with 24-hour sodium excretion. Additional studies are merited to further evaluate the role of the spot urine sample in assessing sodium intake.