Abstract
Phosphate binders are the main treatment for hyperphosphatemia in patients with chronic kidney disease, and iron-based phosphate binders have been used with increasing frequency in recent ...years. This study examined the association of the use of iron-based, rather than non-iron-based, phosphate binders with the incidence of cardiovascular events, in a real-world setting. We used data from a cohort comprising representative adult patients on maintenance hemodialysis in Japan. The exposure of interest was the time-varying use of phosphate binders, classified into “iron-based”, “only non-iron-based”, and “no use”. The primary outcome was a composite of cardiovascular events and all-cause deaths. A marginal structural Cox regression model was used to deal with possible time-dependent confounding. Of the 2247 patients from 58 hemodialysis facilities, iron-based and only non-iron-based phosphate binders were used in 328 (15%) and 1360 (61%), respectively, at baseline. Hazard ratios (95% confidence intervals) for iron-based and non-iron-based phosphate binders versus no use of phosphate binders were 0.35 (0.24, 0.52) and 0.44 (0.33, 0.58), respectively. The hazard ratio for iron-based relative to non-iron-based phosphate binders was 0.81 (0.58, 1.13), which was not statistically significant. Further studies are warranted to elucidate whether the use of iron-based phosphate binders reduces the event rate.
Background
A Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown a one-to-one male-to-female mortality ratio, notwithstanding the statistically longer life expectancy of women in the ...general population. This finding contrasts with the recent report that Japanese women on dialysis treatment have a more favorable longevity. Accordingly, we further investigated the clinical procedures and outcomes to clarify the sex differences in Japanese patients undergoing dialysis treatment.
Methods
Subjects were incident dialysis patients who participated in a multicenter prospective cohort study from October 2011 to September 2013. The all-cause mortality was analyzed by a Cox proportional hazard regression model and studied separately in women and men with or without cardiovascular disease (CVD) at baseline.
Results
Overall, 492 (32.3%) of the 1520 test subjects were women. All-cause mortality was higher in men (28.6%) than in women (19.9%,
p
< 0.001). Female sex (hazard ratio HR: 0.70, 95% confidence interval CI: 0.54–0.90) and history of CVD (HR: 1.51, 95% CI: 1.18–1.95) were independent predictors of all-cause mortality. In patients without CVD, female gender was strong independent contributor (HR = 0.46, 95% CI: 0.30–0.70,
p
< 0.001). In contrast, patients with CVD showed no difference in survival between the sexes (HR: 0.92, 95% CI: 0.67–1.24,
p
= 0.597).
Conclusion
Our study demonstrated that women undergoing chronic dialysis therapy had a lower mortality risk than men. However, complication with CVD canceled out the survival advantage in Japanese women on chronic dialysis. We should reevaluate the risk of women with CVD undergoing dialysis and apply the optimal care for CVD.
ObjectivesPatients with peripheral artery disease (PAD) are reported to have a poorer prognosis than those without PAD. PAD is sometimes found at dialysis initiation, but its influence on the ...prognosis in these patients has not been investigated. We aimed to compare the mortality rate between patients with PAD at the time of dialysis initiation and those without PAD.DesignWe undertook an observational prospective multicenter study of patients starting dialysis treatment. Data were collected on patients’ sex, age, presence of PAD, medication, medical history and clinical and laboratory data.SettingSeventeen centers participated in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis.ParticipantsA total of 1524 patients with chronic kidney disease started dialysis from October 2011 to September 2013. The patients were followed-up until March 2015. During this time, there were two patients who lost the follow-up.Primary and secondary outcome measuresThe primary outcome was defined as all-cause mortality. The secondary outcomes were defined as each cause of mortality.ResultsThis study included 1030 men and 492 women with a mean age of 67.50±13.10 years. Of these, 71 had PAD and 1451 did not have PAD. After a median follow-up of 814.5 days, 33.80% of the former group and 17.00% of the latter group had died in March 2015 (p=0.001). After adjusting for confounding factors, PAD at dialysis initiation remained an independent risk factor for mortality (p<0.01).ConclusionsPatients with PAD at the time of dialysis initiation had a poorer prognosis than patients without PAD. Therefore, the presence of PAD in patients starting dialysis should be considered for their monitoring and follow-up.
A common renal disease, immunoglobulin A (IgA) nephropathy (IgAN), is associated with glomerular deposition of IgA1-containing immune complexes. IgA1 hinge region (HR) has up to six clustered ...O-glycans consisting of Ser/Thr-linked N-acetylgalactosamine with β1,3-linked galactose and variable sialylation. IgA1 glycoforms with some galactose-deficient (Gd) HR O-glycans play a key role in IgAN pathogenesis. The clustered and variable O-glycans make the IgA1 glycomic analysis challenging and better approaches are needed. Here, we report a comprehensive analytical workflow for IgA1 HR O-glycoform analysis. We combined an automated quantitative analysis of the HR O-glycopeptide profiles with sequential deglycosylation to remove all but Gd O-glycans from the HR. The workflow was tested using serum IgA1 from healthy subjects. Twelve variants of glycopeptides corresponding to the HR with three to six O-glycans were detected; nine glycopeptides carried up to three Gd O-glycans. Sites with Gd O-glycans were unambiguously identified by electron-transfer/higher-energy collision dissociation tandem mass spectrometry. Extracted ion chromatograms of isomeric glycoforms enabled quantitative assignment of Gd sites. The most frequent Gd site was T
, followed by S
, T
, T
, and S
. The new workflow for quantitative profiling of IgA1 HR O-glycoforms with site-specific resolution will enable identification of pathogenic IgA1 HR O-glycoforms in IgAN.
Background
Chronic kidney disease (CKD) eventually progresses to end-stage renal disease (ESRD). However, risk factors associated with CKD progression have not been well characterized in Japanese ...patients with CKD who are less affected with coronary disease than Westerners.
Methods
A large-scale, multicenter, prospective, cohort study was conducted in patients with CKD and under nephrology care, who met the eligibility criteria Japanese; age 20–75 years; and estimated glomerular filtration rate (eGFR): 10–59 mL/min/1.73 m
2
. The primary endpoint was a composite of time to a 50 % decline in eGFR from baseline or time to the initiation of renal replacement therapy (RRT). The secondary endpoints were the rate of decline in eGFR from baseline, time to a 50 % decline in eGFR from baseline, time to the initiation of RRT, and time to doubling of serum creatinine (Cre) concentration.
Results
2966 patients (female, 38.9 %; age, 60. 3 ± 11.6 years) were enrolled. The incidence of the primary endpoint increased significantly (
P
< 0.0001) in concert with CKD stage at baseline. The multivariate Cox proportional hazards models revealed that elevated systolic blood pressure (SBP) hazard ratio (HR) 1.203, 95 % confidence interval (CI) 1.099–1.318) and increased albumin-to-creatinine ratio (UACR ≥ 1000 mg/g Cre; HR: 4.523; 95 % CI 3.098–6.604) at baseline were significantly associated (
P
< 0.0001, respectively) with the primary endpoint.
Conclusions
Elevated SBP and increased UACR were risk factors that were significantly associated with CKD progression to ESRD in Japanese patients under nephrology care.
UMIN clinical trial registry number: UMIN000020038.
Abstract
Background
Although the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification was proposed recently, until now, no reports have been made ...comparing the association of renal prognosis between the 2018 revised ISN/RPS classification and the 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised ISN/RPS classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003.
Methods
We retrospectively collected medical records of 170 LN patients from the database of renal biopsy at Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as a 30% decline of estimated glomerular filtration rate (eGFR).
Results
A total of 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). The mean age was 42 years, 88% were female, and the median observation period was 50.5 months. Renal prognosis was significantly different among the classes and significantly poor in the patients with higher modified National Institute of Health (mNIH) chronicity index (C index, ≥ 4) by a log-rank test (
p
= 0.05 and
p
= 0.02, respectively). By Cox proportional hazard models, only the C index was significantly associated with renal outcome (hazard ratio 1.32, 95% CI 1.11–1.56,
p
≤ 0.01), while the classes, the 2003 activity and chronicity subdivision, and the mNIH activity index had no significant association with renal outcome. Each component of the C index was significantly associated with renal outcome in different models.
Conclusion
This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification.
Artificial intelligence is increasingly being adopted in medical fields to predict various outcomes. In particular, chronic kidney disease (CKD) is problematic because it often progresses to ...end-stage kidney disease. However, the trajectories of kidney function depend on individual patients. In this study, we propose a machine learning-based model to predict the rapid decline in kidney function among CKD patients by using a big hospital database constructed from the information of 118,584 patients derived from the electronic medical records system. The database included the estimated glomerular filtration rate (eGFR) of each patient, recorded at least twice over a period of 90 days. The data of 19,894 patients (16.8%) were observed to satisfy the CKD criteria. We characterized the rapid decline of kidney function by a decline of 30% or more in the eGFR within a period of two years and classified the available patients into two groups-those exhibiting rapid eGFR decline and those exhibiting non-rapid eGFR decline. Following this, we constructed predictive models based on two machine learning algorithms. Longitudinal laboratory data including urine protein, blood pressure, and hemoglobin were used as covariates. We used longitudinal statistics with a baseline corresponding to 90-, 180-, and 360-day windows prior to the baseline point. The longitudinal statistics included the exponentially smoothed average (ESA), where the weight was defined to be 0.9*(t/b), where t denotes the number of days prior to the baseline point and b denotes the decay parameter. In this study, b was taken to be 7 (7-day ESA). We used logistic regression (LR) and random forest (RF) algorithms based on Python code with scikit-learn library (
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
Background
Hyperphosphatemia in patients undergoing dialysis is common and is associated with mortality. Recently, the link between phosphate metabolism and iron dynamics has received ...increasing attention. However, the association between this relationship and prognosis remains largely unexplored.
Methods
We conducted an observational study of patients who initiated dialysis in the 17 centers participating in the Aichi Cohort Study of the Prognosis in Patients Newly Initiated into Dialysis. Data were available on sex, age, use of phosphate binder, drug history, medical history and laboratory data. After excluding patients with missing values of phosphate, hemoglobin, ferritin and transferrin saturation, we used the Gaussian mixture model to divide the cohort into clusters based on phosphate, hemoglobin, logarithmic ferritin and transferrin saturation. We investigated the prognosis of patients in these clusters. The primary outcome was all-cause death. In each cluster, the prognostic impact of phosphate binder was also studied.
Results
The study included 1175 patients with chronic kidney disease who initiated dialysis between October 2011 and September 2013. Among them, 785 were men and 390 were women, with a mean ± SD age of 67.9 ± 13.0 years. The patients were divided into three clusters, and mortality was higher in cluster c than in cluster a (P = 0.005). Moreover, the use of phosphate binders was associated with a lower risk of all-cause death in two clusters (a and c) that were characterized by older age and higher prevalence of diabetes mellitus, among other things.
Conclusions
We used an unsupervised machine learning method to cluster patients, using phosphate, hemoglobin and iron-related markers. In two of the clusters, the oral use of a phosphate binder might improve prognosis.
Graphical Abstract
Graphical Abstract
Abstract
Background
The present study aimed to investigate associations between long-term renal function, whether IgG4-related tubulointerstitial nephritis (TIN) was diagnosed by renal biopsy at ...initial examination, chronic kidney disease (CKD) stage, and histological stage in patients with IgG4-related TIN.
Methods
This study used a retrospective cohort design including almost all patients who underwent renal biopsy at Fujita Health University Hospital and Nagoya University or its affiliated hospitals in Aichi between April 2003 and March 2015 (
n
= 6977 renal biopsies). The primary outcome was longitudinal changes in eGFR. Main exposures were whether IgG4-related TIN was diagnosed by renal biopsy at the initial examination, CKD stage, and its histological stage. Linear mixed models were performed to examine associations.
Results
Of the 6977 samples, there were 24 patients (with 201 records due to repeated measures) with IgG4-related TIN (20 men, mean age, 68.7 ± 9.7 years). They were followed up 6.6 ± 2.8 years after the renal biopsy and underwent glucocorticoid treatment. We found significant increase in eGFR from the baseline to 2 and 6 months after treatment initiation, which was maintained until 60 months. Patients initially diagnosed with IgG4-related TIN had higher eGFR from the baseline (at the start of treatment) to 60 months than those who were not. Compared with patients with CKD stage 3, patients with CKD stages 4 and 5 had lower eGFR at the baseline and other time points. Patients with histological stage B had comparatively lower eGFR at each point than stage A patients. Those mean differences of eGFR were stable from the baseline to 60 months.
Conclusions
After the treatment initiation, renal function rapidly improved and maintained for a long period, even with advanced CKD stage. We showed importance of early diagnosis of IgG4-related TIN in maintaining eGFR.
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