SET DOMAIN GROUP 711-mediated H3K27me3 methylation of cytokinin metabolism genes regulates organ size in rice.

Organ size shapes plant architecture during rice (Oryza sativa) growth and development, affecting key factors influencing yield, such as plant height, leaf size, and seed size. Here, we report that the rice Enhancer of Zeste [E(z)] homolog SET DOMAIN GROUP 711 (OsSDG711) regulates organ size in rice. Knockout of OsSDG711 produced shorter plants with smaller leaves, thinner stems, and smaller grains. We demonstrate that OsSDG711 affects organ size by reducing cell length and width and increasing cell number in leaves, stems, and grains. The result of chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) using an antitrimethylation of histone H3 lysine 27 (H3K27me3) antibody showed that the levels of H3K27me3 associated with cytokinin oxidase/dehydrogenase genes (OsCKXs) were lower in the OsSDG711 knockout line Ossdg711. ChIP-qPCR assays indicated that OsSDG711 regulates the expression of OsCKX genes through H3K27me3 histone modification. Importantly, we show that OsSDG711 directly binds to the promoters of these OsCKX genes. Furthermore, we measured significantly lower cytokinin contents in Ossdg711 plants than in wild-type plants. Overall, our results reveal an epigenetic mechanism based on OsSDG711-mediated modulation of H3K27me3 levels to regulate the expression of genes involved in the cytokinin metabolism pathway and control organ development in rice. OsSDG711 may be an untapped epigenetic resource for ideal plant type improvement.

Burden of kidney disease among patients with peritoneal dialysis versus conventional in-centre haemodialysis: A randomised, non-inferiority trial.

BACKGROUND: Little is known about the impact of haemodialysis (HD) and peritoneal dialysis (PD) on health-related quality of life (HRQoL). We compared HRQoL between conventional in-centre HD and home-based PD in 1082 newly diagnosed kidney failure patients. METHODS: This was an open-label, randomised, non-inferiority trial of adult patients with a diagnosis of end-stage kidney disease (estimated glomerular filtration rate ≤ 15 mL/min/1.73 m2) requiring maintenance dialysis from 36 sites in China randomised 1:1 to receive PD or conventional in-centre HD. The primary outcome was the 'Burden of Kidney Disease' assessed using the Kidney Disease Quality of Life-Short Form (KDQoL-SF) survey over 48 weeks and the main secondary outcomes were the remaining scales of KDQoL-SF and all-cause mortality. The effect of PD versus HD on the primary outcome was compared by their geometric mean (GM) ratio, and non-inferiority was defined by the lower bound of a one-sided 95% confidence interval (CI) >0.9. RESULTS: A total of 725 subjects completed the trial per protocol (395 PD and 330 HD, mean age 49.8 (standard deviation (SD) 14.4) years, 41.4% women). For the primary outcome, the mean (SD) change in 'Burden of Kidney Disease' over 48 weeks was 2.61 (1.27) in PD group and 2.58 (1.35) in HD group, and the GM ratio (95% CI) was 1.059 (0.908-1.234), exceeding the limit for non-inferiority. For the secondary outcomes, the PD and HD groups were similar in all scales. There were 17 and 31 deaths in PD and HD groups, respectively. Patients receiving PD had more adverse events, adverse event leading to hospitalisation and serious adverse events compared to those allocated to HD, but adverse events leading to death and discontinuation of the trial were not different between PD and HD. CONCLUSIONS: In this trial, PD may be non-inferior to HD on the 'Burden of Kidney Disease' among Chinese kidney failure patients who are of younger age and have lower comorbidity after 48 weeks' follow-up.

Low expression of estrogen receptor ß in renal tubular epithelial cells may cause hyperuricemia in premenopausal patients with systemic lupus erythematosus.

We investigated the impact of estrogen receptor (ER) expression in renal tubular epithelial cells on serum uric acid (UA) levels in premenopausal patients with systemic lupus erythematosus (SLE). Thirty patients underwent renal biopsy: 18 with SLE (LN group) and 12 with IgA nephritis (IgAN group). ERs (ERα and ERß) in renal tubular epithelial cells were measured using immunohistochemistry. The ER expression levels of the two groups were compared, and the relationship between the expression of ERs and serum UA levels was analyzed. Mean serum UA levels in the LN group were significantly higher than those of the IgA nephropathy group, while the mean creatinine levels and GFRs of the two groups were similar. Pathological changes in the LN group were significantly more severe than those in the IgAN group. ERß was expressed in renal tubular epithelial cells in both groups, but not in the glomeruli. ERß expression in the LN group was significantly lower than that in the IgAN group. ERß expression scores significantly negatively correlated with serum UA levels. These findings suggest that the expression of ERß in premenopausal female SLE patients may cause hyperuricemia, and may subsequently promote glomerular damage, suggesting that ERß may be involved in UA excretion.

Estimating total small solute clearance in patients treated with continuous ambulatory peritoneal dialysis without urine and dialysate collection.

BACKGROUND: International Society for Peritoneal Dialysis guidelines recommend to routinely monitor the total measured clearance (mCl) of small solutes such as creatinine; however, collection of 24-h urine and peritoneal dialysis (PD) fluid is burdensome to patients and prone to errors. We hypothesized that equations could be developed to estimate mCl (estimated clearance (eCl)) using endogenous filtration markers. METHODS: In the Guangzhou PD Study (n = 980), we developed eCl equations using linear regression in two-third and validated them in the remaining one-third. Reference tests were mCl for urea nitrogen (UN) (mClUN, ml/min) and average mCl for UN and creatinine (mClUN-cr, ml/min/1.73 m2). Index tests were various eCl equations using UN, creatinine, low-molecular-weight proteins (LMWPs) (beta-trace protein (BTP), beta-2 microglobulin (B2M), and cystatin C), demographic variables, and body size. After reexpression of the equations in the combined data set, we analyzed accuracy (eCl within ± 2.0 units of mCl) and the predictive value of eCl to detect a weekly total standard Kt/V (weekly mClUN indexed for total body water) > 1.7 using receiver operating characteristic curve. RESULTS: Mean age of the cohort was 50 ± 15 years, 53% were male; mClUN was 6.9 ± 1.8 and mClUN-cr was 7.5 ± 2.8. Creatinine but not UN contributed to eCl for both mCl. LMWP did not improve accuracy for mClUN (range 88-89%). BTP and B2M improved the accuracy for mClUN-cr (82% vs. 80%); however, differences were small. The area under the curve for predicting a weekly Kt/V > 1.7 was similar for all equations (range 0.79-0.80). CONCLUSIONS: Total small solute clearance can be estimated moderately well in continuous ambulatory PD patients using serum creatinine and demographic variables without urine and dialysate collection.

Development and Validation of Residual Kidney Function Estimating Equations in Dialysis Patients.

RATIONALE & OBJECTIVE: Measurement of residual kidney function is recommended for the adjustment of the dialysis prescription, but timed urine collections are difficult and prone to errors. Equations to calculate residual kidney function from serum concentrations of endogenous filtration markers and demographic parameters would simplify monitoring of residual kidney function. However, few equations to estimate residual kidney function using serum concentrations of small solutes and low-molecular-weight proteins have been developed and externally validated. STUDY DESIGN: Study of diagnostic test accuracy. SETTING & PARTICIPANTS: 823 Chinese peritoneal dialysis (PD) patients (development cohort) and 826 PD and hemodialysis patients from the Netherlands NECOSAD study (validation cohort). TESTS COMPARED: Equations to estimate residual kidney function (estimated clearance [eCl]) using serum creatinine, urea nitrogen, cystatin C, ß2-microglobulin (B2M), ß-trace protein (BTP), and combinations, as well as demographic variables (age, sex, height, and weight). Equations were developed using multivariable linear regression analysis in the development cohort and then tested in the validation cohort. Equations were compared with published validated equations. OUTCOMES: Residual kidney function measured as urinary clearance (mCl) of urea nitrogen (mClUN) and average of creatinine and urea nitrogen clearance (mClUN-cr). RESULTS: In external validation, bias (difference between mCl and eCl) was within ± 1.0 unit for all equations. Accuracy (percent of differences within ± 2.0 units) was significantly better for eClBTP, eClB2M, and eClBTP-B2M than eClUN-cr for both mClUN (78%, 80%, and 81% vs 72%; P < 0.05 for all) and mClUN-cr (72%, 78%, and 79% vs 68%; P < 0.05 for all). The area under the curve for predicting mClUN > 2.0 mL/min was highest for eClB2M (0.853) and eClBTP-B2M (0.848). Results were similar for other validated equations. LIMITATIONS: Development cohort only consisted of PD patients, no gold-standard method for residual kidney function measurement. CONCLUSIONS: These results confirm the validity and extend the generalizability of residual kidney function estimating equations from serum concentrations of low-molecular-weight proteins without urine collection.