Effectiveness and safety of KunXian capsule for the treatment of IgA nephropathy.

BACKGROUND: Tripterygium Wilfordii Hook F (TwHF) preparation has been widely used in the treatments of IgA nephropathy (IgAN) in China. However, the effectiveness and safety of the new generation of TwHF preparation, KuxXian capsule, on the treatment of IgAN remains unknown. METHODS: Here, we retrospectively describe our experience treating 55 consecutive IgAN patients with KunXian. We defined complete remission as proteinuria < 0.5 g/24 h and partial remission as proteinuria < 1 g/24 h, each also having > 50% reduction in proteinuria from baseline. RESULTS: At first follow-up after KunXian treatment (5.7 weeks, IQR 4.7-7.9), all but two patients (96%) showed a reduction in proteinuria. The overall median proteinuria decreased from 2.23 g/day at baseline to 0.94 g/day (P < 0.001) at the first follow-up. During a median follow-up of 28 weeks after KunXian administration, 25(45.5%) patients achieved complete remission, 34 (61.8%) patients achieved complete/partial remission. Of the 12 patients discontinued KunXian treatment during the follow-up, the median proteinuria was increased from 0.97 g/24 h to 2.74 g/24 h after a median of 10.9 weeks (P = 0.004). Multivariable Cox models showed that female, treatment switching from previous generation of TwHF preparation, lower initial KunXian dosage, and higher proteinuria at baseline were independently associated proteinuria remission. Of the 20 pre-menopausal females, 12 of them developed oligomenorrhea or menstrual irregularity and ten of them developed amenorrhea. CONCLUSION: KunXian is effectiveness and safety for the treatment of IgA nephropathy. Woman of childbearing age to be informed of the risk of ovarian failure after being treated with TwHF preparations.

An equation to estimate 24-hour total urine protein excretion rate in patients who underwent urine protein testing.

BACKGROUND: The urine protein-creatinine ratio (UPCR) in a spot first-morning urine sample is used to estimate 24-h urine proteinuria (24hUP) in patients who underwent urine protein testing. UPCR cannot be directly compared with 24-h proteinuria. Thus, an equation to estimate 24-h total protein excretion rate, using age, gender, and the UPCR may improve its bias and accuracy in patients who underwent urine protein testing. METHODS: We simultaneously measured 24-h urine protein and the same day's first-morning spot urine from patients with kidney disease. Generalized linear and no-linear models, using age, gender, and UPCR, were constructed to estimate for 24-h urine protein and the best model (NJ equation) was selected to estimated 24 hUP (e24hUP). RESULTS: A total of 5435 paired samples (including a training cohort of 3803 patients and a validation cohort of 1632 patients) were simultaneously measured for UPCR and 24-h urine protein. In the training cohort, the unadjusted UPCR obviously underestimated 24-h urine protein when UPCR ≤1.2 g/g (median bias - 0.17 g/24 h) and overestimated 24-h urine protein when UPCR > 1.2 g/g (median bias 0.53 g/24 h). In the validation cohort, the NJ equation performed better than the unadjusted UPCR, with lower root mean square error (0.81 vs. 1.02, P < 0.001), less bias (median difference between measured and estimated urine protein, - 0.008 vs. 0.12), improved precision (interquartile range of the differences, 0.34 vs. 0.50), and greater accuracy (percentage of estimated urine protein within 30% of measured urine protein, 53.4% vs. 32.2%). Bland-Altman plot indicated that the agreement of spot and daily estimates was less pronounced with 24 hUP > 2 g than lower values. CONCLUSIONS: The NJ e24hUP equation is more accurate than unadjusted UPCR to estimate 24 hUP in patients with kidney disease and could be used for laboratory application.

HLA Alleles and Prognosis of PLA2R-Related Membranous Nephropathy.

BACKGROUND AND OBJECTIVES: Associations between HLA alleles and susceptibility to M-type phospholipase A2 receptor (PLA2R)-related membranous nephropathy have been well defined previously in Chinese patients. However, the relationships between HLA alleles and kidney outcome remain unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Five HLA genes (DRB1, DQA1, DQB1, DRB3, and DRB5) were genotyped in a prospective cohort of 392 patients with PLA2R-related membranous nephropathy. The associations between HLA alleles and kidney outcomes were studied. RESULTS: A total of 79 HLA alleles were identified in this study. Four HLA alleles, DRB1*13:01 (n=12; hazard ratio, 3.7; 95% confidence interval, 1.8 to 7.8; P<0.001), DQB1*06:03 (n=12; hazard ratio, 3.7; 95% confidence interval, 1.8 to 7.8; P<0.001), DRB1*04:05 (n=12; hazard ratio, 3.8; 95% confidence interval, 1.5 to 9.5; P=0.004), and DQB1*03:02 (n=21; hazard ratio, 3.1; 95% confidence interval, 1.4 to 6.7; P=0.005), were associated with a ≥40% eGFR decline during follow-up. DRB1*13:01 and DQB1*06:03 were tightly linked with each other. Forty-four of the 392 patients (11%) carried at least one of the four identified risk HLA alleles in this study. Compared with patients who were negative for all risk HLA alleles, those carrying at least one risk HLA allele had a significant risk of a ≥40% eGFR decline during follow-up (hazard ratio, 3.9; 95% confidence interval, 2.3 to 6.7; P<0.001). After adjusting for age, sex, proteinuria, albumin, eGFR, and anti-PLA2R antibody levels, multivariable Cox analysis showed that patients carrying any of the four risk HLA alleles remained associated with a higher risk of a ≥40% decline in eGFR (hazard ratio, 4.1; 95% confidence interval, 2.3 to 7.1; P<0.001). CONCLUSIONS: Carrying any of the HLA alleles, DRB1*13:01/DQB1*06:03, DRB1*04:05, and DQB1*03:02, was independently associated with poor prognosis in Chinese patients with PLA2R-related membranous nephropathy.