The Role of Epithelial Sodium Channel ENaC and the Apical Cl-/HCO3- Exchanger Pendrin in Compensatory Salt Reabsorption in the Setting of Na-Cl Cotransporter (NCC) Inactivation

Background

The absence of NCC does not cause significant salt wasting in NCC deficient mice under basal conditions. We hypothesized that ENaC and pendrin play important roles in compensatory salt absorption in the setting of NCC inactivation, and their inhibition and/or downregulation can cause significant salt wasting in NCC KO mice.

Methods

WT and NCC KO mice were treated with a daily injection of either amiloride, an inhibitor of ENaC, or acetazolamide (ACTZ), a blocker of salt and bicarbonate reabsorption in the proximal tubule and an inhibitor of carbonic anhydrases in proximal tubule and intercalated cells, or a combination of acetazolamide plus amiloride for defined durations. Animals were subjected to daily balance studies. At the end of treatment, kidneys were harvested and examined. Blood samples were collected for electrolytes and acid base analysis.

Results

Amiloride injection significantly increased the urine output (UO) in NCC KO mice (from 1.3 ml/day before to 2.5 ml/day after amiloride, p<0.03, n = 4) but caused only a slight change in UO in WT mice (p>0.05). The increase in UO in NCC KO mice was associated with a significant increase in sodium excretion (from 0.25 mmol/24 hrs at baseline to 0.35 mmol/24 hrs after amiloride injection, p<0.05, n = 4). Daily treatment with ACTZ for 6 days resulted in >80% reduction of kidney pendrin expression in both WT and NCC KO mice. However, ACTZ treatment noticeably increased urine output and salt excretion only in NCC KO mice (with urine output increasing from a baseline of 1.1 ml/day to 2.3 ml/day and sodium excretion increasing from 0.22 mmole/day before to 0.31 mmole/day after ACTZ) in NCC KO mice; both parameters were significantly higher than in WT mice. Western blot analysis demonstrated significant enhancement in ENaC expression in medulla and cortex of NCC KO and WT mice in response to ACTZ injection for 6 days, and treatment with amiloride in ACTZ-pretreated mice caused a robust increase in salt excretion in both NCC KO and WT mice. Pendrin KO mice did not display a significant increase in urine output or salt excretion after treatment with amiloride or ACTZ.

Conclusion

1. ENaC plays an important role in salt reabsorption in NCC KO mice. 2. NCC contributes to compensatory salt reabsorption in the setting of carbonic anhydrase inhibition, which is associated with increased delivery of salt from the proximal tubule and the down regulation of pendrin. 3. ENaC is upregulated by ACTZ treatment and its inhibition by amiloride causes significant diuresis in NCC KO and WT mice. Despite being considered mild agents individually, we propose that the combination of acetazolamide and amiloride in the setting of NCC inhibition (i.e., hydrochlorothiazide) will be a powerful diuretic regimen.     

Pendrin as a novel target for diuretic therapy

The Cl(-)/HCO(3)(-) exchanger pendrin (SLC26A4, PDS) and the thiazide-sensitive NaCl cotransporter NCC (SLC12A3) are expressed on the apical membranes of distal nephron segments and mediate salt absorption, with pendrin working in tandem with the epithelial Na channel (ENaC) and NCC working by itself. Pendrin is expressed on the apical membrane of intercalated cells in late distal convoluted tubule (DCT), connecting tubule (CNT) and the cortical collecting duct (CCD) whereas the thiazide-sensitive NaCl cotransporter NCC is primarily detected on the apical membrane of DCT cells. Recent studies indicate that pendrin expression is increased in kidneys of NCC knockout mice, raising the possibility that pendrin and NCC can compensate for loss of the other by increasing their expression and activity. Current investigations in our laboratories demonstrate that pendrin plays an important role in compensatory salt absorption in response to the loop diuretics and the thiazide derivatives. These studies further demonstrate that whereas single deletion of pendrin or NCC does not cause salt wasting in mutant mice under baseline conditions, double knockout of pendrin and NCC causes profound polyuria and polydipsia, along with salt wasting under basal conditions. As a result, animals develop significant dehydration. We propose that pharmacologic inhibition of pendrin and NCC can provide a novel and strong diuretic regimen for patients with fluid overload, including those with congestive heart failure, nephrotic syndrome or renal failure.     

Does Parenteral Nutrition Influence Electrolyte and Fluid Balance in Preterm Infants in the First Days after Birth?

Background

New national guidelines recommend more restricted fluid intake and early initiation of total parenteral nutrition (TPN) in very preterm infants. The aim was study the effect of these guidelines on serum sodium and potassium levels and fluid balance in the first three days after birth.

Methods

Two cohorts of infants <28 weeks gestational age, born at the Leiden University Medical Center in the Netherlands, were compared retrospectively before (2002–2004, late-TPN) and after (2006–2007, early-TPN) introduction of the new Dutch guideline. Outcome measures were serum sodium and potassium levels, diuresis, and changes in body weight in the first three postnatal days.

Results

In the first three postnatal days no differences between late-TPN (N = 70) and early-TPN cohort (N = 73) in mean (SD) serum sodium (141.1 (3.8) vs 141.0 (3.7) mmol/l) or potassium (4.3 (0.5) vs 4.3 (0.5) mmol/l) were found, but in the early-TPN cohort diuresis (4.5 (1.6) vs 3.2 (1.4) ml/kg/h) and loss of body weight were decreased (−6.0% (7.7) vs −0.8% (8.0)).

Conclusions

Initiation of TPN immediately after birth and restricted fluid intake in very preterm infants do not seem to influence serum sodium and potassium levels in first three postnatal days. Further research is needed to see if a decreased diuresis and loss of body weight in the first days is the result of a delayed postnatal adaptation or better energy balance.     

Added Value of Antigen ELISA in the Diagnosis of Neurocysticercosis in Resource Poor Settings

Background

Neurocysticercosis (NCC) is the most common cause of acquired epilepsy in Taenia solium endemic areas, primarily situated in low-income countries. Diagnosis is largely based upon the “Del Brutto diagnostic criteria” using the definitive/probable/no NCC diagnosis approach. Neuroimaging and specific T. solium cysticercosis antibody detection results are at the mainstay of this diagnosis, while antigen detection in serum has never been included. This study aimed at evaluating the addition of antigen detection as a major diagnostic criterion, especially in areas where neuroimaging is absent.

Methods

The B158/B60 monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating cysticercus antigen was carried out retrospectively on serum samples collected during a hospital-based study from 83 people with epilepsy (PWE) in an endemic area.

Results

The addition of antigen results as a major criterion allowed the correct diagnosis of definitive NCC in 10 out of 17 patients as opposed to 0/17 without antigen results in the absence of neuroimaging. A sensitivity of 100% and a specificity of 84% were determined for the diagnosis of active NCC using antigen ELISA. While the use of a higher cutoff improves the specificity of the test to 96%, it decreases its sensitivity to 83%.

Conclusions

In areas where neuroimaging is absent, NCC diagnosis according to the existing criteria is problematic. Taking into account its limitations for diagnosis of inactive NCC, antigen detection can be of added value for diagnosing NCC in PWE by supporting diagnostic and treatment decisions. Therefore, we recommend a revision of the “Del Brutto diagnostic criteria” for use in resource poor areas and suggest the inclusion of serum antigen detection as a major criterion.     

Epilepsy and Neurocysticercosis in Latin America: A Systematic Review and Meta-analysis

Background

The difference in epilepsy burden existing among populations in tropical regions has been attributed to many factors, including the distribution of infectious diseases with neurologic sequels. To define the burden of epilepsy in Latin American Countries (LAC) and to investigate the strength of association with neurocysticercosis (NCC), considered one of the leading causes of epilepsy, we performed a systematic review and meta-analysis of the literature.

Methodology

Studies published until 2012 were selected applying predefined inclusion criteria. Lifetime epilepsy (LTE) prevalence, active epilepsy (AE) prevalence, incidence, mortality, treatment gap (TG) and NCC proportion among people with epilepsy (PWE) were extracted. Median values were obtained for each estimate using random effects meta-analysis. The impact of NCC prevalence on epilepsy estimates was determined using meta-regression models. To assess the association between NCC and epilepsy, a further meta-analysis was performed on case-control studies.

Principal findings

The median LTE prevalence was 15.8/1,000 (95% CI 13.5–18.3), the median AE prevalence was 10.7/1,000 (95% CI 8.4–13.2), the median incidence was 138.2/100,000 (95% CI 83.6–206.4), the overall standardized mortality ratio was 1.4 (95% CI 0.01–6.1) and the overall estimated TG was 60.6% (95% CI 45.3–74.9). The median NCC proportion among PWE was 32.3% (95% CI 26.0–39.0). Higher TG and NCC estimates were associated with higher epilepsy prevalence. The association between NCC and epilepsy was significant (p<0.001) with a common odds ratio of 2.8 (95% CI 1.9–4.0).

Significance

A high burden of epilepsy and of NCC in LAC and a consistent association between these two diseases were pointed out. Furthermore, NCC prevalence and TG were identified as important factors influencing epilepsy prevalence to be considered in prevention and intervention strategies.     

A Pilot Study of the Effect of Sodium Thiosulfate on Urinary Lithogenicity and Associated Metabolic Acid Load in Non-Stone Formers and Stone Formers with Hypercalciuria

Background and Objectives

Sodium thiosulfate (STS) reduced calcium stone formation in both humans and genetic hypercalciuric stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people.

Design, Setting, Participants & Measurements

STS was given to healthy and hypercalciuric stone forming adults. Five normal non-stone forming adults (mean age 33 years), and 5 people with idiopathic hypercalciuria and calcium kidney stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry.

Results

STS administration did not cause a significant change in urinary calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P<0.05) in hypercalciuric participants but not in non-stone formers. Among stone formers with hypercalciuria, 3 of 5 patients had measurement of serum HCO₃ concentration after the STS period: it did not change. The net effect was an increase in supersaturation of uric acid, and no change in supersaturation of calcium oxalate or calcium phosphate.

Conclusions

The basis for studies demonstrating that STS prevented stones in rats and people was not reflected by the changes in urine chemistry reported here. Although serum HCO₃ did not change, urine tests suggested an acid load in both non-stone forming and hypercalciuric stone-forming participants. The long term safety of STS needs to be determined before the drug can be tested in humans for long-term prevention of stone recurrence.     

Cognitive changes and quality of life in neurocysticercosis: a longitudinal study

Background

Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls.

Methodology/Principal Findings

The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC.

Conclusions/Significance

Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment.     

Urinary Vitamin D Binding Protein and KIM-1 Are Potent New Biomarkers of Major Adverse Renal Events in Patients Undergoing Coronary Angiography

Background

Vitamin-D-binding protein (VDBP) is a low molecular weight protein that is filtered through the glomerulus as a 25-(OH) vitamin D 3/VDBP complex. In the normal kidney VDBP is reabsorbed and catabolized by proximal tubule epithelial cells reducing the urinary excretion to trace amounts. Acute tubular injury is expected to result in urinary VDBP loss. The purpose of our study was to explore the potential role of urinary VDBP as a biomarker of an acute renal damage.

Method

We included 314 patients with diabetes mellitus or mild renal impairment undergoing coronary angiography and collected blood and urine before and 24 hours after the CM application. Patients were followed for 90 days for the composite endpoint major adverse renal events (MARE: need for dialysis, doubling of serum creatinine after 90 days, unplanned emergency rehospitalization or death).

Results

Increased urine VDBP concentration 24 hours after contrast media exposure was predictive for dialysis need (no dialysis: 113.06 ± 299.61ng/ml, n = 303; need for dialysis: 613.07 ± 700.45 ng/ml, n = 11, Mean ± SD, p<0.001), death (no death during follow-up: 121.41 ± 324.45 ng/ml, n = 306; death during follow-up: 522.01 ± 521.86 ng/ml, n = 8; Mean ± SD, p<0.003) and MARE (no MARE: 112.08 ± 302.00ng/ml, n = 298; MARE: 506.16 ± 624.61 ng/ml, n = 16, Mean ± SD, p<0.001) during the follow-up of 90 days after contrast media exposure. Correction of urine VDBP concentrations for creatinine excretion confirmed its predictive value and was consistent with increased levels of urinary Kidney Injury Molecule-1 (KIM-1) and baseline plasma creatinine in patients with above mentioned complications. The impact of urinary VDBP and KIM-1 on MARE was independent of known CIN risk factors such as anemia, preexisting renal failure, preexisting heart failure, and diabetes.

Conclusions

Urinary VDBP is a promising novel biomarker of major contrast induced nephropathy-associated events 90 days after contrast media exposure.     

Increased CSF Levels of Phosphorylated Neurofilament Heavy Protein following Bout in Amateur Boxers

Introduction

Diagnosis of mild TBI is hampered by the lack of imaging or biochemical measurements for identifying or quantifying mild TBI in a clinical setting. We have previously shown increased biomarker levels of protein reflecting axonal (neurofilament light protein and tau) and glial (GFAP and S-100B) damage in cerebrospinal fluid (CSF) after a boxing bout. The aims of this study were to find other biomarkers of mild TBI, which may help clinicians diagnose and monitor mild TBI, and to calculate the role of APOE ε4 allele genotype which has been associated with poor outcome after TBI.

Materials and Methods

Thirty amateur boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in a prospective cohort study. CSF and blood were collected at one occasion between 1 and 6 days after a bout, and after a rest period for at least 14 days (follow up). The controls were tested once. CSF levels of neurofilament heavy (pNFH), amyloid precursor proteins (sAPPα and sAPPβ), ApoE and ApoA1 were analyzed. In blood, plasma levels of Aβ42 and ApoE genotype were analyzed.

Results

CSF levels of pNFH were significantly increased between 1 and 6 days after boxing as compared with controls (p<0.001). The concentrations decreased at follow up but were still significantly increased compared to controls (p = 0.018). CSF pNFH concentrations correlated with NFL (r =  0.57 after bout and 0.64 at follow up, p<0.001). No significant change was found in the other biomarkers, as compared to controls. Boxers carrying the APOE ε4 allele had similar biomarker concentrations as non-carriers.

Conclusions

Subconcussive repetitive trauma in amateur boxing causes a mild TBI that may be diagnosed by CSF analysis of pNFH, even without unconsciousness or concussion symptoms. Possession of the APOE ε4 allele was not found to influence biomarker levels after acute TBI.     

Receptor-Associated Protein Blocks Internalization and Cytotoxicity of Myeloma Light Chain in Cultured Human Proximal Tubular Cells

Background

Free light chains (LCs) are among the many ligands that bind to cubilin/megalin for endocytosis via the clathrin-dependent endosomal/lysosomal pathway. Receptor associated protein (RAP), is a 39 kDA high-affinity, chaperone-like ligand for megalin that assists in the proper folding and functioning of megalin/cubilin. Although RAP is known to inhibit ligand binding to megalin/cubilin, its effect on LC endocytosis has not been shown directly.

Methods and Principal Findings

We investigated whether RAP can block the endocytosis of LC in cultured human proximal tubule cells and whether this can prevent LC cytotoxicity. Immunofluorescence microscopy and flow cytometry showed that fluorescently labeled LC endocytosis was markedly inhibited in HK-2 cells pretreated with human RAP. The effect of RAP was dose-dependent, and was predominantly on endocytosis as it had no effect on the small acid-washable fraction of LC bound to cell membrane. RAP significantly inhibited LC induced cytokine production and phosphorylation of ERK1/2 and p38 MAPK. Prolonged exposure to LC for 48 h resulted in epithelial-to-mesenchymal transformation in HK-2 cells as evidenced by marked reduction in the expression of the epithelial cell marker E-cadherin, and increased the expression of the mesenchymal marker α-SMA, which was also prevented by RAP in the endocytosis medium.

Conclusions

RAP inhibited LC endocytosis by ∼88% and ameliorated LC-induced cytokine responses and EMT in human PTCs. The results not only provide additional evidence that LCs endocytosis occurs via the megalin/cubilin endocytic receptor system, but also show that blocking LC endocytosis by RAP can protect proximal tubule cells from LC cytotoxicity.     

The Association of Thyroid Nodule with Non-Iodized Salt among Chinese Children

Objective

The controversy that iodized salt may increase the risk of thyroid disorders has been aroused in China during the past decade. Most of studies focused on adult rather than children. We aimed to explore whether iodized salt was associated with an increased risk of thyroid nodule in Chinese children.

Methods

The cross-sectional study was conducted in Hangzhou, China, in 2010. Iodized salt intake, urine iodine concentration (UIC) and thyroid nodule (by ultrasonography) were measured in 3026 children. The associations of iodized salt with thyroid nodule were evaluated using multiple logistic regression models.

Results

The prevalence of thyroid nodule was 10.59% among Chinese children. Girls (11.89%) had higher prevalence of thyroid nodule than boys (9.26%). No significant association was observed between type of salt and thyroid nodule in pooled samples, boys and girls, respectively. Similar associations were observed between UIC and thyroid nodule. There was no significant association between milk consumption and thyroid nodule as well.

Conclusion

The present study indicated that non-iodized salt may not increase the risk of thyroid nodules among Chinese children. Similar associations were observed between milk consumption, UIC and thyroid nodules.     

Salt intake and mental distress among rural community-dwelling Japanese men

Background

Activated mineralocorticoid receptors influence the association between daily salt intake and blood pressure. A relatively low mineralocorticoid receptor function is reported to be a risk for mental distress such as depression. Since mental distress is also a known risk for hypertension and cardiovascular disease, understanding of the association between estimated daily salt intake and mental distress contributing to hypertension is important for risk estimation for cardiovascular disease. However, no single study has reported this association.

Methods

We conducted a cross-sectional study of 1014 Japanese men undergoing general health check-ups. Mental distress was diagnosed as a Kessler 6 scale score ≥5. We also classified mental distress by levels of hypertension. Estimated daily salt intake was calculated from a causal urine specimen.

Results

Independent from classical cardiovascular risk factors and thyroid disease, we found a significant inverse association between estimated daily salt intake and mental distress. When we analyzed for mental distress and hypertension, we also found a significant association. With the reference group being the lowest tertiles of estimated daily salt intake, the multivariable odds ratios (ORs) of mental distress and mental distress with hypertension for the highest tertiles were 0.50 (0.29–0.88) and 0.46 (0.22–0.96).

Conclusions

Lower estimated daily salt intake is a significant risk of mental distress for rural community-dwelling Japanese men. Since depression is reported to be associated with cardiovascular disease, risk estimation for the lower intake of salt on mental distress, especially for mental distress with hypertension, may become an important tool to prevent cardiovascular disease.     

Clinical manifestations associated with neurocysticercosis: a systematic review

Background

The clinical manifestations of neurocysticercosis (NCC) are poorly understood. This systematic review aims to estimate the frequencies of different manifestations, complications and disabilities associated with NCC.

Methods

A systematic search of the literature published from January 1, 1990, to June 1, 2008, in 24 different electronic databases and 8 languages was conducted. Meta-analyses were conducted when appropriate.

Results

A total of 1569 documents were identified, and 21 included in the analysis. Among patients seen in neurology clinics, seizures/epilepsy were the most common manifestations (78.8%, 95%CI: 65.1%–89.7%) followed by headaches (37.9%, 95%CI: 23.3%–53.7%), focal deficits (16.0%, 95%CI: 9.7%–23.6%) and signs of increased intracranial pressure (11.7%, 95%CI: 6.0%–18.9%). All other manifestations occurred in less than 10% of symptomatic NCC patients. Only four studies reported on the mortality rate of NCC.

Conclusions

NCC is a pleomorphic disease linked to a range of manifestations. Although definitions of manifestations were very rarely provided, and varied from study to study, the proportion of NCC cases with seizures/epilepsy and the proportion of headaches were consistent across studies. These estimates are only applicable to patients who are ill enough to seek care in neurology clinics and likely over estimate the frequency of manifestations among all NCC cases.     

Salt-Restriction-Spoon Improved the Salt Intake among Residents in China

Objective

To evaluate the effect of an improved salt-restriction spoon on the attitude of salt-restriction, the using rate of salt-restriction-spoon, the actual salt intake, and 24-hour urinary sodium excretion (24HUNa).

Design

A community intervention study.

Setting

Two villages in Beijing.

Participants

403 local adult residents being responsible for home cooking.

Intervention

Participants were randomly assigned to the intervention group or the control group. Those in the intervention group were provided with an improved salt-restriction-spoon and health education, and were informed of their actual salt intake and 24HUNa. Not any intervention was given to those in the control group.

Main Outcome Measures

The scores on the variables of Health Belief Model, the using rate of salt-restriction-spoon, the actual salt intake, and 24HUNa.

Analysis

Covariance analyses, Chi-square tests, Student’s t tests, and repeated measures analyses of variance.

Results

After 6 months of intervention, the intervention group felt significantly less objective barriers, and got access to significantly more cues to action as compared to the control group. The using rate and the correctly using rate of salt-restriction-spoon were significantly higher in the intervention group. The daily salt intake decreased by 1.42 g in the intervention group and by 0.28 g in the control group, and repeated measures analysis of variance showed significant change over time (F = 7.044, P<0.001) and significant difference between groups by time (F = 2.589, P = 0.041). The 24HUNa decreased by 34.84 mmol in the intervention group and by 33.65 mmol in the control group, and repeated measures analysis of variance showed significant change over time (F = 14.648, P<0.001) without significant difference between groups by time (F = 0.222, P = 0.870).

Conclusions

The intervention effect was acceptable, therefore, the improved salt-restriction-spoon and corresponding health education could be considered as an alternative for salt reduction strategy in China and other countries where salt intake comes mainly from home cooking.     

Urinary Sodium Excretion and Dietary Sources of Sodium Intake in Chinese Postmenopausal Women with Prehypertension

Background

Reducing salt intake in communities is one of the most effective and affordable public health strategies to prevent hypertension, stroke and renal disease. The present study aimed to determine the sodium intake in Hong Kong Chinese postmenopausal women and identify the major food sources contributing to sodium intake and urine excretion.

Methods

This was a cross-sectional study among 655 Chinese postmenopausal women with prehypertension who were screened for a randomized controlled trial. Data collection included 24 h urine collection for the measurement of sodium, potassium and creatinine, 3-day dietary records, anthropometric measures and questionnaire survey on demographic data and dietary habits.

Results

The average salt intake estimated from urinary excretion was 7.8±3.2 g/d with 82.1% women above WHO recommendation of 5 g/day. Food groups as soup (21.6%), rice and noodles (13.5%), baked cereals (12.3%), salted/preserved foods (10.8%), Chinese dim sum (10.2%) and sea foods (10.1%) were the major contributors of non-discretionary salt. Discretionary salt use in cooking made a modest contribution to overall intake. Vegetable and fruit intake, age, sodium intake from salted foods, sea foods and soup were the independent determinants of urinary sodium excretion.

Conclusions

Our data revealed a significant room for reduction of the sodium intake. Efforts to reduce sodium from diets in Hong Kong Chinese postmenopausal women should focus on both processed foods and discretionary salt during cooking. Sodium reduction in soup and increase in fruit intake would be potentially effective strategy for reducing sodium.     

Compensatory Growth of Congenital Solitary Kidneys in Pigs Reflects Increased Nephron Numbers Rather Than Hypertrophy

Background

Patients with unilateral MultiCystic Kidney Dysplasia (MCKD) or unilateral renal agenesis (URA) have a congenital solitary functioning kidney (CSFK) that is compensatory enlarged. The question whether this enlargement is due to increased nephron numbers and/or to nephron hypertrophy is unresolved. This question is of utmost clinical importance, since hypertrophy is associated with a risk of developing hypertension and proteinuria later in life with consequent development of CKD and cardiovascular disease.

Methodology/Principal Findings

In a cohort of 32,000 slaughter pigs, 7 congenital solitary functioning kidneys and 7 control kidneys were identified and harvested. Cortex volume was measured and with a 3-dimensional stereologic technique the number and volume of glomeruli was determined and compared. The mean total cortex volume was increased by more than 80% and the mean number of glomeruli per kidney was 50% higher in CSFKs than in a single control kidney, equaling 75% of the total nephron number in both kidneys of control subjects. The mean total glomerular volume in the CSFKs was not increased relative to the controls.

Conclusions/Significance

Thus, in pigs, compensatory enlargement of a CSFK is based on increased nephron numbers. Extrapolation of these findings to the human situation suggests that patients with a CSFK might not be at increased risk for developing hyperfiltration-associated renal and cardiovascular disease in later life due to a lower nephron number.     

Serum Inflammatory Cytokine Levels Correlate with Hand-Foot-Mouth Disease Severity: A Nested Serial Case-Control Study

Background

Hand-food-mouth disease (HFMD) cases can be fatal. These cases develop rapidly, and it is important to predict the severity of HFMD from mild to fatal and to identify risk factors for mild HFMD. The objective of this study was to correlate the levels of serum inflammatory cytokines with HFMD severity.

Methods

This study was designed as a nested serial case-control study. The data collected included general information, clinical symptoms and signs, laboratory findings and serum cytokine levels.

Results

The levels of IL-4, IL-6, IL-10, TNF-α and IFN-γ in patients with severe HFMD were significantly higher than in mild patients during the 2nd to 5th day after disease onset. The levels of IL-4, IL-6, IL-10 and IFN-γ increased from the 2nd day to the 4th day and later decreased. The levels of TNF-α were high on the first two days and subsequently decreased. The changes of IL-10, TNF-α and IFN-γ in the controls were similar for all cases. The levels of IL-4, IL-6 and IL-17 in the controls were not significantly different with the progression of HFMD.

Conclusions

Our findings indicate that the IL-4, IL-6, IL-10, TNF-α and IFN-γ levels correlate with HFMD severity.     

Gastric Bypass Surgery Is Followed by Lowered Blood Pressure and Increased Diuresis - Long Term Results from the Swedish Obese Subjects (SOS) Study

Objective

To compare two bariatric surgical principles with regard to effects on blood pressure and salt intake.

Background

In most patients bariatric surgery induces a sustained weight loss and a reduced cardiovascular risk profile but the long-term effect on blood pressure is uncertain.

Methods

Cohort study with data from the prospective, controlled Swedish Obese Subjects (SOS) study involving 480 primary health care centres and 25 surgical departments in Sweden. Obese patients treated with non-surgical methods (Controls, n = 1636 and n = 1132 at 2 y and 10 y follow up, respectively) were compared to patients treated with gastric bypass (GBP, n = 245 and n = 277, respectively) or purely restrictive procedures (vertical banded gastroplasty or gastric banding; VBG/B, n = 1534 and n = 1064, respectively).

Results

At long-term follow-up (median 10 y) GBP was associated with lowered systolic (mean: −5.1 mm Hg) and diastolic pressure (−5.6 mmHg) differing significantly from both VBG/B (−1.5 and −2.1 mmHg, respectively; p<0.001) and Controls (+1.2 and −3.8 mmHg, respectively; p<0.01). Diurnal urinary output was +100 ml (P<0.05) and +170 ml (P<0.001) higher in GBP subjects than in weight-loss matched VBG/B subjects at the 2 y and 10 y follow-ups, respectively. Urinary output was linearly associated with blood pressure only after GBP and these patients consumed approximately 1 g salt per day more at the follow-ups than did VBG/B (P<0.01).

Conclusions

The purely restrictive techniques VBG/B exerted a transient blood pressure lowering effect, whereas gastric bypass was associated with a sustained blood pressure reduction and an increased diuresis. The daily salt consumption was higher after gastric bypass than after restrictive bariatric surgery.