Association of calciprotein particles with serum phosphorus among patients undergoing conventional and extended-hours haemodialysis.

Background and hypothesis: Extended-hours haemodialysis (HD) is associated with better clinical outcomes than conventional HD. We investigated whether extended-hours HD and conventional HD have varying effects on blood levels of calciprotein particles (CPPs) and phosphorus, which have been identified as major pathogenic molecules for vascular calcification. Methods: Patients who underwent conventional or extended in-centre daytime HD between January and March 2020 were included. Plasma CPP levels, representing only secondary CPPs (CPP-II), were measured in pre-dialysis samples. Linear and non-linear associations between CPPs and serum phosphorus levels were examined across dialysis modalities. Results: A total of 382 participants (185 undergoing extended-hours HD and 197 undergoing conventional HD) were included in the analysis. The median age of participants was 71 years, 65% of the patients were men and the mean phosphorus level was 5.4 mg/dl. Plasma CPP (CPP-II) levels were lower in the extended-hours HD group than in the conventional HD group [40 018 (arbitrary units) AU versus 75 728 AU; P < .01]. Multivariable linear regression analysis showed that extended-hours HD was associated with lower natural logarithmic plasma CPP (CPP-II) levels: -0.64 (95% confidence interval -0.74 to -0.55). A restricted cubic spline function indicated that extended-hours HD was associated with lower plasma CPP (CPP-II) levels across levels of serum phosphorus, with significant differences observed between groups, especially in hyperphosphataemic conditions (P for interaction <.01). Conclusions: The extended-hours HD group had lower CPP levels than the conventional HD group despite no significant differences in serum phosphorus levels, which may contribute to better clinical outcomes in patients on extended-hours HD.

Association between stopping renin-angiotensin system inhibitors immediately before hemodialysis initiation and subsequent cardiovascular events.

It is controversial whether renin-angiotensin system inhibitors (RASIs) should be stopped in patients with advanced chronic kidney disease (CKD). Recently, it was reported that stopping RASIs in advanced CKD was associated with increased mortality and cardiovascular (CV) events; however, it remains unclear whether stopping RASIs before dialysis initiation affects clinical outcomes after dialysis, which this study aimed to evaluate. In this multicenter prospective cohort study in Japan, we included 717 patients (mean age, 67 years; 68% male) who had a nephrology care duration ≥90 days, initiated hemodialysis, and used RASIs 3 months before hemodialysis initiation. The multivariable adjusted Cox models were used to compare mortality and CV event risk between 650 (91%) patients who continued RASIs until hemodialysis initiation and 67 (9.3%) patients who stopped RASIs. During a median follow-up period of 3.5 years, 170 (24%) patients died and 228 (32%) experienced CV events. Compared with continuing RASIs, stopping RASIs was unassociated with mortality (adjusted hazard ratio [aHR]: 0.82; 95% confidence interval [CI]: 0.50-1.34) but was associated with higher CV events (aHR: 1.59; 95% CI: 1.06-2.38). Subgroup analyses showed that the risk of stopping RASIs for CV events was particularly high in patients aged <75 years, with a significant interaction between stopping RASIs and age. This study revealed that patients who stopped RASIs immediately before dialysis initiation were associated with subsequent higher CV events. Active screening for CV disease may be especially beneficial for these patients.

Relationship between peak aortic jet velocity and progression of aortic stenosis in patients undergoing hemodialysis.

BACKGROUND: The natural history of aortic stenosis (AS) progression, especially before severe AS development, is not well documented. We aimed to investigate the time course of peak aortic jet velocity (Vmax) and AS progression risk according to baseline Vmax, particularly whether there is a Vmax threshold. METHODS: In a retrospective multicenter cohort study of patients on hemodialysis with aortic valve calcification, we investigated the time series of Vmax and the relationship between the baseline Vmax and progression to severe AS by analyzing longitudinal echocardiographic data. RESULTS: Among 758 included patients (mean age, 71 years; 65% male), patients with Vmax <1.5, 1.5-1.9, 2.0-2.4, 2.5-2.9, and 3.0-3.9 m/s were 395 (52%), 216 (29%), 85 (11%), 39 (5.1%), and 23 (3.0%), respectively. The Vmax slope was gradual (mean 0.05-0.07 m/s/year) at Vmax <2 m/s, but steeper (mean 0.13-0.21 m/s/year) at Vmax ≥2 m/s. During a median 3.2-year follow-up, 52 (6.9%) patients developed severe AS. While patients with Vmax <2 m/s rarely developed severe AS, the risk of those with Vmax ≥2 m/s increased remarkably with an increasing baseline Vmax; the adjusted incidence rates in patients with Vmax <1.5, 1.5-1.9, 2.0-2.4, 2.5-2.9, and 3.0-3.9 m/s were 0.59, 0.57, 4.25, 13.8, and 56.1 per 100 person-years, respectively; the adjusted hazard ratio per 0.2 m/s increase in the baseline Vmax was 1.49 (95% confidence interval: 1.32-1.68) when Vmax ≥2 m/s. CONCLUSIONS: The risk of progression to severe AS increased with the baseline Vmax primarily at ≥2 m/s; a Vmax threshold of 2 m/s was observed.

Number of calcified aortic valve leaflets: natural history and prognostic value in patients undergoing haemodialysis.

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.

Echocardiography-Based Cardiac Structure Parameters for the Long-term Risk of End-Stage Kidney Disease in Black Individuals: The Atherosclerosis Risk in Communities Study.

OBJECTIVE: To assess whether echocardiographic parameters of left ventricular (LV) structure and function relate to the long-term risk of incident end-stage kidney disease (ESKD). PATIENTS AND METHODS: We conducted a prospective cohort study analyzing 2137 Black participants from the Jackson site of the Atherosclerosis Risk in Communities Study from January 1, 1993, through July 31, 2017. Echocardiographic parameters of LV structure and function were obtained from 1993 to 1995. The primary outcome incident ESKD was identified through the linkage to the United States Renal Data System. Cox proportional hazards models were used to estimate the hazard ratios (HRs) according to each echocardiographic parameter. RESULTS: There were 117 incident ESKD cases during a median follow-up of 22.2 (interquartile range, 15.0-23.3) years. Multivariable Cox models revealed that a higher LV mass index was significantly associated with the risk of ESKD (HR, 2.38; 95% CI, 1.21 to 4.68 for highest vs lowest quartile, P = 0.012). The HRs were significant and even higher for LV posterior wall thickness, with slightly higher HRs when their measures in end-systole (HR for highest vs lowest quartile, 4.38; 95% CI, 1.94 to 9.92, P < 0.001) vs end-diastole (HR, 3.50; 95% CI, 1.53 to 8.01, P = 0.003) were used. The associations were not significant for LV function parameters. CONCLUSION: In Black individuals residing in the community, echocardiographic parameters of LV structure, including LV wall thickness, were robustly associated with the risk of subsequently incident ESKD. These results have potential implications for novel prevention and management strategies for persons with abnormal LV structure.

Echocardiographic measures and subsequent decline in kidney function in older adults: the Atherosclerosis Risk in Communities Study.

AIMS: Heart failure increases the risk of kidney disease progression. However, whether cardiac function and structure are associated with the risk of incident chronic kidney disease (CKD) is not well characterized in a community setting. METHODS AND RESULTS: Among 4188 participants (mean age 75 years and 22% blacks) of the Atherosclerosis Risk in Communities Study without prevalent CKD in 2011-13, we examined the association of echocardiographic measures of left ventricular (LV) mass index, ejection fraction, left atrial volume index (LAVi), right ventricular (RV) fractional area change, and peak RV-right atrium (RA) gradient, with the subsequent risk of incident CKD, as defined by >25% decline to estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, hospitalization with CKD diagnosis, or incident end-stage kidney disease. Multivariable Cox regression models were used to estimate hazard ratios (HRs). The risk of incident CKD was monotonically increased with each of higher LV mass index [adjusted HR 2.61 (1.92-3.55) for highest quartile (Q4) vs. lowest (Q1)], lower ejection fraction [1.54 (1.17-2.04) for Q1 vs. Q4], higher LAVi [2.12 (1.56-2.89) for Q4 vs. Q1], and higher peak RV-RA gradient [2.17 (1.45-3.25) for Q4 vs. Q1] but not with RV function. The associations were consistent between subgroups by sex and race. CONCLUSION: Among community-dwelling older individuals, LV mass index, ejection fraction, LAVi, and peak RV-RA gradient were independently associated with the risk of incident CKD. Our results further support that heart disease is associated with the risk of kidney disease progression and suggest the value of echocardiography for assessing cardiac and kidney health in older populations.

All-cause and cardiovascular mortality in patients undergoing hemodialysis with aortic sclerosis and mild-to-moderate aortic stenosis: A cohort study.

BACKGROUND AND AIMS: Mild-to-moderate aortic stenosis (AS) and aortic sclerosis, a precursor of AS, are associated with mortality in the general population; however, their association in patients undergoing hemodialysis with higher morbidity of AS is unknown. Thus, we investigated the mortality of aortic sclerosis and mild-to-moderate AS in patients undergoing hemodialysis. METHODS: This was a retrospective multicenter cohort study of consecutive patients undergoing hemodialysis at nine dialysis facilities who underwent screening echocardiography between January 2008 and December 2019. We investigated the mortality of patients with aortic sclerosis or mild-to-moderate AS using multivariable Cox proportional hazards regression. RESULTS: Among 1,878 patients undergoing hemodialysis, those with normal aortic valves, aortic sclerosis, mild AS, moderate AS, severe AS, and prosthetic aortic valves were 844 (45%), 793 (42%), 161 (8.6%), 38 (2.0%), 11 (0.6%), and 31 (1.7%), respectively. After excluding patients with severe AS and prosthetic aortic valves, we performed comparative analysis on 1,836 patients (mean age, 67 years; 66% male). In a median follow-up of 3.6 years, crude death rates (per 100 person-years) were 5.2, 10.6, and 13.0 in patients with normal aortic valves, aortic sclerosis, and mild-to-moderate AS, respectively. Compared with normal aortic valves, both aortic sclerosis and mild-to-moderate AS were associated with all-cause and cardiovascular death: adjusted hazard ratios (95% confidence intervals) were 1.36 (1.13-1.65) and 1.36 (1.02-1.80) for all-cause death; and 1.52 (1.06-2.17) and 1.74 (1.04-2.92) for cardiovascular death, respectively. CONCLUSIONS: Aortic sclerosis and mild-to-moderate AS were independent risk factors for all-cause and cardiovascular death in patients undergoing hemodialysis.

Economic Consequences of Adult Living Kidney Donation: A Systematic Review.

OBJECTIVES: Current guidelines mandate organ donation to be financially neutral such that it neither rewards nor exploits donors. This systematic review was conducted to assess the magnitude and type of costs incurred by adult living kidney donors and to identify those at risk of financial hardship. METHODS: We searched English-language journal articles and working papers assessing direct and indirect costs incurred by donors on PubMed, MEDLINE, Scopus, the National Institute for Health Research Economic Evaluation Database, Research Papers in Economics, and EconLit in 2005 and thereafter. Estimates of total costs, types of costs, and characteristics of donors who incurred the financial burden were extracted. RESULTS: Sixteen studies were identified involving 6158 donors. Average donor-borne costs ranged from US$900 to US$19 900 (2019 values) over the period from predonation evaluation to the end of the first postoperative year. Less than half of donors sought financial assistance and 80% had financial loss. Out-of-pocket payments for travel and health services were the most reported items where lost income accounted for the largest proportion (23.2%-83.7%) of total costs. New indirect cost items were identified to be insurance difficulty, exercise impairment, and caregiver income loss. Donors from lower-income households and those who traveled long distances reported the greatest financial hardship. CONCLUSIONS: Most kidney donors are undercompensated. Our findings highlight gaps in donor compensation for predonation evaluation, long-distance donations, and lifetime insurance protection. Additional studies outside of North America are needed to gain a global prospective on how to provide for financial neutrality for kidney donors.

A Prospective, Randomized Clinical Trial of Etelcalcetide in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism (the DUET Trial).

INTRODUCTION: The clinical trial on the Development of a treatment strategy for chronic kidney disease‒mineral and bone disorder by a mUltilateral mechanism of ETelcalcetide hydrochloride, or the DUET trial, was designed to determine the efficacy of etelcalcetide, an intravenous calcimimetic, for control of secondary hyperparathyroidism (SHPT). METHODS: Eligible SHPT maintenance hemodialysis patients (n = 124) were randomized (1:1:1) for inclusion in the DUET trial, a 12-week, multicenter, open-label, parallel-group study (jRCTs041180108), and assigned to either an etelcalcetide + active vitamin D group (group E+D), an etelcalcetide + oral calcium preparation group (group E+Ca), or a control group (group C). The primary endpoint was number of patients with a 50% reduction from baseline of intact parathyroid hormone (iPTH) levels, and iPTH levels ≤ 240 pg/mL at 12 weeks after start of the trial. RESULTS: The proportion of patients reaching the primary endpoint (95% confidence interval [CI]) was 90.0% (76.3%-97.2%) in group E+D, 56.8% (39.5%-72.9%) in group E+Ca, and 19.5% (8.8%-34.9%) in group C. Etelcalcetide treatment led to a significant increase in the number of patients achieving the endpoint (odds ratio, 13.4; 95% CI, 5.10-35.3) on logistic regression analysis, with iPTH, corrected serum calcium, and phosphate at baseline as covariates. Significantly more patients achieved the endpoint in group E+D compared with group E+Ca (odds ratio, 6.35; 95% CI, 1.79-22.48). There were fewer hypocalcemic visits in group E+D compared with group E+Ca (P = 0.018), yet the former group was prone to hyperphosphatemia. CONCLUSION: Etelcalcetide showed good control of iPTH for maintenance hemodialysis patients with SHPT. Active vitamin D was useful in correcting hypocalcemia, but the oral calcium preparation was superior for suppression of hyperphosphatemia.

Additional prognostic value of toe-brachial index beyond ankle-brachial index in hemodialysis patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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]). CONCLUSIONS: 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.

Impact of old age on the association between in-center extended-hours hemodialysis and mortality in patients on incident hemodialysis.

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.

Survival Benefit of Maintained or Increased Body Mass Index in Patients Undergoing Extended-Hours Hemodialysis Without Dietary Restrictions.

OBJECTIVE: Low body mass index (BMI) is a potential risk factor for mortality in patients on maintenance hemodialysis. This suggests the usefulness of BMI as a prognostic factor and implies the importance of nutritional status, inflammation, and oxidative stress, all of which affect BMI. We aimed to evaluate BMI changes over time and the mortality risk in patients undergoing a novel combination therapy consisting of an extended-hours hemodialysis protocol without dietary restrictions, which enabled sufficient nutrition. DESIGN AND METHODS: This is a retrospective cohort study. Patients were divided into 2 groups based on BMI change (ΔBMI < 0, ΔBMI ≥ 0) between the 3rd and 12th month after transfer to the clinic. We studied the associations of BMI changes with all-cause mortality. Further subgroup analyses were performed using Cox models. We finally studied 187 patients who were receiving the combined therapy. The main outcome measure was all-cause mortality of the study group. RESULTS: The median (interquartile range) follow-up time was 4.9 (3.0-8.6) years. Overall, 138 patients were in the ΔBMI ≥ 0 group. As per unadjusted and adjusted Cox models, maintained or increased BMI during this period was associated with hazard ratios of 0.45 (confidence interval 0.23-0.87, P < .05) and 0.35 (confidence interval 0.17-0.75, P < .01) for all-cause mortality, respectively. In the same group, maintained or increased BMI was found to be significantly associated with decreased mortality in female, older, and nondiabetic patients. The data indicated that diabetic status could have a modifying effect on the association between variation in BMI and mortality (P = .006). CONCLUSIONS: Extended-hours hemodialysis without dietary restrictions led to a beneficial effect of maintenance or increase in BMI, especially in females, patients aged ≥65 years, and those without diabetic nephropathy, which could lead to prolonged survival.

Lower levels of proteinuria are associated with elevated mortality in incident dialysis patients.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Circulating levels of CD34+ cells predict long-term cardiovascular outcomes in patients on maintenance hemodialysis.

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.

Clinical impact of endocapillary proliferation with modified cutoff points in IgA nephropathy 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.

Seasonal proteinuria changes in IgA nephropathy patients after proteinuria remission.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: In IgAN patients in proteinuria remission, proteinuria exacerbation frequently occurred in autumn and winter. Exacerbations occurring in autumn and winter tended to remit early.

The Japanese Histologic Classification and T-score in the Oxford Classification system could predict renal outcome in Japanese IgA nephropathy patients.

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.

Aichi cohort study of the prognosis in patients newly initiated into dialysis (AICOPP): baseline characteristics and trends observed in diabetic nephropathy.

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 m2, 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.

Two brothers with collagenofibrotic glomerulopathy.

Collagenofibrotic glomerulopathy is a rare glomerular disease characterized by extensive accumulation of atypical type III collagen fibers within the mesangial matrix and subendothelial space. Laboratory evaluation of this disease shows a marked increase in serum procollagen III peptide (P III P) levels. Here, we report the case of two brothers with collagenofibrotic glomerulopathy confirmed by histology. Patient 1 presented with proteinuria and hypertension and patient 2 presented with nephrotic-range proteinuria. Immunohistochemistry revealed strong staining for antibodies to type III collagen in the widened subendothelial spaces in both patients. Electron microscopy revealed numerous collagenous fibers in the mesangium and subendothelial space. P III P levels were elevated in both patients. Most reported cases of collagenofibrotic glomerulopathy, including the adult-onset type, have been sporadic. Within the limits of our literature search, this is only the third report of adult siblings with collagenofibrotic glomerulopathy confirmed by histology. This report indicates that it may be beneficial to measure serum P III P levels in the siblings of patients diagnosed with adult-onset collagenofibrotic glomerulopathy.