Anemia as a risk factor for all-cause mortality: obscure synergic effect of chronic kidney disease

Background

Anemia is common in chronic kidney disease (CKD) and may be associated with mortality in CKD patients. However, few studies have examined this relationship in Asian populations.

Methods

A total of 62,931 Japanese people (age 64.0 ± 8.0 years; men 38.5%) were followed up from 2008 to 2012. Participants were divided into six groups in accordance with their estimated glomerular filtration rate (eGFR) (<45, 45–59, ≥60 mL/min/1.73 m²) and by hemoglobin levels (13.0 g/dL for men; 12.0 g/dL for women). Hazard ratio and confidence interval (CI) for mortality with a combination of eGFR and anemia were calculated. After matching using propensity score (PS) for anemia, survival analysis between anemic and non-anemic people, independent from some variables, including eGFR, was performed.

Results

A total of 828 (1.3%) participants died (non-anemic vs. anemic, 1.2 vs. 2.3%, p < 0.01). Multivariable Cox analysis showed that, independent of eGFR levels, anemic people had significantly higher mortality. Anemic people were found to have significantly poorer survival than non-anemic people as per a log-rank test (p < 0.01) for the PS-matching cohort. Further stratified logistic analysis using PS in the overall cohort odds ratio (95% CI) showed 2.25 (1.89–2.67) with p < 0.01.

Conclusion

The results of the present study showed that anemia was an independent risk factor of all-cause mortality.

     

U-shaped association between body mass index and proteinuria in a large Japanese general population sample

Background

There is little data on the association between body mass index (BMI) and proteinuria.

Methods

This was a cross-sectional cohort study assessing the association between BMI and proteinuria in a large Japanese population. Using a nationwide health check-up database of 212,251 Japanese aged >20 years with no pre-existing cardiovascular diseases (185,183 men, median age 66 years; 127,068 women, median age 65 years), we examined the association between BMI and proteinuria (≥1+ on dipstick).

Results

Subjects were divided into 11 subgroups by BMI grading in 1 kg/m² intervals from 18.5?27.5 kg/m². A BMI of approximately 22 ± 0.5 kg/m² was considered optimal for Japanese; therefore, this subgroup was set as a reference when logistic analysis was applied. Age, waist circumference, height, weight, smoking and drinking habits, use of medications such as antihypertensive, antidiabetic, or antihyperlipidemic, as well as proteinuria, estimated glomerular filtration rate (eGFR), chemistry data, and blood pressure levels were significantly different between subgroups in both genders. The odds ratio for proteinuria showed a U-shape in men and women, even after adjustment for significant covariates such as age, waist circumference, systolic blood pressure, eGFR, fasting plasma glucose, triglyceride, low-density lipoprotein, antihypertensive use, antidiabetic use, antihyperlipidemic use, and lifestyle factors (smoking and drinking). Gender differences were also prominent—a BMI <20.4 kg/m² was significantly associated with proteinuria in men compared to a BMI <18.4 kg/m² in women. On the other hand, a BMI ≥ 25.5 kg/m² was also significantly associated with proteinuria in men compared to a BMI ≥ 22.5 kg/m² in women.

Conclusions

We found that BMI levels were associated with proteinuria in a U-shaped manner and showed marked gender differences. Health guidance should not only focus on higher BMI subjects, but also on thin subjects, in terms of the prevention of chronic kidney disease.     

Neonatal hepatitis in 2 siblings with Seckel syndrome.

Seckel syndrome was described as the prototype of the primordial bird-head type of dwarfism. We report 2 cases of Seckel syndrome in siblings. Both cases showed peculiar phenotypic features. Autopsy was performed and microscopic examination of the livers displayed histologic features of neonatal hepatitis. In addition, our younger patient had central nervous system anomalies such as agenesis of corpus callosum, cerebral cyst, and primitive convolutional pattern. No previous reports of liver disease exist in patients with Seckel syndrome. The pathologic findings of such an unusual association and a review of literature are presented.     

Suppressive effects of valsartan on microalbuminuria and CRP in patients with metabolic syndrome (Val-Mets)

The presence of metabolic syndrome (Mets) increases the risk for cardiovascular disease. There is a significant correlation between the levels of urinary albumin to creatinine ratio (UACR) and high-sensitive C-reactive peptide (hs-CRP), and accumulation of each Mets component. Increasing evidence has shown the importance of blockade of renin-angiotensin-systems (RAS) for reducing urinary albumin excretion and hs-CRP levels in Mets patients. However, the impact of RAS blockade on these effects in hypertensive (HT) Mets patients without diabetes mellitus (DM) has not been evaluated. We prospectively measured the levels of UACR and hs-CRP in 153 HT patients with and without Mets. Body weight; waist circumference; presence of dyslipidemia and DM, and levels of HOMA-R, UACR, and hs-CRP were significantly higher in HT patients with Mets than in those without Mets. After we treated these Mets patients with valsartan for 6 months, blood pressure (BP), UACR, and hs-CRP were decreased, whereas body weight, HOMR-R, and the lipid profile were not changed. In HT Mets patients without DM, 6 months after valsartan administration, levels of UACR and hs-CRP were also significantly decreased by 37.8% (-9.0-56.5%, p < 0.05) and 23.6% (-28.7-73.4%, p < 0.05), respectively. However, the percentage change of UACR and hs-CRP was not correlated with the reduction in BP. Valsartan administration lowered increased levels of chronic inflammation in both HT Mets patients with DM and in those without DM. These results indicate that the anti-inflammatory properties of valsartan might also have beneficial effects in Mets patients without DM.     

Therapeutic effect of tirilazad mesylate (U-74006F), mannitol, and their combination on experimental ischemia

The effect of tirilazad mesylate (U-74006F), mannitol, and their combination was investigated on focal cerebral ischemia induced by permanent middle cerebral artery (MCA) occlusion in rabbits. Rabbits were divided into four groups receiving vehicle, U-74006F, mannitol, and U-74006F plus mannitol. Hematocrit (hct), glucose, mean arterial blood pressure (MABP), pH, PCO₂, and PO₂ were measured both before and after occlusion. Seventy-two hours following the permanent MCA occlusion, the neurological outcome was assessed and a quantitative neuropathologic examination was performed in all rabbits. The neurological outcome was better in the rabbits treated with U-74006F plus mannitol than in the other groups. The size of infarction of the affected hemisphere following MCA occlusion was 49.7% in the control group, 30.6% in the U-74006F group, 47.6% in the mannitol group, and 24.1% in the U-74006F plus mannitol group. There was a statistically significant reduction in infarct size in the U-74006F plus mannitol group compared with the other groups (P<0.05). The ratio of ischemic neurons to total neurons in the cortex was smaller in the U-74006F plus mannitol group than in the other groups. The ratio of ischemic neurons to total neurons in the subcortex was significantly lower in the U-74006F plus mannitol group than in the other groups (P<0.05). Our data provide evidence for the beneficial effects of both U-74006F and U-74006F plus mannitol in promoting neurological recovery and preservation of the ischemic area.     

Cytotoxicity and genotoxicity of clothianidin in human lymphocytes with or without metabolic activation system

Clothianidin (CHN) is a broad-spectrum neonicotinoid insecticide. Limited studies have been carried out on the cytotoxic and genotoxic effects of both CHN using different genotoxicity tests in human cells with or without human metabolic activation system (S9 mix). Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of CHN and its metabolites on human lymphocyte cultures with or without S9 mix using chromosomal aberration (CA) and micronucleus (MN) tests. The cultures were treated with 25, 50, and 100?µg/ml of CHN in the presence (3?h treatment) and absence (48?h treatment) of S9 mix. Dimethyl sulfoxide (DMSO) was used as a solvent control. CHN showed cytotoxic and genotoxic effects due to significant decreases in mitotic index (MI) and nuclear division index (NDI), and significant increases in the CAs, aberrant cells, and MN formation in the absence of S9 mix when compared with solvent control. However, CHN did not significantly induce cytotoxicity and genotoxicity in the presence of S9 mix. Our results indicated that CHN has cytotoxic, cytostatic, and genotoxic potential on human peripheral blood lymphocyte cultures, but not its metabolites under the experimental conditions.     

Cryoglobulin nephropathy with nodular glomerulosclerosis and IgM hyperglobulinemia

Type II cryoglobulin nephropathy usually shows membranoproliferative glomerulonephritis-like glomerular lesions, such as endocapillary proliferation and double-contoured glomerular basement membrane. However, nodular glomerulosclerosis is rarely detected in this type of nephropathy. We report a patient who had nodular glomerulosclerosis and IgM hyperglobulinemia (1060 mg/dl) in addition to typical findings of cryoglobulin nephropathy. No signs of plasma cell dyscrasia, diabetes mellitus, or amyloidosis were detected by histological or laboratory examinations. The nodular lesion was negative for Congo-red stain. Electron micrography revealed that subendothelial and mesangial deposits were granular and tubular in part, showing no microfibril component. Oral prednisolone therapy abrogated proteinuria and no relapsing signs were noted after termination of the therapy. Although the mechanism of nodular lesion formation is unclear, this case suggests a relationship between this kind of nodular formation and high IgM plasma concentrations in cryoglobulin nephropathy. Received: May 24, 1999 / Accepted: September 6, 1999     

Association between renal function and cardiovascular and all-cause mortality in the community-based elderly population: results from the Specific Health Check and Guidance Program in Japan

Background

Chronic kidney disease is a significant risk factor for end-stage kidney disease, cardiovascular events, and premature death. However, the prognostic value of low estimated glomerular filtration rate (eGFR) in the elderly is debatable.

Methods

We determined eGFR using the Japanese equation in 132,160 elderly subjects (65–75 years) who attended the special health checkup (Tokutei-Kenshin) in 2008 and investigated the association between baseline eGFR and 5-year all-cause and cardiovascular mortality.

Results

The median (SD) eGFR was 70.5 ± 15.3 mL/min/1.73 m². During follow-up, we noted 2045 all-cause deaths including 408 from cardiovascular events. A J-shaped curve was obtained when all-cause and cardiovascular mortality rates were compared with decreases in eGFR, with the highest mortality observed for eGFR <45 mL/min/1.73 m². These trends were statistically significant in the Kaplan–Meier analysis (P < 0.001). In the Cox proportional hazard analysis, after adjusting for possible confounders, those with eGFR <45 mL/min/1.73 m², but not eGFR 45–59 mL/min/1.73 m² showed a higher all-cause and cardiovascular mortality than those with eGFR >90 mL/min/1.73 m² [hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.06–1.91 for all-cause mortality, HR 2.28, 95% CI 1.28–4.03 for cardiovascular mortality]. Sex-based subgroup analyses showed similar results for both men and women.

Conclusions

We conclude that eGFR <45 mL/min/1.73 m² is an independent risk factor for all-cause and cardiovascular mortality in the elderly population.