The screening, diagnosis, and management of patients with autosomal dominant polycystic kidney disease: A national consensus statement from Taiwan.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage kidney disease (ESKD) worldwide. Guidelines for the diagnosis and management of ADPKD in Taiwan remains unavailable. In this consensus statement, we summarize updated information on clinical features of international and domestic patients with ADPKD, followed by suggestions for optimal diagnosis and care in Taiwan. Specifically, counselling for at-risk minors and reproductive issues can be important, including ethical dilemmas surrounding prenatal diagnosis and pre-implantation genetic diagnosis. Studies reveal that ADPKD typically remains asymptomatic until the fourth decade of life, with symptoms resulting from cystic expansion with visceral compression, or rupture. The diagnosis can be made based on a detailed family history, followed by imaging studies (ultrasound, computed tomography, or magnetic resonance imaging). Genetic testing is reserved for atypical cases mostly. Common tools for prognosis prediction include total kidney volume, Mayo classification and PROPKD/genetic score. Screening and management of complications such as hypertension, proteinuria, urological infections, intracranial aneurysms, are also crucial for improving outcome. We suggest that the optimal management strategies of patients with ADPKD include general medical care, dietary recommendations and ADPKD-specific treatments. Key points include rigorous blood pressure control, dietary sodium restriction and Tolvaptan use, whereas the evidence for somatostatin analogues and mammalian target of rapamycin (mTOR) inhibitors remains limited. In summary, we outline an individualized care plan emphasizing careful monitoring of disease progression and highlight the need for shared decision-making among these patients.

Prevention and management of cytomegalovirus infection and disease in kidney transplant: A consensus statement of the Transplantation Society of Taiwan.

Kidney transplant recipients have an increased risk of cytomegalovirus (CMV) infection and disease. A strategy for mitigating the risk of CMV infection in kidney transplant recipients has not yet been established in Taiwan. The Transplantation Society of Taiwan aimed to develop a consensus by expert opinion on the prevention and management of CMV infection. Based on the results of Consensus Conference, we suggested low-dose valganciclovir prophylaxis (450 mg once daily) for kidney transplant recipients. The prophylaxis duration was ≥6 months for high-risk (D+/R-) patients and 3 months for moderate-risk (R+) patients. Even for low-risk (D-/R-) patients, prophylaxis for at least 3 months is recommended because of the high seroprevalence of CMV in Taiwan. CMV prophylaxis was suggested after anti-thymocyte globulin treatment but not after methylprednisolone pulse therapy. Routine surveillance after prophylaxis, secondary prophylaxis after CMV disease treatment, and mTOR inhibitors for primary CMV prophylaxis were not recommended. Letermovir and marabavir are emerging CMV agents used for prophylaxis and refractory CMV disease. CMV immunoglobulins have been used to treat refractory CMV disease in Taiwan. We hope this consensus will help professionals manage patients with CMV in Taiwan to improve the quality of care.

Risk Stratification for Hepatitis B Virus Reactivation in Kidney Transplant Recipients With Resolved HBV Infection.

The prophylaxis strategy for hepatitis B virus (HBV) reactivation in kidney transplant recipients (KTRs) with resolved HBV infection remains unclear. In this hospital-based retrospective cohort study, consecutive KTRs with resolved HBV infection were screened from the years 2000 through 2020. After excluding confounding conditions, 212 and 45 patients were respectively recruited into Anti-HBs positive and Anti-HBs negative groups. Cumulative incidences of, and subdistribution hazard ratios (SHRs) for HBV reactivation were analyzed after adjusting the competing risk. During a median 8.3 (mean 8.4 ± 4.9) years of follow-up, the 10-year cumulative incidence of HBV reactivation was significantly higher in Anti-HBs negative group when compared to that in Anti-HBs positive group (15.2%, 95% CI: 3.6-26.7 vs. 1.3%, 95% CI: 0.0-3.0; p < 0.001). In multivariable regression analysis, absence of anti-HBs (SHR 14.2, 95% CI: 3.09-65.2; p < 0.001) and use of high-dose steroids, i.e., steroid dose ≥20 mg/day of prednisolone equivalent over 4 weeks (SHR 8.96, 95% CI: 1.05-76.2; p = 0.045) were independent risk factors related to HBV reactivation. Accordingly, the 10-year cumulative incidence of HBV reactivation occurring in patients with two, one and zero risk factors was 42.7% (95% CI: 0.0-87.1), 7.9% (95% CI: 1.2-14.7) and 0%, respectively (p < 0.001). In conclusion, the strategy of HBV antiviral prophylaxis may be defined according to the risk stratification.

Grazoprevir/Elbasvir Treatment in Liver or Kidney Transplant Recipients with Genotype 1b Hepatitis C Virus Infection.

More options regarding the choice of direct-acting antivirals (DAAs) are helpful for avoiding individual limitations in treating hepatitis C virus (HCV) infection. We aimed to assess the efficacy and tolerability of grazoprevir (GZR)/elbasvir (EBR) treatment in genotype-1b (GT-1b) HCV-infected liver or kidney transplant recipients. In this phase 4, single-arm, open-label, multicenter trial, patients received GZR 100 mg/EBR 50 mg daily for 12 weeks. Patients with any HCV infection other than GT-1b, liver decompensation, human immunodeficiency virus, or hepatitis B virus co-infection, a history of NS5A inhibitor exposure, or any severe drug-drug interactions (DDIs), was excluded. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12). Of the 14 patients (10 kidney and 4 liver transplant subjects) enrolled in this study, 9 (64%) were females; the median age was 64.0 (range: 43-73) years. The regularly used immunosuppressants were tacrolimus (93%), everolimus (29%), and sirolimus (7%), with patient blood levels easily managed and generally stable (all P > 0.05 in quantile regression analysis). The rate of SVR12 was 100% in intent-to-treat analysis. Only one patient discontinued GZR/EBR therapy at 6 weeks posttreatment, due to a treatment-unrelated adverse event (AE); however, this patient remained, achieving SVR12. Most AEs were mild in severity and deemed to be not treatment-related. No organ rejection episodes or deaths occurred during the study period. The single-tablet regimen of GZR/EBR for 12 weeks is highly effective and well tolerated in GT-1b HCV-infected liver or kidney transplant recipients, and its DDIs are generally easy to manage. (This study has been registered at ClinicalTrials.gov under identifier NCT03723824.).

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.

Hyperuricemia and diabetes mellitus when occurred together have higher risks than alone on all-cause mortality and end-stage renal disease in patients with chronic kidney disease.

INTRODUCTION: Hyperuricemia and diabetes mellitus (DM) are associated with increased mortality risk in patients with chronic kidney disease (CKD). Here we aimed to evaluate the independent and joint risks of these two conditions on mortality and end stage kidney disease (ESKD) in CKD-patients. METHODS: This retrospective cohort study enrolled 4380 outpatients (with CKD stage 3-5) with mortality and ESKD linkage during a 7-year period (from 2007 to 2013). All-causes mortality and ESKD risks were analyzed by multivariable-adjusted Cox proportional hazards models (adjusted for age, sex, smoke, previous coronary arterial disease, blood pressure, and medications for hyperlipidemia, hyperuricemia and renin-angiotensin system inhibitors). RESULTS: Overall, 40.5% of participants had DM and 66.4% had hyperuricemia. In total, 356 deaths and 932 ESKD events occurred during the 7 years follow-up. With the multivariate analysis, increased risks for all-cause mortality were: hyperuricemia alone, HR = 1.48 (1-2.19); DM alone, and HR = 1.52 (1.02-2.46); DM and hyperuricemia together, HR = 2.12 (1.41-3.19). Similar risks for ESKD were: hyperuricemia alone, HR = 1.34 (1.03-1.73); DM alone, HR = 1.59 (1.15-2.2); DM and hyperuricemia together, HR = 2.46 (1.87-3.22). CONCLUSIONS: DM and hyperuricemia are strongly associated with higher all-cause mortality and ESKD risk in patients with CKD stage 3-5. Hyperuricemia is similar to DM in terms of risk for all-cause mortality and ESKD. DM and hyperuricemia when occurred together further increase both risks of all-cause mortality and ESKD.

Trends of kidney transplantation from the 2020 annual report on kidney disease in Taiwan.

BACKGROUND: Renal transplantation (RTX) is the treatment of choice for end-stage kidney disease (ESKD). Taiwan has the highest incidence and prevalence of ESKD in this world. This is the first study to illustrate the national registry database of RTX. METHODS: All patients who received RTX in Taiwan between 2010 and 2018 were enrolled in this study. Demographic data and comorbidities were obtained from the National Health Insurance Research Database and Transplantation Society of Taiwan. Graft and patient survival rates were also analyzed. RESULTS: Men were more likely to receive RTX. During the observation periods, > 30% of the recipients were relatively young (20-44 years). The percentage of preemptive RTX (p = 0.014) and living RTX (p = 0.022) increased annually with statistical significance (linear regression model). Recently, recipients had more cardiovascular disease (p = 0.014), diabetes mellitus (p = 0.097), and hypertension (p = 0.021). The mean duration of graft survival increased yearly (p = 0.001). The proportion of patients surviving till age of ≧65 years increased significantly with time (2.2% in 2010, 33.1% in 2018) (p < 0.0001). Younger recipients (<44 years) had significantly better survival than the elderly (≧65 years). Patients with diabetes were more likely to have worse graft and patient survival rates. Recipients enrolled in pre-ESRD care program had better graft and patient survival rates than those not enrolled in these care program. CONCLUSION: The proportion of preemptive and livingdonor RTX increased but was still low. Despite increased number of commodities in recipients, graft and patient survival have increased recently. Enrolling patients with CKD in pre-ESRD care program was associated with better graft and patient survival.

Gender Differences in microRNA Expressions as Related to Long-Term Graft Function in Kidney Transplant Patients.

In recent studies, much has been discussed about biomarkers used in the evaluation of the transplanted graft function. However, there remains a lack of research regarding the long-term effects of microRNAs (miRNAs) on the different genders for kidney transplant (KTx) patients. In this study, we aim to assess the functions of miRNAs on long term outcomes of KTx patients by extracting differently expressed miRNAs between patients of normal graft function and graft dysfunction, while further analyzing their impact on the different genders. We analyzed the data of 40 patients who had received KTx for a period of more than ten years and included data regarding renal function, immuno-related markers and plasma miRNAs. Data were classified by gender for further studies. Twelve out of 17 females and 8 out of 23 males had undergone graft dysfunction. Renal function analysis showed significantly worse outcomes in the female patients. There were five differently expressed miRNAs between the female control group and female dysfunction group: miR-128-3p, miR-21-5p, miR-150-5p, miR-92a-3p and miR-15a-5p, and five between the male control group and male dysfunction group: miR-23a-3p, miR-126-3p, miR-142-3p, miR-223-3p and miR-26a-5p. Gender differences exist in incidences of kidney graft dysfunction, with male patients displaying better preservation in graft functions. Overall, these differently expressed miRNAs either enhance or suppress host immune responses. They can be predictive markers for graft survival and can also be important factors that lead to worse long term kidney graft function in females when compared to males.

Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model.

CONTEXT: Protocatechuic aldehyde (PCA) is a natural product that has various benefits for fibrosis. OBJECTIVE: This study evaluated the effects of PCA on renal fibrosis. MATERIALS AND METHODS: Epithelial-mesenchymal transition (EMT) was induced by 20 ng/mL transforming growth factor-ß1 (TGF-ß1), followed by treatment with 1 and 5 µM PCA, in the rat renal proximal tubular cell line NRK-52E. Cell viability, protein expression, and scratch wound-healing assays were conducted. Sprague-Dawley (SD) rats underwent unilateral ureteral obstruction (UUO) surgery for renal fibrosis indication and were treated with 50 and 100 mg/kg PCA for 14 days. RESULTS: The IC50 of PCA was appropriately 13.75 ± 1.91 µM in NRK-52E cells, and no significant difference at concentrations less than 5 µM. PCA ameliorated TGF-ß1-induced EMT, such as enhanced E-cadherin and decreased vimentin. Fibrotic markers collagen IV and α-smooth muscle actin (α-SMA) increased in TGF-ß1-induced NRK-52E. Moreover, PCA reduced TGF-ß1-induced migration in the wound-healing assay. Analysis of rat kidneys indicated that PCA reduced UUO-induced hydronephrosis (control: 15.11 ± 1.00%; UUO: 39.89 ± 1.91%; UUO + PCA50: 18.37 ± 1.61%; UUO + PCA100: 17.67 ± 1.39%). Protein level demonstrated that PCA not only decreased vimentin expression and enhanced E-cadherin expression, but inhibited UUO-induced collagen IV and α-SMA upregulation, indicating that it could mitigate EMT in a rat model of UUO-induced renal fibrosis. DISCUSSION AND CONCLUSIONS: This study suggested that PCA decreases TGF-ß1-induced fibrosis and EMT in vitro and in vivo. These findings demonstrate pharmacological effects of PCA and might be a potential strategy for the prevention of organ fibrosis in clinics.

Pneumococcal pneumonia in adult hospitalised solid organ transplant recipients: Nationwide, population-based surveillance.

BACKGROUND: Pneumococcal disease poses a burden to the community in high risk population. Most early studies focused on invasive pneumococcal disease. However, the epidemiology of pneumococcal pneumonia (PP) requiring hospitalisation in solid organ transplant recipients (SOTRs) is poorly defined. METHODS: We conducted a retrospective cohort study (January 1, 2000 and December 31, 2012) to evaluate the risk of PP requiring hospitalisation in SOTRs. SOTRs and non-SOT cohorts, propensity score-matched at a 1:1 ratio for age, sex, index date and underlying comorbidities, were identified from the National Health Insurance Research Database. RESULTS: Each cohort consisted of 7507 patients. In the SOT cohort, 26 episodes of PP requiring hospitalisation were identified (incidence rate of 52.4 per 100,000 person-years). The risk of PP requiring hospitalisation in the SOT cohort was 1.50 times greater than in the non-SOT cohort [adjusted hazard ratio: 1.50, 95% confidence interval = 1.31-1.71, P < .001]. The nested case control study identified older age, kidney transplant, and concomitant chronic obstructive pulmonary disease, chronic kidney disease and heart failure as predictors of PP requiring hospitalisation in the SOT cohort. The highest risk period for PP requiring hospitalisation occurred within the first year of transplantation (36.47 per 1000 patients). Amongst kidney transplant recipients, patients with PP requiring hospitalisation exhibited higher cumulative incidences of graft failure than those without PP (log-rank test: P value = .004). CONCLUSIONS: SOTRs are at risk of PP requiring hospitalisation with its attendant morbidity. Strategies to reduce risk of PP requiring hospitalisation using preventive vaccinations warrant further study.

Risk of severe herpes zoster infection in patients with polycystic kidney disease: A nation-wide cohort study with propensity score matching analysis.

BACKGROUND: Polycystic kidney disease (PKD) is suggested to be likely associated with underlying immunological dysregulation. This lymphopenia poses a risk of viral infection. Data to elucidate the herpes virus infection risk in patients with PKD are lacking; therefore, we conducted a national-wide population-based cohort study to investigate the herpes virus risk in PKD patients. METHODS: From the Taiwan National Health Insurance Research Database (NHIRD), patients who were hospitalised with a diagnosis of polycystic kidney disease were defined as case group of PKD patients; patients without any diagnosis of PKD during the study period were grouped into the non-PKD cohort. The index date was set as the date when the patients were newly diagnosed with PKD. All study patients were followed up until the occurrence of herpes zoster infection, death, withdrawal from the NHIRD for other reasons, or until December 31, 2013. RESULTS: We included 4366 PKD patients and 4366 non-PKD patients. The incidence rate and the risk of developing herpes zoster infection were estimated using multivariate stratified analyses. PKD patients had a 1.97-fold risk of herpes zoster virus infection (aHR = 1.97, 95% CI 1.17-3.31) compared with the non-PKD cohort. On multilayer stratification, PKD patients without any comorbidities had a significantly increased risk of herpes zoster infection (aHR = 3.10, 95% CI 1.37-7.00). CONCLUSION: This is the first study to reveal a high risk of severe herpes zoster infection in patients with PKD. High index suspicion of severe herpes zoster infection should be maintained in clinical professionals.

Risk factors and prognosis assessment for acute kidney injury: The 2020 consensus of the Taiwan AKI Task Force.

Risk and prognostic factors for acute kidney injury (AKI) have been published in various studies across various populations. We aimed to explore recent advancements in and provide updated recommendations on AKI risk stratification and information about local AKI risk factors. The Taiwan Acute Kidney Injury Task Force reviewed relevant recently published literature and reached a consensus after group meetings. Systemic review and group discussion were performed. We conducted a meta-analysis according to the PRISMA statement for evaluating the diagnostic performance of the furosemide stress test. Several risk and susceptibility factors were identified through literature review. Contrast-associated AKI prediction models after coronary angiography were one of the most discussed prediction models we found. The basic approach and evaluation of patients with AKI was also discussed. Our meta-analysis found that the furosemide stress test can be used as a prognostic tool for AKI progression and to identify patients with AKI who are at low risk of renal replacement therapy. Factors associated with de novo chronic kidney injury or renal non-recovery after AKI were identified and summarized. Our review provided practical information about early identification of patients at high risk of AKI or disease progression for Taiwan local clinics.

Ongoing donor-transmitted diabetic kidney disease in kidney transplant recipients with fair sugar control: a single center retrospective study.

BACKGROUND: Transplantation with a diabetic donor kidney may have some benefits compared to remaining on the waitlist for selected patients. However, we found that some kidney transplant recipients have ongoing donor-transmitted diabetic kidney disease (DT-DKD) despite fair blood sugar control. This study aimed to survey the incidence and clinical pattern of DT-DKD in kidney transplant recipients. METHODS: We retrospectively reviewed the medical records of kidney transplantations in our hospital. We found 357 kidney transplantations from February 2006 to April 2018. Among these, 23 (6.4%) diabetic donor kidney transplantations were done in the study period. RESULTS: Among the 23 recipients, 6 (26.1%) displayed biopsy-proven DKD. Recipients with biopsy-proven DKD had longer dialysis vintage, higher proteinuria amount, lower last estimated glomerular filtration rate (eGFR), and a more rapid decline in the eGFR. The median fasting blood sugar level in the biopsy-proven DKD group was unexpectedly lower than the non-DKD group. Most of the pre-implantation frozen sections in biopsy-proven DKD group showed diabetic lesions worse than diabetic nephropathy (DN) class IIa. In the biopsy-proven DKD group, 5 recipients had no history of diabetes before or after transplantation. Among the 23 recipients, 5 (21.7%) were diagnosed with DT-DKD. Serial post-transplant biopsies showed the histological progression of allograft DN. CONCLUSIONS: To the best of our knowledge, this is the first study to report the phenomenon of ongoing DT-DKD in kidney transplant recipients with fair blood sugar control. The zero-time pre-transplant kidney biopsy may be an important examination before the allocation of diabetic donor kidneys. Further study is needed to elucidate the possible mechanism of ongoing DT-DKD in non-diabetic recipients with fair blood sugar control as well as the impaction of pre-implantation diabetic lesion on the graft outcome.

Treatment of chronic active antibody-mediated rejection in renal transplant recipients - a single center retrospective study.

BACKGROUND: Chronic active antibody-mediated rejection is a major etiology of graft loss in renal transplant recipients. However, there is no consensus on the optimal treatment strategies. METHODS: Computerized records from Taichung Veterans General Hospital were collected to identify renal transplant biopsies performed in the past 7 years with a diagnosis of chronic active antibody-mediated rejection. The patients were divided into two groups according to treatment strategy: Group 1 received aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2 received supportive treatment. RESULTS: From February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 (P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was not significantly different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis. CONCLUSIONS: Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for patients undergoing aggressive treatment.

Is combined peritoneal dialysis and hemodialysis redundant? A nationwide study from Taiwan.

BACKGROUND: Combined peritoneal dialysis (PD) and hemodialysis (HD) therapy (combined therapy) has numerous clinical benefits and should be emphasized for PD patients encountering technique failure. METHODS: This 12-year nationwide retrospective study was conducted to compare long-term outcomes (including admission and mortality risks) between combined therapy patients (combined group) and patients directly transferred from PD to HD (transfer group). RESULTS: All 12,407 incidental PD patients from 2000 to 2010 were enrolled and followed up until the end of 2011. A total of 688 patients in the combined group and 688 patients in the transfer group were selected after 1:1 frequency matching based on age, sex, and PD duration. The overall admission and mortality risks of the two groups were comparable in a Cox proportional hazards model (adjusted hazard ratio [HR] = 1.06 [95% confidence interval (CI) = 0.95-1.19] and 1.02 [95% CI = 0.80-1.30]), respectively). Compared with the transfer group, combined group patients with recent peritonitis or frequent hemodialysis (four HD sessions per month) had significantly higher risk of admission while combined group patients without peritonitis had significantly lower risk. The number of incidents in the combined group increased over time. On average, patients stayed on combined therapy for 2 years. CONCLUSIONS: Combined therapy (two HD sessions per month) is not redundant but a rational and cost-effective treatment, particularly for patients without recent peritonitis. Dialysis staff should be familiar with the advantages and disadvantages of combined therapy and consider it an essential part of integrated dialysis care.

Epidemiology of haemodialysis patients and haemodialysis performance in Nauru.

AIM: There is limited literature on haemodialysis in island countries in the Central Pacific. The primary aim of this study was to report on the epidemiology of haemodialysis patients and haemodialysis performance in Nauru. METHODS: We obtained registry data from the haemodialysis unit in Nauru to calculate the incidence rate, prevalence, and survival probability of haemodialysis patients in Nauru. We also reviewed medical records from January 2015 to February 2017 to evaluate the haemodialysis performance in Nauru. RESULTS: In total, 177 patients received long-term haemodialysis in the Nauru dialysis unit from 1987 to 2017. The 1-year, 2-year, and 5-year survival probabilities during the 30-year study period were 76.5%, 58.3% and 25.9%, respectively. From 2011 to 2014, the incidence rate and prevalence of treated end-stage renal disease in Nauru were significantly higher than Australia. From 2015 to 2017, there were 36 patients with a median age of 55 years who received long-term haemodialysis. Of these, 25 patients (69.4%) had diabetes. The median haemoglobin, serum albumin, and urea reduction ratio were 9.6 mg/dL, 35 g/L, and 64.7%, respectively. Multivariate analysis showed that lower serum albumin and lower urea reduction ratio were associated with mortality. CONCLUSION: To our knowledge, this is the first study to report the haemodialysis status in Nauru. The epidemiology of haemodialysis patients in Nauru is unique in the Central Pacific. Improvement of primary health care in disease detection and prevention of progression should be considered to decrease the need for dialysis and optimise the care of haemodialysis patients in Nauru.

Nephrotic Syndrome is Associated with Increased Risk of Ischemic Stroke.

BACKGROUND: To determine if the nephrotic syndrome (NS) is an independent risk factor of ischemic stroke. METHODS: This is a retrospective nationwide cohort study through an analysis of the National Health Insurance Research Database in Taiwan. To evaluate the risk of stroke, the corresponding controls were selected at a 4:1 ratio in the number of subjects, and they were matched with the study group in age, gender, Charlson comorbidity index (CCI), and index date. RESULTS: From a total of 16,245 surveyed subjects, ischemic stroke occurred in 1235 (7.6%) and hemorrhagic stroke in 129 (.74%) of them. The incidence of ischemic stroke was significantly higher in patients with NS (n = 3496) compared to control patients without NS (n = 13,984) (9.92 versus 7.10, per 1000 person-year, P < .001). In the multivariate analysis, the overall adjusted hazard ratio (aHR) of stroke in NS patients was 1.37 (95% CI, 1.21-1.54, P < .001). The risk factors of ischemic stroke were NS (aHR, 1.38 [95% confidence interval {CI}, 1.21-1.57]; P < .001), age greater than 45 years (aHR, 7.98 [95% CI, 6.47-9.48]; P < .001), male gender (aHR, 1.23 [95% CI, 1.10-1.38]; P < .001), CCI greater than or equal to 1 (aHR ≥ 1.25 in different CCI score groups, all at P ≤ .003), ischemic heart disease (aHR, 1.95 [95% CI, 1.67-2.29]; P < .001), heart failure (HR, 1.77 [95% CI, 1.30-2.42]; P < .001). Risk factors of hemorrhagic stroke were those aged greater than 45 years, or with systemic lupus erythematosus, but not NS. CONCLUSIONS: We provided the first evidence that patients with NS had an increased risk of ischemic stroke.

The attenuation of renal fibrosis by histone deacetylase inhibitors is associated with the plasticity of FOXP3+IL-17+ T cells.

BACKGROUND: The histone deacetylase (HDAC) inhibitor, which has potential effects on epigenetic modifications, had been reported to attenuate renal fibrosis. CD4+ forkhead box P3 (FOXP3)+ T regulatory (Treg) cells may be converted to inflammation-associated T helper 17 cells (Th17) with tissue fibrosis properties. The association between FOXP3+IL-17+ T cells and the attenuation of renal fibrosis by the HDAC inhibitor is not clear. METHODS: This study evaluated the roles of the HDAC inhibitor, Treg cells and their differentiation into Th17 cells, which aggravate chronic inflammation and renal fibrosis in a unilateral ureteral obstruction (UUO) mouse model. The study groups included control and UUO mice that were monitored for 7, 14 or 21 days. RESULTS: Juxtaglomerular (JG) hyperplasia, angiotensin II type 1 receptor (AT1R) expression and lymphocyte infiltration were observed in renal tissues after UUO but were decreased after trichostatin A (TSA) treatment, a HDAC inhibitor. The number of CD4+FOXP3+ T cells increased progressively, along with the number of FOXP3+interleukin (IL)-17+ T cells, after 14 days, and their numbers then progressively decreased with increasing CD4+IL-17+ T cell numbers, as demonstrated by double immunohistochemistry. Progressive renal fibrosis was associated with the loss of CD4+FOXP3+IL-17+ T cells in splenic single-cell suspensions. FOXP3+IL-17+ T cells expressed TGF-ß1 both in vitro and in vivo, and TGF-ß1 expression was significantly knockdown by IL-17 siRNA in vitro. These cells were found to play a role in converting Tregs into IL-17- and TGF-ß1-producing cells. CONCLUSIONS: TSA treatment decreased JG hyperplasia, the percentage of FOXP3+IL-17+ cells and the degree of fibrosis, suggesting that therapeutic benefits may result from epigenetic modifications.

Long-Term Follow-Up of a Homozygous Familial Hypercholesterolemic Patient Receiving Regular Double Filtration Plasmapheresis - Case Report and Literature Review.

Homozygous familial hypercholesterolemia (HoFH) is a very rare condition (1 case per 1 million people) with a dismal outcome due to inevitable coronary artery disease that occurs when left untreated. Lipoprotein apheresis (LA), previously known as low-density lipoprotein (LDL) apheresis, is very effective in reducing LDL-cholesterol (LDL-C) if HoFH is refractory to aggressive drug therapy and diet control. In this study, we report a case with HoFH, who presented with xanthomata over the 4 limbs when she was 3 years old. When she was 11 years old, she began treatment with semi-selective LA with double filtration plasmapheresis (DFPP) once per week because HoFH was refractory to high-dose statin and diet control. LDL-C was reduced from 8.2 ± 0.9 to 2.69 ± 0.75 mmol/l (reduction rate = 67.3 ± 6.1%). The xanthomata over the 4 limbs were nearly completely resolved after 2 years of DFPP. Two years later, after the initiation of DFPP, we performed coronary angiography and echocardiography for regular checkup in the absence of chest pain, and the result was negative. To date (11 years after initiation of DFPP), she has not complained of any chest pain, shown intolerance to exercise, or exhibited ST-T change on electrocardiography. At the age of 20, multidetector computed tomography showed no significant stenosis over the coronary arteries. At the most recent follow-up visit, she was found to have good heart function and no xanthomata. LA is effective in the treatment of HoFH when drug therapy and diet control fail. With this treatment, pre-existing xanthomata can regress and coronary artery disease can be prevented.