Immunosuppression versus Supportive Care on Kidney Outcomes in IgA Nephropathy in the Real-World Setting.

BACKGROUND: The efficacy of immunosuppression in the management of immunoglobulin A (IgA) nephropathy remains highly controversial. The study was conducted to assess the effect of immunosuppression, compared with supportive care, in the real-world setting of IgA nephropathy. METHODS: A cohort of 3946 patients with IgA nephropathy, including 1973 new users of immunosuppressive agents and 1973 propensity score-matched recipients of supportive care, in a nationwide register data from January 2019 to May 2022 in China was analyzed. The primary outcome was a composite of 40% eGFR decrease of the baseline, kidney failure, and all-cause mortality. A Cox proportional hazard model was used to estimate the effects of immunosuppression on the composite outcomes and its components in the propensity score-matched cohort. RESULTS: Among 3946 individuals (mean [SD] age 36 [10] years, mean [SD] eGFR 85 [28] ml/min per 1.73 m 2 , and mean [SD] proteinuria 1.4 [1.7] g/24 hours), 396 primary composite outcome events were observed, of which 156 (8%) were in the immunosuppression group and 240 (12%) in the supportive care group. Compared with supportive care, immunosuppression treatment was associated with 40% lower risk of the primary outcome events (adjusted hazard ratio, 0.60; 95% confidence interval, 0.48 to 0.75). Comparable effect size was observed for glucocorticoid monotherapy and mycophenolate mofetil alone. In the prespecified subgroup analysis, the treatment effects of immunosuppression were consistent across ages, sexes, levels of proteinuria, and values of eGFR at baseline. Serious adverse events were more frequent in the immunosuppression group compared with the supportive care group. CONCLUSIONS: Immunosuppressive therapy, compared with supportive care, was associated with a 40% lower risk of clinically important kidney outcomes in patients with IgA nephropathy.

Urinary Matrix Metalloproteinase 7 and Prediction of IgA Nephropathy Progression.

RATIONALE & OBJECTIVE: A major challenge in the management of immunoglobulin A nephropathy (IgAN) is the inability to identify patients at high risk for disease progression at an early stage. Our objective was to determine whether urinary matrix metalloproteinase 7 (MMP-7) is a promising predictor for IgAN progression and whether its addition to clinical data at the time of biopsy improves risk prediction. STUDY DESIGN: Prospective observational cohort study in China. SETTING & PARTICIPANTS: 946 Chinese patients with IgAN followed up for a median of 40 months in 1 clinical center serving as the training set (n=554) and for 28 months in a second clinical center serving as the validation set (n = 392). PREDICTORS: Urinary MMP-7 and 7 previously reported biomarkers measured at the time of kidney biopsy and a score of histologically defined disease severity (MEST-C). OUTCOMES: IgAN progression was defined as a composite of >40% loss of estimated glomerular filtration rate, kidney failure, or death. ANALYTICAL APPROACH: Cox proportional hazard models adjusted for clinical characteristics, kidney function, relevant medications, and MEST-C score. Risk classification statistics were calculated for IgAN progression at 3 years, including C statistic, net reclassification index, and integrated discrimination index. RESULTS: High levels (>3.9µg/g of creatinine) of urinary MMP-7 were associated with a 2.7-fold higher risk for IgAN progression in adjusted analyses. Urinary MMP-7 level outperformed (C statistic, 0.78) levels of urinary angiotensinogen (C statistic, 0.75), epidermal growth factor (C statistic, 0.75), kidney injury molecule 1 (C statistic, 0.68), and serum galactose-deficient IgA1 (C statistic, 0.59) for predicting IgAN progression. The addition of urinary MMP-7 level to a model with clinical data from the time of biopsy (estimated glomerular filtration rate, mean arterial blood pressure, and proteinuria) and MEST-C score significantly improved the C statistic from 0.79 to 0.85, improved the 3-year risk prediction of IgAN progression (from 0.84 to C statistic of 0.90), and improved risk reclassification (category-free net reclassification improvement, 0.60). The predictive performance of urinary MMP-7 level, alone or combined with clinical data, was consistent in the external validation set. LIMITATIONS: Lack of validation in other ethnic populations. CONCLUSIONS: In this study cohort, urinary MMP-7 level is an independent predictor of IgAN progression. The addition of urinary MMP-7 level to MEST-C score and clinical data at the time of biopsy significantly improved risk prediction of IgAN progression.

Proteomics Investigations into Serum Proteins Adsorbed by High-Flux and Low-Flux Dialysis Membranes.

Hemodialysis is one of the most important therapies for patients with uremia, and the dialysis membrane is the predominant factor that impacts the efficiency of dialysis. Here, a protein adsorption on two different membranes is investigated to provide a basis for improving dialysis materials. Two cases treated with the Polyflux 14L low-flux dialyzer and the Polyflux 140H high-flux dialyzers during two continuous therapies are selected. Four used dialyzers from selected patients are infused with C12Im-Cl to elute the adsorbed proteins. Then labeled digested proteins adsorb by Polyflux 140H and Polyflux 14L with 13 CD2 O and NaCNBD3 (light labeling, L) and CD2 O and NaCNBH3 (heavy labeling, H), respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to identify the proteins. According to the ratio (Light labeling/Heavy labeling), the eluted proteins are divided into three groups: significantly higher, significantly lower, and no significant differences with a ratio of >2, <0.5, and 0.5-2, respectively. A total of 668 proteins are identified by LC-MS/MS, among which 177 proteins are retained more by the Polyflux 140H membrane (ratio >2), 320 proteins are retained more by the Polyflux 14L membrane (ratio <0.5), and 171 proteins show no significant difference (ratio 0.5-2) between the two types of membranes. Statistical significance is shown in the percentage of adsorbed proteins with an isoelectric point (pI) ranging from 9 to 10 (19.08 versus 7.69%; χ2 = 11.87, p = 0.0006). Proteins with a molecular weight (MW) of 10-15 kDa tend to deposit on Polyflux 140H compared with Polyflux 14L (25 versus 9.23%; χ2 = 18.66, p = 0.0000) and proteins with a MW of 30-60 kDa tend to deposit on Polyflux 14L compared with Polyflux 140H (36.54 versus 22.37%; χ2 = 8.96, p = 0.0028). According to gene ontology analysis, the proteins adsorbed by dialysis membranes are closely related to activation of complement system and the coagulation cascade. The proteins adsorbed by Polyflux 140H and Polyflux 14L show significant differences in PI, MW, and protein class. Proteomic techniques are an effective approach for studying hemodialysis membranes.

Proteomic study provides new clues for complications of hemodialysis caused by dialysis membrane.

The complications of hemodialysis accompanied the hemodialysis and threaten the patients' life. Besides the loss of nutrient substance, such as amino acid and vitamin, we found new clues that the adsorbed proteins on common-used polysulfone-based dialysis membrane might be the reason according to the qualitative proteomic study by ionic liquid assisted sample preparation method. Our results indicated that the adsorbed proteins on the membrane were related with complement activation, blood coagulation, and leukocyte-related biological process. The quantitative proteome further demonstrated some significant changes of signal proteins in the post-dialysis plasma after the hemodialysis, such as beta-2-microglobulin and platelet factor-4, which would further verify these new clues.

Efficacy and safety of Changfu peritoneal dialysis solution: a multi-center prospective randomized controlled trial.

BACKGROUND: A multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage. METHODS: Adult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices. RESULTS: Changes of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that. CONCLUSIONS: The domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.