Serum Creatinine Modifies Associations between Body Mass Index and Mortality and Morbidity in Prevalent Hemodialysis Patients

Background

High body mass index (BMI) is paradoxically associated with better outcomes in hemodialysis (HD) patients. This study aimed to examine whether serum creatinine (Cr), a marker of muscle mass, could modify the association between BMI, and mortality and morbidity in prevalent HD patients.

Methods

A retrospective study was conducted using a nationwide database from the registry of the Japanese Society for Dialysis Therapy. A total of 119,099 patients were selected (age: 65±12 years; median time on HD: 5.6 years; male: 62%), and we examined the association of basal BMI with mortality and morbidity after a 1-year period. Patients were stratified either by BMI into 4 groups or by serum Cr levels into 3 tertiles. Odds ratio (OR) [95% confidence interval] was calculated by multivariate logistic regression analysis.

Results

Higher BMI did not predict a higher 1-year total mortality. However, when we stratified the patients by serum Cr levels, the risk of cardiac death became significantly higher in obese patients with the lowest Cr levels, in both males (OR 2.82 [1.51–5.27], p<0.01) and females (OR 2.00 [1.03–3.90], p<0.05). The risk of new cerebral infarction was also higher in obese male patients within the lowest Cr tertile. In contrast, there was a significantly lower risk of cardiac, cerebrovascular, and infection-related death in non-obese patients with higher levels of Cr. Higher serum Cr was also related to a lower risk of cardiovascular events and hip fracture in non-obese HD patients.

Conclusions

The obesity paradox was found to be present in HD patients only when obesity was defined by BMI. Decreased serum Cr levels were found to be positively associated with clinical poor outcomes in all BMI groups. Thus, irrespective of BMI, the evaluation of serum Cr levels is important to predict mortality and morbidity in patients receiving regular HD.     

A Development of Nucleic Chromatin Measurements as a New Prognostic Marker for Severe Chronic Heart Failure

Background

Accurate prediction of both mortality and morbidity is of significant importance, but it is challenging in patients with severe heart failure. It is especially difficult to detect the optimal time for implanting mechanical circulatory support devices in such patients. We aimed to analyze the morphometric ultrastructure of nuclear chromatin in cardiomyocytes by developing an original clinical histopathological method. Using this method, we developed a biomarker to predict poor outcome in patients with dilated cardiomyopathy (DCM).

Methods and Results

As a part of their diagnostic evaluation, 171 patients underwent endomyocardial biopsy (EMB). Of these, 63 patients diagnosed with DCM were included in this study. We used electron microscopic imaging of cardiomyocyte nuclei and an automated image analysis software program to assess whether it was possible to detect discontinuity of the nuclear periphery. Twelve months after EMB, all patients with a discontinuous nuclear periphery (Group A, n = 11) died from heart failure or underwent left ventricular assist device (VAD) implantation. In contrast, in patients with a continuous nuclear periphery (Group N, n = 52) only 7 patients (13%) underwent VAD implantation and there were no deaths (p<0.01). We then evaluated chromatin particle density (Nuc-CS) and chromatin thickness in the nuclear periphery (Per-CS) in Group N patients; these new parameters were able to identify patients with poor prognosis.

Conclusions

We developed novel morphometric methods based on cardiomyocyte nuclear chromatin that may provide pivotal information for early prediction of poor prognosis in patients with DCM.     

Histochemical quantification of dopa-oxidase (tyrosinase) activity in epidermal melanocytes.

The graphical method of Lineweaver-Burk was applied to the histochemical system to obtain quantitative information on the dopa-oxidase activity in human epidermal melanocytes. In vitro experiment showed that the incubation time necessary for yielding a certain amount of dopa-melanin is related to the amount of enzyme present. In the case of histochemical experiment, the time required for the first appearance of dopa-melanin deposition in melanocytes at various substrate concentrations was plotted against the reciprocal of the substrate concentration. This technique made it possible to compare the dopa-oxidase activity at various sites of the tissue.     

Out-of-plane distortion of the iron in ferrohemoglobin due to pseudo-Jahn-Teller effect

The large out-of-plane distortion of the iron atom of deoxyform ferrous hemoglobin is attributed to the pseudo-Jahn-Teller effect, which is caused by the odd parity vibrational mode and the electronic states of different parity. It is suggested that this effect in general may be seen in transition metal or rare earth ion compounds.     

Chromosaponin I increases mechanical extensibility of lettuce root cell walls

Chromosaponin I (CSI), at 3 m M , stimulates the growth of lettuce roots ( Lactuca sativa L. cv. Grand Rapids) with increasing fresh weight and decreasing root diameter compared with control. To analyze the mechanism of action of CSI, mechanical properties of lettuce root cell walls were examined with a tensiometer and the osmotic potential of the cell sap was measured with a vapor pressure osmometer. The mechanical extensibility of the cell wall was increased by CSI treatment, while the osmotic potential remained constant. Under osmotic stress, through addition of 0.225 M mannitol, the mechanical extensibility of the cell wall was increased before stimulation of growth was observed. These results suggest that cell wall-loosening is involved in the growth stimulation induced by CSI.