Guobin Su

Colon may provide new therapeutic targets for treatment of chronic kidney disease with Chinese medicine

Chronic kidney disease (CKD) has become a worldwide health and social problem. Retarding its progression to end-stage renal disease is beneficial both to the patients and the healthcare system. Plenty of clinical trials have indicated that enema with Chinese medicine could effectively prevent chronic renal failure, and was widely used in the clinical practice. However, studies on mechanism were still nearly blank, which may prevent further improvement of therapeutic efficacy. Recent studies had discovered that colon was an important organ where uremic toxins were generated. The uremic toxins involved could not only promote CKD progression, but also was closely correlated with CKD mortality. Reducing production and promoting excretion of toxins were confirmed to reduce renal tubule interstitial fibrosis and delay renal progression. On the basis of the theory of gut-kidney axis above, we had conducted pilot clinical researches to evaluate the effect of enema with Chinese medicine on the intestinal flora, gut barrier, enterogenous uremic toxins and renal protection. The preliminary results revealed that rheum enema through colon could accelerate intestinal dynamics, improve intestinal barrier function, regulate intestinal flora and reduce production and absorption of intestine-derived uremic toxins such as indoxyl sulfate, which may reduce renal fibrosis and delay renal progression. Further studies could provide more evidence for colon as a new therapeutic target for the treatment of CKD with Chinese medicine.

eGFR and the Risk of Community-Acquired Infections

BACKGROUND AND OBJECTIVES Community-acquired infections are common, contributing to adverse outcomes and increased health care costs. We hypothesized that, with lower eGFR, the incidence of community-acquired infections increases, whereas the pattern of site-specific infections varies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Among 1,139,470 health care users (mean age =52±18 years old, 53% women) from the Stockholm CREAtinine Measurements Project, we quantified the associations of eGFR with the risk of infections, overall and major types, over 12 months. RESULTS A total of 106,807 counts of infections were recorded throughout 1,128,313 person-years. The incidence rate of all infections increased with lower eGFR from 74/1000 person-years for individuals with eGFR=90-104 ml/min per 1.73 m2 to 419/1000 person-years for individuals with eGFR<30 ml/min per 1.73 m2. Compared with eGFR of 90-104 ml/min per 1.73 m2, the adjusted incidence rate ratios of community-acquired infections were 1.08 (95% confidence interval, 1.01 to 1.14) for eGFR of 30-59 ml/min per 1.73 m2 and 1.53 (95% confidence interval, 1.39 to 1.69) for eGFR<30 ml/min per 1.73 m2. The relative proportions of lower respiratory tract infection, urinary tract infection, and sepsis became increasingly higher along with lower eGFR strata (e.g., low respiratory tract infection accounting for 25% versus 15% of community-acquired infections in eGFR<30 versus 90-104 ml/min per 1.73 m2, respectively). Differences in incidence associated with eGFR were in general consistent for most infection types, except for nervous system and upper respiratory tract infections, for which no association was observed. CONCLUSIONS This region-representative health care study finds an excess community-acquired infections incidence in individuals with mild to severe CKD. Lower respiratory tract infection, urinary tract infection, and sepsis are major infections in CKD.

Ginkgo biloba Extract for Patients with Early Diabetic Nephropathy: A Systematic Review

Objectives. To evaluate the effectiveness and safety of a Ginkgo biloba extract for patients with early diabetic nephropathy. Methods. Randomised controlled trials (RCTs) conducted on adults with early diabetic nephropathy which used Gingko biloba extract were included. The major databases were searched, and manufacturers of Gingko biloba products were contacted for information on any published or unpublished studies. Two authors independently extracted the data from the included studies. Data analysis was conducted using Review Manager 5.0 software. Results. Sixteen RCTs were included. Ginkgo biloba extract decreased the urinary albumin excretion rate (UAER), fasting blood glucose (FBG), serum creatinine (SCR), and blood urea nitrogen (BUN). The extract also improved hemorheology. The methodological quality in the included studies was low. The explicit generation of the allocation sequence was described in only 6 trials. None of the included trials were confirmed to use blinding. Three studies had observed adverse events. One study using angiotensin-converting enzyme inhibitor (ACEi) reported mild cough in both groups. No serious adverse effects were reported. Conclusions. Gingko biloba extract is a valuable drug which has prospect in treating early diabetic nephropathy, especially with high UAER baseline level. The safety for early diabetic nephropathy is uncertain. Long-term, double-blinded RCTs with large sample sizes are still needed to provide stronger evidence.

Efficacy and Safety of Sanfu Herbal Patch at Acupoints for Persistent Allergic Rhinitis: Study Protocol for a Randomized Controlled Trial

Background. The Sanfu herbal patch (SHP) has been widely used to treat allergic rhinitis (AR) in China. SHP has been reported to be effective for managing the symptoms of AR, but the evidence suffers from methodological limitations. Therefore, we designed a three-armed, randomized, and placebo-controlled trial to evaluate the efficacy and safety of SHP for persistent allergic rhinitis (PAR). Methods. The trial consists of 5 treatment sessions along with a one-year follow-up. This process is then repeated in the second and third years. Eligible participants diagnosed with PAR were randomized at a ratio of 2 : 2 : 1 into one of three groups: (a) SHP group; (b) placebo group; or (c) waiting-list group. The waiting-list group will receive no treatment in the first year but will receive SHP in the following two years. The primary outcome, total nasal symptoms score, is self-assessed at the beginning of each treatment session and during each annual follow-up. Secondary outcomes include the Rhinoconjunctivitis Quality-of-Life Questionnaire, allergic rhinitis attacks, and relief medications. The trial will be stopped if early termination criteria are met during the interim analysis. Ethics. This protocol has been approved by site ethics committee (number B2014-014-01) and is registered with ClinicalTrials.gov NCT02192645.

Astragalus in the Prevention of Upper Respiratory Tract Infection in Children with Nephrotic Syndrome: Evidence-Based Clinical Practice

Aims. To explore whether Astragalus or its formulations could prevent upper respiratory infection in children with nephrotic syndrome and how best to use it. Methods. We transformed a common clinical question in practice to an answerable question according to the PICO principle. Databases, including the Cochrane Library (Issue 5, 2012), PUBMED (1966–2012.8), CBM (1978–2012.8), VIP (1989–2012.8), and CNKI (1979–2012.8), were searched to identify Cochrane systematic reviews and clinical trials. Then, the quality of and recommendations from the clinical evidence were evaluated using the GRADEpro software. Results. The search yielded 537 papers. Only two studies with high validity were included for synthesis calculations. The results showed that Astragalus granules could effectively reduce URTI in children with nephrotic syndrome compared with prednisone treatment alone (23.9% versus 42.9%; RR = 0.56 and 95% CI = 0.33–0.93). The dose of Astragalus granules was 2.25 gram (equivalent to 15 gram crude Astragalus) twice per day, at least for 3–6 months. The level of evidence quality was low, but we still recommended the evidence to the patient according to GRADEpro with the opinion of the expert. Followup showed the incidence of URTI in this child decreased significantly. Conclusions. Astragalus granules may reduce the incidence of URTI in children with nephrotic syndrome.

Association of Kidney Function with Infections by Multidrug-Resistant Organisms: An Electronic Medical Record Analysis

Antibiotic resistance is a major global health threat. High prevalences of colonization and infection with multi-drug resistance organisms (MDROs) have been reported in patients undergoing dialysis. It is unknown if this finding extends to patients with mild and moderate/severe kidney disease. An observational study included all adult incident patients hospitalized with a discharge diagnosis of infection in four hospitals from Guangzhou, China. Inclusion criteria: Serum creatinine measurement at admission together with microbial culture confirmed infections. Exclusion criterion: Undergoing renal replacement therapy. Four categories of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) were compared: eGFR ≥ 105, 60–104 (reference), 30–59, and <30 ml/min/1.73 m2. The odds ratio of MDROs, defined as specific pathogens (Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp.) resistant to three or more antibiotic classes, were calculated using a multivariable logistic regression model across eGFR strata. Of 94,445 total microbial culture records, 7,288 first positive cultures matched to infection diagnosis were selected. Among them, 5,028 (68.9%) were potential MDROs. The odds of infections by MDROs was 19% and 41% higher in those with eGFR between 30–59 ml/min/1.73 m2 (Adjusted odds ratio, AOR): 1.19, 95% CI:1.02–1.38, P = 0.022) and eGFR < 30 ml/min/1.73 m2 (AOR: 1.41, 95% CI:1.12–1.78, P = 0.004), respectively. Patients with impaired renal function have a higher risk of infections by MDROs. Kidney dysfunction at admission may be an indicator for need of closer attention to microbial culture results requiring subsequent change of antibiotics.

Association between reduced renal function and cardiovascular mortality in patients hospitalized with infection: A multi-center cohort study

BACKGROUND Infection is one of the main reasons for hospitalization worldwide, and is associated with an increased risk of cardiovascular mortality. It is unclear whether this association is modified by the presence of reduced renal function. The aim of this study was to analyze the relationship between estimated glomerular filtration rate (eGFR) and cardiovascular mortality in patients hospitalized with infection. METHODS This cohort study included all adult, incident patients who were hospitalized at one of four hospitals in China between 2012 and 2015, had a discharge diagnosis of infection, and had a serum creatinine measurement at admission. Patients receiving renal replacement therapy were excluded. Hospital data were linked to death registry data. All-cause and cardiovascular mortality were evaluated according to admission eGFR [≥60 (reference), 30-59 and < 30 mL/min/1.73m2] using multivariable Cox regression and competing risk analyses. RESULTS During a median follow-up period of 2.39 years, 40,524 patients were hospitalized with infection (mean age 61 years, 54.3% female 18.4% diabetic). Of these, 4781 died. Lower admission eGFR was associated with progressively increased risks of cardiovascular mortality (≥60 mL/min/1.73m2 reference; 30-59 mL/min/1.73m2 subdistribution hazard ratio [SHR] 2.15, 95% CI 1.85-2.50, P< .01; <30 mL/min/1.73m2 SHR 3.19, 95% CI 2.68-3.80, P < .01). The proportion of deaths due to cardiovascular disease increased as the eGFR decreased, predominantly due to ischemic heart disease. CONCLUSIONS Patients hospitalized with infections and reduced renal function have significantly increased risks of cardiovascular mortality. Heart status should be carefully monitored following infections, especially for those with reduced renal function.

Kidney function and in-hospital outcomes in patients admitted to hospital with infections: a cross-sectional analysis of electronic records in China

Abstract Background Reduced estimated glomerular filtration rate (eGFR) has been associated with increased risk of infections and infection-related hospital admissions (IRHs). It is unknown whether and to what extent patients with reduced renal function admitted to hospital with infections are predisposed to poorer outcomes and higher medical costs than people with normal renal function. In the context of Chinas single-disease reimbursement-payment policy, the reimbursement to the hospital is the same if patients are admitted for the same cause, regardless of comorbidities. Methods In this cross-sectional analysis, we included adults from four hospitals in Guangzhou, China, between 2012 and 2015, who had not on renal-replacement therapy and who had a discharge diagnosis of infection (identified by established ICD-10 algorithms) and an eGFR 1–12 months before index hospital admission. We compared in-hospital outcomes (death, intensive-care unit [ICU] admission, length of hospital stay [LOHS]) and medical expenses between patients with and without chronic kidney disease, defined as estimated Glomerular Filtration Rate (eGFR) of 60 mL/min per 1·73 m2 or less by mixed-effect logistic regression model or generalised linear model. Findings Among 321 571 hospital admissions, 58 166 were IRHs. 6283 (10·8%) IRHs had eGFR measured at outpatient visit. After adjusting for age, sex, and Charlson comorbidity index (excluding renal disease score), the odds ratios for in-hospital mortality (1·41; 95% CI 1·02–1·96) and ICU admission (2·18; 1·64–2·91) were highest among patients with chronic kidney disease. The median LOHS was longer for patients with chronic kidney disease than for patients without disease (11 days [IQR 8–15] days vs 10 days [7–14]; p Interpretation Patients with chronic kidney disease who were admitted to hospital with infections are at high risk of poor in-hospital outcomes, conveying higher medical costs. These findings suggest that comorbidities such as chronic kidney disease should be considered in the China Single Disease Reimbursement-Payment Policy. Increased awareness of kidney dysfunction might be required for more effective prevention of adverse modifiable outcomes due to infections. Funding This work was supported by a research grant from a project between the Guangdong Provincial Hospital of Chinese Medicine, China and the Department of Public Health Sciences, Karolinska Institutet, Sweden, and funding from Foreign Experts Project, Foreign Experts Bureau of Guangdong Province, China (GDT20164400034). GBS has a China Government scholarship from China scholarship council (201508440214). JJC acknowledges funding from Stockholm County Council, Westman and Martin Rind Foundations and the Swedish Heart and Lung Association. Baxter Novum is the result of a grant from Baxter Healthcare Corporation to Karolinska Institutet. The funding sources were not involved in data analysis, interpretation of the data, preparation, review, or approval of the manuscript. The contents are solely the responsibility of the authors and do not necessarily represent the official view of Foreign Experts Project, Foreign Experts Bureau of Guangdong Province, China.

Chronic kidney disease is associated with poorer in-hospital outcomes in patients hospitalized with infections: Electronic record analysis from China

Predominantly based on studies from high-income countries, reduced estimated glomerular filtration rate (eGFR) has been associated with increased risk of infections and infection-related hospitalizations (IRHs). We here explore in-hospital outcomes of IRHs in patients with different kidney function. A total of 6,283 adults, not on renal replacement therapy, with a discharge diagnosis of infection, and with an eGFR 1–12 months before index hospitalization, were included from four hospitals in China. We compared in-hospital outcomes (death, intensive care unit (ICU) admission, length of hospital stay (LOHS) and medical expenses), between patients with and without chronic kidney disease (CKD, defined as eGFR ≤ 60 ml/min per 1.73 m2 of body surface area) by mixed-effects logistic regression model or generalized linear model. The odds for in-hospital mortality (adjusted odds ratios (OR) = 1.41; 95% CI 1.02–1.96) and ICU admission (OR = 2.18; 95% CI 1.64–2.91) were higher among patients with CKD. The median LOHS was significantly higher for CKD patients (11 days vs. 10 days in non-CKD, P < 0.001), and inferred costs were 20.0% higher adjusted for inflation rate based on costs in 2012 (P < 0.001). Patients with CKD hospitalized with infections are at increased risk of poorer in-hospital outcomes, conveying higher medical costs.

Gifts from Chinese Medicine for diabetic nephropathy: Ancient formulas in modern times

To provide inspiration for developing new therapies of diabetic nephropathy, our study combed ancient formulas for diabetic nephropathy recorded in China from Tang dynasty to Qing dynasty, and discussed their application in modern times. A total of 87 ancient formulas for diabetic nephropathy were collected. Six-Ingredient Rehmannia Pill and Supplemented Kidney Qi Pill were recorded at higher frequency. Radix Astragali liqid, Xuan Bu Pill, and Ass Hide Glue Decoction were the earliest formulas for diabetic nephropathy recorded in Tang dynasty. Ginseng Powder was recorded by doctors in 4 dynasties, with the highest dynastic repeated frequency. Only formulas with high recorded frequency, such as Six-Ingredient Rehmannia Pill, Supplemented Kidney Qi Pill, Poria Pill, Four Ingredients Decoction, Pilose Antler Pill, were applied or studied in modern times keeping original medicinal combination. Most ancient formulas have not been made good use, and just sovereign medicinals in them were applied. In order to have better guidance from valuable experiences in ancient China, we should pay more attention to apply and study ancient formulas with original combination, not only the single Chinese medicinal.