Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

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.

Effect of Sheng Xue Ning Tablets on Renal Anemia in Patients Subject to Maintenance Hemodialysis and Safety Evaluation: A Multi-setting Prospective Randomized Study.

This study compared Sheng Xue Ning (SXN) tablets with ferrous succinate (FS) tablets in terms of their efficacy for the treatment of iron-deficient renal anemia and safety in patients subject to maintenance hemodialysis (MHD). A total of 94 patients undergoing MHD were randomly assigned to an experiment group (receiving oral SXN tablets, SXN group) and a control group (orally given FS tablets, FS group) and followed up for 12 weeks. Erythropoietin (EPO) was used in both groups. The efficacy was assessed by detecting the subsequent changes in hemoglobin (Hb), serum iron (SI), SF and transferrin saturation (TSAT). At the 12th week, Hb and TSAT levels in both groups were significantly increased compared to those in the screening period (P<0.05). However, no significant difference in Hb and TSAT was found between the two groups. The average weekly EPO dosage used was lower in SXN group than in FS group (P<0.05) at the 10th week and the 12th week. Our study showed that SXN tablets can effectively ameliorate renal anemia and keep iron metabolism stable in MHD patients, and its efficacy is virtually close to that of FS tablets. Meanwhile, SXN tablets can reduce the dosage of EPO and have a good safety profile.

Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study.

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min-1•1.73 m-2, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) µmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min-1•1.73 m-2, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min-1•1.73 m-2 per year. CONCLUSION: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

Safety, Effectiveness, and Manipulability of Peritoneal Dialysis Machines Made in China: A Randomized, Crossover, Multicenter Clinical Study.

BACKGROUND: Automated peritoneal dialysis (APD) can cater to individual needs, provide treatment while asleep, take into account the adequacy of dialysis, and improve the quality of life. Currently, independent research and development of APD machines made in China are more conducive to patients. A randomized, multicenter, crossover study was conducted by comparing an APD machine made in China with an imported machine. The safety, effectiveness, and manipulability of the two machines were compared. METHODS: Two hundred and sixty patients who underwent peritoneal dialysis (PD) on a regular basis in 18 centers between August 2015 and February 2016 were included. The inclusion criteria include age ≥18 years and PD ≥30 days. The exclusion criteria were as follows: hemodialysis; exit site or tunnel infection; and peritonitis ≤30 days. The patients were randomly divided into Group A, who were first treated with a FM machine made in China, then changed to an imported machine; and Group B, who were treated using the reverse sequence. APD treatment was performed with 10 L/10 h and 5 cycles of exchange. After 72 h, the daily peritoneal Kt/V, the accuracy of the injection rate, accuracy of the injection temperature, safety, and manipulability of the machine were assessed. Noninferiority test was conducted between the two groups. RESULTS: The daily peritoneal Kt/V in the APD machine made in China and the imported APD machine were 0.17 (0.14, 0.25) and 0.16 (0.13, 0.23), respectively. There was no significant difference between the groups (Z = 0.15, P = 0.703). The lower limit of the daily Kt/V difference between the two groups was 0.0069, which was greater than the noninferiority value of -0.07 in this study. The accuracy of the injection rate and injection temperature was 89.7% and 91.5%, respectively, in the domestic APD machine, which were both slightly better than the accuracy rates of 84.0% and 86.8% in the imported APD machine (89.7% vs. 84.0%, P = 0.2466; 91.5% vs. 86.8%, P = 0.0954). Therefore, the APD machine made in China was not inferior to the imported APD machine. The fuselage of the imported APD machine was space-saving, while the APD machine made in China was superior with respect to body mobility, man-machine dialog operation, alarm control, and patient information recognition. CONCLUSIONS: The FM machine made in China was not inferior to the imported APD machine. In addition, the FM machine made in China had better operability. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02525497; https://clinicaltrials.gov/ct2/results?cond=&term=NCT02525497&cntry=& state=&city=&dist=.

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction: A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study.

BACKGROUND: Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. METHODS: The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min-1·1.73 m-2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. RESULTS: A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was -0.2 (-4.3-2.7) and -2.2 (-5.7-0.8) ml·min-1·1.73 m-2, respectively (Z = -2.408, P = 0.016). There were no significant differences in adverse events between the groups. CONCLUSIONS: Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.

Analysis of Factors Associated with Death in Maintenance Hemodialysis Patients: A Multicenter Study in China.

BACKGROUND: Patients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death. METHODS: Participants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality. RESULTS: In total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094-1.886), age (OR: 1.046, 95% CI: 1.036-1.057), and presence of DN (OR: 1.837, 95% CI: 1.322-2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346-0.989), hemoglobin (OR: 0.974, 95% CI: 0.967-0.981), albumin (OR: 0.939, 95% CI: 0.915-0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070-0.386) were protective factors based on a multivariate analysis. CONCLUSIONS: Hemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.

Abelmoschus manihot - a traditional Chinese medicine versus losartan potassium for treating IgA nephropathy: study protocol for a randomized controlled trial.

BACKGROUND: IgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, but effective therapy remains limited and many patients progress to end-stage renal disease (ESRD). Only angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blockers (ARB) show a high level of evidence (1B level) of being of value in the treatment for IgAN according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. However, traditional Chinese medicine has raised attention in kidney disease research. Abelmoschus manihot, a single medicament of traditional Chinese medicine has shown therapeutic effects in primary glomerular disease according to the randomized controlled clinical trial that we have completed. Here, we conduct a new study to assess the efficacy and safety of Abelmoschus manihot in IgAN. Also, this study is currently the largest double-blind, randomized controlled registered clinical research for the treatment of IgAN. METHODS: We will conduct a multicenter, prospective, double-blind, double-dummy randomized controlled study. The study is designed as a noninferiority clinical trial. Approximately 1600 biopsy-proven IgAN patients will be enrolled at 100 centers in China and followed up for as long as 48 weeks. IgAN patients will be randomized assigned to the Abelmoschus manihot group (in the form of a huangkui capsule, 2.5 g, three times per day) and the losartan potassium group (losartan potassium, 100 mg/d). The primary outcome is the change in 24-h proteinuria from baseline after 48 weeks of treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after 48 weeks of treatment, the incidence of endpoint events (proteinuria ≥3.5 g/24 h, the doubling of serum creatinine, or receiving blood purification treatment) are the secondary outcomes. Twenty-four-hour proteinuria and eGFR are measured at 0, 4, 12, 24, 36 and 48 weeks. DISCUSSION: This study will be of sufficient size and scope to evaluate the efficacy and safety of Abelmoschus manihot compared to losartan potassium in treating patients with IgAN. The results of this study may provide a new, effective and safe treatment strategy for IgAN. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02231125 . Registered on 30 August 2014.

Mitochondrial DNA sequence of ruffe (Gymnocephalus cernua).

The complete mitochondrial genome (mitogenome) of the Gymnocephalus cernua has been studied. The genome sequence was 16,614 bp in length, including the typical structure of 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes, and the non-coding control region. The overall base composition of G. cernua mitogenome is 27.84% A, 27.60% T, 16.61% G, and 27.94% C, with a high A + T content of 55.45%. The complete mitochondrial genome of G. cernua provides basic genome data for relative studies on Perciformes.

Treatment of complicated urinary tract infection and acute pyelonephritis by short-course intravenous levofloxacin (750 mg/day) or conventional intravenous/oral levofloxacin (500 mg/day): prospective, open-label, randomized, controlled, multicenter, non-inferiority clinical trial.

OBJECTIVE: To compare the efficacy and safety of short-course intravenous levofloxacin (LVFX) 750 mg with a conventional intravenous/oral regimen of LVFX 500 mg in patients from China with complicated urinary tract infections (cUTIs) and acute pyelonephritis (APN). METHODS: This was a prospective, open-label, randomized, controlled, multicenter, non-inferiority clinical trial. Patients with cUTI and APN were randomly assigned to a short-course therapy group (intravenous LVFX at750 mg/day for 5 days) or a conventional therapy group (intravenous/oral regimen of LVFX at 500 mg/day for 7-14 days). The clinical, laboratory, and microbiological results were evaluated for efficacy and safety. RESULTS: The median dose of LVFX was 3555.4 mg in the short-course therapy group and 4874.2 mg in the conventional therapy group. Intention-to-treat analysis indicated the clinical effectiveness in the short-course therapy group (89.87%, 142/158) was non-inferior to that in the conventional therapy group (89.31%, 142/159). The microbiological effectiveness rates were also similar (short-course therapy: 89.55%, 60/67; conventional therapy: 86.30%, 63/73; p > 0.05). There were no significant differences in other parameters, including clinical and microbiological recurrence rates. The incidence of adverse effects and drug-related adverse effects were also similar for the short-course therapy group (21.95%, 36/164; 18.90%, 31/164) and the conventional therapy group (23.03%, 38/165; 15.76%, 26/165). CONCLUSION: Patients with cUTIs and APN who were given short-course LVFX therapy and conventional LVFX therapy had similar outcomes in clinical and microbiological efficacy, tolerance, and safety. The short-course therapy described here is a more convenient alternative to the conventional regimen with potential implication in anti-resistance and cost saving.

Prevalence, awareness, and treatment of anemia in Chinese patients with nondialysis chronic kidney disease: First multicenter, cross-sectional study.

This was the first multicenter, cross-sectional survey to assess the prevalence of anemia, patient awareness, and treatment status in China. Data of patients with chronic kidney disease (CKD; age, 18-75 years; both out- and inpatients) from 25 hospitals in Shanghai, seeking medical treatment at the nephrology department, were collected between July 1, 2012 and August 31, 2012. The prevalence, awareness, and treatment of anemia in patients with nondialysis CKD (ND-CKD) were assessed. Anemia was defined as serum hemoglobin (Hb) levels ≤12 g/dL in women and ≤13 g/dL in men. A total of 2420 patients with ND-CKD were included. Anemia was established in 1246 (51.5%) patients: 639 (51.3%) men and 607 (48.7%) women. The prevalence of anemia increased with advancing CKD stage (χtrend = 675.14, P < 0.001). Anemia was more prevalent in patients with diabetic nephropathy (68.0%) than in patients with hypertensive renal damage (56.6%) or chronic glomerulonephritis (46.1%, both P < 0.001). Only 39.8% of the anemic patients received treatment with erythropoietin and 27.1% patients received iron products; furthermore, 22.7% of the patients started receiving treatment when their Hb level reached 7 g/dL. The target-achieving rate (Hb at 11-12 g/dL) was only 8.2%. Of the 1246 anemia patients, only 7.5% received more effective and recommended intravenous supplementation. Anemia is highly prevalent in patients with ND-CKD in China, with a low target-achieving rate and poor treatment patterns. The study highlights the need to improve multiple aspects of CKD management to delay the progression of renal failure.

A Clinical Multicenter Randomized Controlled Study on JianpiQinghua Decoction in Treating Stage 3 Chronic Kidney Disease with A Syndrome Type of Dampness-heat due to Spleen Deficiency.

Objective To evaluate the clinical effectiveness of JianpiQinghua decoction in treating stage 3 chronic kidney disease (CKD3) with syndrome type of dampness-heat due to spleen deficiency. Methods A multicenter, randomized, controlled, prospective, double-blind, and double-simulation study was undertaken. A total of 270 CKD3 patients with syndrome type of dampness-heat due to spleen deficiency from the outpatient departments of six general hospitals were randomly divided into telmisartan+analog traditional Chinese medicine (TA) group, traditional Chinese medicine+analog telmisartan (TCMA) group, and telmisartan+traditional Chinese medicine (TTCM) group, in which the corresponding treatment was applied in addition to basic treatment. Six months later, changes in the traditional Chinese medicine (TCM) clinical symptom scores and renal functions before and after treatment were compared among these three groups. Results Of these 270 CKD3 patients who had been enrolled in this study, 30 cases lost to follow-up. The baseline data were comparable among these three groups. After treatment, the TCM clinical symptom scores of both syndrome of spleen-qi deficiency and dampness-heat in TA group were significantly higher than those in TCMA group and TTCM group (P<0.001). With the treatment time prolonged, the TCM clinical symptom scores showed similar descending trends in TCMA group and TTCM group but were different from that in TA group. After treatment, abnormal creatinine rate decreased (P=0.003), and these three treatments and their interactions with each visit had no effect on serum urea nitrogen value (P=0.270, P=0.520); with prolonged treatment, the estimated glomerular filtration rates in three groups tended to be relatively stable after the first rise. The liver function and abnormal serum potassium rate were not statistically significant before and after treatment (P>0.05). Conclusions JianpiQinghua decoction can improve clinical symptoms of TCM in CKD3 patients with syndrome type of dampness-heat due to spleen deficiency and thus improve the quality of life and prognosis. The clinical efficacy of JianpiQinghua decoction alone or combined with telmisartan is superior to telmisartan monotherapy.

Alteration of thyroid hormone levels and related gene expression in Chinese rare minnow larvae exposed to mercury chloride.

Mercury is a prominent environmental contaminant that causes endocrine disorder to human and other organisms. But little is known about the response of the thyroid functions and hypothalamic-pituitary-thyroid (HPT) axis to mercury in teleosts and the few studies that are available have not yielded consistent results. In this study, expression profiles of corticotropin-releasing hormone (crh), thyroid stimulating hormone beta (tshß), solute carrier family 5 (sodium iodide symporter) member 5 (slc5a5), thyroglobulin (tg), thyroid hormone receptor alpha (trα) and thyroid hormone receptor beta (trß) genes were determined in whole-body of Chinese rare minnow (Gobiocypris rarus) larvae after exposure to different levels of Hg(2+) (0, 0.1 and 0.3 mg/l) for 4 days, as well as the thyroid hormones (THs) levels. Moreover, the 96-h lethal concentration of Hg(2+) on rare minnow larvae was determined as 0.32 mg/l. The results showed that crh, tg, trα and trß mRNA levels were significantly up-regulated in the larvae, but the gene expression of tshß and slc5a5 was not significantly changed in our study. Besides, the THs levels increased in the whole-body of fish, especially the thyroxine (T4) level. The above results indicated that Hg(2+) could alter some genes expression in the HPT axis which could be used as the potential biomarkers for evaluating the environmental Hg(2+)-induced stress in fish.

Effects of mercury on oxidative stress and gene expression of potential biomarkers in larvae of the Chinese rare minnow Gobiocypris rarus.

Mercury levels have increased in aquatic food webs throughout the world and can be found at toxic levels in some biota. However, the molecular mechanisms and effects of mercuric chloride (Hg(2+)) remain poorly understood. In the present study, antioxidant parameters (superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde)-as well as a series of gene expressions, including cortisol receptor (cr), Na(+)/K(+)-ATPase (aptase), and prolactin (prl) genes involved in ion-regulatory process, insulin-like growth factor I (igf1) and growth hormone (gh) related to growth rate, as well as heat shock protein70 (hsp70) and metallothionein (mt) used as physiological stress identification-were measured in whole body of Chinese rare minnow larvae (Gobiocypris rarus) after exposure to Hg(2+) (0, 0.1, and 0.3 mg/L) for 4 days. Results show that oxidative stress was generated in fish exposed to Hg(2+) and that the transcription levels of cr, atpase, gh, hsp70, and mt genes increased in a dose-dependent manner, but expression levels of prl and igf1 genes were showed to be decreased in the treated groups. Based on principal component analysis, the correlation between gh and igf1 genes and cr and prl genes was negative. In conclusion, exposure to Hg(2+) could alter multiple physiological and molecular indices in fish; however, before those parameters are used as special biomarkers for monitoring Hg(2+) in aquatic environment, more detailed experiments in laboratory must be performed in the future.

Effects of waterborne cadmium on thyroid hormone levels and related gene expression in Chinese rare minnow larvae.

Cadmium is a heavy metal abundant in the environment that can induce endocrine disorder and toxicity in aquatic organisms at low levels. However, its effects on the thyroid system in fish are still unclear. In this study, the thyroid hormone (TH) levels and the expression profiles of genes related to hypothalamic- pituitary-thyroid (HPT) axis, including corticotropin-releasing hormone (crh), thyroid stimulating hormone beta (tshß), solute carrier family 5 (sodium iodide symporter) member 5 (slc5a5), thyroglobulin (tg), thyroid hormone receptor alpha (trα) and thyroid hormone receptor beta (trß), were determined in whole body of Chinese rare minnow (Gobiocypris rarus) larvae after exposure to different levels of Cd(2+) (0, 0.5 and 2.5mg/L) for 4days. And the 96-h lethal concentration of Cd(2+) on rare minnow larvae was determined as 2.59mg/L. The results showed that crh, slc5a5, tg and tshß mRNA levels were significantly up-regulated in the larvae, but the gene expression of trα and trß was down-regulated in a concentration-dependent manner. Besides, the THs levels decreased in the whole-body of fish, especially the thyroxine (T4) level. The above results indicated that Cd(2+) could alter gene expression in the HPT axis that might subsequently contribute to thyroid disruption.

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.

Prevalence, awareness, treatment, and control of hypertension in the non-dialysis chronic kidney disease patients.

BACKGROUND: Data on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China. METHODS: The survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients. RESULTS: The analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05). CONCLUSIONS: The prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Lanthanum carbonate for the treatment of hyperphosphatemia in CKD 5D: multicenter, double blind, randomized, controlled trial in mainland China.

BACKGROUND: Serum phosphorus control is critical for chronic kidney disease (CKD) 5D patients. Currently, clinical profile for an oral phosphorus binder in the mainland Chinese population is not available. OBJECTIVE: To establish the efficacy, safety, and tolerability of lanthanum carbonate in CKD 5D patients. DESIGN: Multicenter, randomized, double blind, placebo-controlled study. A central randomization center used computer generated tables to allocate treatments. SETTING: Twelve tertiary teaching hospitals and medical university affiliated hospitals in mainland China. PARTICIPANTS: Overall, 258 hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) adult patients were enrolled. INTERVENTION: After a 0-3-week washout period and a 4-week lanthanum carbonate dose-titration period, 230 patients were randomized 1:1 to receive lanthanum carbonate (1500 mg-3000 mg) or placebo for a further 4-week maintenance phase. MAIN OUTCOME MEASURES: Efficacy and safety of lanthanum carbonate to achieve and maintain target serum phosphorus concentrations were assessed. RESULTS: In the titration phase, serum phosphorus concentrations of all patients decreased significantly. About three-fifths achieved target levels without significantly disturbing serum calcium levels. At the end of the maintenance period, the mean difference in serum phosphorus was significantly different between the lanthanum carbonate and placebo-treated groups (0.63±0.62 mmol/L vs. 0.15±0.52 mmol/L, P < 0.001). The drug-related adverse effects were mild and mostly gastrointestinal in nature. CONCLUSION: Lanthanum carbonate is an efficacious and well-tolerated oral phosphate binder with a mild AE profile in hemodialysis and CAPD patients. This agent may provide an alternative for the treatment of hyperphosphatemia in CKD 5D patients in mainland China. TRIAL REGISTRATION: No. ChiCTR-TRC-10000817.

[Analysis of associated factors for remission and relapse in proliferative and membranous lupus nephritis patients: a 4-year follow-up study].

OBJECTIVE: To explore the related factors of remission and relapse in lupus nephritis (LN) patients. METHODS: A retrospective study was conducted for proliferation and membrane LN patients diagnosed from 2003 to 2010. Their clinical, laboratory and pathological parameters were collected. According to the response to treatment, they were divided into 3 groups of complete remission (CR), partial remission (PR) and no response (NR). Those in remission were divided into 2 groups of relapsing and non-relapsing during maintenance period. Associated factors for remission and relapse were analyzed. RESULTS: (1) Among a total of 105 patients, there were 99 females and 6 males with an average follow-up period of (51 ± 30) months. Eighty-six patients achieved remission after 6-month treatment. (2) The outcomes were CR (n = 36), PR (n = 50) and NR (n = 19). Proteinuria in PR group was higher than that in CR group (4.7 (3.1-7.6) vs 1.7 (1.4-3.8), P < 0.01) while proteinuria of CR group was lower than that of NR group (1.7 (1.4-3.8) vs 3.0 (2.3-5.9), P < 0.01). Serum albumin level of CR group was significantly higher than those of PR (30.6 (27.8-34.6) vs 22.4 (19.3-29.4), P < 0.01) and NR groups (30.6 (27.8-34.6) vs 23.1 (18.9-28.6), P < 0.01). Serum creatinine was significantly higher in NR group than those of CR (128.9 (69.9-184.3) vs 58.1 (53.0-70.9), P < 0.01) and PR group (128.9 (69.9-184.3) vs 67.5 (53.5-129.1), P < 0.05). Acute index (AI) and chronic index (CI) were lower in CR group than those of PR and NR groups. (3) A total of 86 cases achieved remission (CR/PR) while 20 cases (23.3%) had relapse. During the maintenance period, the relapse rate was higher in the group on prednisone alone than those on combined therapy of prednisone plus immunosuppressant (P < 0.05). Sixty patients (90.9%) in non-relapse group and 12 cases (60.0%) in recurrence group had good compliance. CONCLUSIONS: Initial proteinuria, serum creatinine, serum albumin, estimated glomerular filtration rate and AI were related with remission of induction period. Prednisone-alone therapy is an independent risk factor for relapse during maintenance period. Poor compliance of patients may be one of the risk factors for relapse during maintenance period. It may be useful to maintain sustained remission and reduce relapse in LN patients by improving their compliance and using steroids plus immunosuppressant during maintenance period.

Analysis of early kidney damage in hospitalized patients with chronic kidney disease: a multicenter study.

BACKGROUND: To identify the risk factors for early kidney damage in hospitalized Chinese patients with chronic kidney disease (CKD). METHODS: A total of 12 multicenter cross-sectional studies were conducted between January 2005 and January 2006 in Chinese CKD patients with estimated glomerular filtration rate (eGFR) equal to or more than 30 mL/min/1.73 m2 in Shanghai. CKD was defined according to the K/DOQI guideline. GFR was estimated by the simplified modification of diet in renal disease equation. The demographic, clinical, and laboratory data were collected through a questionnaire and analyzed among eligible patients stratified by three different CKD groups (CKD stages 1, 2, and 3). The relevant clinical and laboratory risk factors for early kidney damage with a GFR < 90 mL/min/1.73 m2 were determined by logistic regression. RESULTS: A total of 822 CKD patients were enrolled in this study. There were significant differences in age and gender among patients with CKD stages 1, 2, and 3. The prevalence of hypertension, cardiovascular disease, cerebral vascular disease, anemia, and hyperuricemia increases when the eGFR declines. Logistic analysis showed that age, hypertension, anemia, and hyperuricemia were independently associated with early kidney damage. CONCLUSIONS: In CKD patients, we have identified only age, hypertension, anemia, and hyperuricemia as the risk factors for early kidney damage. Risk factors should be managed to prevent accelerated kidney damage in CKD patients.