Urinary renal tubular epithelial cells and casts as predictors of renal outcomes in patients with biopsy-proven diabetic nephropathy.

BACKGROUND: Urine sediment examination is a time-tested and non-invasive diagnostic tool. This study investigated the characteristics of urine sediment and its association with severity and renal outcomes in diabetic nephropathy (DN) patients. METHODS: A total of 201 biopsy-proven diabetic nephropathy patients (according to the pathological classification of diabetic nephropathy proposed by the Renal Pathology Society in 2010) who underwent manual urine sediment microscopic examination were included. We compared the clinicopathological characteristics of diabetic nephropathy patients with and without urinary renal tubular epithelial cells (RTECs) or renal tubular epithelial cell casts. The predictive value of urinary renal tubular epithelial cells or renal tubular epithelial cell casts for renal outcomes in diabetic nephropathy was analyzed. RESULTS: Fifty of 201 (24.9%) diabetic nephropathy patients had renal tubular epithelial cells or renal tubular epithelial cell casts in urine sediment. Diabetic nephropathy patients with renal tubular epithelial cells or renal tubular epithelial cell casts in urine sediment had a significantly higher level of proteinuria [6.0 (3.1, 9.7) vs. 3.6 (1.8, 6.8) g/24 h, p = 0.001], higher serum creatinine [227.9 (151.6, 338.1) vs. 177.0 (104.4, 288.4) µmol/L, p = 0.016] and lower estimated glomerular filtration rate (eGFR) [25.8 (15.8, 44.8) vs. 35.7 (19.9, 65.0) mL/min/1.73 m2, p = 0.025] than those without. Cox regression analysis demonstrated that the presence of urinary renal tubular epithelial cells or renal tubular epithelial cell casts was independently associated with the development of end-stage kidney disease (ESKD) in diabetic nephropathy patients [HR 1.670, 95% CI (1.042, 2.676), p = 0.033]. Adding the presence of urinary renal tubular epithelial cells or renal tubular epithelial cell casts to the predictive model could improve the effectiveness of the model for predicting the risk of ESKD within one year after renal biopsy. CONCLUSIONS: The presence of urinary renal tubular epithelial cells or renal tubular epithelial cell casts was associated with more severe kidney injury and worse renal outcomes in patients with diabetic nephropathy, thus perhaps providing a noninvasive biomarker for predicting diabetic nephropathy.

New insights into fibrotic signaling in renal cell carcinoma.

Fibrotic signaling plays a pivotal role in the development and progression of solid cancers including renal cell carcinoma (RCC). Intratumoral fibrosis (ITF) and pseudo-capsule (PC) fibrosis are significantly correlated to the disease progression of renal cell carcinoma. Targeting classic fibrotic signaling processes such as TGF-ß signaling and epithelial-to-mesenchymal transition (EMT) shows promising antitumor effects both preclinically and clinically. Therefore, a better understanding of the pathogenic mechanisms of fibrotic signaling in renal cell carcinoma at molecular resolution can facilitate the development of precision therapies against solid cancers. In this review, we systematically summarized the latest updates on fibrotic signaling, from clinical correlation and molecular mechanisms to its therapeutic strategies for renal cell carcinoma. Importantly, we examined the reported fibrotic signaling on the human renal cell carcinoma dataset at the transcriptome level with single-cell resolution to assess its translational potential in the clinic.

Long-term outcomes of add-on direct renin inhibition in igA nephropathy: a propensity score-matched cohort study.

INTRODUCTION: The long-term clinical outcomes in biopsy proven IgAN patients treated with aliskiren on top of a maximally tolerated dose of ACEi/ARB remain unknown. METHODS: Patients with IgAN treated with a direct renin inhibitor and ACEi/ARB for at least 6 months were compared with a 1:1 propensityscore-matched cohort (including MEST-C score and the 12-months pre-exposure slope of eGFR matching) who received ACEi/ARB without aliskiren exposure to compute the hazard ratio of reaching the primary endpoint of a composite of 40% reduction in eGFR, initiation of KRT and all-cause mortality. Secondary outcome measures included changes in mean UPCR, blood pressure, eGFR, incidence of hyperkalemia and other adverse events during follow-up. RESULTS: After a median follow-up of 2.5 years, 8/36 (22.2%) aliskiren-treated patients and 6/36 (16.7%) control patients reached the primary composite outcome (HR = 1.60; 95% CI 0.52-4.88; P = 0.412). Aliskiren treatment increased the risk of ≥ 40% eGFR decline (HR = 1.60; 95% CI 0.52-4.88; P = 0.412), and hyperkalemia (HR = 8.60; 95% CI 0.99-73.64; P = 0.050). At 10.8 years, renal composite outcome was reached in 69.4% vs 58.3% (HR = 2.16; 95% CI 1.18-3.98; P = 0.013) of patients in the aliskiren and control groups, respectively. The mean UPCR reduction between treatment and control was not statistically different (52.7% vs 42.5%; 95% CI 0.63-2.35; P = 0.556). The mean intergroup difference in eGFR decline over 60 months was 7.75 ± 3.95 ml/min/1.73 m2 greater in the aliskiren group (12.83 vs 5.08; 95% CI - 0.17 to 15.66; P = 0.055). CONCLUSION: Among patients with IgAN, add-on aliskiren was associated with less favorable long-term kidney outcomes despite an initial anti-proteinuric effect.

Long-term spill-over impact of COVID-19 on health and healthcare of people with non-communicable diseases: a study protocol for a population-based cohort and health economic study.

INTRODUCTION: The COVID-19 pandemic has a significant spill-over effect on people with non-communicable diseases (NCDs) over the long term, beyond the direct effect of COVID-19 infection. Evaluating changes in health outcomes, health service use and costs can provide evidence to optimise care for people with NCDs during and after the pandemic, and to better prepare outbreak responses in the future. METHODS AND ANALYSIS: This is a population-based cohort study using electronic health records of the Hong Kong Hospital Authority (HA) CMS, economic modelling and serial cross-sectional surveys on health service use. This study includes people aged ≥18 years who have a documented diagnosis of diabetes mellitus, hypertension, cardiovascular disease, cancer, chronic respiratory disease or chronic kidney disease with at least one attendance at the HA hospital or clinic between 1 January 2010 and 31 December 2019, and without COVID-19 infection. Changes in all-cause mortality, disease-specific outcomes, and health services use rates and costs will be assessed between pre-COVID-19 and-post-COVID-19 pandemic or during each wave using an interrupted time series analysis. The long-term health economic impact of healthcare disruptions during the COVID-19 pandemic will be studied using microsimulation modelling. Multivariable Cox proportional hazards regression and Poisson/negative binomial regression will be used to evaluate the effect of different modes of supplementary care on health outcomes. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of the University of Hong Kong, the HA Hong Kong West Cluster (reference number UW 21-297). The study findings will be disseminated through peer-reviewed publications and international conferences.

LncRNA-Dependent Mechanisms of Transforming Growth Factor-ß: From Tissue Fibrosis to Cancer Progression.

Transforming growth factor-ß (TGF-ß) is a crucial pathogenic mediator of inflammatory diseases. In tissue fibrosis, TGF-ß regulates the pathogenic activity of infiltrated immunocytes and promotes extracellular matrix production via de novo myofibroblast generation and kidney cell activation. In cancer, TGF-ß promotes cancer invasion and metastasis by enhancing the stemness and epithelial mesenchymal transition of cancer cells. However, TGF-ß is highly pleiotropic in both tissue fibrosis and cancers, and thus, direct targeting of TGF-ß may also block its protective anti-inflammatory and tumor-suppressive effects, resulting in undesirable outcomes. Increasing evidence suggests the involvement of long non-coding RNAs (lncRNAs) in TGF-ß-driven tissue fibrosis and cancer progression with a high cell-type and disease specificity, serving as an ideal target for therapeutic development. In this review, the mechanism and translational potential of TGF-ß-associated lncRNAs in tissue fibrosis and cancer will be discussed.

Personalized immunosuppression after kidney transplantation.

With advances in immunosuppressive therapy, there have been significant improvements in acute rejection rates and short-term allograft survival in kidney transplant recipients. However, this success has not been translated into long-term benefits by the same magnitude. Optimization of immunosuppression is important to improve the clinical outcome of transplant recipients. It is important to note that each patient has unique attributes and immunosuppression management should not be a one-size-fits-all approach. Elderly transplant patients are less likely to develop acute rejection but more likely to die from infectious and cardiovascular causes than younger patients. For those with post-transplant cancers and BK polyomavirus-associated nephropathy, reduction of immunosuppression can increase the risk of rejection. Therapeutic drug monitoring (TDM) is routinely used for dosage adjustment of several immunosuppressive drugs. It has been hoped that pharmacogenetics can be used to complement TDM in optimizing drug exposure. Among the various drug-genotype pairs being investigated, tacrolimus and CYP3A5 gives the most promising results. Different studies have consistently shown that CYP3A5 expressers require a higher tacrolimus dose and take longer time to achieve target blood tacrolimus levels than nonexpressers. However, for pharmacogenetics to be widely used clinically, further trials are necessary to demonstrate the clinical benefits of genotype-guided dosing such as reduction of rejection and drug-related toxicities. The development of different biomarkers in recent years may help to achieve true personalized therapy in transplant patients.

HLA-B*58:01 screening to prevent allopurinol-induced severe cutaneous adverse reactions in Chinese patients with chronic kidney disease.

Human leukocyte antigen (HLA)-B*58:01 allele is a significant risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs) which is potentially fatal. In some studies, chronic kidney disease (CKD) was also implicated to compound the risk of SCARs. We aim to investigate if pre-treatment HLA-B*58:01 screening can prevent allopurinol-induced SCARs in Chinese patients with CKD and its cost-effectiveness. We prospectively recruited Chinese CKD patients who required allopurinol during 2011-2015 and performed pre-treatment HLA testing (HLA screening group). Patients tested positive for HLA-B*58:01 were refrained from allopurinol while those tested negative were prescribed allopurinol. The incidence of SCARs in the HLA screening group was compared with the historical control in previous 5 years and the cost-effectiveness of HLA testing was analyzed. In the historical control (2006-2010), 3605 patients on allopurinol were screened, 22 out of 1027 (2.14%) CKD Chinese patients newly started on allopurinol developed SCARs, including 6 SJS/TEN. In the HLA screening group, 28 out of 192 patients (14.6%) tested HLA-B*58:01 positive were advised to avoid allopurinol; 156 out of 164 HLA-B*58:01-negative patients received allopurinol and none developed SCARs. The incidence rate of SCARs was significantly lower in the HLA screening group compared with controls (0% vs 2.14% respectively, p = 0.037*). The targeted HLA screening approach was associated with lower healthcare costs compared with no HLA screening (US$ 92,430 vs US$ 281,226). Pre-treatment HLA-B*58:01 screening is cost-effective to target on patients with CKD in Chinese to prevent allopurinol-induced SCARs.

Global REnal Involvement of CORonavirus Disease 2019 (RECORD): A Systematic Review and Meta-Analysis of Incidence, Risk Factors, and Clinical Outcomes.

Introduction: The quantitative effect of underlying non-communicable diseases on acute kidney injury (AKI) incidence and the factors affecting the odds of death among coronavirus disease 2019 (COVID-19) AKI patients were unclear at population level. This study aimed to assess the association between AKI, mortality, underlying non-communicable diseases, and clinical risk factors. Methods: A systematic search of six databases was performed from January 1, 2020, until October 5, 2020. Peer-reviewed observational studies containing quantitative data on risk factors and incidence of renal manifestations of COVID-19 were included. Location, institution, and time period were matched to avoid duplicated data source. Incidence, prevalence, and odds ratio of outcomes were extracted and pooled by random-effects meta-analysis. History of renal replacement therapy (RRT) and age group were stratified for analysis. Univariable meta-regression models were built using AKI incidence as dependent variable, with underlying comorbidities and clinical presentations at admission as independent variables. Results: Global incidence rates of AKI and RRT in COVID-19 patients were 20.40% [95% confidence interval (CI) = 12.07-28.74] and 2.97% (95% CI = 1.91-4.04), respectively, among patients without RRT history. Patients who developed AKI during hospitalization were associated with 8 times (pooled OR = 9.03, 95% CI = 5.45-14.94) and 16.6 times (pooled OR = 17.58, 95% CI = 10.51-29.38) increased odds of death or being critical. At population level, each percentage increase in the underlying prevalence of diabetes, hypertension, chronic kidney disease, and tumor history was associated with 0.82% (95% CI = 0.40-1.24), 0.48% (95% CI = 0.18-0.78), 0.99% (95% CI = 0.18-1.79), and 2.85% (95% CI = 0.93-4.76) increased incidence of AKI across different settings, respectively. Although patients who had a kidney transplant presented with a higher incidence of AKI and RRT, their odds of mortality was lower. A positive trend of increased odds of death among AKI patients against the interval between symptom onset and hospital admission was observed. Conclusion: Underlying prevalence of non-communicable diseases partly explained the heterogeneity in the AKI incidence at population level. Delay in admission after symptom onset could be associated with higher mortality among patients who developed AKI and warrants further research.

Mass Screening Is Associated with Low Rates of Acute Kidney Injury among COVID-19 Patients in Hong Kong.

INTRODUCTION: Renal involvement in COVID-19 is less well characterized in settings with vigilant public health surveillance, including mass screening and early hospitalization. We assessed kidney complications among COVID-19 patients in Hong Kong, including the association with risk factors, length of hospitalization, critical presentation, and mortality. METHODS: Linked electronic records of all patients with confirmed COVID-19 from 5 major designated hospitals were extracted. Duplicated records due to interhospital transferal were removed. Primary outcome was the incidence of in-hospital acute kidney injury (AKI). Secondary outcomes were AKI-associated mortality, incident renal replacement therapy (RRT), intensive care admission, prolonged hospitalization and disease course (defined as >90th percentile of hospitalization duration [35 days] and duration from symptom onset to discharge [43 days], respectively), and change of estimated glomerular filtration rate (GFR). Patients were further stratified into being symptomatic or asymptomatic. RESULTS: Patients were characterized by young age (median: 38.4, IQR: 28.4-55.8 years) and short time (median: 5, IQR: 2-9 days) from symptom onset to admission. Among the 591 patients, 22 (3.72%) developed AKI and 4 (0.68%) required RRT. The median time from symptom onset to in-hospital AKI was 15 days. AKI increased the odds of prolonged hospitalization and disease course by 2.0- and 3.5-folds, respectively. Estimated GFR 24 weeks post-discharge reduced by 7.51 and 1.06 mL/min/1.73 m2 versus baseline (upon admission) in the AKI and non-AKI groups, respectively. The incidence of AKI was comparable between asymptomatic (4.8%, n = 3/62) and symptomatic (3.7%, n = 19/519) patients. CONCLUSION: The overall rate of AKI among COVID-19 patients in Hong Kong is low, which could be attributable to a vigilant screening program and early hospitalization. Among patients who developed in-hospital AKI, the duration of hospitalization is prolonged and kidney function impairment can persist for up to 6 months post-discharge. Mass surveillance for COVID-19 is warranted in identifying asymptomatic subjects for earlier AKI management.

An update on cancer after kidney transplantation.

The emergence of onconephrology in recent years highlights the importance of the interaction between kidney disease and cancer. Chronic kidney disease (CKD) and cancer are linked with each other in different ways bidirectionally: cancer can cause CKD, whereas CKD itself may be a risk factor for cancer. Kidney transplant recipients (KTRs) have a 2- to 3-fold increased cancer risk when compared with the general population. The elevated risk covers a wide range of cancers. Some are related to CKD, including cancers of the kidney, urinary tract and thyroid, whereas others are related to oncogenic viruses that include non-Hodgkin lymphoma, cervical cancer, nonmelanoma skin cancer and Kaposi's sarcoma. There is no standard protocol regarding how immunosuppressive drugs should be adjusted in patients who develop posttransplant cancers. However, any modification of immunosuppressive regimens should be balanced against the risk of allograft rejection or deterioration in kidney function. Cancer surveillance can be used as a strategy to improve the clinical outcome in KTRs. Although guidelines adopted in the general population have been used as the reference, a personalized approach based on individual cancer risk, life expectancy and concurrent comorbidities has to be adopted.

Downregulation of Aquaporin 9 Exacerbates Beta-amyloid-induced Neurotoxicity in Alzheimer's Disease Models In vitro and In vivo.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, characterized by progressive cognitive dysfunction. Aquaporin 9 (AQP9) is an aquaglyceroporin membrane channel shown biophysically to conduct water, glycerol, and other small solutes. In our study, we reported for the first time an age-associated decrease in AQP9 mRNA and protein expressions in both hippocampus and cerebral cortex of APPswe/PS1dE9 (Tg) AD mice at 3, 6 and 10 months of age. Consistently, we observed a dose-dependent downregulation of AQP9 expression in PC12 cells after treatment with amyloid-beta protein 1-40 (Aß1-40). Pre-treatment with AQP9 small interfering RNA led to a more severe neurotoxicity in PC12 cells in response to Aß1-40. Furthermore, we corroborated that the active participation of AQP9 in AD progression is associated with Aß-induced apoptosis both in vitro and in vivo. Taken together, our results reveal an important role of AQP9 in Aß-induced pathogenesis of AD which deserves further investigation.

Ellagitannins from Pomegranate Ameliorates 5-Fluorouracil-Induced Intestinal Mucositis in Rats while Enhancing Its Chemotoxicity against HT-29 Colorectal Cancer Cells through Intrinsic Apoptosis Induction.

Worldwide, colorectal cancer (CRC) is a deleterious disease causing millions of death annually. 5-Fluorouracil (5-FU) is a first-line chemotherapy for CRC, but chemoresistance and gastrointestinal mucositis limit its efficacy. Polyphenol-rich foods are increasingly popular due to their potential beneficial roles in preventing and treating cancer. Ellagitannins are a group of phenolic compounds commonly found in pomegranate, strawberries, raspberries, etc. The objective of this study was to explore whether ellagitannins from pomegranate (PETs) could ameliorate 5-FU-induced intestinal mucositis and enhance the drug's efficacy against CRC. The results showed that PETs (100 mg/kg) counteracted 5-FU-induced intestinal mucositis in rats. The number of apoptotic cells per crypt was reduced from 1.50 ± 0.21 to 0.85 ± 0.18 ( P < 0.05). Moreover, PETs induced HT-29 CRC cell death through intrinsic apoptosis, as demonstrated by dissipation of mitochondrial membrane potential, increased Bax-to-Bcl-2 ratio, and cleavage of caspase 9 and caspase 3. PETs and 5-FU combination treatments exhibited synergistic cytotoxicity against HT-29 cells with a weighted combination index of 0.3494. PETs (80 µg/mL) and 5-FU (40 µg/mL) treatments for 48 h induced 14.03 ± 0.76% and 16.42 ± 1.15% of HT-29 cells to undergo apoptosis, while the combination treatment further increased apoptosis of cells to 34.00 ± 1.54% ( P < 0.05). Combination treatment of the cells also enhanced S phase cell cycle arrest as compared with PETs or 5-FU monotherapy ( P < 0.05). These results suggest that dietary ellagitannins from pomegranate could alleviate intestinal mucositis in rats induced by 5-FU while enhancing its toxicity against HT-29 cells through potentiation of apoptosis and cell cycle arrest.

Posttransplant lymphoproliferative disorders in kidney transplant recipients: a retrospective cohort analysis over two decades in Hong Kong.

OBJECTIVE: To characterize the posttransplant lymphoproliferative disorders (PTLD) including the Epstein-Barr virus (EBV) status, histological subgroups, site of occurrence and the clinical outcome in the Chinese kidney transplant recipients. METHODS: A retrospective cohort study of 1, 227 adult kidney transplant recipients who were followed up in two transplant centers in Hong Kong over two decades. RESULTS: 23 (1.9%) patients developed PTLD. Median duration from transplant to PTLD was 104 (5-252) months. Six patients (26.1%) had early PTLD and 17 (73.9%) had late PTLD. Ten (43%) developed PTLD >10 years after transplant. All patients in early PTLD group were EBV-positive. In the late PTLD group, 60% were EBV-negative and 40% EBV-positive. More than 90% of cases were monomorphic PTLD with majority being diffuse large B cell lymphoma. Bone marrow was the most common extranodal site. The overall treatment response rate was 52.2 %. None of the patients developed rejection or relapse after PTLD. At a median follow-up of 9 (1-79) months after PTLD, 18 patients died. Patient survival was 48% at 1 year and 30% at 3 years and death-censored allograft survival was 82% at 1year and 73% at 3 years. CONCLUSION: Late PTLD is common. Careful adjustment of immunosuppression, close monitoring of patients, increased awareness and early detection of the disease are essential.

Relatives in silent kidney disease screening (RISKS) study: A Chinese cohort study.

AIM: Family members of patients with end-stage renal disease (ESRD) have higher risk for chronic kidney disease (CKD). Limited study has examined the risk of developing CKD in relatives of patients in earlier stages of CKD. METHODS: From January 2008 to June 2009, the Hong Kong Society of Nephrology studied first-degree relatives of stage 1-5 CKD patients from 11 local hospitals. A total of 844 relatives of 466 index CKD patients (stages 1-2: 29.6%; stage 3: 16.7%; stage 4: 10.9%; stage 5: 42.7%) were reviewed for various risk factors of CKD. We also defined a composite marker of kidney damage by the presence of one or more following features: (i) positive urine protein, (ii) spot urine protein-to-creatinine ratio ≥0.15 mg/mg, (iii) hypertension and (iv) estimated glomerular filtration rate (eGFR) ≤60 mL/min per 1.73 m2 and determine its association with participant and index patient factors. RESULTS: Among these 844 relatives, 23.1%, 25.9% and 4.4% of them had proteinuria (urine protein ≥1+), haematuria (urine red blood cell ≥1+) and glycosuria (urine glucose ≥1+), respectively. Proteinuria (P = 0.10) or glycosuria (P = 0.43), however, was not associated with stages of CKD of index patients. Smoking participants had a significantly lower eGFR (102.7 vs. 107.1 mL/min per 1.73 m2 ) and a higher prevalence of proteinuria (33.6% vs. 21.4%). Multivariate analysis showed that older age, male gender, obesity, being parents of index patients and being the relatives of a female index patient were independently associated with a positive composite marker. CONCLUSION: First-degree relatives of all stages of CKD are at risk of developing CKD and deserve screening. Parents, the elderly, obese and male relatives were more likely to develop markers of kidney damage.

Ficus virens proanthocyanidins induced apoptosis in breast cancer cells concomitantly ameliorated 5-fluorouracil induced intestinal mucositis in rats.

5-Fluorouracil (5-FU) is a commonly used chemotherapeutic agent for breast cancer. However, its use often leads to drug resistance and mucositis. This study aimed to investigate whether proanthocyanidins from Ficus virens possessed anti-breast cancer and anti-mucositis activities. The results showed that the cytotoxic effects of the proanthocyanidins against MDA-MB-231 and MCF-7 breast cancer cells were in the order of stem barks proanthocyanidins (SPAs) > leaves proanthocyanidins > fruits proanthocyanidins. Moreover, SPAs induced apoptosis in both cell lines which were accompanied with an increase in loss of mitochondrial membrane potential, production of reactive oxygen species, Bax to Bcl-2 protein expression ratio, and activated caspase 3. Furthermore, intraperitoneal injection of 5-FU (150 mg/kg body weight) resulted in body weight loss and jejunal injury in the rats while administration of SPAs (100 mg/kg body weight) counteracted these changes. Collectively, our study demonstrated that SPAs induced apoptosis cell death in breast cancer cells while ameliorating the symptoms of intestinal mucositis in rats.Therefore, SPAs merits further exploration as a potential therapeutic agent for breast cancer and chemotherapy-induced mucositis.

Cancer risk in patients with diabetic nephropathy: A retrospective cohort study in Hong Kong.

Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease nowadays. Certain cancers are more common in patients with diabetes mellitus. However, there are no data concerning the cancer pattern in patients with DN. The aim of this study is to investigate the site-specific cancer risk and mortality in these patients.A retrospective cohort study of 5643 DN patients between 2000 and 2015 was conducted in 2 large hospitals in Hong Kong. Incidence and mortality of various cancers were compared with those of general population using standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) respectively.With 24,726 person-years follow-up, 250 cancers were diagnosed. Overall cancer incidence was similar between DN patients and the general population (SIR 1.05, 95% confidence interval [CI] 0.92-1.19). However, certain site-specific cancers are increased in DN patients: the highest risk was observed for laryngeal cancer (SIR 3.03, 95% CI 1.11-6.60), followed by cancers of liver (SIR 1.96, 95% CI 1.35-2.76) and colorectum (SIR 1.92, 95% CI 1.53-2.37), but the risk of prostate cancer was lower (SIR 0.48, 95% CI 0.21-0.95) in the males with DN. The SMR of all cancers was 1.17 (95% CI 1.01-1.37). For individual specific site, only colorectal cancer carried a significant higher mortality risk (SMR 2.45, 95% CI 1.82-3.23).Our data suggested that DN is associated with increased incidence of cancers of colorectum, liver, and larynx but decreased incidence of prostate cancer. Moreover, there is increased mortality of colorectal cancer in patients with DN.

Conversion to mammalian target of rapamycin inhibitors in kidney transplant recipients with de novo cancers.

OBJECTIVE: To investigate the impact of mammalian target of rapamycin (mTOR) inhibitor conversion together with minimization of calcineurin inhibitor on allograft outcome and patient survival in kidney transplant recipients with post-transplant cancers. METHODS: A retrospective study of all kidney transplant recipients diagnosed to have post-transplant cancers between the period 1/1/1994 and 30/6/2015. Patients were divided into 2 groups: mTOR inhibitor group and non-conversion group. Outcome included allograft function, patient survival, graft survival, acute rejection and cancer recurrence. RESULTS: 115 patients (56 in mTOR inhibitor group and 59 in non-conversion group) were analyzed. Median follow up was 28 months (range: 1 month - 20 years). The allograft function at 1-year remained similar between both groups. There was no significant difference in the patient survival, graft survival and rejection free survival between both groups. More patients in the non-conversion group developed recurrence of cancers than mTOR inhibitor group but statistically not significant. CONCLUSIONS: Use of mTOR inhibitors together with calcineurin inhibitor minimization offer a reasonable option in kidney transplant recipients who developed post-transplant cancers in view of stable renal function, low rejection rate and low cancer recurrence rate.

Semi-individualised Chinese medicine treatment as an adjuvant management for diabetic nephropathy: a pilot add-on, randomised, controlled, multicentre, open-label pragmatic clinical trial.

INTRODUCTION: Diabetes mellitus and diabetic nephropathy (DN) are prevalent and costly to manage. DN is the leading cause of end-stage kidney disease. Conventional therapy blocking the renin-angiotensin system has only achieved limited effect in preserving renal function. Recent observational data show that the use of Chinese medicine (CM), a major form of traditional medicine used extensively in Asia, could reduce the risk of end-stage kidney disease. However, existing clinical practice guidelines are weakly evidence-based and the effect of CM remains unclear. This trial explores the effect of an existing integrative Chinese-Western medicine protocol for the management of DN. OBJECTIVE: To optimise parameters and assess the feasibility for a subsequent phase III randomised controlled trial through preliminary evaluation on the effect of an adjuvant semi-individualised CM treatment protocol on patients with type 2 diabetes with stages 2-3 chronic kidney disease and macroalbuminuria. METHODS AND ANALYSIS: This is an assessor-blind, add-on, randomised, controlled, parallel, multicentre, open-label pilot pragmatic clinical trial. 148 patients diagnosed with DN will be recruited and randomised 1:1 to a 48-week additional semi-individualised CM treatment programme or standard medical care. Primary end points are the changes in estimated glomerular filtration rate and spot urine albumin-to-creatinine ratio between baseline and treatment end point. Secondary end points include fasting blood glucose, glycated haemoglobin, brain natriuretic peptide, fasting insulin, C peptide, fibroblast growth factor 23, urinary monocyte chemotactic protein-1, cystatin C, nephrin, transforming growth factor-ß1 and vascular endothelial growth factor. Adverse events are monitored through self-completed questionnaire and clinical visits. Outcomes will be analysed by regression models. Enrolment started in July 2015. ETHICS AND REGISTRATION: This protocol is approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (reference number UW 14-301). TRIAL REGISTRATION NUMBER: NCT02488252.

Expression of aquaporin 5 in primary carcinoma and lymph node metastatic carcinoma of non-small cell lung cancer.

Aquaporin 5 (AQP5), a water channel protein, is highly expressed in non-small cell lung cancer (NSCLC) tissues compared with adjacent normal tissues. AQP5 expression in lung cancer tissues is associated with a poor prognosis. The present study aimed to analyze the expression of AQP5 and investigate its role in primary and lymph node metastatic NSCLCs. An immunohistochemical labeled streptavidin-biotin method was used to determine the expression of AQP5 in 94 cases of NSCLC primary carcinoma, which included 51 cases accompanied by lymph node metastasis. The results revealed that the expression of AQP5 was significantly higher in adenocarcinomas compared with squamous cell carcinomas (P=0.002). In addition, the percentage of AQP5 expression in the primary carcinomas with lymph node metastasis was significantly higher compared with those without lymph node metastasis (P=0.024). However, no statistically significant difference in the percentage of AQP5 expression was observed between the metastatic and the primary carcinomas (P=0.377). The expression of AQP5 exhibited a correlation with the tumor-node-metastasis staging of NSCLC (P=0.027). The percentage of AQP5 expression in stage III and IV tumors was higher than that in stage I and II tumors. In addition, AQP5 expression was correlated with the survival rate of NSCLC patients (P=0.051). In conclusion, the results of the present study provide evidence for the AQP5-facilitated incidence, progression and metastasis of NSCLC. Therefore, AQP5 may be used as a potential target to investigate the incidence, progression and metastasis of NSCLC.

Comparative analysis of caffeoylquinic acids and lignans in roots and seeds among various burdock (Arctium lappa) genotypes with high antioxidant activity.

Caffeoylquinic acids and lignans in the crude extracts of both roots and seeds from different burdock ( Arctium lappa L.) genotypes were simultaneously characterized and systematically compared by LC-MS and matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry (MALDI-QIT-TOF MS), and their antioxidant activities were also investigated. A total of 14 lignans were identified in burdock seeds and 12 caffeoylquinic acids in burdock roots. High levels of caffeoylquinic acids were also detected in burdock seeds, but only trace amounts of lignans were found in burdock roots. Burdock seeds contained higher concentrations of lignans and caffeoylquinic acids than burdock roots. Quantitative analysis of caffeoylquinic acids and lignans in roots and seeds of various burdock genotypes was reported for the first time. Great variations in contents of both individual and total phenolic compounds as well as antioxidant activities were found among different genotypes. Burdock as a root vegetable or medicinal plants possessed considerably stronger antioxidant activity than common vegetables and fruits.