Peritoneal dialysis first policy in Hong Kong for 35 years: Global impact.

Peritoneal dialysis (PD) first policy has been established in Hong Kong since 1985. After 35 years of practice, the PD first policy in Hong Kong has influenced many countries around the world including governments, health ministries, nephrologists and renal nurses on the overall health policy structure and clinical practice in treating kidney failure patients using PD as an important dialysis modality. In 2021, the International Association of Chinese Nephrologists and the Hong Kong Society of Nephrology jointly held a symposium celebrating the 35 years of PD first policy in Hong Kong. In that symposium, experts and opinion leaders from around the world have shared their perspectives on how the PD first policy has grown and how it has affected PD and home dialysis practice globally. The advantages of PD during COVID-19 pandemic were highlighted and the use of telemedicine as an important adjunct was discussed in treating kidney failure patients to improve the overall quality of care. Barriers to PD and the need for sustainability of PD first policy were also emphasized. Overall, the knowledge awareness of PD as a home dialysis for patients, families, care providers and learners is a prerequisite for the success of PD first. A critical mass of PD regional hubs is needed for training and mentorship. Importantly, the alignment of policy and clinical goals are enablers of PD first program.

A Double-blind, Randomized Phase 2 Controlled Trial of Intradermal Hepatitis B Vaccination With a Topical Toll-like Receptor 7 Agonist Imiquimod, in Patients on Dialysis.

BACKGROUND: Patients on dialysis are hyporesponsive to the hepatitis B virus vaccines (HBVv). We examined intradermal (ID) HBVv Sci-B-Vac, with topical Toll-like receptor 7 (TLR7) agonist imiquimod pretreatment in dialysis patients. METHODS: We enrolled and prospectively followed adult patients on dialysis between January 2016 and September 2018. Eligible patients were randomly allocated (1:1:1) into 1 treatment group, topical imiquimod cream followed by ID HBVv (IMQ + ID); and 2 control groups: topical aqueous cream (placebo) followed by ID HBVv (AQ + ID) or topical aqueous cream followed by intramuscular HBVv (AQ + IM). The primary endpoint was the seroprotection rate (hepatitis B surface antibody ≥10 mIU/mL) at 52 weeks. RESULTS: Ninety-four patients were enrolled, among which 57.4% were previous nonresponders. Seroprotection rate was significantly better at week 52 for the IMQ + ID group with 96.9% compared to 74.2% and 48.4% for AQ + ID and AQ + IM groups, respectively (P < .0001). The geometric mean concentration was significantly higher at week 52 for the IMQ + ID group: 1135 (95% confidence interval [CI], 579.4-2218.2) mIU/mL, compared to 86.9 (95% CI, 18.5-409.3) mIU/mL and 7.2 (2.0-26.5) mIU/mL for the AQ + ID and AQ + IM groups, respectively (P < .0001). IMQ + ID vaccination (odds ratio, 3.70 [95% CI, 1.16-11.81]; P = .027) was the only factor independently associated with higher 52-week seroprotection rate. Adverse reaction was infrequent. CONCLUSIONS: Pretreatment with topical imiquimod before ID HBVv Sci-B-Vac was safe with favorable seroprotection in dialysis patients. CLINICAL TRIALS REGISTRATION: NCT02621112.

Lifetime cost-effectiveness analysis of first-line dialysis modalities for patients with end-stage renal disease under peritoneal dialysis first policy.

BACKGROUND: This study aimed to determine the lifetime cost-effectiveness of first-line dialysis modalities for end-stage renal disease (ESRD) patients under the "Peritoneal Dialysis First" policy. METHODS: Lifetime cost-effectiveness analyses from both healthcare provider and societal perspectives were performed using Markov modelling by simulating at age 60. Empirical data on costs and health utility scores collected from our studies were combined with published data on health state transitions and survival data to estimate the lifetime cost, quality-adjusted life-years (QALYs) and cost-effectiveness of three competing dialysis modalities: peritoneal dialysis (PD), hospital-based haemodialysis (HD) and nocturnal home HD. RESULTS: For cost-effectiveness analysis over a lifetime horizon from the perspective of healthcare provider, hospital-based HD group (lifetime cost USD$142,389; 6.58 QALYs) was dominated by the PD group (USD$76,915; 7.13 QALYs). Home-based HD had the highest effectiveness (8.37 QALYs) but with higher cost (USD$97,917) than the PD group. The incremental cost-effectiveness ratio (ICER) was USD$16,934 per QALY gained for home-based HD over PD. From the societal perspective, the results were similar and the ICER was USD$1195 per QALY gained for home-based HD over PD. Both ICERs fell within the acceptable thresholds. Changes in model parameters via sensitivity analyses had a minimal impact on ICER values. CONCLUSIONS: This study assessed the cost-effectiveness of dialysis modalities and service delivery models for ESRD patients under "Peritoneal Dialysis First" policy. For both healthcare provider and societal perspectives, PD as first-line dialysis modality was cost-saving relative to hospital-based HD, supporting the existing PD First or favoured policy. When compared with PD, Nocturnal home Home-based HD was considered a cost-effective first-line dialysis modality for ESRD patients.

Direct and indirect costs of end-stage renal disease patients in the first and second years after initiation of nocturnal home haemodialysis, hospital haemodialysis and peritoneal dialysis.

PURPOSE: To estimate the direct and indirect costs of end-stage renal disease (ESRD) patients in the first and second years of initiating peritoneal dialysis (PD), hospital-based haemodialysis (HD) and nocturnal home HD. METHODS: A cost analysis was performed to estimate the annual costs of PD, hospital-based HD and nocturnal home HD for ESRD patients from both the health service provider's and societal perspectives. Empirical data on healthcare resource use, patients' out-of-pocket costs, time spent on transportation and dialysis by ESRD patients and time spent by caregivers were analysed. All costs were expressed in Hong Kong year 2017 dollars. RESULTS: Analysis was based on 402 ESRD patients on maintenance dialysis (PD: 189; hospital-based HD: 170; and nocturnal home HD: 43). From the perspective of the healthcare provider, hospital-based HD had the highest total annual direct medical costs in the initial year (mean ± SD) (hospital-based HD = $400 057 ± 62 822; PD = $118 467 ± 15 559; nocturnal home HD = $223 358 ± 18 055; P < 0.001) and second year (hospital-based HD = $360 924 ± 63 014; PD = $80 796 ± 15 820; nocturnal home HD = $87 028 ± 9059; P < 0.001). From the societal perspective, hospital-based HD had the highest total annual costs in the initial year (hospital-based HD = $452 151 ± 73 327; PD = $189 191 ± 61 735; nocturnal home HD = $242 038 ± 28 281; P < 0.001) and second year (hospital-based HD = $413 017 ± 73 501; PD = $151 520 ± 60 353; nocturnal home HD = $105 708 ± 23 853; P < 0.001). CONCLUSIONS: This study quantified the economic burden of ESRD patients, and assessed the annual healthcare and societal costs in the initial and second years of PD, hospital-based HD and nocturnal home HD in Hong Kong. From both perspectives, PD is cost-saving relative to hospital-based HD and nocturnal home HD, except that nocturnal home HD has the lowest cost in the second year of treatment from the societal perspective. Results from this cost analysis facilitate economic evaluation in Hong Kong for health services and management targeted at ESRD patients.

Health-related quality of life and health utility of Chinese patients undergoing nocturnal home haemodialysis in comparison with other modes of dialysis.

BACKGROUND: To compare the health-related quality of life (HRQOL) and health utility of Chinese patients with end-stage renal disease (ESRD) undergoing nocturnal home haemodialysis (Home HD) against those patients undergoing other modes of dialysis. METHODS: Chinese ESRD patients undergoing Home HD were recruited in renal specialist outpatient clinics at three public hospitals in Hong Kong. SF-12 Health Survey (SF-12) was used to measure HRQOL and generate the SF-6D heath utility score. Mean scores of SF-12 domains, physical and mental component summary and SF-6D health utility of 41 patients undergoing Home HD were compared with available scores of patients receiving other forms of dialysis, namely, peritoneal dialysis (PD) (n = 103), hospital in-centre HD (n = 135) or community in-centre HD (n = 118). Adjusted linear regression models were used to examine the impact of mode of dialysis on the HRQOL and health utility scores, accounting for the sociodemographic and clinical characteristics. RESULTS: ESRD patients undergoing PD and community in-centre HD had better health utility, physical and mental component summary scores than the hospital in-centre HD. Adjusted analysis showed that hospital in-centre HD reported worse physical component summary and health utility scores when compared with PD and community in-centre HD. CONCLUSION: HRQOL and health utility scores of patients undergoing Home HD were similar to those undergoing PD and community in-centre HD. Better physical aspects of HRQOL and health utility was observed in PD and community-based HD than hospital in-centre HD, providing evidence for the increase in capacity of non-hospital-based HD, which provided flexibility as well as patient centredness and empowerment in Hong Kong.

Addressing the burden of dialysis around the world: A summary of the roundtable discussion on dialysis economics at the First International Congress of Chinese Nephrologists 2015.

To address the issue of heavy dialysis burden due to the rising prevalence of end-stage renal disease around the world, a roundtable discussion on the sustainability of managing dialysis burden around the world was held in Hong Kong during the First International Congress of Chinese Nephrologists in December 2015. The roundtable discussion was attended by experts from Hong Kong, China, Canada, England, Malaysia, Singapore, Taiwan and United States. Potential solutions to cope with the heavy burden on dialysis include the prevention and retardation of the progression of CKD; wider use of home-based dialysis therapy, particularly PD; promotion of kidney transplantation; and the use of renal palliative care service.

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.

Cancer Incidence and Mortality in Chronic Dialysis Population: A Multicenter Cohort Study.

BACKGROUND: Different studies in the past have shown that the risk of cancer development is increased in chronic dialysis patients. However, data concerning the cancer risk in Asian dialysis patients was scarce. More importantly, there was lack of information about the cancer-specific mortality in dialysis patients. METHODS: A multicenter retrospective cohort study of 6,254 patients who started either chronic peritoneal dialysis or hemodialysis between 1994 and 2014 in 4 renal units in Hong Kong. Patterns of cancer incidence and mortality in our dialysis patients were compared with those of the general population using standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) respectively. RESULTS: With 14,887 person-years of follow-up, 220 cancers were recorded. The SIR of all cancers was 1.44 (95% CI 1.26-1.65). A trend of an increased SIR was observed in young patients and within the first year of dialysis. Colorectum was the most common site of cancer (20%) while kidney cancer carried the highest risk (SIR 12.28, 95% CI 8.44-17.08). The SMR of all cancers was 0.91 (95% CI 0.72-1.13) and only kidney cancer had higher cancer mortality risk (SMR 4.92, 95% CI 1.80-10.70). SMR was highest in young patients and then decreased with age. CONCLUSIONS: The incidence of cancers in our chronic dialysis patients was elevated. Our findings of substantially increased risks in young patients, particularly in relation to kidney cancer, suggest that we can adopt a more individualized approach to cancer screening in chronic dialysis patients.

Prevalence of CMMSE defined cognitive impairment among peritoneal dialysis patients and its impact on peritonitis.

BACKGROUND: Peritoneal dialysis (PD) exchange procedure is complex. Patients with cognitive impairment (CI) may require assistance. We studied the prevalence of CI among PD patients, its impact on PD-related peritonitis and the outcome of assisted PD. METHODS: Cantonese version of Mini-Mental State examination (CMMSE) was performed in 151 patients newly started on PD. Data on patient characteristics including demographics, co-morbidities, blood parameters, medications, and number of PD-related peritonitis in the first 6 months were collected. RESULTS: 151 subjects were recruited. The age of studied patients was 60 ± 15.0 years, and 45% were female. The prevalence of CI was 13.9% using education-adjusted cut-off of CMMSE. Patients older than 65-year-old, female, and lower education level were independent risk factors for CI (OR 9.27 p = 0.001, OR 14.84 p = 0.005, and OR 6.10 p = 0.009, respectively). Age greater than 65-year old is an independent risk factor for PD-related peritonitis but CI was not. Patients requiring assisted PD were of older age (p < 0.001), lower CMMSE (p < 0.001), and scored higher for age-adjusted Charlson Co-morbidity index (p < 0.001). Compared with self-care PD patients, assisted PD patients did not have higher rates exit site infection (p = 0.30) but had a trend of higher PD peritonitis (p = 0.07). CONCLUSION: CI is common among local PD patients. Overall, CI could not be identified as an independent risk factor for PD peritonitis. There is a higher prevalence of CI among assisted PD patients but helpers may not completely eliminate the risk of PD-related peritonitis.

Prevalence of and associations with reduced exercise capacity in peritoneal dialysis patients.

BACKGROUND: Exercise capacity is reduced in patients with end-stage renal disease on maintenance home peritoneal dialysis therapy, although the potential mechanisms and clinical implications remain unclear. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 95 ambulatory prevalent and incident peritoneal dialysis patients in a well-established renal dialysis center (mean age, 58.26 ± 12.6 [SD] years; 63% men; mean duration of peritoneal dialysis therapy, 3.2 ± 4.1 years). PREDICTOR: Estimated volume status using spectral bioelectrical impedance, echocardiography-derived hemodynamic parameters. OUTCOME: Exercise capacity measured as peak oxygen consumption using symptom-limiting treadmill exercise testing. RESULTS: Exercise capacity was reduced in 96% of patients and severely reduced in 65%. Extracellular to intracellular fluid volume ratio showed the strongest correlation with reduced exercise capacity (R = -0.63; P < 0.001) and was superior to age, pulmonary capillary wedge pressure (E:E' ratio), lean tissue mass index, and hemoglobin and albumin levels in predicting exercise intolerance. LIMITATIONS: Relatively small sample size and echocardiogram that was performed only at rest. CONCLUSIONS: There was a strong relationship between body extracellular to intracellular fluid volume ratio and exercise capacity in peritoneal dialysis patients. These findings provide new evidence for a connection between fluid distribution, muscle mass, and exercise capacity. Therapeutic strategies targeting fluid status and muscle mass may improve the exercise capacity of patients on peritoneal dialysis therapy.

Charlson co-morbidity index and albumin significantly associated with fracture risk in peritoneal dialysis patients.

Published literature on fracture in dialysis patients seldom addressed the effect of co-morbidity and malnutrition. In this study, we reported the incidence and risk factors for fracture in peritoneal dialysis patients. Peritoneal dialysis patients who had fractures between 2006 and 2011 were recruited. Demographic data, details of fracture, Charlson Co-morbidity Index (CCI) and biochemical parameters were also collected. Non-fracture controls, matched for age, gender and duration of dialysis, were also recruited at ratio 1:1 for fracture risk analysis. The incidence of fracture was 1 in 37 patient-years. The commonest site of fracture was neck of femur (n = 16, 55.2%). Twenty-four patients (82.8%) developed fracture after slip and fall injury. Eight out of 17 self-ambulatory patients (47.1%) became non-ambulatory after fracture. Infection was the commonest complication during hospitalization. Univariant analysis demonstrated high CCI (P = 0.001), hypoalbuminaemia (P < 0.001), loss of self autonomy (P = 0.006) and non-ambulatory state (P = 0.011) significantly associated with increased fracture risk. However, only CCI (odds ratio (OR) 1.373, P = 0.028) and albumin (OR 0.893, P = 0.025) increased fracture risk significantly on multivariant analysis. Bone profile and parathyroid hormone were not significant risk factors. To conclude, fracture associated with adverse outcome in peritoneal dialysis patients. High CCI score and hypoalbuminaemia significantly increase risk of fracture.

Add-on Rehmannia-6-Based Chinese Medicine in Type 2 Diabetes and CKD: A Multicenter Randomized Controlled Trial.

BACKGROUND: Diabetes is the leading cause of CKD and kidney failure. We assessed the real-world effectiveness of Rehmannia-6-based Chinese medicine treatment, the most used Chinese medicine formulation, on the change in eGFR and albuminuria in patients with diabetes and CKD with severely increased albuminuria. METHODS: In this randomized, assessor-blind, standard care-controlled, parallel, multicenter trial, 148 adult patients from outpatient clinics with type 2 diabetes, an eGFR of 30-90 ml/min per 1.73 m 2 , and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g were randomized 1:1 to a 48-week add-on protocolized Chinese medicine treatment program (using Rehmannia-6-based formulations in the granule form taken orally) or standard care alone. Primary outcomes were the slope of change in eGFR and UACR between baseline and end point (48 weeks after randomization) in the intention-to-treat population. Secondary outcomes included safety and the change in biochemistry, biomarkers, and concomitant drug use. RESULTS: The mean age, eGFR, and UACR were 65 years, 56.7 ml/min per 1.73 m 2 , and 753 mg/g, respectively. Ninety-five percent ( n =141) of end point primary outcome measures were retrievable. For eGFR, the estimated slope of change was -2.0 (95% confidence interval [CI], -0.1 to -3.9) and -4.7 (95% CI, -2.9 to -6.5) ml/min per 1.73 m 2 in participants treated with add-on Chinese medicine or standard care alone, resulting in a 2.7 ml/min per 1.73 m 2 per year (95% CI, 0.1 to 5.3; P = 0.04) less decline with Chinese medicine. For UACR, the estimated proportion in the slope of change was 0.88 (95% CI, 0.75 to 1.02) and 0.99 (95% CI, 0.85 to 1.14) in participants treated with add-on Chinese medicine or standard care alone, respectively. The intergroup proportional difference (0.89, 11% slower increment in add-on Chinese medicine, 95% CI, 0.72 to 1.10; P = 0.28) did not reach statistical significance. Eighty-five adverse events were recorded from 50 participants (add-on Chinese medicine versus control: 22 [31%] versus 28 [36%]). CONCLUSIONS: Rehmannia-6-based Chinese medicine treatment stabilized eGFR on top of standard care alone after 48 weeks in patients with type 2 diabetes, stage 2-3 CKD, and severely increased albuminuria. CLINICAL TRIAL REGISTRY: Semi-individualized Chinese Medicine Treatment as an Adjuvant Management for Diabetic Nephropathy (SCHEMATIC), NCT02488252 .

A combination of biocompatible peritoneal dialysis solutions and residual renal function, peritoneal transport, and inflammation markers: a randomized clinical trial.

BACKGROUND: The benefits of biocompatible peritoneal dialysis (PD) fluids, particularly for residual renal function (RRF), are controversial. Moreover, the clinical effects of a PD regimen consisting of different biocompatible PD fluids have not been fully established. STUDY DESIGN: Prospective, randomized, controlled, open-label study. SETTING & PARTICIPANTS: Patients with end-stage kidney disease newly started on continuous ambulatory PD therapy (N = 150). INTERVENTION: A 12-month intervention with 3 biocompatible PD fluids (a neutral-pH, low glucose degradation product, 1.5% glucose solution; a solution with 1.1% amino acid; and a fluid with 7.5% icodextrin) or conventional PD fluid. OUTCOMES: The primary outcome was change in RRF and daily urine volume. Secondary outcomes were peritoneal transport and inflammation markers. MEASUREMENTS: RRF, daily urine volume, serum and dialysate cytokine levels. RESULTS: RRF(3.24 ± 1.98 vs 2.88 ± 2.43 mL/min/1.73 m(2); P = 0.9) and rate of decline in RRF (-0.76 ± 1.77 vs -0.91 ± 1.92 mL/min/1.73 m(2) per year; P = 0.6) did not differ between the biocompatible- and conventional-PD-fluid groups. However, patients using the biocompatible PD fluids had better preservation of daily urine volume (959 ± 515 vs 798 ± 615 mL/d in the conventional group, P = 0.02 by comparison of difference in overall change by repeated-measures analysis of variance). Their dialysate-plasma creatinine ratio at 4 hours was higher at 12 months (0.78 ± 0.13 vs 0.68 ± 0.12; P = 0.01 for comparison of the difference in overall change by repeated-measures analysis of variance). They also had significantly higher serum levels of adiponectin and overnight spent dialysate levels of cancer antigen 125, adiponectin, and interleukin 6 (IL-6). No differences between the 2 groups were observed for serum C-reactive protein and IL-6 levels. LIMITATIONS: Unblinded, relatively short follow-up; no formal sample-size calculations. CONCLUSIONS: Use of a combination of 3 biocompatible PD fluids for 12 months compared with conventional PD fluid did not affect RRF, but was associated with better preservation of daily urine volume. The biocompatible PD fluids also lead to changes in small-solute transport and an increase in dialysate cancer antigen 125, IL-6, adiponectin, and systemic adiponectin levels, but have no effect on systemic inflammatory response. The clinical significance of these changes, while of great interest, remains to be determined by further studies.

Remdesivir use and risks of acute kidney injury and acute liver injury among patients hospitalised with COVID-19: a self-controlled case series study.

BACKGROUND AND AIM: To investigate and quantify the risks of AKI and ALI associated with remdesivir use, given the underlying diseases of SARS-CoV-2 infection. METHODS: This self-controlled case series (SCCS) study was conducted using electronic hospital records between 23 January 2020 and 31 January 2021 as retrieved from the Hong Kong Hospital Authority which manages all laboratory-confirmed COVID-19 cases in Hong Kong. Outcomes of AKI and ALI were defined using the KDIGO Guideline and Asia Pacific Association of Study of Liver consensus guidelines. Incidence rate ratios (IRR) for AKI and ALI following the administration of remdesivir (exposure) in comparison to a non-exposure period were estimated using the conditional Poisson regression models. RESULTS: Of 860 COVID-19 patients administered remdesivir during hospitalisation, 334 (38.8%) and 137 (15.9%) had incident ALI and AKI, respectively. Compared with the baseline period, both ALI and AKI risks were increased significantly during the pre-exposure period (ALI: IRR = 6.169, 95% CI = 4.549-8.365; AKI: IRR = 7.074, 95% CI = 3.763-13.298) and remained elevated during remdesivir treatment. Compared to the pre-exposure period, risks of ALI and AKI were not significantly higher in the first 2 days of remdesivir initiation (ALI: IRR = 1.261, 95% CI = 0.915-1.737; AKI: IRR = 1.261, 95% CI = 0.889-1.789) and between days 2 and 5 of remdesivir treatment (ALI: IRR = 1.087, 95% CI = 0.793-1.489; AKI: IRR = 1.152, 95% CI = 0.821-1.616). CONCLUSION: The increased risks of AKI and ALI associated with intravenous remdesivir treatment for COVID-19 may be due to the underlying SARS-CoV-2 infection. The risks of AKI and ALI were elevated in the pre-exposure period, yet no such increased risks were observed following remdesivir initiation when compared to the pre-exposure period.

Anti-fibrotic effect of decorin in peritoneal dialysis and PD-associated peritonitis.

BACKGROUND: Progressive peritoneal fibrosis is a common complication in patients on long-term peritoneal dialysis (PD). PD-associated peritonitis is a major exacerbating factor. We investigated the anti-fibrotic properties of decorin secreted by peritoneal mesothelial cells. METHODS: Dialysate decorin level in stable PD patients and those with peritonitis was measured. In vitro experiments were conducted to investigate the effect of decorin in fibrotic response in human peritoneal mesothelial cells (HPMC). FINDINGS: Increasing PD duration was associated with a progressive decrease of dialysate decorin and CA125 levels. Dialysate decorin level correlated with CA125 level. Peritonitis episodes were associated with a massive drop of dialysate decorin, which persisted for over three months despite clinical recovery. Dialysate decorin level correlated with that of TGF-ß1, but was inversely related to IL-1ß and IL-8. TGF-ß1, IL-1ß, IL-6, IL-8, or TNF-α reduced decorin secretion in HPMC, but induced fibronectin expression. The effects were mediated in part through increased p38 MAPK and AKT/PI3K phosphorylation. Decorin abrogated the induction of fibronectin expression in mesothelial cells by PD fluids or pro-fibrotic cytokines, through decreased TGF-ßRI, p38 MAPK and AKT/PI3K phosphorylation and increased glycogen synthase kinase-3ß phosphorylation. Decorin gene-silencing resulted in increased fibronectin expression under these conditions. INTERPRETATION: Our data demonstrate anti-fibrotic actions of decorin in HPMC, when these cells are subjected to the pro-fibrotic effect of peritoneal dialysate and pro-fibrotic cytokines in PD, especially during peritonitis.

2018 Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C in Chronic Kidney Disease Guideline Implementation: Asia Summit Conference Report.

In 2018, Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). The guideline synthesized recent advances, especially in HCV therapeutics and diagnostics, and provided clinical recommendations and suggestions to aid healthcare providers and improve care for CKD patients with HCV. To gain insight into the extent that the 2018 guideline has been adopted in Asia, KDIGO convened an HCV Implementation Summit in Hong Kong. Participants included nephrologists, hepatologists, and nurse consultants from 8 Southeast Asian countries or regions with comparable high-to-middle economic ranking by the World Bank: mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. Through presentations and discussions, meeting participants described regional practice patterns related to the KDIGO HCV in CKD guideline, identified barriers to implementing the guideline, and developed strategies for overcoming the barriers in Asia and around the world.

Rapamycin attenuates the severity of murine adriamycin nephropathy.

BACKGROUND: Rapamycin is an immunosuppressive drug with potent antifibrotic activity. We evaluated the effect of rapamycin on murine adriamycin nephropathy, a model of progressive glomerulosclerosis and tubulointerstitial fibrosis. METHODS: Adriamycin nephropathy was induced in Balb/c mice by a single intravenous injection of adriamycin. The mice were treated orally with either saline or rapamycin, beginning at the time of adriamycin injection or rapamycin starting 1 week after adriamycin injection. The mice were sacrificed 6 weeks after adriamycin injection. RESULTS: Saline-treated mice developed massive proteinuria and impaired renal function. Kidney sections from saline-treated mice showed marked focal segmental glomerulosclerosis, tubular dilation with protein cast deposition, interstitial fibrosis, and numerous infiltrating macrophages and T lymphocytes. The intrarenal expression of Collagen I and RANTES was also increased. In contrast, both groups of rapamycin-treated mice had markedly reduced proteinuria and preserved renal function, with only mild histological abnormalities. The intrarenal expression of Collagen I and RANTES was reduced, concomitant with a significant reduction in interstitial inflammatory cell infiltration. CONCLUSIONS: Rapamycin is effective in attenuating the glomerular and tubulointerstitial abnormalities in adriamycin nephropathy. The beneficial effects of rapamycin are mediated, at least in part, through reduced RANTES expression and inflammatory cell infiltration.