Cheuk-Chun Szeto

The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Publications (171)489.88 Total impact

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    ABSTRACT: Background/Aims: Endotoxaemia, a driver of systemic inflammation, appears to be driven by dialysis-induced circulatory stress in haemodialysis (HD) patients. More frequent HD regimens are associated with lower ultrafiltration requirements, improved haemodynamic stability and lower systemic inflammation. This study investigated the hypothesis that more frequently dialysed patients, with reduced exposure to dialysis-induced haemodynamic perturbation, would have lower circulating endotoxin (ET) levels. Methods: A cross-sectional study of 86 established HD patients compared three groups: conventional HD 3× per week (HD3, n = 56), frequent HD 5-6× per week (SDHD, n = 20), and nocturnal HD (NHD, n = 10). Data collection included ultrafiltration volume and rate, serial blood pressures and blood sampling with quantification of ET, troponin T and high-sensitivity CRP (hsCRP). Results: Pre-dialysis serum ET was highest in the conventional HD group (HD3 0.66 ± 0.29 EU/ml vs. NHD 0.08 ± 0.04 EU/ml). Across the study population, severity of endotoxaemia was associated with higher ultrafiltration rates, degree of intradialytic hypotension, troponin T and hsCRP levels. NHD patients had the lowest ultrafiltration requirements, the greatest haemodynamic stability and lower ET levels. Conclusion: More frequent HD regimens are associated with lower levels of circulating ET compared with conventional HD. Reduced ET translocation may be related to the greater haemodynamic stability of these treatments, with superior maintenance of splanchnic perfusion. © 2014 S. Karger AG, Basel.
    Nephron Clinical Practice 11/2014; · 1.65 Impact Factor
  • Cheuk-Chun Szeto
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    ABSTRACT: Nephrotic syndrome is a common problem in clinical nephrology. In general, nephrotic syndrome is pathognomonic of glomerular disease, but the underlying pathological etiology is highly variable. Although kidney biopsy is the standard method to classify the histology and determine the extent of renal scarring, it is an invasive procedure with potential complications, and is generally not suitable for serial monitoring. MicroRNAs (miRNA) are short noncoding RNA molecules that regulate gene expression. Recent studies show that urinary levels of several miRNAs are significantly changed in nephrotic syndrome; some appear to be disease specific, others being damage related. Specifically, urinary miR-192 level is lower in patients with diabetic nephropathy than other causes of nephrotic syndrome, while patients with minimal change nephropathy or focal glomerulosclerosis had higher urinary miR-200c level than those with other diagnosis. Elevated urinary miR-21, miR-216a, and miR-494 levels may predict a high risk of disease progression and renal function loss, irrespective of the histological diagnosis. Furthermore, a number of small scale studies suggest that urinary levels of certain miRNA targets may assist in the diagnosis and assessment of disease activity in patients with lupus nephritis. Since miRNA in urinary sediment is relatively stable and easily quantified, it has the potential to be developed as biomarkers for disease diagnosis and monitoring. However, available published evidence is limited to small scale studies. Further research is urgently needed in many areas.
    Clinica Chimica Acta. 06/2014; 436.
  • Cheuk-Chun Szeto, Philip K-T Li
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    ABSTRACT: IgA nephropathy is globally the most common primary glomerulonephritis, but the pathogenesis of this condition is still only partially understood. MicroRNAs (miRNAs) are short, noncoding RNA molecules that regulate gene expression. Genome-wide analysis of renal miRNA expression has identified a number of novel miRNAs related to immunological and pathological changes. Specifically, overexpression of miR-148b might explain the aberrant glycosylation of IgA1, which has a central pathogenetic role in the early phase of IgA nephropathy. By contrast, miR-29c is an antifibrotic miRNA that is probably important in the late stages of disease progression. In addition, urinary levels of several miRNAs are significantly changed in patients with IgA nephropathy compared with healthy individuals; some alterations seem to be disease-specific, whereas others are apparently damage-related. As miRNAs in urinary sediment are relatively stable and easily quantified, they have the potential to be used as biomarkers for the diagnosis and monitoring of disease. However, to date, limited data are available on the role of miRNAs in the pathogenesis of IgA nephropathy and their potential application as biomarkers. Consequently, further studies are urgently needed to address this shortfall. Here, we review the available literature on miRNAs in relation to IgA nephropathy.
    Nature Reviews Nephrology 04/2014; · 7.94 Impact Factor
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    ABSTRACT: Background Secondary hyperparathyroidism is common amongst dialysis patients and is associated with increased morbidity and mortality. Vitamin D analogues are effective treatments, but the adverse effects of traditional vitamin D preparations, especially hypercalcemia, are often dose-limiting. Purpose We studied the efficacy and safety of paricalcitol for the treatment of secondary hyperparathyroidism in hemodialysis patients. Methods We reviewed 13 adult hemodialysis patients treated with oral paricalcitol. The dosage of paricalcitol was adjusted according to the clinical response. Results Serum parathyroid hormone (PTH) level decreased by 47.3 ± 34.3% at 3 months and 74.7 ± 36.8 % by 3 years. Eight patients (62%) responded and had reduction in PTH levels by at least 30%; seven of them (87.5%) responded within the first 3 months. Responders had a significantly lower baseline PTH level than the nonresponders (64.3 ± 32.2 vs. 138.5 ± 64.0 pmol/L, p = 0.02). None of the patients developed hypercalcemia, but hyperphosphatemia was present in all patients. Conclusion There is a substantial improvement in PTH levels by paricalcitol treatment in hemodialysis patients with secondary hyperparathyroidism, and paricalcitol is generally well tolerated. Our results suggest that patients with more advanced secondary hyperparathyroidism tend to have a less favorable response. 背景:在血液透析患者間,次發性甲狀旁腺功能亢進是常見的疾病,會明顯增加患者的死亡與患病率。維生素 D 類似物通常是有效的療法,但傳統製劑的臨床應用常受限於不良作用如高鈣血症的出現。本研究以患有次發性甲狀旁腺功能亢進的血液透析患者為對象,調查了 paricalcitol 在這方面的功效與安全性。 方法:本研究回顧了 13 位成年血液透析患者,正在接受口服 paricalcitol 治療,其劑量根據臨床反應作出調整。 結果:經過 3 個月及 3 年後,血清副甲狀腺素 (PTH) 水平分別下降 47.3 ± 34.3% 及 74.7 ± 36.8%。其中,8 人 (62%) 反應良好,PTH 降幅達至少 30%;他們之中有 7 人 (87.5%) 在首 3 個月呈現反應。相比於不反應者,反應者的基線 PTH 明顯較低 (64.3 ± 32.2 vs 138.5 ± 64.0 pmol/L,p = 0.02)。治療期間,無任何人出現高鈣血症,但所有病人均有高磷酸血症的現象。 結論:對於患有次發性甲狀旁腺功能亢進的血液透析患者,paricalcitol 可有效降低 PTH,且耐受性良好。本研究的結果亦顯示,較晚期的次發性甲狀旁腺功能亢進患者,其療效反應可能較為不明顯。
    Hong Kong Journal of Nephrology 04/2014;
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    ABSTRACT: Residual renal function (RRF) is an important prognostic indicator in continuous ambulatory peritoneal dialysis (CAPD) patients. We determined the predictors of RRF loss in a cohort of incident CAPD patients. We reviewed the record of 645 incident CAPD patients. RRF loss is represented by the slope of decline of residual glomerular filtration rate (GFR) as well as the time to anuria. The average rate of residual GFR decline was -0.083 ± 0.094 mL/min/month. The rate of residual GFR decline was faster with a higher proteinuria (r = -0.506, p < 0.0001) and baseline residual GFR (r = -0.560, p < 0.0001). Multivariate analysis showed that proteinuria, baseline residual GFR, and the use of diuretics were independent predictors of residual GFR decline. Cox proportional hazard model showed that proteinuria, glucose exposure, and the number of peritonitis episodes were independent predictors of progression to anuria, while a higher baseline GFR was protective. Each 1 g/day of proteinuria is associated with a 13.2% increase in the risk of progressing to anuria, each 10g/day higher glucose exposure is associated with a 2.5% increase in risk, while each peritonitis episode confers a 3.8% increase in risk. Our study shows that factors predicting the loss of residual solute clearance and urine output are different. Proteinuria, baseline residual GFR, and the use of diuretics are independently related to the rate of RRF decline in CAPD patients, while proteinuria, glucose exposure, and the number of peritonitis episodes are independent predictors for the development of anuria. The role of anti-proteinuric therapy and measures to prevent peritonitis episodes in the preservation of RRF should be tested in future studies.
    Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 02/2014;
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    ABSTRACT: In the general population, metabolic syndrome (MES) is associated with cardiovascular risk. However, the definition of MES and its prognostic implication among patients undergoing peritoneal dialysis (PD) remain controversial. We studied 329 prevalent PD patients from April 2008 to April 2011 and compared four sets of diagnostic criteria: the original World Health Organization (WHO) criteria, the International Diabetes Federation (IDF) criteria, the original National Cholesterol Education Program (NCEP) criteria, and the modified NCEP criteria. Nutritional status, body composition, and arterial pulse-wave velocity were measured. Patients were followed for 31.7±15.5 months. Among the 329 patients, 175 (53.2%) fulfilled the WHO criteria, 177 (53.8%) the IDF criteria, 199 (60.5%) the original NCEP criteria, and 218 (66.3%) the modified NCEP criteria. The agreement among the four sets of criteria was fair to moderate (Cohen κ=0.35-0.58). Patients with MES defined by all four criteria had higher adipose tissue mass than the others, although the difference in adipose tissue mass was most pronounced with the IDF criteria (MES versus no MES, 18.2±7.9 versus 10.7±5.9 kg; P<0.001). Patients with MES, as defined by the IDF criteria, were hospitalized longer than those without MES (3.82 [interquartile range, 0.00-12.61] versus 1.07 [interquartile range, 0.00-6.43]) days per year of follow-up; P=0.01). Overall survival, cardiovascular survival, or technique survival did not differ between patients with and without MES, irrespective of the diagnostic criteria after adjustment for diabetic status. In patients undergoing PD, overall survival, cardiovascular survival, and technique survival did not differ between patients with and without MES, irrespective of diabetic status and diagnostic criteria. Further studies are needed to establish a new definition or clinical scoring system for risk stratification of PD patients.
    Clinical Journal of the American Society of Nephrology 01/2014; · 5.07 Impact Factor
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    ABSTRACT: Fluid overload probably contributes to the cardiovascular risk of peritoneal dialysis (PD) patients. We studied the relationship between over-hydration as determined by bioimpedance spectroscopy and dialysis adequacy, nutritional status, and arterial stiffness in Chinese PD patients. We studied 122 asymptomatic prevalent PD patients: bioimpedance spectroscopy, arterial pulse wave velocity, dialysis adequacy and nutritional status were determined. Of the 122 patients, 88 (72.1%) had over-hydration of ≥ 1 L, while 25 (20.5%) were ≥ 5 L. Over-hydration significantly correlated with total body water (r = 0.474, p < 0.001) and extracellular water (r = 0.755, p < 0.001). Over-hydration was more severe in male and diabetic patients, and significantly correlated with Charlson's comorbidity score, blood pressure, body mass index, body weight, peritoneal transport characteristics, and carotid-femoral pulse wave velocity. Over-hydration significantly correlated with Kt/V (r = -0.287, p = 0.016), serum albumin level (r = -0.465, p < 0.001) and malnutrition inflammation score (r = 0.410, p = 0.006), but not residual renal function. Over-hydration is common in asymptomatic Chinese PD patients. The degree of over-hydration is particularly pronounced in patients who are inadequately dialyzed, have multiple comorbid conditions and low serum albumin levels. Over-hydration is associated with high blood pressure and arterial stiffness, and may contribute to the excessive risk of cardiovascular disease in this group of patients.
    Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 01/2014;
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    ABSTRACT: Evidence implicated the diagnostic significance of microRNAs in whole urine/urine sediments in urothelial carcinoma of the bladder (UCB). However, the contaminated blood cells in patients with haematouria significantly altered the expression profiles of urinary microRNA, influencing the test accuracy.
    PLoS ONE 01/2014; 9(7):e100793. · 3.53 Impact Factor
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    ABSTRACT: Relapsing and recurrent peritonitis episodes are important causes of treatment failure in patients undergoing peritoneal dialysis (PD). This study explored whether the level of bacteria-derived DNA fragment in PD effluent predicts the development of relapsing or recurrent peritonitis. The study included 143 patients with PD peritonitis in a dialysis unit between September 2010 and December 2011. Every 5 days until antibiotic treatment ended, PD effluent was collected to determine bacteria-derived DNA fragment level, which is represented by the number of PCR cycles at which bacterial DNA could be detected. Patients were followed for the development of relapsing or recurrent peritonitis. Thirty-nine patients were excluded because of immediate treatment failure or incorrect diagnosis. Of the other 104 patients, 15 (14.4%) developed relapsing peritonitis, 3 (2.9%) had recurrent peritonitis, and 5 (4.8%) had repeat episodes. Patients with relapsing or recurrent peritonitis episodes had significantly higher levels of bacterial DNA fragment in PD effluent than those without relapsing or recurrence, both 5 days before (31.9±3.4 versus 34.3±3.0 cycles; P=0.002) and on the day of (32.3±2.6 versus 34.1±1.7 cycles; P<0.001) completion of antibiotics. When bacterial DNA fragment detectable by 34 PCR cycles 5 days before the completion of antibiotics is used as the cutoff, it has a sensitivity of 88.9% and specificity of 60.5% for the prediction of relapsing or recurrent peritonitis. Bacterial DNA fragment levels in PD effluent are significantly higher, both 5 days before and on the date of completion of antibiotics, among patients who subsequently develop relapsing or recurrent peritonitis than among those cured by antibiotics. Further studies are needed to validate these results and confirm the clinical utility of dialysate bacterial DNA fragment level.
    Clinical Journal of the American Society of Nephrology 10/2013; · 5.07 Impact Factor
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    ABSTRACT: Background: Cardiovascular disease is the major cause of mortality and morbidity in dialysis patients. Recently, circulating endotoxin is found to associate with the systemic inflammatory state and cardiovascular disease of dialysis patients. Previous studies showed that the use of ultrapure dialysate for hemodialysis could reduce the exposure to exogenous endotoxin. We studied the effect of using ultrapure dialysate for hemodialysis on circulating endotoxin and bacterial DNA fragment levels and vascular stiffness. Methods: This is an open-labeled prospective study of 25 patients (14 male). Circulating endotoxin and bacterial DNA level, vascular stiffness as represented by arterial pulse wave velocity (PWV), nutrition and hydration status were monitored before and repeatedly throughout 12 months after the use of ultrapure dialysate for hemodialysis. Results: The average age was 58.9 ± 10.2 years; 21 patients completed the study. Within 4 weeks of conversion to ultrapure dialysate for hemodialysis, the plasma endotoxin level fell from 0.302 ± 0.083 to 0.209 ± 0.044 EU/ml (p < 0.0001) and then remained static, while serum bacterial DNA level remained similar. Furthermore, the time-averaged plasma endotoxin level during the study period significantly correlated with serum C-reactive protein level (r = 0.483, p = 0.017), carotid-femoral PWV (r = 0.455, p = 0.033), and malnutrition inflammation score (r = 0.461, p = 0.031). The time-averaged serum bacterial DNA level significantly correlated with malnutrition inflammation score (r = 0.550, p = 0.008) and inversely with subjective global assessment score (r = -0.543, p = 0.009), but not with PWV. Conclusions: In hemodialysis patients, circulating endotoxin level is associated with vascular stiffness and systemic inflammation. Using ultrapure dialysate for hemodialysis effectively reduces circulating endotoxin level in hemodialysis patients. The long-term benefit of using ultrapure dialysate for hemodialysis requires further study. © 2013 S. Karger AG, Basel.
    Nephron Clinical Practice 09/2013; 123(3-4):246-253. · 1.65 Impact Factor
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    ABSTRACT: BACKGROUND: Endotoxemia is common in peritoneal dialysis (PD) patients, and circulating lipopolysaccharide (LPS) level is related to the degree of systemic inflammation and atherosclerosis. We hypothesize that circulating bacterial DNA, another microbial component, correlates with the degree of systemic inflammation and predicts the survival of new PD patients. METHODS: We measured the plasma bacterial DNA level in the archive blood samples of 300 consecutive new PD patients. The result was compared with serum C-reactive protein (CRP) level, patient survival and peritonitis-free survival. RESULTS: The average age was 57.8 ± 12.1 years, average plasma bacterial DNA level 34.3 ± 1.3 cycles and average follow-up 37.9 ± 22.2 months. The plasma bacterial DNA level correlated with serum CRP (r = 0.565, P < 0.001) and LPS levels (r = 0.224, P = 0.029). At 36 months, the patient survival were 77.5, 78.3, 74.6 and 65.2% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (log-rank test, P = 0.034). By multivariate analysis with the Cox proportional hazard model to adjust for confounders, the plasma bacterial DNA level had no independent effect. Similarly, peritonitis-free survival were 60.6, 59.8, 60.3 and 50.4% for plasma bacterial DNA level quartiles I, II, III and IV, respectively, at 36 months (P = 0.020), and the difference was not significant after adjusting for confounding factors. CONCLUSION: We found that the plasma bacterial DNA level correlated with the degree of systemic inflammatory state in PD patients. Although plasma bacterial DNA level seems to predict patient survival and peritonitis-free survival, the association disappears after adjusting for confounding factors. Further prospective studies are needed to delineate the role of plasma bacterial DNA as a prognostic marker of renal failure patients.
    Nephrology Dialysis Transplantation 06/2013; · 3.37 Impact Factor
  • Hong Kong Journal of Nephrology 04/2013; 15(1):51–52.
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    ABSTRACT: 背景 之前的研究顯示,童年病發的微小變化型腎病變(MCN)有高達40%會持續至青春期之後;然而,對於這類病情延續至成年的患者,至今少有研究對其長期腎臟預後及治療相關併發症比率作出報告。 方法 針對經活檢證實的MCN兒童患者,我們回顧了55位於1984至2004在本院接受治療的連續個案,從而對其病情發展、治療用藥、及治療相關併發症作出瞭解。 結果 在所有55位兒童病人中,35人持續接受追蹤至成年期。在成年階段中,13人(37%)出現復發,20人(57%)發生治療相關併發症,後者包括過重(23%)、空腹血糖過高(14%)、不孕症(14%)、持續性輕度蛋白尿(11%)、骨折(9%)、及高血壓(9%)。在最後追蹤中,所有人均呈現正常的腎功能。 結論 不少的童年病發MCN患者會在成年期復發,即使幾乎所有人的腎功能正常,持續使用的類固醇及免疫抑制劑所導致的治療相關併發症風險卻不容忽視。對於這些病人,似乎應予以終生的追蹤,以利於病情復發及治療相關併發症的及早發現。
    Hong Kong Journal of Nephrology 04/2013; 15(1):22–27.
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    ABSTRACT: Background Although 80% of the dialysis patients in Hong Kong are treated with peritoneal dialysis (PD), most received continuous ambulatory PD (CAPD), while automated PD (APD) accounts for 5% of the patients. Recent evidence suggests that clinical outcomes are different for CAPD and APD in specific subgroups of patients. Methods We reviewed the clinical outcome of 90 consecutive incident APD patients and 180 CAPD patients in our center. Results The median follow up was 21.9 months (inter-quartile range, 9.5 to 46.5 months). The APD group was younger and had a lower Charlson's score than the CAPD group. Furthermore, the APD group had a highly skewed distribution of the Charlson's score, indicating the possibility of two different groups of patients. Multivariate analysis showed that in addition to the treatment mode (APD versus CAPD) and Charlson's score, there was a significant interaction between the two (p = 0.043) on patient survival. For patients with Charlson's score ≤6, the APD group had a significantly better patient survival than the CAPD group (78.3% vs 65.4% at 5-year, p = 0.039), while for patients with Charlson's score ≥7, the APD group had a worse patient survival than the CAPD group (16.3% vs 48.4% at 5 years, p = 0.028). Similarly, Charlson's score and its interaction with treatment mode, but not the APD group per se, were independent predictors of technique survival (p = 0.013). For patients with Charlson's score ≥7, the APD group had a significantly lower technique survival than the CAPD group (8.8% vs 34.3%, p = 0.001), while for patients with Charlson's score ≤6, the technique survival was similar (44.4% vs 42.5%, p = 0.15). Peritonitis-free survival was 35.2% and 32.2% for APD and CAPD groups, respectively (p = 0.021), and the difference was not affected by Charlson's score. Conclusions Comorbid diseases had a significant interaction with the mode of PD on patient and technique survival of incident PD patients. Our result suggests that APD may offer benefit in, and only in, young patients with minimal comorbid diseases.
    Nephrology 03/2013; · 1.69 Impact Factor
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    ABSTRACT: BACKGROUND: The treatment of immunoglobulin A (IgA) nephropathy with normal renal function and minimal proteinuria is unknown. METHODS: We randomly assigned 60 patients with IgA nephropathy, proteinuria <0.5 g/day, normal blood pressure and renal function to ramipril 2.5 mg daily or no treatment. Patients were followed for 5 years for the development of hypertension, proteinuria, or impaired renal function. RESULTS: The blood pressure of the treatment group was marginally lower than the control group throughout the study period. At 60 months, the event-free survival was marginally higher for the treatment group as compared with the control group (81.1% vs 70.5%, P=.27). The proteinuria-free survival was similar at 82.9% and 79.3% for the treatment and control groups, respectively (P=.6); hypertension-free survival was 86.4% and 79.3% (P=.2). After 60 months of follow-up, the estimated glomerular filtration rate (GFR) was 108.1±29.0 mL/min/1.73 m(2) for the treatment group and 105.7±17.7 mL/min/1.73 m(2) for the control group (P=.7), but the difference was not statistically significant. None of the patients developed impaired renal function. The rate of GFR decline was similar between the treatment and control groups (-0.39±2.57 vs -0.59±1.63 mL/min/1.73 m(2) per year, respectively, P=.7). In general, the study medication was well tolerated. Two patients needed to stop prematurely because of cough and dizziness. CONCLUSION: For early IgA nephropathy patients with minimal proteinuria, normal blood pressure, and normal renal function, treatment with 2.5 mg/daily of ramipril for 5 years does not offer any benefit.
    The American journal of medicine 02/2013; 126(2):162-168. · 5.30 Impact Factor
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    ABSTRACT: BACKGROUND: There is no reliable clinical test to predict the reversibility of acute-on-chronic renal failure. We study whether urinary biomarkers could be used as a noninvasive prognostic marker in patients with acute-on-chronic renal failure. METHODS: We studied 39 adult patients with pre-existing chronic renal impairment presenting to us with acute-on-chronic renal failure. Urinary neutrophil gelatinase-associated lipocalin (NGAL) level was measured. The mRNA of kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), alpha-1-microglobulin (α1M), sodium/hydrogen exchanger-3 (NHE3), beta-2 microglobulin (β2M), and N-acetyl-β-D-glucosaminidase (NAG) in urinary sediment were quantified.RESULTS: Urinary NGAL level significantly correlated with the serum creatinine at presentation (r=0.762, p< 0.0001) but not baseline serum creatinine. Urinary sediment β2M expression significantly correlated with baseline glomerular filtration rate (GFR) (r= -0.400, p=0.012). Urinary α1M and NHE3 expressions were significantly higher in ischemic acute tubular necrosis than other causes of acute kidney injury (p< 0.0001 and p=0.006, respectively). Urinary α1M expression significantly correlated with the degree of improvement in renal function (r=0.387, p=0.026), as well as the estimated GFR 6 months later (r=0.386, p=0.027).CONCLUSION: In patients with acute-on-chronic renal failure, urinary NGAL level correlates with the severity of renal failure, while urinary α1M expression correlates with the degree of renal function recovery. Quantification of urinary α1M mRNA may be developed as an non-invasive tool for risk stratification of this group of patients.
    Disease markers 01/2013; · 2.14 Impact Factor
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    ABSTRACT: BACKGROUND: MicroRNAs are a group of non-coding RNA molecules that play important roles in the pathogenesis of various kidney diseases. We investigate the urinary sediment miRNA levels of adult patients with nephrotic syndrome. METHODS: We study 20 patients with diabetic glomerulosclerosis (DGS), 21 with minimal change nephropathy (MCN) or focal glomerulosclerosis (FGS), 23 with membranous nephropathy (MGN), and 10 healthy controls. Urinary sediment miRNA levels are quantified. RESULTS: Urinary sediment miR-29a, miR-192, and miR-200c levels were significantly different between diagnosis groups. Post hoc analysis showed that urinary miR-638 level was significantly lower in all causes of nephrotic syndrome than healthy controls, while the DGS group had lower urinary miR-192 level than other diagnosis groups. In contrast, the MCN/FGS group had higher urinary miR-200c level than other diagnosis groups. For each specific pathology group, urinary level of several miRNA targets significantly correlated with kidney function and histological scarring. CONCLUSIONS: Urinary miR-29a, miR-192 and miR-200c levels have characteristic alterations amongst patients with different causes of nephrotic syndrome. Our results suggest that urinary miRNA levels has the potential of being developed as the diagnosis tool and marker of disease severity in adult nephrotic syndrome.
    Clinica chimica acta; international journal of clinical chemistry 01/2013; · 2.54 Impact Factor
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    ABSTRACT: Laboratory research and previous study suggest that aliskiren, a direct renin inhibitor, has anti-proteinuric effects. We conducted a randomized crossover study to evaluate the anti-proteinuric effect of aliskiren in patients with immunoglobulin A (IgA) nephropathy. We studied 22 patients with biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Patients were randomized to either oral aliskiren 300 mg/day or placebo for 16 weeks and then crossed over to the other treatment arm after a washout period. Proteinuria, estimated glomerular filtration rate (eGFR), blood pressure, and serum potassium were monitored. After aliskiren treatment, there was a significant reduction in proteinuria in 4 weeks (1.76±0.95 to 1.03±0.69 g:g-Cr, p<0.0001), which remained at a low level throughout the treatment period. There was a significant difference in proteinuria between the aliskiren and placebo groups from 4 to 16 weeks after treatment (p<0.01 for all comparisons). After aliskiren treatment, there were modest but statistically significant reductions in eGFR (57.2±29.1 to 54.8±29.3 ml/min/1.73 m(2), p = 0.013) and diastolic blood pressure (72.6±12.3 to 66.2±11.2 mmHg, p<0.0001). None of the patient developed severe hyperkalemia (serum potassium ≥6.0 mmol/l) during the study period. Aliskiren has anti-proteinuric effect in patients with IgA nephropathy and persistent proteinuria despite ACE inhibitor or ARB. Further studies are needed to confirm the renal protecting effect of direct renin inhibition in chronic proteinuric kidney diseases. ClinicalTrials.gov NCT00870493.
    PLoS ONE 01/2013; 8(5):e62736. · 3.53 Impact Factor
  • Cheuk-Chun Szeto, Bonnie Ching-Ha Kwan, Lai-Shan Tam
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    ABSTRACT: Systemic lupus erythematosus (SLE) is a relapsing autoimmune disease with clinical manifestations that affect multiple organ systems. Lupus nephritis is recognized as one of the most severe organ involvements in SLE and affects half of the lupus patients. Notably, lupus nephritis is characterized by intrarenal lymphocyte activation and inflammation. Since most of the cytokines exert their effects in a paracrine fashion, measuring their expression at the site of pathology should be of biological relevance. Although kidney biopsy is widely used to determine the histology and severity of lupus nephritis, this invasive procedure has its own risk and is not practical for serial monitoring. In the past decade, extraction and quantification of messenger RNA (mRNA) from urinary sediment has emerged as a robust laboratory technique. Quantification of mRNA expression in urinary sediment has been tested as a noninvasive means to assess the disease activity of SLE patients. Available published evidence, however, is limited to small-scale studies. Based on the result of these studies, a number of cytokine and transcript factor genes have been found to have potential for the differentiation between active and inactive SLE, between proliferative and membranous types of lupus nephritis, assessment of the systemic lupus activity or histological activity of kidney biopsy specimen, monitoring of treatment response in active lupus nephritis, or detection of lupus disease flare in clinically quiescent patients. Being a simple and noninvasive method, urinary mRNA level deserves further studies to validate its role in risk stratification and monitoring of therapeutic response in patients with lupus nephritis.
    Advances in clinical chemistry 01/2013; 62:197-219. · 3.67 Impact Factor
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    ABSTRACT: Background: MicroRNAs (miRNAs) play important roles in the progression of renal fibrosis. We studied the urinary levels of miR-21, miR-29 family and miR-93, which are downstream mediators of the transforming growth factor-β(1) (TGF-β(1)), in patients with immunoglobulin A (IgA) nephropathy. Methods: We studied the urinary miRNA levels of 43 IgA nephropathy patients and 13 healthy controls. Results: The IgA nephropathy group had significantly lower urinary miR-29b and miR-29c, but higher miR-93 levels than controls. Proteinuria significantly correlated with urinary levels of miR-29b (r = -0.388, p = 0.003) and miR-29c (r = -0.409, p = 0.002). Glomerular filtration rate significantly correlated with urinary levels of miR-21 (r = 0.338, p = 0.028), miR-29b (r = 0.333, p = 0.031) and miR-29c (r = 0.304, p = 0.050). Urinary miR-93 level significantly correlated with glomerular scarring (r = -0.392, p = 0.010). Urinary miRNA level of SMAD3, but not TGF-β(1), correlated with urinary miR-21 (r = 0.624, p < 0.001), miR-29b (r = 0.566, p < 0.001), miR-29c (r = 0.619, p < 0.001) and miR-93 (r = 0.332, p = 0.032). Conclusions: Urinary miR-29b and miR-29c levels correlated with proteinuria and renal function, while urinary miR-93 level correlated with glomerular scarring. More importantly, urinary levels of these miRNA targets significantly correlated with urinary SMAD3 level. Our results suggest that these miRNA targets are regulated by the TGF-β(1)/SMAD3 pathway and they may play important roles in the development of progressive renal fibrosis in IgA nephropathy.
    American Journal of Nephrology 10/2012; 36(5):412-418. · 2.62 Impact Factor

Publication Stats

2k Citations
489.88 Total Impact Points

Institutions

  • 2000–2014
    • The Chinese University of Hong Kong
      • • Prince of Wales Hospital
      • • Department of Medicine and Therapeutics
      Hong Kong, Hong Kong
  • 2000–2013
    • Prince of Wales Hospital, Hong Kong
      Chiu-lung, Kowloon City, Hong Kong
  • 2011
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China
    • Second Military Medical University, Shanghai
      Shanghai, Shanghai Shi, China