Search

Background and hypothesis Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a major genetic contributor to end-stage kidney disease (ESKD). Current evidence on tolvaptan primarily focuses on slowing estimated glomerular filtration rate (eGFR) decline and kidney volume growth. However, direct confirmation of its effectiveness in reducing the need for hemodialysis in ESKD remains limited.Methods We included ADPKD patients aged ≥18 years using TriNetx data from Sep 2, 2018, to Sep 3, 2023. Propensity score matching (PSM) ensured baseline comparability (standardized mean difference (SMD)

Abstract Validation of the Oxford classification (MEST and MEST-C) for Immunoglobulin A nephropathy (IgAN) in the Taiwanese population is lacking. Our study aimed to validate this classification and assess individual lesion impact. We conducted a retrospective cohort study at Taichung Veterans General Hospital, Taiwan (Jan 2011–Jul 2023). Composite renal outcomes were evaluated using clinical conditions and estimated glomerular filtration rate (eGFR). We used Kaplan–Meier, univariable/multivariable logistic regression and ROC curves. Subgroup analysis considered eGFR

Introduction: No markers have been used to diagnose historical peritoneal dialysis (PD)-related peritonitis. Cyclophilin A (CypA) is associated with glucose toxicity and inflammation. We hypothesize that dialysate CypA can be a marker for historical peritonitis (at least 3 months free from peritonitis). Method: An enzyme-linked immunosorbent assay kit was used to measure the concentration of dialysate CypA. Clinical and laboratory data were collected to correlate with historical peritonitis. Mann-Whitney U test and Chi-square test were used for analysis. Receiver operating characteristic (ROC) analysis was used to evaluate predictive power. Results: Out of a total of 31 patients who had undergone PD for at least 2 years, 18 had no history of PD-related peritonitis, while 13 had experienced PD-related peritonitis at least once. Overall, the patients in this population were in good health (normal white blood cell count, no anemia, normal electrolyte and serum albumin levels). There were no significant differences between patients with and without a history of peritonitis, except for blood white blood cell count (5650.6 ± 1848.4 vs. 7154.6 ± 2056.8, p = 0.032) and dialysate CypA value (24.27 ± 22.715 vs. 54.41 ± 45.63, p = 0.020). In the univariate analysis, only the dialysate CypA level showed a statistically significant association with historical peritonitis (HR = 1.030, 95 % CI = 1.010–1.062, p = 0.046). The AUC for dialysate CypA (>34.83 ng/mL) was 0.748, with a sensitivity of 0.615 and specificity of 0.833. Conclusion: PD peritonitis poses a significant threat to the long-term use of peritoneal dialysis. Based on our study, even in the absence of concurrent infection, dialysate CypA can serve as a predictive marker for historical peritonitis, demonstrating high predictive power along with fair sensitivity and good specificity.

Background: Heart failure with reduced ejection fraction (HFrEF) poses significant health risks. Midodrine for maintaining blood pressure in HFrEF, requires further safety investigation. This study explores midodrine’s safety in HFrEF through extensive matched analysis.Methods: Patients with HFrEF (LVEF

Cigarette smoking is a critical issue in caring for patients of chronic kidney disease (CKD). However, there is no routine care program designed for combining both smoking cessation and CKD care. The process of our quality improvement (QI) collaboration used data under our routine payment-for-performance for pre-end-stage renal disease (P4P Pre- ESRD) in Taichung Veterans General hospital from 2020 to 2022. We share our experience with a QI project that integrates the Ottawa model for smoking cessation (OMSC) with the Pre-ESRD care program as part of routine CKD care. The electronic health information systems were improved to reduce workload of medical staff. The number was more for both qualified CKD educators and nephrologists for smoking cessation. The access and availability for smoking cessation were immediate and convenient for patients. Specifically, all the actions were performed by CKD educators, with nephrologists overseeing the process in routine care. By combining OMSC with the Pre-ESRD program, we were able to provide smokers with satisfactory access and availability to smoking cessation services within our healthcare facility. The smoker cases found were more in number (206 in 2020, 344 in 2021, and 421 in 2022). Before the integrated OSTC-Pre-ESRD program (in 2020), the proportion of smokers was 3.88%. After implementing the integrated program, smokers increased significantly on a yearly basis (9.69% in 2021 and 9.82% in 2022). Finally, case numbers of on-site smoking cessations increased significantly after implementing the integrated system (0 in 2020, 17 in 2021, and 20 in 2022). All CKD patients for smoking cessation were also more (8 in 2020, 46 in 2021, and 38 in 2022). After implementing the QI program, focusing on the integrated OMSC-Pre- ESRD program, we found more smokers undergoing smoking cessation. This QI program highlighted the importance of better access and availability for smoking cessation.

Summary: Background: This study aimed to evaluate the renal safety and effectiveness of COVID-19 vaccination in patients with immunoglobulin A nephropathy (IgAN). Methods: We conducted a global and retrospective collaborative network analysis using TriNetX data from September 11, 2018 to September 11, 2023, to address this question. The study recorded diagnoses of IgAN, COVID-19 vaccinations, and outcomes of effectiveness using International Classification of Diseases, Tenth Revision, Clinical Modification codes and procedure codes. Propensity score matching (PSM) created matched groups (1:1). Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated for outcomes of effectiveness, and Kaplan–Meier method assessed survival probability. Safety outcomes regarding renal function were compared with estimated glomerular filtration rate (eGFR), proteinuria, and hematuria. Subgroup analyses were based on sex and age group. Sensitivity analysis was done before the outbreak of Omicron (from September 11, 2018 to October 31, 2021). Findings: The study involved 1010 vaccinated and 2776 unvaccinated patients with IgAN without COVID-19 infection at baseline. After PSM (1:1) with 25 variables, both groups consisted of well-matched 979 patients who were relatively young (around 55 years old) and in good health (eGFR: 78–80 ml/min/1.732 m2). Compared to the non-vaccinated group, vaccinated patients had significantly lower risks of COVID-19 infection and complications, including COVID-19 infection (HR: 0.050, 95% CI: 0.026, 0.093), COVID-19 pneumonia (HR: 0), severe lung complication (0.647, 95% CI: 0.421, 0.994), acute respiratory failure (0.625, 95% CI: 0.400, 0.978), sepsis (0.545, 95% CI: 0.334, 0.890), emergency department visits (0.716, 95% CI: 0.615, 0.833), all hospitalizations (0.573, 95% CI: 0.459, 0.715), and mortality (0.595, 95% CI: 0.366, 0.969). However, one month after the follow-up, the vaccinated group exhibited a slightly, but statistically significantly, lower eGFR compared to the non-vaccinated group (73.58 vs. 83.05 ml/min/1.732 m2, p = 0.047). Nine months after the follow-up, the difference in eGFR between the two groups disappeared. The lower risk of COVID-19 infection was observed across genders (male and female) and age groups (young and old). For the period before Omicron outbreak, results were also similar. Interpretation: In the largest TriNetX matched cohort study of IgAN, COVID-19 vaccination was associated with a reduced risk of COVID-19 infection and associated complications. However, careful monitoring of renal function, especially GFR, is advisable. Funding: This study was supported by grant TCVGH-1103602C, TCVGH-1103601D, and TCVGH-1113602D from Taichung Veterans General Hospital.

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-β1 (TGF-β1), 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-β1-induced EMT, such as enhanced E-cadherin and decreased vimentin. Fibrotic markers collagen IV and α-smooth muscle actin (α-SMA) increased in TGF-β1-induced NRK-52E. Moreover, PCA reduced TGF-β1-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-β1-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.

Abstract Sodium-glucose cotransporter 2 inhibitor (SGLT2i) potentially decrease all-cause and cardiovascular death, however, associations with non-cardiovascular death remain unclear. Therefore, we investigated SGLT2i associations with death and the cause of death. We used the Taiwanese National Health Institutes Research database linked to the National Register of Deaths (NRD). Incident type 2 diabetes mellitus (T2DM) patients and propensity score matched T2DM SGLT2i and Dipeptidyl peptidase 4 inhibitor (DPP4i) users were investigated. The index year was the SGLT2i or DPP4i prescription date from May 2016. Patients were followed-up until death or December 2018. Deaths verified by the NRD and grouped accordingly. Multiple Cox proportional hazards models were used. In total, 261,211 patients were included in the population; 47% of the patients were female and the average age was 62 years. The overall incidence of all-cause death was 8.67/1000 patient-years for SGLT2i and 12.41 for DPP4i users during follow-up. After adjusting for potential risk factors in the propensity score matched population, SGLT2i users were associated with lower risks of all-cause death, cardiovascular death, cancer death, and non-cancer, non-vascular death compared with DPP4i-users. For specific death causes, significantly lower death risks from heart disease, cerebrovascular disease, and accidents were associated with SGLT2i-use. SGLT2i benefits for T2DM patients were not different across subgroups. Compared with DPP4i-use, SGLT2i-use for T2DM was associated with lower disease and death risk.

Abstract 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.

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.

Abstract We analyzed database from the Taiwan National Health Insurance to investigate whether primary aldosteronism (PA) increases the risk of bladder stones. This retrospective nationwide population-based cohort study during the period of 1998–2011 compared patients with and without PA extracted by propensity score matching. Cox proportional hazard models and competing death risk model were used to estimate the hazard ratios (HRs), sub-hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs). There were 3442 patients with PA and 3442 patients without PA. The incidence rate of bladder stones was 5.36 and 3.76 per 1000 person-years for both groups, respectively. In adjusted Cox hazard proportional regression models, the HR of bladder stones was 1.68 (95% CI 1.20–2.34) for patients with PA compared to individuals without PA. Considering the competing risk of death, the SHR of bladder stones still indicates a higher risk for PA than a comparison cohort (SHR, 1.79; 95% CI 1.30–2.44). PA, age, sex, and fracture number were the variables significantly contributing to the formation of bladder stones. In conclusion, PA is significantly associated with risk of bladder stones.

Early prediction of clinical deterioration such as adverse events (AEs), improves patient safety. National Early Warning Score (NEWS) is widely used to predict AEs based on the aggregation of 6 physiological parameters. We took the same parameters as the features for AE prediction using deep learning algorithms (AEP-DLA) among hospitalized adult patients. The aim of this study is to get better performance than traditional naïve mathematical calculations by introducing novel vital sign data preprocessing schemes. We retrospectively collected the data from our electronic medical record data warehouse (2007 ~ 2017). AE rate of all 99,861 admissions was 6.2%. The dataset was divided into training and testing datasets from 2007–2015 and 2016–2017 respectively. In real-life clinical care, physiological parameters were not recorded every hour and missed frequently, for example, Glasgow Coma Scale (GCS). The expert domain suggested that missed GCS was rated as 15. We took two strategies (stack series records and align by hour) in the data preprocessing and tripling the values of negative samples for class balancing (CB). We used the last 28 hours’ serial data to predict AEs 3 hours later with Random Forest, XGBoost, Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN). It is shown that CNN with CB and align by hour got the best results comparing to the other methods. The precision, recall and area under curve were 0.841, 0.928 and 0.995 respectively. The performance of the model is also better than those proposed in the published literatures.

BackgroundFor patients with Acute Kidney Injury (AKI), a strong and graded relationship exists between AKI severity and mortality. One of the most severe entities of AKI is Dialysis-Requiring Acute Kidney Injury (D-AKI), which is associated with high rates of mortality and end-stage renal disease (ESRD). For this high-risk population group, there is a lack of evidence regarding optimal post-AKI care. We propose that post-AKI care through the combined efforts of the nephrologist and the multidisciplinary care team may improve outcomes. Our aim here is to study for survivors of dialysis-requiring acute kidney injury, the effects of implementing early comprehensive kidney care.MethodsThis is a retrospective longitudinal cohort study of Taiwanese through analyzing the National Health Insurance Research Database (NHIRD). We included patients with acute dialysis during hospitalization from January 1, 2015 to December 31, 2018. Propensity match was done at 1:1, including estimated glomerular filtration rate (eGFR) based on CKD-EPI which was performed due to large initial disparities between these two cohorts.ResultsAfter the propensity match, each cohort had 4,988 patients. The mean eGFR based on CKD-EPI was 27.5 ml/min/1.73 m2, and the mean follow-up period was 1.4 years.The hazard ratio for chronic dialysis or ESRD was 0.55 (95% CI, 0.49–0.62; p < 0.001). The hazard ratio for all-cause mortality was 0.79 (95% CI, 0.57–0.88; p < 0.001). Both outcomes favored early comprehensive kidney care.ConclusionsFor survivors of dialysis-requiring acute kidney injury, early comprehensive kidney care significantly lowered risks of chronic dialysis and all-cause mortality.

Abstract 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.

Abstract 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.

We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis.

Abstract 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.

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

Background We explored the long-term safety and efficacy of ferric citrate in hemodialysis patients in Taiwan, and further evaluated the iron repletion effect and change of iron parameters by different baseline groups. Methods This was a 12-month, Phase IV, multicenter, open-label study. The initial dose of ferric citrate was administered by patients’ clinical condition and further adjusted to maintain serum phosphorus at 3.5–5.5 mg/dL. The primary endpoint was to assess the safety profiles of ferric citrate. The secondary endpoints were to evaluate the efficacy by the time-course changes and the number of subjects who achieved the target range of serum phosphorus. Results A total of 202 patients were enrolled. No apparent or unexpected safety concerns were observed. The most common treatment-emergent adverse events were gastrointestinal-related with discolored feces (41.6%). Serum phosphorus was well controlled, with a mean dose of 3.35±1.49 g/day, ranging from 1.5 to 6.0 g/day. Iron parameters were significantly improved. The change from baseline of ferritin and TSAT were 227.17 ng/mL and 7.53%, respectively (p-trendConclusions Ferric citrate is an effective phosphate binder with favorable safety profile in ESRD patients. The iron-repletion by ferric citrate is effective, and the increase is limited in patients with a higher baseline. In addition to controlling hyperphosphatemia, ferric citrate also shows additional benefits in the treatment of renal anemia. Clinical trial registration ClinicalTrials.gov ID: NCT03256838; 12/04/2017.

Contrast associated kidney injury is caused by side effects of iodinated contrast media (ICM), including inflammation. Chronic inflammation among dialysis patient contributes to atherosclerosis, which leads to simultaneous conditions of the kidney, brain, and vasculature. Data to investigate the pathologic effects of ICM on cardiovascular complications in dialysis patients are lacking. Dialysis patients who had been exposed to ICM from computed tomography (ICM-CT) were allocated as the ICM-CT cohort (N = 3751), whereas dialysis patients without ICM exposure were randomly allocated as the non-ICM cohort (N = 17,196). Furthermore, 540 pairs were selected for analyses through propensity score-matching in terms of age, sex, comorbidities, dialysis vintage, and index date. During a median follow-up of 10.3 years, ICM-CT cohort had significantly higher risks in the following, compared with non-ICM cohort: all-cause mortality (adjusted hazard ratio [aHR], 1.36; 95% confidence interval [CI], 1.26–1.47), cardiovascular events (aHR,1.67; 95% CI, 1.39–2.01), acute coronary syndrome (adjusted HR: 2.92; 95% CI, 1.72–4.94), sudden cardiac arrest (aHR, 1.69; 95% CI, 0.90–3.18), heart failure (aHR, 1.71; 95% CI,1.28–2.27), and stroke (aHR, 1.84; 95% CI,1.45–2.35). The proinflammatory ICM is significantly associated with an increased risk of major cardiovascular events in patients on dialysis.

Objective: The trajectory patterns of estimated glomerular filtration rates (eGFR) in chronic kidney disease (CKD) older adults with malnourishment and their association with subsequent patient outcomes have not been elucidated. We aimed to assess the eGFR trajectory patterns for predicting patient survival and kidney failure in the elderly without or with malnourishment.Materials and Methods: Based on a prospective longitudinal cohort, CKD patients aged 65 years or older were enrolled from 2001 to 2013. Among the 3,948 patients whose eGFR trajectory patterns were analyzed, 1,872 patients were stratified by the absence or presence of malnourishment, and 765 patients were identified and categorized as having malnourishment. Four eGFR trajectory patterns [gradual decline (T0), early non-decline and then persistent decline (T1), persistent increase (T2), and low baseline and then progressive increase (T3)] were classified by utilizing a linear mixed-effect model with a quadratic term in time. The malnourishment was defined as body mass index < 22 kg/m2, serum albumin < 3.0 mg/dL, or Geriatric Nutritional Risk Index (GNRI) < 98. This study assessed the effectiveness of eGFR trajectory patterns in a median follow-up of 2.27 years for predicting all-cause mortality and kidney failure.Results: The mean age was 76.9 ± 6.7 years, and a total of 82 (10.7%) patients with malnourishment and 57 (5.1%) patients without malnourishment died at the end of the study. Compared with the reference trajectory T0, the overall mortality of T1 was markedly reduced [adjusted hazard ratio (aHR) = 0.52, 95% confidence interval (CI) 0.32–0.83]. In patients with trajectory, T3 was associated with a high risk for kidney failure (aHR = 5.68, 95% CI 3.12–10.4) compared with the reference, especially higher risk in the presence of malnourishment. Patients with high GNRI values were significantly associated with a lower risk of death and kidney failure, but patients with malnourishment and concomitant alcohol consumption had a higher risk of kidney failure.Conclusions: Low baseline eGFR and progressively increasing eGFR trajectory were high risks for kidney failure in CKD patients. These findings may be attributed to multimorbidity, malnourishment, and decompensation of renal function.

Contrast-medium-associated kidney injury is caused by the infusion of contrast media. Small vessel disease is significantly associated with various diseases, including simultaneous conditions of the kidney and brain, which are highly vulnerable to similar vascular damage and microvascular pathologies. Data to investigate the adverse effect of contrast media on the brain remain extremely lacking. In this study, 11,332,616 NHI enrollees were selected and divided into two groups, exposed and not exposed to a contrast medium during the observation period, from which 1,461,684 pairs were selected for analyses through matching in terms of age, sex, comorbidities, and frequency of outpatient visits during the previous year. In total, 1,461,684 patients exposed to a contrast medium and 1,461,684 controls not exposed to one were enrolled. In multivariable Cox proportional hazard models, patients exposed to a contrast medium had an overall 2.09-fold higher risk of dementia. In multivariable-stratified analyses, the risk of Alzheimer’s disease was remarkably high in younger patients without any underlying comorbidity. This study is the first to discover that exposure to contrast media is significantly associated with the risk of dementia. A four-fold increased risk of vascular dementia was observed after exposure to a contrast medium. Further studies on the influence of exposure to contrast media on the brain are warranted.

Background and objectives: For patients with end-stage renal disease (ESRD), the best replacement therapy is renal transplant (RTx) to ensure life with good quality. Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder and a common cause of ESRD. Different from ESRD of other causes, ADPKD patients need careful pre-RTx evaluations like detecting the presence of intracranial aneurisms, cardiac manifestations, and complications of liver and renal cysts. Materials: We retrieved a total of 1327 RTx patients receiving 1382 times RTx (two recipients with three times, 48 recipients with two times) over the last 35 years. Only 41 of these patients were diagnosed with ADPKD. Results: At the first RTx, patients’ ages were 42.9 ± 12.6 (mean ± SD) years. Ages of the ADPKD group (52.5 ± 10.1 years) were older than the non-ADPKD group (42.7 ± 12.7 years, p = 0.001). We found more cell mediated and antibody mediated rejection (29.3% vs. 26.0%, and 22.0% vs. 7.0%; both p < 0.001), new onset diabetes after transplant (NODAT) (21, 51.2% vs. 326, 25.3%; p = 0.005), and worse graft survival (p < 0.001) in the ADPKD group, and with the development of more malignancies (18; 43.9% vs. 360; 28.0%; p = 0.041). The long-term patient survivals were poorer in the ADPKD group (38.9% vs. 70.3%; p = 0.018). ADPKD was found as an independent risk factor for long-term patient survival (HR = 2.64, 95% CI 1.03–6.76, p = 0.04). Conclusions: Patients with ADPKD-related ESRD developed more NODAT, and also more malignancies if not aggressively surveyed before surgery. Due to poor long-term graft and patient survivals, regular careful examinations for NODAT and malignancies, even in the absence of related symptoms and signs, are highly recommended in the follow-ups.

Background: Renal biopsy is the gold standard for diagnosing renal disease. The major concern is bleeding. Shared decision making (SDM) has been reported to improve communication but has never been used regarding renal biopsy. Methods: We launched a 5-year project on SDM for renal biopsy. We collected cases of renal biopsy and bleeding, and cases of SDM. The process of quality improvement (QI) for SDM is also shared. Results: Taichung Veterans General Hospital has the largest number of renal biopsy cases, and the lowest bleeding rate in Taiwan. We enlisted a core team for this QI project and conducted stakeholder mapping. In 2017, we conducted a small pilot study for SDM based on printed material as a decision aid. The satisfaction rate was 95.5%. From 2018 to 2019, we improved SDM patients’ decision aid from printed material to four videos, designing questions to consolidate their understanding, and a unique information platform. The above improvements facilitated the utilization of SDM for renal biopsy (81.27% in 2020 and 100% in 2021). Even with higher bleeding complications in 2019 and 2020, patients remained satisfied when we launched SDM prior to renal biopsy. Conclusion: This is the first study regarding SDM on renal biopsy. Through SDM, patients had time to understand renal biopsy, including risk and benefit. We recommend SDM to elaborate renal biopsy in clinical practice.

Diabetic nephropathy (DN) is the main cause of end-stage kidney disease (ESKD). DN-related ESKD has the worst prognosis for survival compared with other causes. Due to the complex mechanisms of DN and the heterogeneous presentations, unmet needs exist for the renal outcome of diabetes mellitus. Clinical evidence for treating DN is rather solid. For example, the first Kidney Disease: Improving Global Outcomes (KDIGO) guideline was published in October 2020: KDIGO Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. In December of 2020, the International Society of Nephrology published 60 (+1) breakthrough discoveries in nephrology. Among these breakthroughs, four important ones after 1980 were recognized, including glomerular hyperfiltration theory, renal protection by renin-angiotensin system inhibition, hypoxia-inducible factor, and sodium-glucose cotransporter 2 inhibitors. Here, we present a review on the pivotal and new mechanisms of DN from the implications of clinical studies and medications.

Introduction: Iodinated contrast medium (CM) is the third most common cause of acute kidney injury (AKI). However, the association is poorly known between the definitions of AKI between different stages of chronic kidney disease after intravenous CM administration. Methods: The dataset, covering a period of ~15 years (1 June 2008 to 31 March 2015), consisted of 20,018 non-dialytic adult patients who had received intravenous injections of non-ionic iso-osmolar CM, iodixanol, for enhanced computed tomography imaging. Contrast-associated AKI (CA-AKI), dialysis-required AKI, and mortality were analyzed. Results: A total of 12,271 participants were enrolled. CA-AKI increased significantly starting from stage 3A onward (p < 0.001). In summary, incidences of CA-AKI against different levels of chronic kidney disease were as follows: stage 1 (8.3%) = stage 2 (6.7%) < stage 3A (9.9%) < stage 3B (14.3%) < stage 4 (20.5%) = stage 5 (20.4%). The incidences of dialysis within 30 days were as follows: stage 1 (1%) = stage 2 (1.4%) = stage 3A (2.7%) < stage 3B (5.7%) < stage 4 (18%) < stage 5 (54.1%). The prediction of dialysis was good based on the baseline serum creatinine > 1.5 mg/dL (72.78% of sensitivity, 86.07% of specificity, 0.851 of area under curve) or baseline estimated glomerular filtration rate ≤ 38.49 mL/min/1.732 m2 (70.19% of sensitivity, 89.08% of specificity, 0.853 of area under curve). In multivariate Cox regression analysis model for CA-AKI, independent risk factors were stage 4 chronic kidney disease (p = 0.001) and shock (p = 0.001). Conclusion: Baseline serum creatinine and estimated glomerular filtration rate were good predictors for dialysis-required AKI. CA-AKI increased significantly since stage 3A chronic kidney disease. Stage 4 and 5 chronic kidney disease have the same risk for CA-AKI, but stage 5 chronic kidney disease has markedly higher risk for dialysis.

Background: The effect of glucose control, especially variability of glycated hemoglobin (HbA1c), on estimated glomerular filtration rate (eGFR) decline in type 2 diabetes is still debatable. Methods: We used tertiles of coefficient of variation (CV) to determine the variability of HbA1c (HbA1c_CV). Mixed model repeated measures (MMRM) were used to evaluate the annual eGFR decline rate. Results: In 1383 type 2 diabetic patients, we found the greater the HbA1c_CV, the greater the eGFR decline ( p = 0.01, −0.99 in low, −1.73 in mid, and −2.53 ml/min/1.73 m 2 /year in high HbA1c_CV). Regardless of eGFR (⩾60 or

Background and objectivesImmunoglobulin A Nephropathy (IgAN) is the most common type of glomerulonephritis with variable renal outcome. The association between IgAN and patient survival is limited. The effect of crescents on patient survival was never studied.MaterialsWe conducted a retrospective cohort study between January 2003 and December 2013. All patients with the biopsy-proved IgAN was enrolled for the analysis of patient survival and renal survival. Cox regression model was used analyze the associated factors for patient survival.ResultsAll 388 participants with IgAN were enrolled, in which 45 patients with crescents. The mean percentage of glomeruli involvement was 23±18.9%. After long-term follow-up, crescents group had both worse renal (p = 0.034) and patient survivals (p = 0.016). In univariate Cox regression model, the age (HR = 1.08, 95% CI = 1.05-1.12, pConclusionsThe major strengths of the present study is that crescents IgAN had worse patient survival compared to non-crescents IgAN. Clinicians should be more careful to care patients with crescents IgAN.

Diabetic nephropathy (DN) is one of the most severe chronic kidney diseases in diabetes and is the main cause of end-stage renal disease (ESRD). Protocatechuic aldehyde (PCA) is a natural product with a variety of effects on pulmonary fibrosis. In this study, we examined the effects of PCA in C57BL/KS db/db male mice. Kidney morphology, renal function indicators, and Western blot, immunohistochemistry, and hematoxylin and eosin (H&E) staining data were analyzed. The results revealed that treatment with PCA could reduce diabetic-induced renal dysfunction, as indicated by the urine albumin-to-creatinine ratio (db/m: 120.1 ± 46.1μg/mg, db/db: 453.8 ± 78.7 µg/mg, db/db + 30 mg/kg PCA: 196.6 ± 52.9 µg/mg, db/db + 60 mg/kg PCA: 163.3 ± 24.6 μg/mg, p < 0.001). However, PCA did not decrease body weight, fasting plasma glucose, or food and water intake in db/db mice. H&E staining data revealed that PCA reduced glomerular size in db/db mice (db/m: 3506.3 ± 789.3 μm2, db/db: 6538.5 ± 1818.6 μm2, db/db + 30 mg/kg PCA: 4916.9 ± 1149.6 μm2, db/db + 60 mg/kg PCA: 4160.4 ± 1186.5 μm2p < 0.001). Western blot and immunohistochemistry staining indicated that PCA restored the normal levels of diabetes-induced fibrosis markers, such as transforming growth factor-beta (TGF-β) and type IV collagen. Similar results were observed for epithelial–mesenchymal transition-related markers, including fibronectin, E-cadherin, and α-smooth muscle actin (α-SMA). PCA also decreased oxidative stress and inflammation in the kidney of db/db mice. This research provides a foundation for using PCA as an alternative therapy for DN in the future.

Abstract 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-β1 both in vitro and in vivo, and TGF-β1 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-β1-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.

PurposeData for elucidating post-kidney transplantation (KT) acute pancreatitis (AP) risk are limited and no large-scale cohort study has investigated the impact of AP after KT.MethodData from Taiwan National Health Insurance (NHI) Research Database (NHIRD) were calculated through the method of propensity score matching to compare the pancreatitis risk in patients with and without KT.ResultsThe overall pancreatitis incidence rates were 1.71 and 0.61 per 1,000 person-years in the KT and non-KT groups, respectively and corresponding adjusted HR (aHR [95% CI]) for pancreatitis was 2.48 (1.51-4.09) in the KT group. In the multivariable model, AP risk was higher in transplant patients with alcohol-related illnesses (aHR: 3.78, 95% CI: 1.32-10.8), gall stone disease (aHR: 3.53, 95% CI: 1.48-8.44), or past history of pancreatitis (aHR: 10.3, 95% CI: 5.08-20.8). Of note, recurrent AP risk was significantly higher in the KT group (aHR: 8.19, 95% CI: 2.89-23.2). Patients with post-KT AP demonstrated shorter patient and allograft survival than did those without (both P < 0.001, respectively).ConclusionIn conclusion, KT recipients are very likely to be associated with AP. Moreover, their inferior outcomes are strongly associated with post-KT AP.

Hyponatremia is the most common electrolyte disorder and also a predictor of mild cognition impairment. However, the association between hyponatremia and dementia in long follow up periods is rarely investigated. A retrospective cohort study was performed using the claims data of all insured residents who were covered by Taiwan's universal health insurance from 2000 to 2011. A total of 4900 hyponatremia patients and 19545 matched comparisons were recruited for the analysis. The incidences of hyponatremia and dementia were diagnosed with clinical protocol and defined using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). Cox proportional hazard regression and Kaplan-Meier curves were used for the analyses. Independent of adjusting factors, hyponatremia patients had 2.36-fold higher chances of suffering dementia, including Alzheimer's disease (AD) and non-AD dementia, than the comparisons. Severe hyponatremia patients had higher risks of suffering dementia than the non-severe hyponatremia patients (adjusted hazard ratio: 4.29 (95% CI: 3.47-5.31) versus 2.08 (95% CI: 1.83-2.37)). A dose response relationship was observed between hyponatremia and dementia. Those hyponatremia patients with baseline or incident stroke had significantly higher chances of suffering dementia compared with those patients without hyponatremia and stroke. Stroke is a significant modifier of the relationship between hyponatremia and dementia. Cerebrovascular disease after incident hyponatremia must be prevented to reduce the incidence of dementia.