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ImportanceThe benefits and disadvantages of different pretransplant dialysis modalities and their posttransplant outcomes remain unclear in contemporary kidney transplant care.ObjectiveTo summarize the available evidence of the association of different pretransplant dialysis modalities, including hemodialysis and peritoneal dialysis (PD), with posttransplant outcomes.Data SourcesMEDLINE, Embase, PubMed, Cochrane Library, Scopus, CINAHL, and gray literature were searched from inception to March 18, 2022 (updated to April 1, 2022), for relevant studies and with no language restrictions.Study SelectionRandomized clinical trials and nonrandomized observational (case-control and cohort) studies that investigated the association between pretransplant dialysis modality and posttransplant outcomes regardless of age or donor sources (living or deceased) were abstracted independently by 2 reviewers.Data Extraction and SynthesisFollowing Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology reporting guidelines, 2 reviewers independently extracted relevant information using a standardized approach. Random-effects meta-analysis was used to estimate pooled adjusted hazard ratio (HR) or odds ratio and 95% CI.Main Outcomes and MeasuresPrimary outcomes included all-cause mortality, overall graft failure, death-censored graft failure, and delayed graft function. Secondary outcomes included acute rejection, graft vessel thrombosis, oliguria, de novo heart failure, and new-onset diabetes after transplant.ResultsThe study analyzed 26 nonrandomized studies (1 case-control and 25 cohort), including 269 715 patients (mean recipient age range, 14.5-67.0 years; reported proportions of female individuals, 29.4%-66.9%) whose outcomes associated with pretransplant hemodialysis vs pretransplant PD were compared. No significant difference, with very low certainty of evidence, was observed between pretransplant PD and all-cause mortality (13 studies; n = 221 815; HR, 0.92 [95% CI, 0.84-1.01]; P = .08) as well as death-censored graft failure (5 studies; n = 96 439; HR, 0.98 [95% CI, 0.85-1.14]; P = .81). However, pretransplant PD was associated with a lower risk for overall graft failure (10 studies; n = 209 287; HR, 0.96 [95% CI, 0.92-0.99]; P = .02; very low certainty of evidence) and delayed graft function (6 studies; n = 47 118; odds ratio, 0.73 [95% CI, 0.70-0.76]; P Conclusions and RelevanceResults of the study suggest that pretransplant PD is a preferred dialysis modality option during the transition to kidney transplant. Future studies are warranted to address shared decision-making between health care professionals, patients, and caregivers as well as patient preferences.

Introduction: An outbreak of coronavirus disease-19 (COVID-19) has occurred in different parts of the world. Although a large piece of information regarding the epidemiology, clinical features, and management of COVID-19 has been reported in the general population, there is very limited data regarding organ transplant recipients, particularly regarding the management of maintenance immunosuppressive agents during infection. Methodology: We described a case of kidney transplant recipient from Thailand who had COVID-19 pneumonia and severe acute kidney injury. Results: The patient’s serum creatinine peaked at 7.0 mg/dL on day 15 of illness and returned to baseline value of 2.0 mg/dL on day 26 of illness. We have shown how we modified tacrolimus, mycophenolate, and steroids in the patient who had received favipiravir and lopinavir/ritonavir for COVID-19 pneumonia. Conclusions: In this case, successful modification of this immunosuppressive regimen was accomplished to reduce drug interaction complications, aiming to avoid calcineurin inhibitor nephrotoxicity while maintaining appropriate levels of immunosuppression to prevent organ rejection and to promote the patient’s recovery from infection.

AIM Mycophenolic acid (MPA) is an immunosuppressive drug commonly used for prophylaxis of graft rejection in solid organ transplant recipients. The main concern with the prolonged use of immunosuppressive drugs is the risk of developing cancer. However, it remains unclear whether the immunosuppressive regimens containing MPA confer an increased degree of cancer risk. The present study aimed to determine the association between MPA exposure and the incidence of cancer in solid organ transplant recipients. METHODS A systematic search was performed on the PubMed, EMBASE and Cochrane Library databases. Relevant articles that had findings on the incidence (or event) of cancer in cohorts with and without MPA exposure were retrieved for data extraction. A meta-analysis was conducted by means of the random-effects model, and the relative risk (RR) and its 95% confidence interval (95% CI) were used as a summary effect measure. RESULTS A total of 39 studies were eligible for inclusion, with 32 studies that enabled meta-analysis. MPA exposure was significantly associated with a lower risk of cancer when compared to azathioprine exposure (RR = 0.66, 95% CI = 0.53-0.81, P

The COVID-19 pandemic has evolved quickly, with different variants of concern resulting in the need for countries to offer booster vaccinations. Although studies have assessed homologous schedules in detail, the effectiveness of heterologous booster vaccine schedules against severity and mortality with newer variants remains to be explored fully.Utilizing a Hospital Information System for COVID-19 established in Chiang Mai, Thailand, we conducted a cohort study by linking patient-level data on laboratory-confirmed COVID-19 cases to the national immunization records, during delta-predominant and omicron-predominant periods.Compared to omicron, COVID-19 cases during the delta period were 10 times more likely to have severe outcomes and in-hospital deaths. During omicron, a third vaccine dose had an 89% reduced risk of both severe COVID-19 and death. The third dose received 14-90 days before the date of the positive test showed the highest protection (93%). Severe outcomes were not observed with the third dose during delta, and the fourth dose during the omicron period. All the vaccine types used for boosting in Thailand offered similar protection against severe COVID-19.Booster doses provided a very high level of protection against severe COVID-19 outcomes and deaths. Booster campaigns should focus on improving coverage by utilizing all available vaccines to ensure optimal protection.

Background The Coronavirus disease 2019 (COVID-19) pandemic has evolved quickly, with numerous waves of different variants of concern resulting in the need for countries to offer continued protection through booster vaccinations. To ensure adequate coverage, Thailand has proactively adopted heterologous vaccination schedules. While studies have assessed homologous schedules in detail, the effectiveness of heterologous booster vaccine schedules against severity and mortality of COVID-19 patients, particularly with newer variants, remains to be explored fully. Methods Utilising an active Hospital Information System for COVID-19 established in Chiang Mai, Thailand, we conducted a cohort study by linking patient-level data on laboratory-confirmed COVID-19 cases to the national immunization records, during delta-predominant (1st October – 31st December 2021) and omicron predominant (1st February – 30th April 2022) periods. Demographic and baseline clinical characteristics associated with severe COVID-19 outcomes and mortality were examined for each period. Results COVID-19 cases during delta predominance were ten times more likely to have severe outcomes and in-hospital deaths as compared to omicron predominance. During omicron predominance, a third vaccine dose was associated with 89% reduced risk of both severe COVID-19 and deaths, as compared to the unvaccinated group. Those who received the third dose 14–90 days prior to the date of positive SARS-CoV-2 test had the highest protection against severe COVID-19 outcomes (93%) followed by a drop to 87% among those who received their last dose > 90 days prior. Severe outcomes were not observed among third dose recipients during delta predominance and fourth dose recipients during omicron predominance. All the vaccine types used for boosting in Thailand offered similar protection against severe COVID-19. Conclusions The risk of severe outcomes were significantly lower for COVID-19 patients with omicron as compared to delta. Booster doses provided very high level of protection against severe COVID-19 outcomes and deaths. Ongoing booster campaigns should focus on improving coverage utilising all available vaccines to ensure optimal protection.

Introduction: Intradialytic hypotension (IDH) is an important complication during chronic hemodialysis due to its adverse cardiovascular and hemodialysis outcomes. Case reports have demonstrated that administration of fludrocortisone before undergoing hemodialysis might increase intradialytic blood pressure. This study is a randomized crossover study aiming to evaluate the intradialytic hemodynamic effects of fludrocortisone. Material and Methods: A randomized, controlled two-period crossover trial was conducted at Lampang Hospital in stable chronic hemodialysis patients who experienced IDH >30% in their sessions during the past 3 months. All participants have randomly received a single dose of 0.2-mg fludrocortisone 30 min before each hemodialysis session, or had no treatment for 4 weeks. After a 2-week washout period, the participants were then switched to the other treatment for 4 weeks. The primary outcome was the mean lowest intradialytic mean arterial pressure (MAP) during the hemodialysis session. Results: A total of 17 patients were recruited with a mean age of 61.7 ± 14.8 years. By analysis of crossover design, the mean lowest intradialytic MAP was not different between receiving fludrocortisone or with no treatment (76.1 ± 12.5 vs. 73.9 ± 11.5 mm Hg, p for treatment effect = 0.331, p for period effect = 0.855, p for sequence effect = 0.870). There was no difference in the incidence of IDH between the two groups (34.4% in fludrocortisone vs. 42.7% in no treatment, p = 0.137). However, in diabetic patients and patients with residual kidney function, the incidence of IDH was significantly lower when receiving fludrocortisone (30.8 vs. 52.6%, p < 0.001, and 27.6 vs. 74.3%, p < 0.001, respectively). Conclusions: In chronic hemodialysis patients who had IDH, fludrocortisone administration did not improve intradialytic hemodynamics and did not decrease the incidence of IDH.

Rationale & Objective First-line therapy for syndrome of inappropriate antidiuresis (SIAD) is fluid restriction. Additional treatment for patients who do not respond to fluid restriction are water restriction with furosemide or water restriction with furosemide and salt supplementation. However, the efficacy of these treatments has never been tested in a randomized controlled study. The objective of this study was to investigate whether, combined with fluid restriction, furosemide with or without sodium chloride (NaCl) supplementation was more effective than fluid restriction alone in the treatment of hyponatremia in SIAD. Study Design Open-label randomized controlled study. Setting & Participants Patients with serum sodium concentrations ([Na+]) ≤ 130mmol/L due to SIAD. Intervention(s) Random assignment to 1 of 3 groups: fluid restriction alone (FR), fluid restriction and furosemide (FR+FM), or fluid restriction, furosemide, and NaCl (FR+FM+NaCl). Strictness of fluid restriction ( Outcomes The primary outcome was change in [Na+] at days 4, 7, 14, and 28 after randomization. Results 92 patients were recruited (FR, n=31; FR+FM, n=30; FR+FM+NaCl, n=31). Baseline [Na+] was 125±4mmol/L, and there were no significant differences between groups. Mean [Na+] on day 4 in all treatment groups was significantly increased from baseline by 5mmol/L (P Limitations Open-label treatment. Conclusions In patients with SIAD, furosemide with NaCl supplement in combination with fluid restriction did not show benefits in correction of [Na+] compared with treatment with fluid restriction alone. Incidences of acute kidney injury and hypokalemia were increased in patients receiving furosemide. Funding None. Trial Registration Registered at the Thai Clinical Trial Registry with study number TCTR20170629004.

Background Several kidney transplantation (KT) prediction models for patient and graft outcomes have been developed based on Caucasian populations. However, KT in Asian countries differs due to patient characteristics and practices. To date, there has been no equation developed for predicting outcomes among Asian KT recipients. Methods We developed equations for predicting 5- and 10-year patient survival (PS) and death-censored graft survival (DCGS) based on 6662 patients in the Thai Transplant Registry. The cohort was divided into training and validation data sets. We identified factors significantly associated with outcomes by Cox regression. In the validation data set, we also compared our models with another model based on KT in the United States. Results Variables included for developing the DCGS and PS models were recipient and donor age, background kidney disease, dialysis vintage, donor hepatitis C virus status, cardiovascular diseases, panel reactive antibody, donor types, donor creatinine, ischemic time, and immunosuppression regimens. The C statistics of our model in the validation data set were 0.69 (0.66-0.71) and 0.64 (0.59-0.68) for DCGS and PS. Our model performed better when compared with a model based on US patients. Compared with tacrolimus, KT recipients aged ≤44 years receiving cyclosporine A had a higher risk of graft loss (adjusted hazard ratio = 1.26; P = 0.046). The risk of death was higher in recipients aged >44 years and taking cyclosporine A (adjusted hazard ratio = 1.44; P = 0.011). Conclusions Our prediction model is the first based on an Asian population, can be used immediately after transplantation. The model can be accessed at www.nephrochula.com/ktmodels.

Evidence shows that lower serum albumin concentrations are associated with the risk of peritoneal dialysis (PD)-related peritonitis. However, little is known regarding its relationship and magnitude of change before PD initiation and peritonitis risk. We performed a multicenter retrospective cohort study on 1169 adult cases of PD in Thailand. The associations of serum albumin at concentration ( 3.5 [reference] g/dL) and changes (unchanged + 0.1 to − 0.1 [reference], decrease or increase > 0.1 g/dL) over 3- and 6-month before PD initiation with PD-related peritonitis were examined. Time-to-first and longitudinal rates of peritonitis were examined using the multivariable Cox proportional hazards model and Poisson regression analyses, respectively. At baseline PD initiation, patients with serum albumin concentration 3.5 g/dL), respectively. Compared to the unchanged group, patients with a decrease and increase in serum albumin concentrations during transitioning to dialysis were significantly associated with higher and lower risk of peritonitis, adjusted HR of 2.25 (95% confidence interval [CI] 1.85–2.75) and 0.53 (95% CI 0.42–0.68) over three-month, and 1.43 (95% CI 1.15–1.79) and 0.64 (95% CI 0.52–0.79) over six-month, respectively. Similar trends of longitudinal rates of serum albumin concentrations and peritonitis risk were observed. Serum albumin concentrations at PD initiation and its magnitude of change during the transition to dialysis are strongly associated with subsequent risk of peritonitis. Further studies are required on strategies modifying serum albumin concentration during the transition to PD.

Belimumab improved renal outcomes in patients with active lupus nephritis (LN) in BLISS-LN, leading to its approval in the USA and EU. As data on treatment of East Asian patients with LN are limited, we evaluated the efficacy and safety of belimumab in the BLISS-LN East Asian subgroup.Pre-specified subgroup analysis of BLISS-LN, a Phase 3, placebo-controlled, randomized 104-week trial.Adults with biopsy-proven, active LN were randomized (1:1) to belimumab or placebo, plus standard therapy.Patients were administered intravenous belimumab 10 mg/kg, or placebo, plus standard therapy (oral glucocorticoids and either cyclophosphamide for induction followed by azathioprine for maintenance, or mycophenolate mofetil for both induction and maintenance). At the investigator's discretion, 1-3 intravenous pulses of methylprednisolone, 500-1000 mg each, could be administered during induction.The primary endpoint was Primary Efficacy Renal Response (PERR; urine protein:creatinine ratio [uPCR] ≤0.7, eGFR no more than 20% below pre-flare value or ≥60 ml/min/1.73 mPERR and CRR were analyzed using a logistic regression model, and time to a renal-related event or death were analyzed using a multivariable Cox proportional-hazards regression model.142 patients from mainland China, Hong Kong, South Korea, and Taiwan were included (belimumab: n=74; placebo: n=68). At week 104, more belimumab than placebo patients achieved PERR (52.7% vs 36.8%, OR [95% CI] 1.76 [0.88, 3.51]) and CRR (35.1% vs 25.0%, OR [95% CI] 1.73 [0.80, 3.74]). At Week 52, more belimumab than placebo patients achieved PERR (62.2% vs 36.8%; OR [95% CI] 2.74 [1.33, 5.64]). Belimumab reduced the risk of a renal-related event or death compared to placebo at any time (HR [95% CI] 0.37 [0.15, 0.91]). Safety was similar across treatment groups.Small sample size and lack of formal significance testing.Safety and efficacy profiles were consistent with BLISS-LN overall population, supporting benefits of belimumab treatment in the East Asian population with LN.

Differences in transplant characteristics limit the application of kidney donor profile index (KDPI) and estimated post-transplant survival (EPTS) models developed in Western countries to Asian populations.We analyzed data of the Thai Transplant Registry and the Thai Red Cross Society on 2558 DDKTs performed between 2001 and 2014. Thai KDPI and EPTS models were developed using Cox regression, and validation against the US models.Thai KDPI was developed based on seven donor factors: age, height, best estimated glomerular filtration rate, diabetes mellitus, hypertension, cerebrovascular accident, and adrenaline infusion. The Thai and US donor risk index had comparable predictive abilities for transplant survival (C-statistics .5871 vs. .5548; P = .429). KTs from donors with a US KDPI 70% demonstrated significantly worse 5-year transplant survival. The Thai EPTS model was developed from four recipient factors: age, body weight, diabetes mellitus, and hepatitis C infection. The C-statistics of the Thai and US EPTS models were comparable (.5924 vs. .6039; P = .360). A US EPTS 70% was revealed in only 2.5% of our cohort.The first simplified KDPI and EPTS models for an Asian population were developed. Our models are available at www.thai-kdpi-epts.org.

Previous studies showed that long interdialytic interval of chronic hemodialysis increased risk of sudden cardiac death compared to short interdialytic interval. Diabetes mellitus (DM) and autonomic dysfunction are the strong adverse predictors of survival in ESRD patients. We aimed to compare autonomic function between long and short interdialytic interval of chronic hemodialysis in patients with and without DM. One-hundred sixty-three patients receiving chronic hemodialysis were enrolled. The electrocardiogram recording was performed twice in each patient during 4-h hemodialysis session after long and short interdialytic intervals to assess heart rate variability (HRV). Mean age was 61.4 ± 14.3 years. HRV parameters during hemodialysis did not differ between long and short interdialytic interval in overall population. Nevertheless, in 82 (50.3%) patients, SDNN (47.4 ± 23.8 vs. 43.4 ± 19.5 ms, P = 0.039), ASDNN (24.8 ± 14.3 vs. 22.7 ± 12.3 ms, P = 0.025), LF (8.4 ± 6.8 vs. 7.6 ± 6.6 ms2, P = 0.040) increased after long interdialytic interval. The greater change of SDNN, ASDNN, VLF and LF between long and short interdialytic intervals was noted in DM, compared to non-DM patients. We demonstrated that there was no difference of HRV parameters after short and long interdialytic interval. However, there was greater autonomic alteration observed in DM than non-DM patients between 2 interdialytic intervals.

Variation of high-sensitivity cardiac troponin I and T (hs-cTn) during hemodialysis has been observed. Observational studies demonstrated the increased incidence of adverse cardiovascular events after long compared to short interdialytic intervals. Therefore, we aimed to compare variation of hs-cTnI and hs-cTnT before and after hemodialysis and between short and long interdialytic intervals. We enrolled 200 asymptomatic patients receiving regular hemodialysis. The hs-cTnI and hs-cTnT levels were measured before and after hemodialysis on the day after short and long interdialytic intervals. Mean age was 62.3 ± 14.8 years (Male 55.5%). Prevalence of increased hs-cTnI and hs-cTnT was 34.5% and 99.0%, respectively. The median ± interquartile range of hs-cTnT increased significantly after hemodialysis during short and long interdialytic intervals. However, hs-cTnI level did not increase after hemodialysis during short and long intervals. We found that levels of hs-cTnI and T did not differ between short interdialytic and long interdialytic intervals. We demonstrated higher prevalence of elevated hs-cTnT in patients with regular hemodialysis compared to hs-cTnI. The rise of hs-cTnT was observed immediately after hemodialysis but no significant change of hs-cTnI was noted. Accordingly, hs-cTnI may be preferable as a diagnostic marker in patients with suspected acute myocardial infarction than hs-cTnT.

Introduction: Tenofovir disoproxil fumarate (TDF) is associated with a risk of chronic kidney disease (CKD), especially when used with protease inhibitors or in Asian populations. Data from the Thai national health insurance system were used to assess the incidence of CKD in patients receiving antiretroviral therapy (ART) in real-world practice. Materials and methods We analyzed data from patients who initiated one of the following first-line ART regimens: (i) zidovudine+lamivudine+nevirapine (AZT+3TC+NVP); (ii) zidovudine+lamivudine+efavirenz (AZT+3TC+EFV); (iii) tenofovir+lamivudine+nevirapine (TDF+3TC+NVP); (iv) tenofovir+lamivudine/emtricitabine+efavirenz (TDF+3TC/FTC+EFV); and (v) tenofovir+lamivudine+lopinavir/ritonavir (TDF+3TC+LPV/r). CKD was defined as glomerular filtration rate 2 for >3 months, or a confirmed 2010 WHO diagnosis (ICD-10 code N183, N184, or N185). Death competing risks survival regression models were used for the analysis. Results Among 27,313 participants, median age 36.8 years, body mass index 20.4 kg/m2, and absolute CD4 cell count 146 cells/mm3, followed for a median 2.3 years, 245 patients (0.9%) were diagnosed CKD (incidence 3.2 per 1,000 patient-years of follow-up; 95% confidence interval [CI] 2.8-3.6). Compared with patients receiving AZT+3TC+NVP, the risk of CKD measured by adjusted sub-distribution hazard ratio (aSHR) was higher in patients on TDF+3TC+LPV/r (6.5, 95% CI 3.9-11.1), on TDF+3TC+NVP (3.8, 95% CI 2.3-6.0) and on TDF+3TC/FTC+EFV (1.6, 95% CI 1.2-2.3). Among patients receiving TDF, compared with those receiving TDF+3TC/FTC+EFV, the risk was higher on TDF+3TC+LPV/r (4.0, 95%CI 2.3-6.8) on TDF+3TC+NVP (2.3, 95%CI 1.4-3.6) . Conclusions This real-world study suggest that the role of TDF in increasing the risk of CKD, especially when combined with LPV/r or NVP.

Background and Aims In patients (pts) with SLE, activation of the CD40–CD40L pathway results in stimulation and proliferation of B cells and other inflammatory cell types. The subsequent generation of autoantibodies and their deposition in the kidney, as well as activation of myeloid and resident kidney cells, result in local inflammation and eventually, kidney injury. Thus, CD40 is an appealing therapeutic target in lupus nephritis (LN). BI 655064 is a humanised anti-CD40 monoclonal antibody that blocks the CD40 pathway in a nanomolar range and downregulates activated B cells. This study assessed the efficacy and safety over 52 weeks (wks) of three doses of subcutaneous BI 655064 compared with placebo, as add-on to mycophenolate and steroids, in pts with active proliferative LN (ClinicalTrials.gov number: NCT02770170). Method Overall, 121 pts with LN were randomised, double blind, in a 2:1:1:2 ratio to placebo or BI 655064 120 mg, 180 mg or 240 mg, and received a weekly loading dose for the first 3 wks, followed by dosing every 2 wks for the 120 and 180 mg doses, and weekly (120 mg) for the 240 mg group. Key inclusion criteria included an active ISN/RPS class III or IV (±V) renal biopsy within 3 months prior to screening and a screening protein/creatinine ratio of ≥1 mg/mg. Randomisation was stratified based on race (Asian vs non-Asian) and screening protein/creatine (UP/UC) ratio ( Results The placebo response in this trial was higher than expected (48.3%; Table 1); none of the BI 655064 doses increased rates of CRR at Wk 52 compared with placebo. However, CRR at Wk 52 based on creatinine-adjusted proteinuria, assessed using spot urine, showed a better response in the 180 mg group (50%) vs placebo (42.5%), and the 180 mg dose showed a greater change from baseline over time vs placebo from Wk 4. Time to CRR was shorter in the 180 mg group (17.3 wks) vs placebo (20.4 wks). The 180 mg group also showed improvement vs placebo in total SLEDAI (SELENA) and its subscores. The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR), whereby confirmation of the endpoint was required at both Wks 46 (penultimate visit on treatment) and 52. A 15.2% higher cCRR in the 180 mg group (44.3%) vs placebo (29.1%) was observed (p=0.26). While based on a small sample size, there were more reports of infection-related severe and serious adverse events and neutropenia in the 240 mg group compared with placebo. Of note, in those who experienced neutropenia, a clinical impact (e.g. increase in infections) was not established. Aside from these observations, safety data were comparable across treatment groups. Larger decreases from baseline were observed in the percentage of CD27−IgD−CD95+, CD27−IgD+CD95+, CD27+IgD+CD95+ and CD27+IgD−CD95+ B-cell subsets in the 180 and 240 mg groups compared with placebo. Treatment-emergent anti-drug antibodies (ADAs) were detected in five pts treated with BI 655054, all at low titre, and in one who received placebo; ADAs had no impact on pharmacokinetics or safety. Conclusion The trial did not meet its primary CRR endpoint. However, when confirmation of CRR was required at both Wks 46 and 52, the resultant decrease in the placebo response generated an effect size of 15.2% and 9.1% in favour of 180 mg and 240 mg BI 655064, respectively.

Background: The use of thiazide diuretics is associated with skin cancer risk; however, whether this applies to all skin cancer types is unclear. Methods: In this meta-analysis, we searched multiple electronic databases and gray literature up to 10 April 2022, with no language restrictions, to identify relevant randomized controlled trials (RCTs) and non-randomized studies (cohort, case-control) that investigated the association between thiazide diuretics and skin cancer. The primary outcomes of interest were malignant melanoma and non-melanoma skin cancer (basal cell carcinoma [BCC], squamous cell carcinoma [SCC]). Secondary outcomes included other skin cancers (lip cancer, Merkel cell carcinoma, malignant adnexal skin tumors, oral cavity cancer, and precursors of skin cancer). We used a random-effects meta-analysis to estimate pooled adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: Thirty non-randomized studies (17 case-control, 13 cohort, no RCTs) were included. Thiazide diuretic users had a higher risk of malignant melanoma (17 studies; n = 10,129,196; pooled adjusted OR, 1.10; 95% CI, 1.04–1.15; p < 0.001; strength of evidence, very low; very small harmful effect), BCC (14 studies; n = 19,780,476; pooled adjusted OR, 1.05; 95% CI, 1.02–1.09; p = 0.003; strength of evidence, very low; very small harmful effect), and SCC (16 studies; n = 16,387,862; pooled adjusted OR, 1.35; 95% CI, 1.22–1.48; p < 0.001; strength of evidence, very low; very small harmful effect) than non-users. Thiazide diuretic use was also associated with a higher risk of lip cancer (5 studies; n = 161,491; pooled adjusted OR, 1.92; 95% CI, 1.52–2.42; p < 0.001; strength of evidence, very low; small harmful effect), whereas other secondary outcomes were inconclusive. Conclusions: Thiazide diuretics are associated with the risk of all skin cancer types, including malignant melanoma; thus, they should be used with caution in clinical practice.

A retrospective cohort study was conducted to evaluate the association between the plasma volume treated by double filtration plasmapheresis and allograft outcomes for the treatment of acute antibody-mediated rejection in kidney transplant recipients. Patients were divided into two groups: group 1, plasma volume treated between 1 and

Supplemental Digital Content is available in the text, Background: Based on the International Society for peritoneal dialysis (PD) recommendations, blockade of renin-angiotensin systems with an angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) improves residual kidney function in PD patients. However, the long-term effectiveness of ACEI/ARB use in PD patients has not been fully elucidated. We, therefore, intend to perform a systematic review and meta-analysis to summarize the effects of ACEI/ARB use on long-term mortality, cardiovascular outcomes, and adverse events among PD patients. Methods: This systematic review will include both randomized controlled trials and non-randomized studies in adult PD patients. We also plan to incorporate data from our cohort study in Thai PD population into this review. We will search PubMed, Medline, EMBASE, Cochrane Library, Web of Science, Scopus, CINAHL, and grey literature from inception to February 29, 2019, with no language restrictions. The process of study screening, selection, data extraction, risk of bias assessment, and grading the strength of evidence will be performed independently by a pair of reviewers. Any discrepancy will be resolved through a team discussion and/or consultation with the third reviewer. The pooled effects estimate and 95% confidence intervals will be estimated using DerSimonian-Laird random-effects models. Heterogeneity will be assessed by the Cochran Q test, I2 index and tau-squared statistics. The funnel plots along with the Begg and Egger test and trim and fill method will be performed to investigate any evidence of publication bias. Preplanned subgroup analyses and random-effects univariate meta-regressions will be performed to quantify the potential sources of heterogeneity based on studies- and patient-characteristics. Results: This will be the first systematic review and meta-analysis to summarize the long-term effectiveness of renin-angiotensin system inhibitors in PD populations. Conclusion: In summary, this systematic review and meta-analysis will summarize the effectiveness of ACEI/ARB on long-term mortality, cardiovascular outcomes, and adverse events among adult PD patients by integrated all available evidences. Ethics and dissemination: Based on the existing published data, an ethical approval is not required. The findings will be disseminated through scientific meetings and publications in peer-reviewed journals. PROSPERO registration number: CRD42019129492.

Background:In patients with SLE, activation of the CD40–CD40L pathway results in stimulation and proliferation of B cells and other inflammatory cell types. The subsequent generation of autoantibodies and their deposition in the kidney, as well as activation of myeloid and resident kidney cells, result in local inflammation and eventually, kidney injury. Thus, CD40 is an appealing therapeutic target in lupus nephritis (LN). BI 655064 is a humanised anti-CD40 monoclonal antibody that blocks the CD40 pathway in a nanomolar range and downregulates activated B cells.Objectives:To assess the efficacy and safety over 52 weeks of three doses of subcutaneous BI 655064 compared with placebo, as add-on to mycophenolate and steroids, in patients with active proliferative LN (ClinicalTrials.gov number: NCT02770170).Methods:Overall, 121 patients with LN were randomised, double blind, in a 2:1:1:2 ratio to placebo or BI 655064 120 mg, 180 mg or 240 mg, and received a weekly loading dose for the first 3 weeks, followed by dosing every 2 weeks for the 120 and 180 mg doses, and weekly (120 mg) for the 240 mg group. Key inclusion criteria included an active ISN/RPS class III or IV (±V) renal biopsy within 3 months prior to screening and a screening protein/creatinine ratio of ≥1 mg/mg. Randomisation was stratified based on race (Asian vs non-Asian) and screening protein/creatine (UP/UC) ratio (Results:The placebo response in this trial was higher than expected (48.3%; Table 1); none of theBI 655064 doses increased rates of CRR at Week 52 compared with placebo. However, CRR at Week 52 based on creatinine-adjusted proteinuria, assessed using spot urine, showed a better response in the 180 mg group (50%) vs placebo (42.5%), and the 180 mg dose showed a greater change from baseline over time vs placebo from Week 4. Time to CRR was shorter in the 180 mg group (17.3 weeks) vs placebo (20.4 weeks). The 180 mg group also showed improvement vs placebo in total SLEDAI (SELENA) and its subscores.The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR), whereby confirmation of the endpoint was required at both Weeks 46 (penultimate visit on treatment) and 52. A 15.2% higher cCRR in the 180 mg group (44.3%) vs placebo (29.1%) was observed (p=0.26).While based on a small sample size, there were more reports of infection-related severe and serious adverse events and neutropenia in the 240 mg group compared with placebo. Of note, in those who experienced neutropenia, a clinical impact (e.g. increase in infections) was not established. Aside from these observations, safety data were comparable across treatment groups.Larger decreases from baseline were observed in the percentage of CD27−IgD−CD95+, CD27−IgD+CD95+, CD27+IgD+CD95+ and CD27+IgD−CD95+ B-cell subsets in the 180 and 240 mg groups compared with placebo.Treatment-emergent anti-drug antibodies (ADAs) were detected in five patients treated with BI 655054, all at low titre, and in one who received placebo; ADAs had no impact on pharmacokinetics or safety.Conclusion:The trial did not meet its primary CRR endpoint. However, when confirmation of CRR was required at both Weeks 46 and 52, the resultant decrease in the placebo response generated an effect size of 15.2% and 9.1% in favour of 180 mg and 240 mg BI 655064, respectively.Table 1.Efficacy endpoints at Week 52Placebo (n=40)BI 655064120 mg (n=21)180 mg (n=20)240 mg (n=40)Observed CRR, n208918Adjusted* CRR, %48.338.34544.6Observed cCRR, n135916Adjusted* cCRR, %29.122.544.338.2Mean change from baseline in SLEDAITotal score−6.5−6.1−9.7−8.2Non-renal score−1.4−3.0−2.8−3.1Renal score−5.1−3.7−6.8−5.0Clinical score−5.7−3.9−7.9−6.5CRR based on 24 h proteinuria; cCRR based on UP/UC (spot urine) at Weeks 46 and 52. *Logistic regression model including treatment and the covariates race and proteinuria at screening.Disclosure of Interests:David Jayne Consultant of: DRJ has received consulting fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline Research & Development Ltd, Novartis, and Roche, Juergen Steffgen Employee of: JS is employed by Boehringer Ingelheim., Juanita Romero-Diaz Consultant of: JRD has received research consulting fees from Boehringer Ingelheim, Hirofumi Amano Grant/research support from: HA has received research grants from Boehringer Ingelheim, Kajohnsak Noppakun Consultant of: KN has received honoraria from Boehringer Ingelheim, Novartis, Roche, Jansen, AstraZeneca, Otsuka Pharmaceuticals, Astellas Pharma, Abbott, Sanofi and Novo Nordisk, Grant/research support from: KN has received research grants from Boehringer Ingelheim, GlaxoSmithKline Research & Development Ltd, Visterra Inc., Kalbe Genexine Biologics, Aurinia Pharmaceuticals Inc., and Omeros Corporation., Harold Michael Gomez Speakers bureau: HMG has received speaker’s fees for Pfizer, MSD, Unilab, Astellas Pharma, AstraZeneca, GlaxoSmithKline Research & Development Ltd, and Aurinia Pharmaceuticals Inc., Rhona Recto: None declared, Valérie Belsack Employee of: Boehringer Ingelheim, Nora Fagan Employee of: Boehringer Ingelheim, Steven Padula Employee of: Boehringer Ingelheim, Ivette Revollo Employee of: Boehringer Ingelheim, Jing Wu Employee of: Boehringer Ingelheim, Sudha Visvanathan Employee of: Boehringer Ingelheim, Richard Furie Consultant of: RF has received research consulting fees, Grant/research support from: RF has received clinical trial support

Background The Uremic Pruritus in Dialysis Patients (UP-Dial) scale is valid and reliable for uremic pruritus (UP) assessment. However, it remains unknown how the scores should be interpreted in clinical practices. Objectives To establish a clinical interpretation of the UP-Dial by identifying severity cut-off scores according to the disease severity and burden of pruritus. Methods This cross-sectional study developed a classification system for the UP-Dial scores using the patient-based anchors method. From May 2012 through January 2017, 697 dialysis patients were screened. Of these, a total of 258 met the criteria for UP and completed the UP-Dial scale and three sets of patient-assessed anchor questions: (i) global UP intensity by visual analogue scale (VAS)-UP, (ii) Dermatology Life Quality Index, and (iii) global kidney disease-related quality of life. The cut-off scores were generated based on the kappa (κ) coefficient of agreement and the area under receiver operating characteristic curve (AuROC) statistics. Subgroup analyses were performed to explore associations between patient characteristics and the UP-Dial severity bands. Results The proposed scores were ≤12 (mild), 13-21 (moderate), and ≥22 (severe) with κ coefficient ranging between 0.39 and 0.46. Assigned scores were associated with all patient-based anchors. The highest association was with the VAS-UP, AuROC were 0.80 (mild; 95% CI, 0.75-0.86), 0.66 (moderate; 0.60-0.71), and 0.83 (severe; 0.77-0.89). In subgroup analysis according to patient characteristics, we did not find any significant difference. Conclusions The estimated UP-Dial severity band can facilitate the interpretation of UP in practice-based research settings and can be used to support treatment decisions. This article is protected by copyright. All rights reserved.

Introduction Data regarding the prevalence, risk factors and outcome of scleroderma renal crisis (SRC) in Asian patients with systemic sclerosis (SSc) are limited. Objective To determine the prevalence, risk factors and outcomes of SRC in Thai SSc patients. Method Medical records of all SSc patients seen at the Division of Rheumatology, Chiang Mai University, Thailand, from January 1990 to December 2015 were retrospectively reviewed. For each SRC case, a disease duration (±1 year) matched control (four SSc patient without SRC for each SRC patient) was identified. Result Of 608 SSc patients seen during the study period, 19 SRC cases were identified, resulting in an SRC prevalence of 3.13%, with 76 matched controls. Of the 19 cases, mean ± SD age and median (interquartile range 1–3) disease duration was 56.2 ± 13.8 years and 5 (3–22) months, respectively. Seventeen patients (89.5%) had diffuse cutaneous SSc. Twelve patients (63.2%) had hypertensive renal crisis and seven (36.8%) had normotensive renal crisis. Multivariate conditional logistic regression analyses showed that digital gangrene (adjusted odd ratio [AOR] 31.41, 95% CI = 1.16–852.23, P = 0.041), current prednisolone dose ≥ 15 mg/day (AOR 31.22, 95% CI = 1.59–613.85, P = 0.024), serum albumin < 3 mg/dL (AOR 7.97, 95% CI = 1.49–42.56, P = 0.015), and cardiac involvement (AOR = 6.62, 95% CI = 1.08–40.63, P = 0.041) were independent risk factors for SRC. Fifteen SRC patients (78.9%) required dialysis and 10 (52.6%) died. Conclusion SRC was an uncommon complication in Thai patients with SSc, but is associated with high mortality. Digital gangrene, current prednisolone dose ≥ 15 mg/day, serum albumin < 3 mg/dL and cardiac involvement were independent risk factors for SRC.

Background Existing epidemiological studies illustrate that proton pump inhibitors (PPIs) may be related to adverse kidney outcomes. To date, no comprehensive meta-analysis has been conducted to evaluate and quantify this association. Methods We performed a systematic review and meta-analysis of studies to assess the association between PPI use and the risk of adverse kidney outcomes. We searched MEDLINE, Embase, SCOPUS, Web of Science, CINAHL, Cochrane Library and grey literature with no language restrictions (through 31 October 2016). Adverse kidney outcomes were acute interstitial nephritis (AIN), acute kidney injury (AKI), chronic kidney disease (CKD) and end-stage renal disease (ESRD). The risk ratios (RRs) and confidence intervals (CIs) were pooled using a random effects model. The strength of evidence (SOE) for each outcome was assessed using the Grading of Recommended Assessment, Development and Evaluation system. Results Of 2037 identified studies, four cohort and five case-control studies with ∼2.6 million patients were included. Of these, 534 003 (20.2%) were PPI users. Compared with non-PPI users, PPI users experienced a significantly higher risk of AKI [RR 1.44 (95% CI 1.08-1.91); P = 0.013; SOE, low] and CKD [RR 1.36 (95% CI 1.07-1.72); P = 0.012; SOE, low]. Moreover, PPIs increased the risk of AIN [RR 3.61 (95% CI 2.37-5.51); P