Abstract
Aims
Aortic valve calcification in aortic sclerosis, a precursor of aortic stenosis (AS), is not always present in all three leaflets; how calcification develops in each leaflet is unknown. ...We aimed to investigate the natural history of calcification development in each aortic valve leaflet and the prognostic value of the number of calcified leaflets.
Methods and results
In a retrospective multicentre cohort study of patients undergoing haemodialysis without AS, we observed calcification development in each aortic valve leaflet using echocardiography. We investigated the association between the number of calcified leaflets and AS development and mortality using time-to-event analysis. Among the 1507 patients (mean age, 66 years; 66% male) included in the longitudinal echocardiography analysis, 709 (47%) had aortic sclerosis at baseline: one-leaflet calcified, 370 (52%); two-leaflet calcified, 215 (30%); and three-leaflet calcified, 124 (17%). The median time for one calcified leaflet increase was 3–4 years, and 251 (17%) patients developed AS during a median 3.2-year follow-up. The increased number of calcified aortic valve leaflets was associated with developing AS; compared with that of one-leaflet calcified, the adjusted hazard ratios (aHRs) 95% confidence intervals (CIs) of two- and three-leaflet calcified were 2.12 (1.49–3.00) and 4.43 (3.01–6.52), respectively; the aHR (95% CI) per one calcified leaflet increase was 2.24 (1.96–2.55). It was also associated with all-cause mortality; the aHR (95% CI) per one calcified leaflet increase was 1.18 (1.08–1.27).
Conclusion
The number of calcified aortic valve leaflets strongly predicted AS development and even mortality in patients undergoing haemodialysis, suggesting the usefulness of assessing calcification for each valve leaflet separately using echocardiography.
Graphical Abstract
Graphical Abstract
Aortic valve calcification in patients undergoing haemodialysis typically progresses by one leaflet within 3–4 years, and aortic stenosis (AS) develops approximately 4 years after all three leaflets are calcified. The number of calcified aortic valve leaflets is a predictor of AS development and all-cause mortality.
Proteinuria is a potent predictor of adverse events in general, although a few large studies have reported a J-shaped association between proteinuria and mortality in individuals with glomerular ...filtration rate <30 ml/min/1.73m2. However, this association has not been specifically evaluated among incident dialysis patients.
Among 1,380 Japanese patients who initiated dialysis, we quantified the association of pre-dialysis dipstick proteinuria (negative/trace, 1+, 2+, and ≥3+) with mortality using Cox models adjusting for potential confounders, such as age, gender, clinical history of hypertension, diabetes, and cardiovascular disease.
Mean age of study participants was 67.4 (SD 13.0) years, and 67.6% were men. The most common dipstick proteinuria category was ≥3+ (55.4%), followed by 2+ (31.2%), 1+ (9.9%), and negative or trace (3.5%). Patients with lower proteinuria level were older than those with higher proteinuria. Lower proteinuria was significantly associated with a higher risk of all-cause mortality, even after accounting for potential confounders (p for trend <0.001). In those with negative/trace dipstick proteinuria compared to those with dipstick proteinuria ≥3+, the adjusted hazard ratio was 2.60 95% CI: 1.62-4.17 in the fully adjusted model. Similar findings were observed when analyses were restricted to patients older than 70 years, and when cardiovascular mortality and non-cardiovascular mortality were analyzed separately.
In incident dialysis patients, pre-dialysis proteinuria was inversely associated with mortality risk. Although future studies are needed to identify mechanisms, our findings suggest the need to carefully interpret proteinuria in patients with incident dialysis.
With the global problem of aging, it has become more difficult to improve the prognosis of older dialysis patients. Extended-hours hemodialysis offers longer treatment time compared to conventional ...hemodialysis regimen and provides favorable metabolic status, hemodynamic stability, and increased dietary intake. Despite prior studies reporting that in-center extended-hours hemodialysis can reduce the mortality rate, the treatment impact on elderly patients remains unclear. Therefore, we examined the association between extended-hours hemodialysis compared to conventional hemodialysis and all-cause mortality. Survival analyses using Cox proportional hazard model with multivariable adjustments and propensity-score based method were performed to compare mortality risk between 198 consecutive patients who started in-center extended-hours hemodialysis (Extended-HD) and 1407 consecutive patients who initiated conventional hemodialysis. The median age was 67.1 years in the Extended-HD group and 70.7 years in the conventional hemodialysis group. Extended-HD was associated with lower all-cause mortality in overall patients and the subgroup >70 years (adjusted hazard ratios of 0.60 95% CI, 0.39–0.91 and 0.35 95% CI, 0.18–0.69, respectively). There was a significant interaction between age >70 years and Extended-HD. In conclusion, extended-hours hemodialysis was associated with a lower mortality rate, especially in elderly patients.
Predictive values of mesangial proliferation (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and crescents (C) among 19 validation studies of the Oxford Classification of IgA ...nephropathy (IgAN) were discrepant, especially in Asian patients. These validation studies indicate that cutoffs of MESC score in the Oxford Classification may not be generalizable. Thus, we aimed to improve the clinical value of MESC scores by modifying the cutoff points. A total of 104 patients with IgAN were diagnosed from 2001 to 2012 vai renal biopsy and retrospectively evaluated at Nagoya University Hospital. The cutoff point for modified (M´E´S´C´) was determined using the receiver operating characteristic curve in association with renal outcome in the training cohort. Clinical values of the Oxford MESTC vs M´E´S´C´ cutoff points were analyzed using Kaplan-Meier and Cox regression in association with poor renal outcome in the validation and the entire cohort. Of 104 patients, 12.5% reached poor renal outcome over a median of 6.25 4.16-9.61 years of follow-up. The modified cutoffs were defined as ≥40%, ≥10%, ≥20%, and ≥5% in the glomeruli for M´E´S´, and C´ respectively. In univariate analysis, E´, S ´, and T were significantly associated with poor renal outcome, whereas Oxford MESC, M´, and C´ in the training and validation cohort were not associated with poor renal outcome. Using multivariate analysis in the presence of estimated glomerular filtration rate (eGFR), only E´ was a significant predictive factor for poor renal outcome. The E´ with modified cutoff point of 10% significantly improved predictive value for poor renal outcome in IgAN. Therefore, the clinical value of modified cutoff points for M´E´S´C´ scores should be validated with various cohort studies in different regions.
CD34+ cells maintain vascular homeostasis and predict cardiovascular outcomes. We previously evaluated the association of CD34+ cells with cardiovascular disease (CVD) events over 23 months, but ...long-term CVD outcomes in relation to levels of CD34+ cells in patients on maintenance hemodialysis are unclear. Herein, we analyzed the long-term predictive potential levels of CD34+ cells for CVD outcomes and all-cause mortality. Between March 2005 and May 2005, we enrolled 215 patients on maintenance hemodialysis at Nagoya Kyoritsu Hospital and followed them up to 12.8 years. According to the CD34+ cell counts, patients were classified into the lowest, medium, and highest tertiles. Levels of CD34+ cells were analyzed in association with four-point major adverse CV events (MACEs), CVD death, and all-cause mortality. In univariate analysis age, smoking habit, lower geriatric nutrition risk index, lower calcium × phosphate product, and lower intact parathyroid hormone were significantly associated with the lowest tertile. Whereas, in multivariate analysis, age and smoking habit were significantly associated with the lowest tertile. Among 139 (64.7%) patients who died during a mean follow-up period of 8.0 years, 39 (28.1%) patients died from CVD. Patients in the lowest tertile had a significantly lower survival rate than those in the medium and highest tertiles (p ≤ 0.001). Using multivariable analyses, the lowest tertile was significantly associated with four-point MACEs (hazard ratio 1.80, p = 0.023) and CVD death (hazard ratio 2.50, p = 0.011). In conclusion, our long-term observational study revealed that a low level of CD34+ cells in the circulation predicts CVD outcomes among patients on maintenance hemodialysis.
Proteinuria is a powerful prognostic factor for end-stage renal disease in IgA nephropathy (IgAN) patients. However, it is not known whether proteinuria exacerbations are related to seasonal changes.
...We retrospectively enrolled consecutive patients diagnosed with IgAN by kidney biopsy at our hospital between 2002 and 2014. Proteinuria remission was defined as urinary protein <0.3 g/gCr in two consecutive outpatient urinalyses and exacerbation as urinary protein ≥0.75 g/gCr. Four seasons were defined: spring (March-May), summer (June-August), autumn (September-November), and winter (December-February). We performed a multivariate analysis to identify factors associated with the second remission following a proteinuria exacerbation.
We analyzed 116 patients. Proteinuria remission and exacerbation occurred in 77, and 43 patients, respectively. The incidence of proteinuria exacerbation was significantly higher in autumn and winter than in spring and summer (p = 0.040). The cumulative second remission rate was significantly higher in patients with autumn and winter proteinuria exacerbation than in patients with spring and summer exacerbations (p = 0.0091). In multivariate analyses, exacerbation onset in autumn and winter (hazard ratio HR, 3.51; 95% confidence interval CI, 1.41-8.74) and intensive therapy (HR, 2.26; 95% CI, 1.05-4.88) were significantly associated with a second proteinuria remission.
In IgAN patients in proteinuria remission, proteinuria exacerbation frequently occurred in autumn and winter. Exacerbations occurring in autumn and winter tended to remit early.
Ankle-brachial index (ABI), the first-line diagnostic test for peripheral artery disease, can be falsely elevated when ankle arteries are incompressible, showing a J-shaped association with ...mortality. In this situation, toe-brachial index (TBI) is the recommended test. However, whether TBI provides additional prognostic information beyond ABI in patients on hemodialysis is unknown.
In this retrospective cohort study of 247 Japanese prevalent hemodialysis patients (mean age 66.8 SD 11.6 years), we evaluated mortality (116 deaths over a median follow-up of 5.2 years) related to quartiles of ABI and TBI, as well as three categories of low ABI (≤0.9), normal/high ABI (> 0.9) + low TBI (≤0.6), and normal/high ABI + normal TBI (> 0.6) using multivariable Cox models.
ABI showed a J-shaped association with mortality (adjusted hazard ratio 2.72 95% CI, 1.52-4.88 in the lowest quartile and 1.59 95% CI, 0.87-2.90 in the highest quartile vs. the second highest). Lower TBI showed a potentially dose-response association with mortality (e.g., adjusted hazard ratios 2.63 95% CI, 1.36-5.12 and 2.89 95% CI, 1.49-5.61 in the lowest two quartiles vs. the highest). When three categories by both ABI and TBI were analyzed, those with low ABI (≤0.9) experienced the highest risk followed by normal/high ABI (> 0.9) + low TBI (≤0.6). Among patients with normal/high ABI (> 0.9), the increased mortality risk in individuals with low TBI (≤0.6) compared to those with normal TBI (> 0.6) were significant (adjusted hazard ratio 1.84 95% CI, 1.12-3.02).
Lower TBI was independently associated with mortality in patients on hemodialysis and has the potential to classify mortality risk in patients with normal/high ABI. Our results support the importance of evaluating TBI in addition to ABI in this clinical population.
Background
Over 300,000 patients receive maintenance dialysis in Japan; managing these patients is extremely important. This study aimed to report on prior management of chronic kidney diseases and ...prognostication after dialysis initiation.
Patients and methods
Seventeen institutions participated in the Aichi cohort study of prognosis in patients newly initiated into dialysis and recruited patients over a period of 2 years. Exclusion criteria were (1) patients under 20 years; (2) patients who died before hospital discharge; and (3) patients who could not provide consent.
Result
Here, we showed data on dialysis initiation time. Of 1524 patients with mean age of 67.5 ± 13.0 years, 659 patients were put on dialysis following diabetic nephropathy diagnosis. At dialysis initiation time, creatinine and estimated glomerular filtration rate levels were 8.97 ± 3.21 mg/dl and 5.45 ± 2.22 ml/min/1.73 m
2
, respectively. Medications taken were angiotensin II receptor blockers in 866; angiotensin-converting enzyme inhibitors in 135; calcium antagonist in 1202; and diuretics, alone or in combination, in 1059. Among patients with diabetic nephropathy, many had increased body weight and systolic blood pressure and were taking loop and thiazide diuretics at dialysis initiation time. Many patients with diabetic nephropathy had coronary artery disease and percutaneous coronary intervention.
Conclusion
Many patients with diabetic nephropathy who registered for this study had coronary artery disease and problems with excess body fluid. Further analyses may clarify how underlying conditions and disease management before and after dialysis initiation affect prognosis.
Gouty arthritis is a metabolic disorder associated with hyperuricemia. Despite the development of novel pharmacotherapies, some hyperuricemia patients are drug refractory and develop gout. A ...74-year-old man with frequent gouty attacks and chronic renal failure presented with asymmetrical polyarthritis affecting multiple joints. The diagnosis of gout was confirmed based on the presence of monosodium urate crystals in the patient's right wrist. The administration of systemic corticosteroids relieved the joint inflammation and pain; however, the urate level increased to 28 mg/dL and the gout attacks recurred. Combined allopurinol, febuxostat, and benzbromarone therapy reduced the urate level to <6 mg/dL, and the attacks gradually declined. This is the first report of two xanthine oxidase inhibitors being used to treat refractory gout.
Background
The Oxford Classification is utilized globally, but has not been fully validated. In this study, we conducted a comparative analysis between the Oxford Classification and Japanese ...Histologic Classification (JHC) to predict renal outcome in Japanese patients with IgA nephropathy (IgAN).
Methods
A retrospective cohort study including 86 adult IgAN patients was conducted. The Oxford Classification and the JHC were evaluated by 7 independent specialists. The JHC, MEST score in the Oxford Classification, and crescents were analyzed in association with renal outcome, defined as a 50% increase in serum creatinine.
Results
In multivariate analysis without the JHC, only the T score was significantly associated with renal outcome. While, a significant association was revealed only in the JHC on multivariate analysis with JHC.
Conclusions
The JHC and T score in the Oxford Classification were associated with renal outcome among Japanese patients with IgAN. Superiority of the JHC as a predictive index should be validated with larger study population and cohort studies in different ethnicities.
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