Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS: Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

Relationship between Traditional Chinese Medicine Syndrome Elements and Prognosis of Patients with IgA Nephropathy.

Objective: It is not clear which Traditional Chinese Medicine- (TCM-) related elements affect primary IgA nephropathy (IgAN) progression. Here, we explored the risk factors, based on TCM syndrome elements, related to the prognosis of primary IgAN patients. Methods: We analyzed patients with newly diagnosed, biopsy-proven IgAN at a single institution from December 2013 to September 2021. Basic clinical and pathological characteristics were assessed at the time of renal biopsy. The study endpoint was end-stage renal disease (ESRD: eGFR <15 ml/min per 1.73 m2, dialysis, or kidney transplantation) and/or eGFR decreased by >30% from baseline. Kaplan‒Meier survival analysis was used to explore the role of TCM syndrome elements in IgAN progression. Multivariate Cox regression analysis with adjustment for traditional risk factors was performed to explore TCM syndrome elements that may influence patient prognosis. The factors correlated with TCM syndrome elements in IgAN patients were further evaluated by logistic regression analysis. Results: During a median follow-up of 22.0 months, 53 (12.5%) of the 423 included IgAN patients reached the study endpoint. The main IgAN disease location elements were the kidney, liver, and spleen. The main IgAN disease nature elements were Yin-deficiency and Qi-deficiency, dampness, Yang-deficiency, phlegm, and Blood-deficiency. Kaplan‒Meier analysis identified three disease locations (liver, spleen, and kidney) and four disease natures (Qi-deficiency, Yang-deficiency, phlegm, and dampness) as elements associated with poor renal survival in IgAN patients. In multivariate Cox regression analysis, baseline Yang-deficiency was an independent risk predictor of poor prognosis in primary IgAN patients (hazard ratio 2.338; 95% confidence interval [CI]: 1.208-4.525; P=0.012) after adjustment for traditional risk factors. Furthermore, logistic regression analysis identified being female (odds ratio [OR] 2.518; 95% CI: 1.538-4.122; P < 0.001), older age (OR 1.043; 95% CI: 1.022-1.065; P < 0.001), low hemoglobin levels (OR 0.984; 95% CI: 0.971-0.996; P=0.013), and cellular/fibrocellular crescents (OR 1.706; 95% CI: 1.068-2.728; P=0.026) as factors affecting Yang-deficiency in IgAN patients. Conclusions: Yang-deficiency independently predicts the risk of poor prognosis in primary IgAN patients. Being female, older age, low hemoglobin levels, and cellular/fibrocellular crescents were independently associated with Yang-deficiency in IgAN patients.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER: NCT02063100 on ClinicalTrials.gov.

Potential Association of Body Constitution with the Prognosis of IgA Nephropathy: A Long-Time Follow-Up of 203 Cases in China.

OBJECTIVE: This study investigated the association between body constitution (BC) and the prognosis of IgA nephropathy. METHODS: We analyzed 203 biopsy-diagnosed IgA nephropathy patients, who were followed up for (63.9±16.2) months. The participants' BC statuses were evaluated with the Constitution in Chinese Medicine Questionnaire; the relationships between clinical parameters and renal outcomes were analyzed by Cox regression. RESULTS: Patients were classified into chronic kidney disease stages with 43.4% in stage 1, 27.1% in stage 2, 26.1% in stage 3, 3.5% in stage 4, and none in stage 5. Qi-deficiency BC type was the most common BC type in IgA nephropathy patients. In univariate analysis, proteinuria of more than 1g/d, hypertension, renal impairment (estimated glomerular filtration rate <60 mL/min), hypoproteinemia, hyperuricemia, Yang-deficiency BC, and blood-stasis BC were associated with poor prognosis. Multivariate analysis identified that hypertension (hazard ratios (HR) 3.5, P=0.009), renal impairment (HR 5.8, P<0.001), Yang-deficiency BC (HR 2.3, P=0.041), and blood-stasis BC (HR 2.5, P=0.017) were independent predictors of unfavorable renal outcomes. CONCLUSIONS: Most patients of IgA nephropathy were biopsied at an early stage. Yang-deficiency BC and blood-stasis BC at biopsy were most closely associated with the worse prognosis of IgA nephropathy along with hypertension and renal impairment.

Retrospective analysis of tacrolimus combined with Tripterygium wilfordii polyglycoside for treating idiopathic membranous nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is one of the most common adult nephrotic syndromes. Some patients with this disorder require immunosuppressive therapy. This retrospective case series was performed to assess the effects of tacrolimus (TAC) combined with Tripterygium wilfordii polyglycoside (TWG) in treating IMN. METHODS: From January 2015 to August 2016, kidney-biopsy-proven IMN patients treated with TAC in the Chinese PLA General Hospital were screened. Data were retrieved from the patients' medical records. The first efficacy evaluation index was remission rate (complete remission and partial remission), and the secondary efficacy evaluation indices included relapse rate, proteinuria, serum albumin and estimated glomerular filtration rate (eGFR). Adverse events were also assessed. RESULTS: The included patients' treatments were tacrolimus monotherapy (TAC group, n = 33), tacrolimus combined with methylprednisolone (MP) (TAC + MP group, n = 24) and tacrolimus combined with Tripterygium wilfordii polyglycoside (TAC + TWG group, n = 21). The remission rates of the TAC, TAC + MP, and TAC + TWG groups in the 10th month were 54.5, 62.5, and 85.7%, respectively (TAC + TWG group vs TAC group, P = 0.037, TAC + TWG group vs TAC + MP group, P = 0.125). Moreover, the complete remission rates of the TAC, TAC + MP, and TAC + TWG groups in the 10th month were 21.2, 20.8, and 57.1%, respectively (TAC + TWG group vs TAC group, P = 0.007, TAC + TWG group vs TAC + MP group, P = 0.012). Compared with the TAC group, the TAC + TWG group had a higher remission rate during these ten months (log-rank, P = 0.005). Compared with the TAC and TAC + MP groups, the TAC + TWG group had a higher complete remission rate (log-rank, P = 0.019 and log-rank, P = 0.005, respectively). CONCLUSION: This retrospective study showed that TAC combined with TWG may be effective for treating IMN. Further randomized controlled trials (RCTs) are needed to assess the efficacy and safety of TAC combined with TWG.

Effect of Huaier On the Proliferation of Mesangial Cells in Anti-Thy-1 Nephritis.

BACKGROUND/AIMS: To determine whether an aqueous extract of Trametes robiniophila Murr. (Huaier) suppresses anti-Thy-1 mesangial proliferative glomerulonephritis (MsPGN) in vivo and platelet-derived growth factor (PDGF)-BB-induced mesangial cell proliferation in vitro. METHODS: Male Wistar rats were randomly categorized into 5 groups: Sham, Thy-1, and 3 Huaier-treated groups (low, medium, and high dose). Two weeks after treatment, urinary proteins were quantified and renal pathological changes were examined. MAX interactor 1 (Mxi-1) and proliferating cell nuclear antigen (PCNA) expression levels in isolated glomeruli, rat mesangial cell viability, cell-cycle distribution, and cell-cycle pathways were assessed. RESULTS: Huaier diminished the proliferative damages and urinary protein secretion in Thy-1 rats. PCNA was downregulated, whereas Mxi-1 was upregulated in the isolated glomeruli of Huaier-treated groups compared with the Thy-1 group. Huaier inhibited PDGF-BB- stimulated proliferation of rat mesangial cells in a time- and dose-dependent manner (50% inhibitory concentration = 6.19 mg/mL) and induced G2 cell-cycle arrest. Cell-cycle pathway proteins were downregulated, whereas Mxi-1 was upregulated in Huaier-treated mesangial cells compared with PDGF-BB-stimulated cells. CONCLUSION: Huaier reduces urinary protein excretion and relieves hyperplasia in mesangial cells in anti-Thy-1 MsPGN as well as inhibits PDGF-BB-stimulated proliferation and DNA synthesis of rat mesangial cells in vitro, suggesting its novel therapeutic potential in MsPGN.