Autopsy study examining non-chronic kidney disease versus chronic kidney disease caused by hypertensive-nephrosclerosis in elderly subjects.

BACKGROUND: The aim of this autopsy study was to clarify the differences of renal histopathology between non-chronic kidney disease (CKD) and CKD caused by hypertensive-nephrosclerosis in the elderly and during the aging process. METHODS: We examined autopsy specimens from 105 elderly patients (53 male subjects; mean age, 86.2 years) including 44 patients with CKD as a result of nephrosclerosis. The analysis was divided into two groups depending on whether they had CKD. RESULTS: The incidences of arterial intimal thickening (AIT), obsolescent-type global glomerulosclerosis (OB), and interstitial fibrosis and tubular atrophy (IF/TA) were higher in the CKD group than in the non-CKD group (all p < 0.01). These factors were all correlated with each other (AIT vs. OB, r = 0.43; AIT vs. IF/TA, r = 0.25; OB vs. IF/TA, r = 0.53). IF/TA had the strongest association with hypertension and decreased eGFR. In the non-CKD group, the frequency of OB was more than 20% in subjects aged 90 years or older. However, the individuals in the non-CKD group tended to have compensatory glomerular hypertrophy with increasing age and a retained eGFR, while the CKD group was unable to obtain compensatory hypertrophy and had a lower eGFR. We also found that AIT, OB and IF/TA occurred independently of systemic atherosclerosis. CONCLUSIONS: Non-CKD in the elderly refers to the so-called aging kidney. The progression from aging kidney to CKD caused by nephrosclerosis was influenced by increases in AIT, OB and IF/TA. IF/TA was thought to be the most important downstream factor in the progression of aging kidney to CKD.

Identification of histopathological and clinical spectrum of diabetic kidney disease based on an unsupervised hierarchical clustering analysis of elderly autopsy specimens.

AIM: Diabetic kidney disease (DKD), a chronic kidney disease caused by diabetes and other comorbidities, is the leading cause of end-stage renal disease. The pathogenesis of DKD is diverse and influenced by various causes, some but not all of which cause proteinuria. Some factors such as hypertension can modify DKD. Therefore, the spectrum of DKD is difficult to elucidate and remains unsolved. This study aims to classify and characterize DKD. METHODS: We examined autopsy specimens from type 2 diabetes mellitus (DM) (n = 44) and non-DM (n = 21) groups. RESULTS: The frequency of interstitial fibrosis and tubular atrophy was higher in patients with proteinuric DKD than in those with non-proteinuric DKD. The presence of polar vasculosis was associated with hypertension in DKD. In addition, an unsupervised hierarchical clustering analysis revealed the spectrum of renal histopathology findings for more-proteinuric and less-proteinuric DKD. With changes in the diagnostic criteria for hypertension and advances in antihypertensive drugs, the pathogenesis of DKD may be changing. Furthermore, a decision tree model suggested how diabetes, hypertension, and dyslipidemia interacted in predicting the characteristics of DKD. CONCLUSION: Polar vasculosis is a good indicator of the presence of DM and hypertension. Furthermore, the histopathological and clinical spectrum of DKD were related to the interaction of diabetes, hypertension, and dyslipidemia. These histopathological and clinical results may help to show the range of patient characteristics when conducting clinical trials and could help to determine whether chronic kidney disease is caused by DM or some other cause.

Geriatric assessment of estimated glomerular filtration rate: a cross-sectional study.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is routinely calculated based on the serum creatinine level. However, the validity of such calculation in the geriatric population has not been sufficiently assessed. To examine whether the discrepancies between the eGFR determined based on the serum creatinine (eGFRcr) and that based on the serum cystatin C (eGFRcys) may be influenced to a lesser degree, by factors such as aging and muscle mass. METHODS: We measured the cystatin C and creatinine levels in 19,764 subjects (mean 77.0 years) and the eGFRcys and eGFRcr using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Japanese, and Berlin Invitation Study (BIS) equations were calculated. RESULTS: The mean measured eGFRcys and eGFRcr values by the CKD-EPI equation were 48.2 and 66.6 ml/min/1.73 m2 body surface area, respectively. The correlation between the eGFRcr (x) and eGFRcys (y) was y = 0.728x (r = 0.867; p < 0.001). Analysis of the slope among all ages could be shown by the relation, eGFRcys = (0.43 + 0.33/(1 + 10^((82-age)* - 0.046)))*eGFRcr. The correlation between the eGFRcr and eGFRcys by the Japanese equation were also similar. However, when it was calculated by the BIS equation, no drop of the slope of the linear regression line was observed with age. CONCLUSIONS: The eGFRcr was overestimated irrespective of whether the CKD-EPI or the Japanese equation was used. We could convert eGFRcr into eGFRcys by an equation using age. Estimation of eGFR including serum cystatin C was more accurate in elderly people.

[Evaluation of sub-maximal aerobic capacity level determined by double product break point (DPBP) among Japanese adults].

OBJECTIVES: The purpose of this study was to determine sub-maximal aerobic capacity levels evaluated by metabolic equivalents (unit is METs) at the double product break point (DPBP) and elucidate the safe and effective average exercise intensity among Japanese adults. A total of 438 subjects (123 males and 315 females) who participated in the exercise prescription course with measurement of the DPBP during a continuous incremental exercise test with a bicycle METHODS: ergometer were enrolled in this study. The DP (heart rate-systolic blood pressure product) featured rapid increase with increasing exercise load during the continuous incremental exercise test. RESULTS: The metabolic equivalents at the DPBP level for males and females were 5.3+/-0.9 METs and 4.9+/-0.7 METs, respectively. Interestingly, the metabolic equivalent at the DPBP level in 87.2% of the study subjects was less than 6 METs. CONCLUSIONS: This study indicated that some physical activities above moderate intensity, such as the stair climbing (8 METs), might be inappropriate as health promotion exercises. Thus, the upper limit of exercise intensity for health promotion was 6 METs, especially if the subject was at cardiovascular risk. In addition, it was found necessary to make synthetic judgments in consideration of heart rate and rating of perceived exertion (RPE) during exercise.

Efficacy and safety of low-dose corticosteroid with azathioprine in the treatment of elderly-onset IgA vasculitis with nephritis.

The diagnosis of elderly-onset IgA vasculitis (IgAV) and its prognosis can be difficult to ascertain because of its rarity and the frequent presence of comorbidities. Furthermore, the treatment of elderly-onset IgAV remains controversial. We report a case of IgAV in an 87-year-old patient. Renal involvement was detected early during the IgAV follow-up. He was treated with low-dose corticosteroid and azathioprine, which led to a complete remission without any adverse effects. This suggests that precise intervention with early diagnosis and careful renal follow-up may prevent renal failure and that low-dose steroids with azathioprine can be an effective treatment for elderly-onset IgAV with nephritis.

Autochthonous sporadic acute hepatitis E caused by two distinct subgenotype 3b hepatitis E virus strains with only 90% nucleotide identity.

Hepatitis E, which is caused by hepatitis E virus (HEV), is a public health concern in Japan, where the zoonotic food-borne transmission of HEV from domestic pigs and wild boars plays an important role. A 44-year-old Japanese man with autochthonous sporadic acute hepatitis E was admitted with general fatigue and moderate liver dysfunction. In the present study, two distinct HEV strains were recovered from the patient, who had consumed the raw or undercooked pig liver and intestine two or three times per week for 3 months before the disease onset. The recovered HEV strains were segregated into two clusters within subgenotype 3b, the open reading frame (ORF)1 and ORF2 sequences of which each showed ~10% difference, indicating HEV mixed infection. Because most notified patients with clinical HEV infection in Japan are diagnosed based on the detection of IgA-class HEV antibodies and because serum samples from only a limited number of HEV-infected patients are subjected to HEV RNA detection and nucleotide sequencing, it is very likely that patients with HEV mixed infection remain largely overlooked. The identification of sources of autochthonous HEV infection remains an important goal. Continued efforts to trace the sources of acute or chronic autochthonous HEV infection are warranted.

Localization and ontogeny of aquaporin-1 and -4 expression in iris and ciliary epithelial cells in rats.

The precise localization of aquaporin (AQP)1 and AQP4 was studied in iris and ciliary epithelial cells, in both mature and developing rats, to elucidate the molecular mechanisms underlying aqueous humor balance. Anterior segments of eyes dissected from embryonic day (E)13, E15, E18, and E20, postnatal day (P)0, P7, and P14, and postnatal week 8 rats were subjected to immunofluorescence analysis with AQP isoform-specific antibodies. In adult rat eye, AQP1 was localized to the apical and basolateral plasma membranes of iris epithelial cell layers and of anterior ciliary non-pigmented epithelial (NPE) cells. Conversely, AQP4 was localized to the basolateral plasma membrane of NPE cells in ciliary epithelium and the posterior iris. Developmentally, AQP1 was detected as early as E15 in immature iris and ciliary epithelial cells, and expression persisted throughout development up to adulthood. In contrast, AQP4 was first observed at P7 in the developing pars plicata, and the AQP4-positive area gradually spread to cover the entire pars plicata as development proceeded. These findings indicate that both AQP1 and AQP4 contribute to aqueous humor secretion in the rat eye, thereby maintaining proper intraocular pressure. Moreover, AQP appears to play a major role in aqueous humor secretion in early eye development. This study thus provides a basis for understanding the molecular mechanisms of aqueous humor secretion in pathological and physiological conditions.