Progression of Vascular Calcification and Clinical Outcomes in Patients Receiving Maintenance Dialysis.

Importance: Baseline findings from the China Dialysis Calcification Study (CDCS) revealed a high prevalence of vascular calcification (VC) among patients with end-stage kidney disease; however, data on VC progression were limited. Objectives: To understand the progression of VC at different anatomical sites, identify risk factors for VC progression, and assess the association of VC progression with the risk of cardiovascular events and death among patients receiving maintenance dialysis. Design, Setting, and Participants: This cohort study was a 4-year follow-up assessment of participants in the CDCS, a nationwide multicenter prospective cohort study involving patients aged 18 to 74 years who were undergoing hemodialysis or peritoneal dialysis. Participants were recruited from 24 centers across China between May 1, 2014, and April 30, 2015, and followed up for 4 years. A total of 1489 patients receiving maintenance dialysis were included in the current analysis. Data were analyzed from September 1 to December 31, 2021. Exposures: Patient demographic characteristics and medical history; high-sensitivity C-reactive protein laboratory values; serum calcium, phosphorus, and intact parathyroid hormone (iPTH) values; and previous or concomitant use of medications. Main Outcomes and Measures: The primary outcome was progression of VC at 3 different anatomical sites (coronary artery, abdominal aorta, and cardiac valves) and identification of risk factors for VC progression. Participants received assessments of coronary artery calcification (CAC), abdominal aortic calcification (AAC), and cardiac valve calcification (CVC) at baseline, 24 months, 36 months, and 48 months. Secondary outcomes included (1) the association between VC progression and the risk of all-cause death, cardiovascular (CV)-related death, and a composite of all-cause death and nonfatal CV events and (2) the association between achievement of serum calcium, phosphorus, and iPTH target levels and the risk of VC progression. Results: Among 1489 patients, the median (IQR) age was 51.0 (41.0-60.0) years; 59.5% of patients were male. By the end of 4-year follow-up, progression of total VC was observed in 86.5% of patients; 69.6% of patients had CAC progression, 72.4% had AAC progression, and 33.4% had CVC progression. Common risk factors for VC progression at the 3 different anatomical sites were older age and higher fibroblast growth factor 23 levels. Progression of CAC was associated with a higher risk of all-cause death (model 1 [adjusted for age, sex, and body mass index]: hazard ratio [HR], 1.97 [95% CI, 1.16-3.33]; model 2 [adjusted for all factors in model 1 plus smoking status, history of diabetes, and mean arterial pressure]: HR, 1.89 [95% CI, 1.11-3.21]; model 3 [adjusted for all factors in model 2 plus calcium, phosphorus, intact parathyroid hormone, and fibroblast growth factor 23 levels and calcium-based phosphate binder use]: HR, 1.92 [95% CI, 1.11-3.31]) and the composite of all-cause death and nonfatal CV events (model 1: HR, 1.98 [95% CI, 1.19-3.31]; model 2: HR, 1.91 [95% CI, 1.14-3.21]; model 3: HR, 1.95 [95% CI, 1.14-3.33]) after adjusting for all confounding factors except the presence of baseline calcification. Among the 3 targets of calcium, phosphorus, and iPTH, patients who achieved no target levels (model 1: odds ratio [OR], 4.75 [95% CI, 2.65-8.52]; model 2: OR, 4.81 [95% CI, 2.67-8.66]; model 3 [for this analysis, adjusted for all factors in model 2 plus fibroblast growth factor 23 level and calcium-based phosphate binder use]: OR, 2.76 [95% CI, 1.48-5.16]), 1 target level (model 1: OR, 3.71 [95% CI, 2.35-5.88]; model 2: OR, 3.62 [95% CI, 2.26-5.78]; model 3: OR, 2.19 [95% CI, 1.33-3.61]), or 2 target levels (model 1: OR, 2.73 [95% CI, 1.74-4.26]; model 2: OR, 2.69 [95% CI, 1.71-4.25]; model 3: OR, 1.72 [95% CI, 1.06-2.79]) had higher odds of CAC progression compared with patients who achieved all 3 target levels. Conclusions and Relevance: In this study, VC progressed rapidly in patients undergoing dialysis, with different VC types associated with different rates of prevalence and progression. Consistent achievement of serum calcium, phosphorus, and iPTH target levels was associated with a lower risk of CAC progression. These results may be useful for increasing patient awareness and developing appropriate strategies to improve the management of chronic kidney disease-mineral and bone disorder among patients undergoing dialysis.

Effectiveness of Chinese herbal medicine combined with Western medicine on deferring dialysis initiation for nondialysis chronic kidney disease stage 5 patients: a multicenter prospective nonrandomized controlled study.

BACKGROUND: In clinical practice, Chinese herbal medicine (CHM) purportedly has beneficial therapeutic effects for chronic kidney disease (CKD), which include delaying disease progression and dialysis initiation. However, there is a lack of high-quality evidence-based results to support this. Therefore, this study aimed to evaluate the efficacy of CHM combined with Western medicine in the treatment of stage 5 CKD. METHODS: This was a prospective nonrandomized controlled study. Stage 5 CKD (nondialysis) patients were recruited form 29 AAA class hospitals across China from July 2014 to April 2019. According to doctors' advice and the patients' wishes, patients were assigned to the CHM group (Western medicine + CHM) and the non-CHM group (Western medicine). Patient demographic data, primary disease, blood pressure, Chinese and Western medical drugs, clinical test results, and time of dialysis initiation were collected during follow-up. RESULTS: A total of 908 patients were recruited in this study, and 814 patients were finally included for further analysis, including 747 patients in the CHM group and 67 patients in the non-CHM group. 482 patients in the CHM group and 52 patients in the non-CHM group initiated dialysis. The median time of initiating dialysis was 9 (7.90, 10.10) and 3 (0.98,5.02) months in the CHM group and non-CHM group, respectively. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis [adjusted hazard ratio (aHR): 0.38; 95% confidence interval (CI): 0.28, 0.53] compared to those in the non-CHM group. After 1:2 matching, the outcomes of 160 patients were analyzed. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis (aHR: 0.32; 95% CI: 0.21, 0.48) compared to patients in the non-CHM group. Also, the Kaplan-Meier analysis demonstrated that the cumulative incidence of dialysis in the CHM group was significantly lower than that in the non-CHM group (log-rank test, P<0.001) before and after matching. CONCLUSIONS: This study suggest that the combination of CHM and Western medicine could effectively reduce the incidence of dialysis and delay the time of dialysis initiation in stage 5 CKD 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.

Prevalence and risk factors for vascular calcification in Chinese patients receiving dialysis: baseline results from a prospective cohort study.

OBJECTIVE: With limited data available on calcification prevalence in chronic kidney disease (CKD) patients on dialysis, the China Dialysis Calcification Study (CDCS) determined the prevalence of vascular/valvular calcification (VC) and association of risk factors in Chinese patients with prevalent hemodialysis (HD) or peritoneal dialysis (PD). METHODS: CKD patients undergoing HD/PD for ≥6 months were enrolled. Prevalence data for calcification and medical history were documented at baseline. Coronary artery calcification (CAC) was assessed by electron beam or multi-slice computed tomography (EBCT/MSCT), abdominal aortic calcification (AAC) by lateral lumbar radiography, and cardiac valvular calcification (ValvC) by echocardiography. Serum phosphorus, calcium, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D and FGF-23 were evaluated. A logistic regression model was used to evaluate the association between risk factors and VC. RESULTS: Of 1,497 patients, 1,493 (78.3% HD, 21.7% PD) had ≥1 baseline calcification image (final analysis cohort, FAC) and 1,423 (78.8% HD, 21.2% PD) had baseline calcification data complete (BCDC). Prevalence of VC was 77.4% in FAC (80.8% HD, 65.1% PD, p < .001) and 77.5% in BCDC (80.7% HD, 65.8% PD). The proportion of BCDC patients with single-site calcification were 20% for CAC, 4.3% for AAC, and 4.3% for cardiac valvular calcification (ValvC), respectively. Double site calcifications were 23.4% for CAC and AAC, 6.5% for CAC and ValvC, and 1.1% for AAC and ValvC, respectively. In total, 17.9% patients had calcification at all three sites. CONCLUSIONS: High prevalence of total VC in Chinese CKD patients will supplement current knowledge, which is mostly limited, contributing in creating awareness and optimizing VC management.

Sevelamer carbonate lowers serum phosphorus effectively in haemodialysis patients: a randomized, double-blind, placebo-controlled, dose-titration study.

BACKGROUND: Hyperphosphataemia in patients with advanced chronic kidney disease (CKD) is associated with adverse outcomes, including vascular calcification and higher mortality rates. While phosphate lowering is an integral aspect of CKD management, the efficacy and safety of phosphate binders in a contemporary cohort of Chinese haemodialysis patients (who have different genetics and dietary patterns than other populations) has not been previously described. Moreover, sparse data are available on strategies for optimal dose titration when transitioning from a calcium-based to a polymer-based phosphate binder. METHODS: This randomized, double-blind, dose-titration study compared sevelamer carbonate (starting dose 800 mg three times daily) with placebo over 8 weeks' duration in Chinese CKD patients on haemodialysis. Patients were required to be using calcium-based binders prior to study start. RESULTS: In all, 205 patients were randomized (sevelamer, n = 135; placebo, n = 70); mean age was 48.6 years, 61% were male and the mean time on dialysis was 4.4 years. The mean serum phosphorus decreased significantly in patients treated with sevelamer carbonate [change -0.69 ± 0.64 mmol/L (-2.14 ± 1.98 mg/dL)] but remained persistently elevated with placebo [change -0.06 ± 0.57 mmol/L (-0.19 ± 1.76 mg/dL)] (P < 0.0001). When compared with placebo, sevelamer carbonate treatment resulted in statistically significant greater mean reductions from baseline in serum total (-17.1 versus -3.3%) and low-density lipoprotein cholesterol (-33.5 versus-7.6%) (P < 0.0001 for both). Sevelamer carbonate was well tolerated with 96% adherence compared with 97% adherence in the placebo arm. Overall, adverse events experienced by patients in the sevelamer carbonate and placebo treatment groups were similar and consistent with their underlying renal disease. CONCLUSIONS: This study demonstrated that hyperphosphataemia developed quickly following the cessation of phosphate binders and remained persistently elevated in end-stage CKD in the placebo-treated group. Gradually titrating up sevelamer carbonate from an initial dose of 2.4 g/day to an average daily dose of 7.1 ± 2.5 g/day was well tolerated, safe and efficacious in contemporary Chinese haemodialysis patients.

Tacrolimus is an alternative therapy option for the treatment of adult steroid-resistant nephrotic syndrome: a prospective, multicenter clinical trial.

BACKGROUND: The optimal therapy for adult steroid-resistant nephrotic syndrome (SRNS) remains a therapeutic challenge. We investigated the efficacy and safety of tacrolimus as a promising regimen in Chinese adult patients. METHODS: A prospective, multicenter trial was conducted in 9 nephrology centers from 2006 to 2008, in patients with SRNS (defined as failure to respond to 1 mg/kg/day of prednisone for 8, and 16 weeks, in focal segmental glomerulosclerosis). Patients were treated with tacrolimus (TAC) plus prednisone for 12 months. TAC dose was titrated to achieve a target trough blood concentration of 5-10 ng/ml for the first 6 months and 4-6 ng/ml for the subsequent 6 months. The primary outcomes included complete or partial remission [complete remission (CR): proteinuria <0.3 g/24 h, with serum albumin ≥ 3.5 g/dl and stable renal function; partial remission (PR): proteinuria between 0.3 and 3.5 g/24 h and a decrease of at least 50 % from the baseline level, with serum albumin ≥ 3.0 g/dl and stable renal function]. Secondary end-points included relapse rate, changes of clinical parameters (proteinuria, serum albumin, and lipid profile) and adverse events. RESULTS: Twenty-four patients with SRNS were enrolled. After 6 months of therapy, CR was achieved in 58.3 % of patients and PR in 16.7 %, yielding a final response rate of 75.0 %. The decrease in proteinuria was 43.1 ± 17.5 % after the first month of treatment (P < 0.001). Complete or PR was achieved in 6 of 8 patients with minimal change disease, 4 of 6 patients with mesangioproliferative glomerulonephritis (MsPGN), 6 of 7 patients with focal segmental glomerulosclerosis (FSGS), and all 2 patients with IgA nephropathy. Two patients (1 with MsPGN and 1 with FSGS) experienced relapses during the subsequent 6 months of follow-up. Adverse events included infection, hand tremor, diarrhea, acute reversible or persistent nephrotoxicity. CONCLUSIONS: In conjunction with prednisone, TAC may be an alternative therapeutic regimen for adult SRNS patients. However, adverse events in these patients should be carefully monitored, especially at the beginning of treatment. Randomized controlled trials with longer follow-up are warranted.

[Effect of losartan on renal expression of monocyte chemoattractant protein-1 and transforming growth factor-ß(1) in rats after unilateral ureteral obstruction].

OBJECTIVE: To investigate the effect of losartan on the expression of monocyte chemoattractant protein-1 (MCP1) and transforming growth factor-ß(1) (TGF-ß(1)) in the kidney of rats with unilateral urethral obstruction (UUO) and evaluate protective effect of losartan against reanal interstitial fibrosis. METHODS: Rat models of UUO were treated with losartan at the routine dose, high dose, and very high dose (50, 200, and 500 mg/kg daily, respectively), and saline was given to UUO model rats and rats with sham operation. At 7, 14, and 21 days, the tail cuff blood pressure (TCP), 24-h urine protein (Upro), serum Scr, BUN, K(+), percentage of renal damage and renal interstitial fibrosis (%INT) were measured in the rats. MCP1 protein in the renal tissues was detected using immunohistochemistry, and MCP1 and TGF-ß(1) mRNA expressions were assayed using RT-PCR. RESULTS: As the UUO prolonged, Upro, TCP, tubular damage, %INT, and MCP1 and TGF-ß(1) mRNA expressions all increased significantly (P<0.05). High and very high doses of losartan, compared with the routine dose, obviously reversed these changes. CONCLUSION: High-dose losartan can effectively control blood pressure, reduce renal damage and fibrosis, and inhibit MCP1 and TGF-ß(1) expression in rats with UUO, and at a very high dose, losartan can more effectively reduce 24-h Upro than the high-dose group. High and very high doses of losartan offer better protective effect on the kidney in rats with UUO.