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Aim: The reported causes of nephrotic syndrome (NS) varies between different countries. Less is known about the causes of nephrotic-range proteinuria (NPU). We aimed to evaluate the underlying causes of NS and NPU., Methods: This was a single-centre, retrospective study of adult patients who underwent renal biopsy between 1983 and 2015 in a tertiary referral hospital in Hong Kong. We determined the distribution of histopathological diagnoses with regard to the age subgroups and time periods., Results: Among 7456 patients who underwent renal biopsy, 982 and 838 patients had NS and NPU, respectively. The most common diagnosis in NS was minimal change disease (MCD) (33.3%), followed by membranous nephropathy (MN) (23.6%) and lupus nephritis (LN) (12.8%); whereas the most common diagnosis in NPU was LN (27.4%), followed by immunoglobulin A nephropathy (IgAN) (21.4%) and diabetic nephropathy (DN) (9.3%). In the NS group, MCD was the most common diagnosis in young adults while MN was the leading cause in the elderly. On the other hand, LN was the most common pathology in the NPU group until the age of 60. Over the past three decades, there was a trend of decrease in the proportion of IgAN in both NS and NPU group, while a combined pathology of hypertensive nephrosclerosis and diabetic nephropathy (HTNS and DN) increased significantly., Conclusions: The causes of NS and NPU in Chinese adults were different and may represent two distinct pathological identities. The spectrum of renal histopathology among these two groups changed significantly over time., (© 2017 Asian Pacific Society of Nephrology.)

Aim: Tranexamic acid (TXA) is a synthetic anti-fibrinolytic agent commonly used for the prevention and treatment of bleeding disorders. The aim of this study is to describe the clinical manifestation of TXA toxicity in chronic kidney disease (CKD) patients., Methods: From 2005 to 2014, we encountered four CKD patients who experienced severe complications related to TXA. Clinical manifestations and outcome of these patients were recorded. We then performed a qualitative literature review of published cases of TXA toxicity in CKD patients in the PubMed database from 1 January 1972 to 31 December 2015., Results: In our centre, two peritoneal dialysis (PD) patients developed neurotoxicity after intravenous TXA use for surgical bleeding and one PD patient developed neurotoxicity after oral TXA use for post-polypectomy colonic bleeding. One kidney transplant recipient developed acute obstructive uropathy due to retention of blood clot at the pelvi-ureteric junction of graft kidney after taking oral TXA for menorrhagia. Dosage of TXA was not adjusted according to renal function in all cases. All of them recovered without permanent disability after TXA was stopped. From our literature search, we identified two cases of neurotoxicity (one PD, one stage 4 CKD patient), one case of retinal toxicity in a haemolysis (HD) patient, one case of ligneous conjunctivitis in a CKD patient, and one case of toxic epidermal necrolysis in a CKD patient., Conclusion: Neurotoxicity is a very common clinical manifestation of TXA toxicity in CKD patients. Thrombotic complication is rare. Dosage adjustment of TXA is essential in CKD patients., (© 2016 Asian Pacific Society of Nephrology.)

Aim: C-reactive protein (CRP) is a mediator of systemic inflammation. Peritoneal dialysis (PD) is known to cause peritoneal inflammation and fibrosis. We compare the degree of peritoneal inflammation and fibrosis in wild-type (WT) and CRP-transgenic (Tg) mice after PD treatment., Methods: WT (n = 7) and CRP-Tg (n = 10) C57BL/6 J mice (all male, 10-12 weeks old) were injected intra-peritoneally with 4.25% dextrose PD solution (3 mL/mouse) daily for 28 days, followed by a 2-h peritoneal equilibration test (PET). The mice were then killed. Parietal peritoneal and omental tissues were collected for the assessment of inflammation and fibrosis., Results: After 28 days of PD treatment, CRP-Tg mice had higher dialysate-to-plasma (D/P) creatinine ratio than that of WT mice. Parietal peritoneum of the CRP-Tg mice was more cellular and thicker than that of the WT mice. CRP-Tg mice also had higher connective tissue growth factor (CTGF), intercellular adhesion molecule 1 (ICAM1) and tumor necrosis factor α (TNFα) RNA expressions as well as immunohistochemical staining in the parietal peritoneum than that of the WT mice., Conclusions: CRP-Tg mice have significantly more inflammation and fibrosis than WT mice after PD treatment. Our results suggest that CRP play a role in inflammation and fibrosis induced by PD. The implication of our results to human PD therapy needs further investigations., (© 2016 Asian Pacific Society of Nephrology.)

Peritonitis is the major complication of peritoneal dialysis (PD). The aim of our present study is to explore the prognostic value of endotoxin level in PD effluent for the prediction of treatment failure in PD-related peritonitis. We studied 325 peritonitis episodes in 223 patients. PD effluent (PDE) was collected every 5 days for endotoxin level and leukocyte count. Patients were followed for relapsing or recurrent peritonitis. We found 20 episodes (6.2%) had primary treatment failure; 41 (12.6%) developed relapsing, 19 (5.8%) had recurrent, and 22 (6.8%) had repeat episodes. Endotoxin was detectable in the PDE of 19 episodes (24.4%) caused by Gram negative organisms, 4 episodes (6.8%) of mixed bacterial growth, and none of the culture negative episodes or those by Gram positive organisms. For episodes caused by Gram negative bacteria, a detectable endotoxin level in PDE on day 5 had a sensitivity and specificity of 66.7% and 83.3%, respectively, for predicting primary treatment failure. In contrast, PDE leukocyte count > 1000 per mm3 on day 5 had a sensitivity and specificity of 88.9% and 89.1%, respectively; the addition of PDE endotoxin assay did not improve the sensitivity or specificity. We conclude that detectable endotoxin in PDE 5 days after antibiotic therapy might predict primary treatment failure in peritonitis episodes caused by Gram negative organisms. However, the sensitivity and specificity of PDE endotoxin assay was inferior to PDE leukocyte count., (© 2016 Asian Pacific Society of Nephrology.)

Aim: To investigate the clinical course and outcome of peritoneal dialysis-associated peritonitis secondary to Gordonia species., Method: We reviewed all Gordonia peritonitis episodes occurring in a single dialysis unit from 1994 to 2013., Results: During the study period, four episodes of Gordonia peritonitis were recorded. All were male patients. One patient responded to vancomycin therapy. One patient had refractory peritonitis despite vancomycin, but responded to imipenem and amikacin combination therapy. One patient had relapsing peritonitis and required catheter removal. The fourth patient had an elective Tenckhoff catheter exchange. No patient died of peritonitis. Causative organism was not fully identified until 7 to 18 days of peritonitis., Conclusion: Gordonia species is increasingly recognized to cause serious infections. In patients undergoing peritoneal dialysis, Gordonia peritonitis should be considered in case of refractory Gram-positive bacilli peritonitis, especially when the exact organism could not be identified one week after the onset of peritonitis. A close liaison with a microbiologist is needed for a timely diagnosis., (© 2014 Asian Pacific Society of Nephrology.)

Aim: Although calcimimetics cinacalcet can reduce parathyroid hormone level and control secondary hyperparathyroidism in end-stage renal disease patients, risk of vascular calcification remains high. Whether cinacalcet can further reduce vascular damage or arterial stiffness is unknown., Methods: We studied the effect of cinacalcet in 33 peritoneal dialysis patients with inadequately controlled secondary hyperparathyroidism despite standard treatment. The primary outcome was the aortic pulse wave velocity at 26 and 52 months after cinacalcet treatment. The pulse wave velocity was compared with that of a matched control cohort of 37 peritoneal dialysis patients with secondary hyperparathyroidism., Results: Thirty-three patients completed the cinacalcet treatment, after median dialysis duration of 1.0 year. Significant improvement of parathyroid hormone level was achieved after 52 weeks, from 87.5 ± 28.7 pmol/L to 34.5 ± 45.5 pmol/L (P < 0.0001). Serial carotid-femoral pulse wave velocity did not differ between cinacalcet treatment group and control group (general linear model with repeated measures, P = 0.19). Among patients receiving cinacalcet, the average carotid-femoral pulse wave velocity increased from 10.46 ± 2.12 m/s at baseline to 11.41 ± 2.79 m/s at 52 weeks (P = 0.001). The change in carotid-femoral pulse wave velocity over 1 year had no significant correlation with the final parathyroid hormone level or change in parathyroid hormone level., Conclusions: Among prevalent patients receiving peritoneal dialysis and with hyperparathyroidism, a reduction of 60.6% parathyroid hormone level after cinacalcet treatment for one year did not reduce the carotid-femoral pulse wave velocity., (© 2014 Asian Pacific Society of Nephrology.)

Aim: To compare the clinical outcome between continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) in specific subgroups of patients., Methods: We reviewed the clinical outcome of 90 consecutive incident APD patients and 180 CAPD patients in our centre., 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 vs 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 years, 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., (© 2013 The Authors. Nephrology © 2013 Asian Pacific Society of Nephrology.)

Aim:   Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can counteract inflammation and atherosclerosis, both common causes of morbidity in peritoneal dialysis (PD) patients. We examined the relation between serum soluble TRAIL (sTRAIL) levels and the outcome of Chinese PD patients., Methods:   We studied 116 new PD patients (67 males, age 56.7 ± 13.4 years). Baseline serum sTRAIL level was determined and grouped to tertiles 1 (lowest) to 3 (highest). All patients were followed for 20.9 ± 7.0 months., Results:   Patient survival was 83.4%, 74.2% and 100% for tertiles 1 to 3, respectively, at 24 months (P = 0.021). Multivariate Cox regression analysis showed that serum sTRAIL level was an independent predictor of patient survival after adjusting for confounding factors (adjusted hazard ratio 0.962, 95% confidence interval [CI] 0.935-0.991, P = 0.010)., Conclusion:   A higher baseline serum sTRAIL level was associated with a better survival of PD patients. The detailed mechanism deserves further investigation., (© 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.)

Aim:   We aimed to gain an understanding of patient concerns while on a transplantation waiting list in areas with long transplant waiting time., Methods:   The study population comprised patients with organ failure on the transplant waiting list in Hong Kong. They were invited to complete a questionnaire survey. Demographic data and waiting time were collected. Respondents rated their chance of getting transplanted, their subjective concerns and feelings, level of happiness and support received., Results:   A total of 442 patients on the waiting list for kidney, liver, lung and heart-lung transplants completed the questionnaire survey. The majority of patients (93.0%) were waiting for kidney transplantation. More than half of the respondents (63.3%) had been waiting for more than 3 years. Patients with longer transplant waiting times had lower self-estimated chance of receiving a transplant (P = 0.004). Self-estimated chance of getting transplanted was positively associated with the happiness score (P < 0.0001). Issues of most concerns to the patients waiting for organ transplants were: inconvenience of therapy (48.2%), disease progression (47.9%), burden to family (59.5%) and financial difficulties (52.3%). More female patients on the waiting list (50.0% vs 25.7% in male) reported concerns about suffering associated with the illnesses. 21.7% of patients considered the level of support received inadequate., Conclusions:   Our patients had long waiting time for transplantation, which is associated with a lower perceived chance of getting a transplant. Attention to more psychosocial support to these patients waiting for organ transplant is important. Promoting and improving organ donation would be the ultimate way to help these patients., (© 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.)

Aim: MicroRNAs (miRNAs) play important roles in the pathogenesis of autoimmune diseases. We studied the intra-renal expression of miRNA targets that were reported to be differentially expressed in peripheral blood or urine between lupus nephritis (LN) patients and normal controls., Methods: We quantified the expression of in glomerulus and tubulointerstitium of miR-146a, miR-155, miR-198 miR-638 and miR-663 in 42 patients with LN and 10 healthy controls., Results: As compared with controls, LN patients had lower glomerular expression of miR-638 (P < 0.001) but higher tubulointerstitial expression of this target (P = 0.001). Both glomerular and tubulointerstitial expression of miR-198 were higher in LN patients than controls (P < 0.001). For miR-146a, LN patients only had higher expression in glomerulus (P = 0.005) but not in tubulointerstitium. Tubulointerstitial miR-638 expression was significantly correlated with proteinuria (r = 0.404; P = 0.022) and disease activity score (r = 0.454; P = 0.008), while glomerular miR-146a expressions were correlated with estimated GFR (r = 0.453; P = 0.028) and histological activity index (r = 0.494; P = 0.027)., Conclusion: We found that intra-renal expression of miR-638, miR-198 and miR-146a are differentially expressed between LN patients and normal controls. Furthermore, the degree of change in glomerular miR-146a and tubulointerstitial miR-638 expression correlated with clinical disease severity. The results suggested that these miRNA targets may play a role in the pathogenesis of lupus nephritis., (© 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.)

Aim: Long term dialysis is life-saving for patients with end stage renal disease (ESRD). However, in ESRD patients with multiple comorbid conditions, dialysis may actually be futile, and conservative management is advisable. We studied the life expectancy of Chinese ESRD patients treated conservatively., Methods: We reviewed 63 consecutive ESRD patients who were treated conservatively in our centre. Duration of survival was calculated from the date of initial assessment for dialysis, as well as the expected date of needing dialysis based on previous trend of renal function decline., Results: At the end of the observation period, 55 patients died. Twelve patients died before the expected date of needing dialysis because of unrelated reasons, while 36 deaths were directly attributed to uraemia. The median overall survival after initial assessment for dialysis was 41.3 months (95% confidence interval (CI), 33.2 to 49.4 months). The median overall survival was 6.58 months (inter-quartile range, 0.92 to 9.33 months) from the theoretical date of needing dialysis. The survival from the theoretical date of needing dialysis did not correlate with patient age, sex, diabetic status, or baseline renal function., Conclusions: In Chinese ESRD patients treated conservatively, the median survival is around 6 months after the theoretical date of needing dialysis. Our result provides an important piece of information for the decision of dialysis and patient counselling., (© 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.)

Aim: The role of the tumour necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 and interferon-inducible protein (IP-10)/CXCR3 axis in the pathogenesis of lupus nephritis were studied., Methods: The mRNA expression of TWEAK, Fn14, IP-10 and CXCR3 were quantified in the glomerulus and tubulointerstitium of 42 patients with lupus nephritis (LN group) and 10 healthy controls., Results: As compared to controls, LN patients had higher glomerular expression of TWEAK and Fn14, but glomerular CXCR3 expression was lower in the LN group. Similarly, the LN group had higher tubulointerstitial expression of TWEAK and Fn14, but lower tubulointerstitial expression of CXCR3, than controls. Glomerular TWEAK expression of class V nephritis was significantly higher than class IV nephritis. Glomerular expression of CXCR3 significantly correlated with proteinuria (r = -0.532; P = 0.019), whereas tubulointerstitial CXCR3 significantly correlated with serum creatinine (r = -0.447; P = 0.029)., Conclusion: In patients with lupus nephritis, there is an increase in intra-renal expression of TWEAK and Fn14, and a decrease in CXCR3 expression. Intra-renal expression of CXCR3 correlates with proteinuria and renal function. Our findings suggest that the TWEAK/Fn14 and IP-10/CXCR3 axis may contribute to the pathogenesis of lupus nephritis., (© 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.)

Aim: Activation of beta1-adrenergic receptor (beta1AR) enhances contractility and heart rate. The polymorphism Arg389Gly in the beta1AR gene was found to be functionally important in determining receptor activity. The relationship between this polymorphism and the risk of cardiovascular disease was investigated in Chinese subjects with overt diabetic nephropathy., Methods: A total of 219 type 2 diabetic subjects with nephropathy were recruited. Genotyping of the beta1AR Arg389Gly polymorphism was determined. Patients were followed up to 96 months for the development of cardiovascular events., Results: There were 122, 86 and 11 patients with Arg/Arg, Arg/Gly and Gly/Gly genotype, respectively. At 96 months, the event-free survival of primary composite cardiovascular end-point was 33.0% and 44.3% for Gly(+) and Gly(-) groups, respectively (log-rank test, P = 0.105), while the event-free survival for first ischaemic heart disease was 62.4% and 75.9%, respectively (log-rank test, P = 0.038). However, with multivariate analysis by the Cox proportional hazard model to adjust for confounders, only low-density lipoprotein and baseline glomerular filtration rate were independent predictors of first ischaemic heart event., Conclusion: The beta1AR Arg389Gly polymorphism is not an independent predictor of cardiovascular events in subjects with overt diabetic nephropathy.

Aim: Interleukin-18 (IL-18) is a pro-inflammatory cytokine and possibly plays an important role in the pathogenesis of cardiovascular disease. The relationship between two IL-18 gene polymorphisms, namely C-607A and G-137C, and cardiovascular disease in patients with diabetic nephropathy was examined., Methods: Two hundred and twenty patients (91 male) with diabetic nephropathy were studied. The IL-18 promoter genotypes were determined. All patients were then prospectively followed for the cardiovascular events. Cardiovascular mortality and all-cause mortality were also compared., Results: Mean age was 64.3 +/- 10.6 years; average follow up was 73.9 +/- 33.6 months. The frequencies of CC, CA and AA genotypes of the C-607A polymorphism were 25.5%, 48.2% and 26.8%, respectively; GG, GC and CC genotypes of the G-137C polymorphism were 71.8%, 25.0% and 3.2%, respectively. Neither of the polymorphisms were associated with the development of primary cardiovascular end-point. Cardiovascular survival was 84.8% and 70.6% at 60 months for GG and GC/CC genotypes of the G-137C polymorphism, respectively (P = 0.027); the corresponding actuarial survival was 69.0% and 54.8%, respectively (P = 0.053). However, the G-137C genotype was not an independent predictor of cardiovascular or actuarial survival after adjusting for confounders by multivariate analysis with the Cox model. The C-607A polymorphism had no significant effect on cardiovascular or actuarial survival., Conclusion: The G-137C polymorphism of the IL-18 promoter is associated with the cardiovascular mortality, and a trend of association with all-cause mortality, in patients with diabetic nephropathy. The association, however, becomes insignificant after adjusting for confounding factors. Further studies are needed to test other genetic determinants of the association between systemic inflammation and cardiovascular disease in renal failure patients.

Aim: The Malnutrition Inflammation Score (MIS) has been proposed for the assessment of nutritional status in peritoneal dialysis (PD) patients. The MIS and the Subjective Global Assessment (SGA) for serial monitoring of nutritional status in PD patients were compared., Methods: The change in the MIS and SGA overall score of 59 PD patients (28 male) over 12 months was studied. Clinical factors relating to the discrepancy between the two instruments were explored., Results: The average patient age was 55.8+/-9.7 years. Thirty of the 59 patients (50.8%) had exact agreement in the changed MIS and SGA scores. Cohen's kappa score was 0.274, indicating a modest degree of agreement. For the detection of deterioration in nutritional status and using the MIS as the reference measure, the SGA had a sensitivity of 61.9% and specificity of 86.8%; serum ferritin level was substantially higher in the ones whose SGA did not detect a deterioration in nutrition (1464.1+/-873.3 vs 800.5+/-561.6 pmol/L, P=0.046). For the detection of improvement in nutritional status, the SGA had a sensitivity of 45.8% and specificity of 82.9%; patients whose SGA did not detect an improvement in nutrition were dialyzed longer (53.8+/-35.3 vs 27.6+/-18.9 months, P=0.038), had higher total iron binding capacity (TIBC) (45.6+/-5.5 vs 38.2+/-8.1 micromol/L, P=0.015), had higher total Kt/V (2.02+/-0.36 vs 1.75+/-0.23, P=0.048) and higher normalized protein nitrogen appearance (1.16+/-0.25 vs 0.95+/-0.23 g/kg per day, P=0.048)., Conclusion: The longitudinal changes in the MIS and SGA score have modest agreement with each other. However, PD patients with a longer duration of dialysis, higher serum ferritin, TIBC, total Kt/V or normalized protein nitrogen appearance tend to have discrepancies between the longitudinal changes in the MIS and SGA overall score.