Additional file 1: of Unfavorable effects of history of volume overload and late referral to a nephrologist on mortality in patients initiating dialysis: a multicenter prospective cohort study in Japan

Table S1. Background characteristics of patients who underwent or did not undergo echocardiography. (DOCX 35 kb

Treatment patterns and steroid dose for adult minimal change disease relapses: A retrospective cohort study

<div><p>Background</p><p>In patients with adult minimal change disease (MCD), proteinuria relapse is a problem to solve. However, the optimal relapse treatment regimen remains unclear regarding steroid dose. We described the treatment pattern of adult MCD patients and evaluated the appropriate steroid dose for relapse treatment.</p><p>Methods</p><p>This retrospective multicenter cohort study included 192 patients with adult biopsy-proven MCD from 14 hospitals in Japan. The prescription pattern of immunosuppressive drugs in relapse was reviewed. To assess the association between steroid dose used for relapse and subsequent outcomes, data of patients with tapered prednisolone (PSL) dosage to <10 mg/day before the first relapse in whom the dose was subsequently increased to ≥10 mg/day were extracted and assigned to the High-PSL or Low-PSL groups, based on the median dose of 20 mg/day. Multivariate Cox proportional hazard model and propensity score analysis with multiple imputations were conducted to compare their clinical course.</p><p>Results</p><p>During a median observation period of 37.6 months, 186/192 (96.9%) patients achieved complete remission (CR) and 100 (52.1%) relapsed. The median urinary protein level at the first relapse was 3.12 g/gCr or g/day. The proportion of non-steroidal immunosuppressant use increased with relapses; cyclosporine was the most common. No significant differences were found in the second relapse, frequent relapses, or adverse events between High-PSL (n = 34) and Low-PSL (n = 36) groups. A multivariate Cox proportional hazard model revealed that the hazard ratios adjusted with propensity score for the second relapse were 0.94 (High-PSL vs. Low-PSL; 95% confidence interval, 0.42–2.10; P = 0.88) and 0.82 (PSL dose per 10 mg/day; 95% confidence interval, 0.58–1.16; P = 0.25).</p><p>Conclusions</p><p>Among patients in CR with PSL dose <10 mg/day, higher steroid dose (PSL >20 mg/day) was not associated with favorable outcomes after the first relapse as compared to lower dose (10–20 mg/day).</p></div

Longitudinal Study of the Decline in Renal Function in Healthy Subjects

<div><p>Background</p><p>Chronic kidney disease is an important concern in preventive medicine, but the rate of decline in renal function in healthy population is not well defined. The purpose of this study was to determine reference values for the estimated glomerular filtration rate (eGFR) and rate of decline of eGFR in healthy subjects and to evaluate factors associated with this decline using a large cohort in Japan.</p><p>Methods</p><p>Retrospective cross-sectional and longitudinal studies were performed with healthy subjects aged ≥18 years old who received a medical checkup. Reference values for eGFR were obtained using a nonparametric method and those for decline of eGFR were calculated by mixed model analysis. Relationships of eGFR decline rate with baseline variables were examined using a linear least-squares method.</p><p>Results</p><p>In the cross-sectional study, reference values for eGFR were obtained by gender and age in 72,521 healthy subjects. The mean (±SD) eGFR was 83.7±14.7ml/min/1.73m². In the longitudinal study, reference values for eGFR decline rate were obtained by gender, age, and renal stage in 45,586 healthy subjects. In the same renal stage, there was little difference in the rate of decline regardless of age. The decline in eGFR depended on the renal stage and was strongly related to baseline eGFR, with a faster decline with a higher baseline eGFR and a slower decline with a lower baseline eGFR. The mean (±SD) eGFR decline rate was ‒1.07±0.42ml/min/1.73m²/year (‒1.29±0.41%/year) in subjects with a mean eGFR of 81.5±11.6ml/min/1.73m².</p><p>Conclusions</p><p>The present study clarified for the first time the reference values for the rate of eGFR decline stratified by gender, age, and renal stage in healthy subjects. The rate of eGFR decline depended mainly on baseline eGFR, but not on age, with a slower decline with a lower baseline eGFR.</p></div

Prednisolone dose for initial treatment and relapses.

<p>Steroid dose in treatment of adult MCD from initial treatment to fifth relapse is shown in box-plots. The dosage at the start of each treatment was selected and the dosage of additional increasing until complete remission was excluded. Abbreviations: PSL, prednisolone; IQR, interquartile range.</p

Clinical characteristics of the patients at first relapse.

<p>Clinical characteristics of the patients at first relapse.</p

PSL dose for the treatment of first relapse as a predictor of second relapse.

<p>PSL dose for the treatment of first relapse as a predictor of second relapse.</p

Predictors of second relapse.

<p>Predictors of second relapse.</p

Second relapse-free survival of minimal change disease after first relapse.

<p>Second relapse-free survival after first relapse in the High-prednisolone (PSL) group (n = 34) and Low-PSL group (n = 36) were calculated using the Kaplan–Meier method and compared by log-rank test. Abbreviations: MCD, minimal change disease; PSL, prednisolone.</p

Overview of this study.

<p>Of the 238 adult patients with minimal change disease in the cohort, 192 were eligible for this study. Analysis 1: For the 100 identified patients with relapse, treatment regimens at every relapse were reviewed. Analysis 2: To evaluate the association between steroid dose and subsequent outcomes, patients who fulfilled the criteria as indicated in the flow chart were divided into two groups: “High-PSL” and “Low-PSL.” Abbreviations: CR; complete remission, PSL; prednisolone; CyA, cyclosporine A.</p

Demographic pattern of immunosuppressive treatment for adult minimal change disease relapses.

<p>Proportion of steroid and other immunosuppressive drugs use in treatment of adult MCD from initial treatment to fifth relapse are shown in bar-graphs. The details about types of used non-steroidal immunosuppressants are summarized in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0199228#pone.0199228.s004" target="_blank">S4 Table</a>. Abbreviations: MCD, minimal change disease; PSL, prednisolone; ISA, non-steroidal immunosuppressive agents; CR, complete remission.</p