(23)Na magnetic resonance imaging of tissue sodium

Hypertension is linked to disturbed total-body sodium (Na(+)) regulation; however, measuring Na(+) disposition in the body is difficult. We implemented (23)Na magnetic resonance spectroscopy ((23)Na-MR) and imaging technique ((23)Na-MRI) at 9.4T for animals and 3T for humans to quantify Na(+) content in skeletal muscle and skin. We compared (23)Na-MRI data with actual tissue Na(+) content measured by chemical analysis in animal and human tissue. We then quantified tissue Na(+) content in normal humans and in patients with primary aldosteronism. We found a 29% increase in muscle Na(+) content in patients with aldosteronism compared with normal women and men. This tissue Na(+) was mobilized after successful treatment without accompanying weight loss. We suggest that, after further refinements, this tool could facilitate understanding the relationships between Na(+) accumulation and hypertension. Furthermore, with additional technical advances, a future clinical use may be possible.     

Elevation of serum and urine levels of TIMP-1 and tenascin in patients with renal disease.

BACKGROUND: Chronic kidney disease is characterized by increased synthesis and inhibited destruction of collagenous and non-collagenous matrix proteins. Elevation of collagen fragments has been demonstrated in the serum and urine of patients with renal disease, but the dynamics of renal matrix deposition remain difficult to determine. METHODS: To obtain a further insight into renal matrix metabolism we have assessed whether serum and urine concentrations of the non-collagenous protein, tenascin, and of the tissue inhibitor of metalloproteinases 1 (TIMP-1) are altered in association with renal disease. Serum and urine concentrations of both proteins were determined using a newly developed magnetic particle enzyme immunoassay and were compared with levels of N-terminal procollagen III-peptide (PIIINP) and related to the degree of renal failure and proteinuria. RESULTS: Circulating levels of tenascin and TIMP-1 were moderately, but significantly, higher in patients with chronic renal disease (n=54; mean creatinine clearance, 62 ml/min) than in healthy controls (n=176). Urine concentrations per mg creatinine of tenascin and TIMP-1 were significantly lower than serum levels, but were on average six- and 18-fold higher, respectively, in patients with renal disease than in controls. Urinary concentrations increased with progressive reduction in renal function, but were unrelated to proteinuria. TIMP-1 concentrations in urine correlated with tenascin, which is compatible with the impact of TIMP-1 on the accumulation of matrix proteins. The concentrations of proteins measured did not differ depending on the aetiology of renal disease. CONCLUSION: Urinary concentrations of tenascin and TIMP-1 are elevated in association with renal disease and may reflect specific aspects of renal fibrosis.     

Frailty prevalence and 10-year survival in community-dwelling older adults: results from the ESTHER cohort study

The frailty index (FI), defined by a deficit accumulation approach, has emerged as a promising concept in gerontological research, but applications have been mostly restricted to populations from Canada and the United States aged 65 years or older. Baseline data from the German ESTHER cohort study (N 9,886; age 50–75; mean follow-up 8.7 years) were used to create a FI through a deficit accumulation approach. For estimation of frailty prevalence, we used cut-points for the FI to define three categories (non-frail 0 to ≤0.20; pre-frail >0.20 to <0.45; frail ≥0.45). We assessed variation of the FI by age and sex: 10-year survival according to baseline FI was assessed by Kaplan–Meier curves and bivariate and multivariate Cox proportional hazard models. Cubic splines were used to assess sex-specific dose–response associations. Prevalence of frailty was 9.2 and 10.5 % in women and men, respectively. Age-specific prevalence of frailty ranged from 4.6 % in 50–54 year old participants to 17.0 % in 70–75 year old participants. Below 60 years of age, men had a higher FI than women. However, the FI showed a stronger increase with age among women (3.1 % per year) than among men (1.7 % per year) and was higher among women than men in older age groups. Adjusted hazard ratios (95 % confidence intervals) for all-cause mortality were 1.08 (0.84–1.39), 1.32 (1.05–1.66), 1.77 (1.41–2.22), and 2.60 (2.11–3.20) for the 2nd, 3rd, 4th, and 5th quintile of the FI compared to 1st quintile, respectively. There was a strong dose–response relationship between the FI and total mortality among both men and women and both younger (<65 years) and older subjects. We found sex differences in the FI and its increase with age, along with a consistent strong association of the FI with mortality in both sexes, even for age group 50–64.     

The use of magnetic resonance imaging to examine ossification of the proximal tibial epiphysis for forensic age estimation in living individuals

The establishment of radiation-free examination procedures in the field of forensic age diagnostics in living persons is to be considered of special scientific interest so as to minimize necessary exposure to X-rays while facilitating additional assessment of skeletal development in all cases. To this end, the advantages offered by magnetic resonance imaging in securing a practical application which is as unrestricted and complication-free as possible should be among the methods exploited in investigating such indicators of skeletal maturity. Within the framework of a retrospective study, we investigated the ossification status of the proximal tibial epiphysis on the MRI scans of 124 females and 166 males aged between 10 and 30 years. All the images had been generated on a 3.0 T scanner using a T1-weighted turbo spin-echo sequence. When evaluating the ossification stage, a combination of modified classifications proposed by Schmeling et al. and by Kellinghaus et al. was used. The statistical evaluation included calculation of a variety of measures to describe specific ossification stages as well as kappa coefficients to assess intra- and inter-observer agreement on diagnoses of individual stages. In forensic contexts, completion of the 14th year of life can be adequately evidenced in females with an ossification stage IV according to Schmeling et al. and in males with an ossification stage III c according to Kellinghaus et al. or an ossification stage IV according to Schmeling et al. In forensic contexts, the presence of an ossification stage IV according to Schmeling et al. can prove that the age of 16 years has been exceeded only in the male sex, whereby for age estimation purposes the diagnosis should be in line with other skeletal maturity indicators. The results available displayed a high degree of intra- and inter-observer agreement. Examination of the ossification status of the proximal tibial epiphysis using magnetic resonance imaging represents an effective additional tool for use in radiation-free forensic age diagnostics in living persons.     

Low-flow CO2 removal integrated into a renal-replacement circuit can reduce acidosis and decrease vasopressor requirements

Introduction

Lung-protective ventilation in patients with ARDS and multiorgan failure, including renal failure, is often paralleled with a combined respiratory and metabolic acidosis. We assessed the effectiveness of a hollow-fiber gas exchanger integrated into a conventional renal-replacement circuit on CO₂ removal, acidosis, and hemodynamics.

Methods

In ten ventilated critically ill patients with ARDS and AKI undergoing renal- and respiratory-replacement therapy, effects of low-flow CO₂ removal on respiratory acidosis compensation were tested by using a hollow-fiber gas exchanger added to the renal-replacement circuit. This was an observational study on safety, CO₂-removal capacity, effects on pH, ventilator settings, and hemodynamics.

Results

CO₂ elimination in the low-flow circuit was safe and was well tolerated by all patients. After 4 hours of treatment, a mean reduction of 17.3 mm Hg (−28.1%) pCO₂ was observed, in line with an increase in pH. In hemodynamically instable patients, low-flow CO₂ elimination was paralleled by hemodynamic improvement, with an average reduction of vasopressors of 65% in five of six catecholamine-dependent patients during the first 24 hours.

Conclusions

Because no further catheters are needed, besides those for renal replacement, the implementation of a hollow-fiber gas exchanger in a renal circuit could be an attractive therapeutic tool with only a little additional trauma for patients with mild to moderate ARDS undergoing invasive ventilation with concomitant respiratory acidosis, as long as no severe oxygenation defects indicate ECMO therapy.     

Formation of cysts by principal-like MDCK cells depends on the synergy of cAMP- and ATP-mediated fluid secretion

It has been suggested that more than 70% of the renal cysts in patients with autosomal dominant polycystic kidney disease (ADPKD) arise from the collecting duct and that within this segment cysts originate almost exclusively from principal rather than intercalated cells. The mechanisms for this predisposition of principal cells have so far remained elusive. We, therefore, used Madin–Darby canine kidney (MDCK) subclones resembling principal cells and alpha-intercalated cells in a three-dimensional in vitro model to determine differences in cystogenesis and cyst growth, including the response to cyclic adenosine monophosphate (cAMP) elevation and the dependence on ATP signaling. We found that in vitro cysts developed only from principal-like but not from intercalated-like MDCK cell clones. This specificity could be verified in mixed MDCK cultures enriched for principal- or intercalated-like cells. In vitro cyst growth upon elevation of intracellular cAMP was mainly driven by fluid secretion, rather than increased cell proliferation. The cAMP-dependent fluid secretion was found to depend on extracellular adenosine-5'-triphosphate (ATP) and to act synergistically with purinergic signaling, as the use of the ATP scavenger apyrase, as well as the P2 receptor inhibitor suramin, reduced cAMP-driven fluid secretion, while increasing extracellular ATP potentiated cAMP-mediated cyst growth. In conclusion, we provide in vitro evidence for the ability of principal rather than intercalated cells to form cysts, based on a synergism of cAMP and ATP signaling in enhancing apical fluid secretion.