Preformed donor-specific HLA antibodies (DSA) are a major risk factor for antibody-mediated rejection (ABMR) and graft loss after kidney transplantation. While pre-transplant desensitization can reduce DSA levels, the impact of persistent vs. resolved DSA on long-term outcomes remains unclear. This study investigated the association between post-transplant DSA status and clinical outcomes in kidney transplant recipients. This retrospective cohort study investigated the impact of post-transplant DSA persistence on clinical outcomes in kidney transplant recipients at King Chulalongkorn Memorial Hospital between 2009 and 2019. Patients with pre-transplant DSA positivity (detected by Luminex but negative by CDC-AHG) were categorized into 'resolved' (DSA < 500 MFI) and 'persistent' (DSA > 500 MFI) groups based on post-transplant Luminex results. Outcomes evaluated included biopsy-proven acute rejection (ABMR and TCMR), graft loss, mortality, and post-transplant complications. A total of 50 KTr were enrolled in the study. The median (interquartile range, IQR) DSA level was 1,556 (3,491) MFI for class I and 0 (888) MFI for class II. 57% of patients underwent pre-transplant desensitization. The median follow-up time after transplantation was 5.5 (IQR 3.3) years. The group with persistent DSA (n = 16) exhibited a significant higher rate of ABMR compared to the group with resolved DSA (n = 34) (p = 0.047, log-rank test). Factors associated with persistent DSA included recipient age over 50 and lower tacrolimus levels at six months (less than 7.25 ng/mL). Monitoring DSA levels is crucial in kidney transplant recipients, as persistent DSA is strongly associated with an increased risk of ABMR. Maintaining higher tacrolimus levels at 6 months tends to resolve DSA post-transplant. For patients with persistent DSA, surveillance biopsies should be considered to facilitate early detection and treatment of rejection, thus preserving kidney allograft function.
Introduction: Corticosteroids are commonly used in severe post-infectious glomerulonephritis (PIGN), but the optimal dosing and long-term outcomes remain unclear. This study investigated the association between cumulative corticosteroid dosage and mortality in patients with biopsy-proven PIGN. Methods: This retrospective cohort study included adult patients (≥18 years) with biopsy-proven PIGN from the King Chulalongkorn Memorial Hospital registry (1996–2023), excluding those with concurrent infections or conditions affecting prognosis. Clinical and histopathological data were collected. The primary outcome was kidney failure (estimated glomerular filtration rate of <15 mL/min/1.73 m2 or long-term kidney replacement therapy). Time-to-event analysis compared outcomes between steroid-treated and untreated patients. Univariable logistic regression and multivariable Cox models identified mortality predictors. Receiver operating characteristic curves identified the optimal cumulative prednisolone dosage, and Kaplan-Meier analysis compared survival between steroid dosage groups. Results: Among 7,005 kidney biopsies, 73 patients with PIGN were analyzed. Over a median follow-up of 15.6 years, 15% died and 15% developed kidney failure. Steroids were used in 62% of patients and were associated with higher rate of skin/soft tissue infections (26% vs. 11%, p = 0.03). Despite similar baseline characteristics, multivariable Cox regression showed that steroid use was independently associated with lower mortality (HR 0.08, 95% CI: 0.01–0.61, p = 0.02). Kaplan-Meier analysis demonstrated significantly lower overall survival in patients receiving cumulative prednisolone ≥73 mg/kg or no steroids, with the best survival observed in those receiving <73 mg/kg (log-rank test, p = 0.02). Steroid-related adverse events included cushingoid appearance (11%) and osteopenia (4%). Conclusion: Corticosteroids improve survival in PIGN, but cumulative doses ≥73 mg/kg increase mortality risk. Low-dose corticosteroids may be beneficial in severe PIGN, but further research is needed to refine dosing strategies.
ABO-incompatible (ABOi) and human leukocyte antigen (HLA)-incompatible (HLAi) kidney transplantations are known as immunological high-risk transplantation. Patients with incompatible living donors have to choose either undergoing desensitization and then transplantation or waiting for deceased donor kidney transplantation (DDKT). Studies on the outcome of ABOi and HLAi living donor kidney transplantations (LDKTs) compared to waiting for and receiving DDKT outside the United States and European countries remain scarce. This single-center retrospective study was conducted in patients who underwent ABOi, HLAi, and DDKT between January 2008 and November 2021. The patient survival rate was 97.7%, 92.5%, and 82.6% at 5, 10, and 15 years, respectively, in the DDKT group compared to 96.8% at 5 and 10 years in the ABOi group (P = 0.84) and 94.8% at 5 years in the HLAi group (P = 0.91). The death-censored graft survival was 95.6%, 83.1%, and 63.8% at 5, 10, and 15 years in the DDKT group, as compared to 90.3% at 5 and 10 years in the ABOi group (P = 0.73) and 92.1% at 5 years in the HLAi group (P = 0.53). Antibody-mediated rejection occurred significantly higher in the HLAi group with a hazard ratio of 2.77 (95% confidence interval: 1.31–5.88; P = 0.008) compared to the DDKT group. ABOi and HLAi KT did not increase rates of BK and cytomegalovirus (CMV) infection compared to DDKT. In summary, ABOi and HLAi transplant recipients had comparable patient, graft survival, and CMV and BK infections to DDKT. Our study emphasizes the usefulness of ABOi and HLAi LDKT to reduce patients’ waiting time and improve their quality of life.
Primary membranous nephropathy (MN) is an autoimmune glomerular disease commonly associated with anti-PLA2R antibodies, with relapses typically attributed to spontaneous immune reactivation. We report the first documented case of a relapse of primary, PLA2R-positive MN that was temporally and immunologically linked to disseminated tuberculosis (TB) infection. A 42-year-old man, previously in complete remission, developed severe nephrotic syndrome and acute kidney injury unresponsive to standard immunosuppressive regimens. Concomitant diagnosis of miliary TB was confirmed by culture and imaging. Remarkably, the MN relapse resolved completely with anti-TB therapy alone, without further immunosuppression, and remission has been sustained for over two years. This case highlights infection, specifically TB, as a modifiable and overlooked trigger of MN relapse, potentially via molecular mimicry or system immune activation. In TB-endemic regions, identifying infectious triggers early in relapsing MN may spare patients from unnecessary immunosuppression and facilitate long-term remission through targeted antimicrobial therapy.
The outcomes of adults with sporadic post-infectious glomerulonephritis (PIGN) are generally poor. The value of glucocorticoid treatment was analyzed in the largest biopsy registry with a long-term follow-up period.
Peritoneal dialysis (PD) catheter malfunction commonly leads to the removal of the catheter and eventually to a transfer to hemodialysis. The most common cause is intraluminal obstruction caused by blood and fibrin clots. Recommended interventions include irrigation of the catheter with heparinized saline; if this method fails, thrombolytic agents may be used. Mechanical methods such as intraluminal brushing are also utilized, typically after medical treatment fails. Here, we present a case of a patient who developed an intraluminal blood clot that persisted despite attempts with intraluminal thrombolytic drugs and intraluminal brushing. To salvage the catheter, targeted thrombolysis was performed using an endoscopic retrograde cholangiopancreatography (ERCP) guidewire to reinforce the coiled PD catheter and puncture the clots. Additionally, a Swing Tip cannula was employed for direct injection of the thrombolytic agent. These interventions successfully preserved the catheter, resolving the clot and ensuring continued functionality.
Viridans-group streptococci, including the Streptococcus mitis/oralis subgroup, can cause peritoneal dialysis (PD)-related peritonitis. The link between dental pathology and PD-related peritonitis remains to be fully elucidated. We report a case of an 83-year-old man undergoing nocturnal intermittent PD due to kidney failure from diabetic nephropathy who developed S. mitis peritonitis and septicemia traced back to a periodontal abscess. Despite having no prior history of peritonitis and maintaining good nutritional status, the patient presented with generalized abdominal pain and a low-grade fever. The initial treatment included intraperitoneal antibiotics. Root cause analysis identified multiple periodontitis and dental abscesses as the primary source of infection, confirmed by DNA sequencing of cultures from the abscesses and blood, which matched S. mitis. This case highlights the critical role of oral flora in causing invasive diseases in immunocompromised individuals, including PD patients, and illustrates how dental infections can lead to PD-related peritonitis through hematogenous spread. Our case also stresses the importance of meticulous dental care and regular dental examinations to prevent such infections in PD patients.
Several studies have reported an increased risk of chronic kidney disease (CKD) outcomes after long-term exposure (more than 1 year) to particulate matter with an aerodynamic diameter of ≤ 2.5 µm (PM2.5). However, the conclusions remain inconsistent. Therefore, we conducted this meta-analysis to examine the association between long-term PM2.5 exposure and CKD outcomes. A literature search was conducted in PubMed, Scopus, Cochrane Central Register of Controlled trials, and Embase for relevant studies published until August 10, 2023. The main outcomes were incidence and prevalence of CKD as well as incidence of end-stage kidney disease (ESKD). The random-effect model meta‐analyses were used to estimate the risk of each outcome among studies. Twenty two studies were identified, including 14 cohort studies, and 8 cross-sectional studies, with a total of 7,967,388 participants. This meta-analysis revealed that each 10 μg/m3 increment in PM2.5 was significantly associated with increased risks of both incidence and prevalence of CKD [adjusted odds ratio (OR) 1.31 (95% confidence interval (CI) 1.24 to 1.40), adjusted OR 1.31 (95% CI 1.03 to 1.67), respectively]. In addition, the relationship with ESKD incidence is suggestive of increased risk but not conclusive (adjusted OR 1.16; 95% CI 1.00 to 1.36). The incidence and prevalence of CKD outcomes had a consistent association across all subgroups and adjustment variables. Our study observed an association between long-term PM2.5 exposure and the risks of CKD. However, more dedicated studies are required to show causation that warrants urgent action on PM2.5 to mitigate the global burden of CKD.
A 60-year-old man with hypertension presented to the hospital owing to fatigue but with no abdominal discomfort, constipation, or diarrhea. Initial investigations revealed that his serum creatinine had risen to 1.54mg/dL (from 1.05mg/dL 4 months earlier). One month later, colonoscopy was performed to screen for colon cancer based on his age, revealing only 3 colorectal polyps located at descending colon (0.5cm), sigmoid colon (1.8cm), and rectum (1.5cm), with no mass. The polypectomy was performed and showed adenocarcinoma with moderate to poorly differentiated cells in the rectal polyp.
Peritonitis caused by dematiaceous molds is uncommon but poses a significant threat to patients undergoing peritoneal dialysis (PD), leading to high mortality and morbidity. This report highlights three cases of peritonitis caused by three distinct species of Diaporthe (D. amygdali, D. eucalyptorum, and D. phaseolorum), initially unidentified through conventional culture methods. The nucleotide sequences of internal transcribed spacer regions (ITS), 18S nuclear ribosomal small subunit (SSU), and 28S nuclear ribosomal large subunit (LSU) of the ribosomal DNA gene correctly identified the isolates. Despite early catheter removal and administration of appropriate antifungal medications, all patients experienced fatal outcomes. DNA barcoding emerges as a valuable tool for accurately diagnosing species within the genus of pathogenic microbes, aiding in identifying the root causes of infections. It emphasizes the importance of strict adherence to aseptic techniques during PD exchanges to prevent peritonitis caused by plant-borne pathogens.
BACKGROUND:Patient-reported outcome measures (PROMs) are widely recognized as valuable predictors of clinical outcomes in peritoneal dialysis (PD). Our study aimed to explore the connections between patient-reported constipation and clinical outcomes.METHODS:We assessed constipation in patients across 22 facilities participating in the Thailand Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) from 2014 to 2017. Constipation diagnosis utilized objective assessment tools such as the Bristol stool form scale (BSFS) and a self-reported questionnaire known as the constipation severity score (CSS). The BSFS is a 7-level scale that visually inspects feces based on texture and morphology, while the CSS measures constipation duration and severity using a 5-point Likert scale for various factors. We employed Cox proportional hazards model regression to determine the associations between constipation and clinical outcomes, including mortality, hemodialysis (HD) transfer and peritonitis.RESULTS:Among 975 randomly selected PD patients from 22 facilities, 845 provided written informed consent, and 729 completed CSS questionnaire. Constipation was prevalent in the PD population (13%), particularly among older patients, those who were caregiver dependent, had diabetes and poorer nutritional status (indicated by lower time-averaged serum albumin, potassium, creatinine and phosphate concentrations). Twenty-seven percent of which experiencing symptoms of constipation for over a year. Notably, self-reported constipation at baseline was significantly associated with a shorter time to first peritonitis and higher rates of peritonitis and death. However, no significant association was found between constipation and HD transfer after adjusting for various factors, including age, gender, PD vintage, comorbidities, shared frailty by study sites and serum albumin.CONCLUSION:Patient-reported constipation independently correlated with increased risks of peritonitis and all-cause mortality, though no such correlation was observed with HD transfer. These findings underscore the need for further investigation to identify effective interventions for constipation in PD patients.
Abstract Background Kidney transplant recipients (KTR) are at increased risk of severe COVID-19 infection due to their immunosuppressive drugs. COVID-19 vaccination is recommended to prevent infection and severe illness. However, the knowledge on the durability of vaccine response and appropriate timing of booster vaccination is not well established. This study aimed to evaluate the anti-SARS-CoV-2 S antibody response > 12 weeks after the fourth vaccination and to identify factors associated with a good antibody response in KTR. Methods This single-center cross-sectional study was conducted at King Chulalongkorn Memorial hospital in Bangkok, Thailand between January and April 2023. It enrolled adult KTR who had been transplanted for more than 6 months and had received the fourth COVID-19 vaccine dose for more than 12 weeks. KTR with prior long acting antibody (LAAB) were excluded. Baseline characteristics, laboratory data, COVID-19 vaccine certificates, and history of prior infection were collected. Blood samples were taken at enrollment for anti-SARS-CoV-2 S antibody testing (Elecsys®, Cobas e 411 analyzer; Roche Diagnostics, Basel, Switzerland). An antibody level ≥ 1,000 BAU/mL was considered a high sustained response. All statistical analyses were performed using Stata 15.1 (Stata Corp., College Station, TX, USA). Results A total of 132 KTR were enrolled. The median age was 52 years, and 60% were male. Most KTR received two doses of viral vector vaccine as their first two primary shots with two doses of mRNA vaccine as the additional primary and booster shots. The overall anti-SARS-CoV-2 S antibody level was 4,917 (IQR 884.4 – 16,888.5) BAU/mL at the median of 261.5 (IQR 202 – 297.5) days since last vaccination. There were 96 (73%) of KTR with antibody level ≥ 1,000 BAU/mL. Baseline characteristics were shown in Table 1. History of COVID-19 infection was significantly associated with a good antibody response after multivariate logistic regression analysis with adjusted OR of 3.87 (95% CI 1.64 – 9.08) (Figure 1). Conclusion This study showed a high anti-SARS-CoV-2 S antibody response in KTR after the 4th vaccine dose, with 73% achieving a good response at > 6 months. Prior COVID-19 infection was associated with a good antibody response, indicating role of hybrid immunity among this patient population. Disclosures All Authors: No reported disclosures
A 25-year-old woman presented with dysuria and intermittent gross hematuria for 2 weeks. She underwent a kidney transplantation 2 years earlier because of end-stage kidney disease of unknown cause. She received basiliximab as induction therapy, followed by maintenance immunosuppression with mycophenolate mofetil 1,000 mg/day, tacrolimus with a target trough level of approximately 5 ng/ml, and prednisolone. Allograft function had been stable, with a serum creatinine of 1.4 mg/dl over the past year.
Introduction: More reports of thrombotic microangiopathy (TMA) in immunoglobulin A (IgA) nephropathy suggests its association with poor clinical outcomes. However, the prevalence and clinical significance of TMA in IgA nephropathy have not been widely studied in different populations.Methods: Kidney biopsies of all patients with primary IgA nephropathy from 1995 to 2015 at King Chulalongkorn Memorial Hospital, Thailand, were retrospectively reviewed and reclassified by two pathologists following the Oxford MEST-C classification. TMA lesions were detected based solely on light microscopic findings. Associations between the presence of TMA and clinical data, other pathologic findings, and clinical outcomes were studied.Results: Among 267 patients with primary IgA nephropathy, 166 had adequate clinical data and kidney tissues for the analysis. TMA was observed in 21 patients (13%) and was associated with higher mean arterial pressure (MAP), history of malignant hypertension, higher proteinuria, and lower estimated glomerular filtration rate (eGFR) at diagnosis compared to those without TMA. According to Oxford MEST-C classification, TMA showed a significant association with severe tubular atrophy/interstitial fibrosis (T2) but not with mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), or crescents (C1-2). After a median follow-up of 50 months, patients with TMA had a significantly higher risk of progression to end-stage kidney disease (ESKD) (hazard ratio [HR] 5.8, 95%CI 3.1-10.9) and all-cause mortality (HR 3.4, 95% CI 1.3-8.8). After adjusting for baseline eGFR, MAP, proteinuria, and other pathological lesions, TMA remained an independent predictor of ESKD (adjusted HR 2.4, 95%CI 1.1-5.4)Conclusions: Kidney TMA in IgA nephropathy is associated with advanced disease stages, carries a poor prognosis, and thus should be considered in the pathological classification of IgA nephropathy.
We report a case of a 60-year-old female who presented with intractable ascites 2 months after switching from peritoneal dialysis (PD) to hemodialysis (HD) due to an episode of refractory culture-negative peritonitis (CNP). Abdominal paracentesis yielded inflammatory ascites, which later grew Cladosporium cladosporioides, establishing the diagnosis of fungal peritonitis. She was successfully treated with a 4-week course of oral voriconazole. Cladosporium spp. are common fungi in the environment but rarely cause PD-associated peritonitis and can be challenging to diagnose with conventional microbiologic evaluation. In summary, PD-associated peritonitis can worsen after a patient switches to HD. Therefore, it is essential to maintain a high level of suspicion for such complications related to their previous dialysis modality to arrive at an accurate diagnosis.
Introduction: The mortality rate of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTR) has significantly decreased with the implementation of vaccination programs. However, the real-world information on the impact of vaccinations, particularly in resource limited settings in Asia, is still limited. Methods: The Thai Transplant Society conducted a prospective multicenter cohort registry, including KTR diagnosed with COVID-19. Cox proportional hazards regression was used to examine factors associated with poor COVID-19 outcomes and complications, including death, COVID-19 pneumonia, and superimposed bacterial infection. Results: A total of 413 patients from 17 transplant centers who developed COVID-19 were analyzed. The COVID-19 mortality rate was 5.6 % and the incidence of pneumonia was 18.8 %. With each 10-year increase in age, the risk of death, pneumonia, and bacterial infection increased by 61 %, 32 %, and 43 %, respectively. A total of 11.4 % of KTR received one dose of COVID vaccination (incomplete vaccination), 25.7 % received two doses (complete primary vaccination), 42.6 % received three doses (first booster dose), and 10.4 % received four doses of vaccination (second booster dose). Even a single dose of vaccination significantly decreased the risk of death, pneumonia, and superimposed bacterial infection among KTR compared to those who remained unvaccinated. Completing the primary vaccination (2-dose) reduced the risk of death by 89 %, pneumonia by 88 %, and bacterial infection by 83 % compared to unvaccinated KTR. Receiving a booster dose (third or fourth dose) further reduced the risk of death by 94 %, pneumonia by 95 %, and bacterial infection by 96 % compared to unvaccinated individuals. Conclusions: This Asian cohort demonstrated that the mortality and complications of COVID-19 significantly decreased in KTR after the national immunization. Our study suggests that any type of COVID-19 vaccine can be beneficial in preventing adverse outcomes. Administering booster vaccinations is strongly recommended.
It has been observed that SARS-CoV-2 infections are associated with the development of various de-novo autoimmune diseases; little is known on new-onset antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) after SARS-CoV-2 infections. We conducted a systematic review of previously reported cases with a presumed association of new-onset antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). No language restrictions were applied during the search. The eligible articles included reports of biopsy-proven pauci-immune glomerulonephritis that occurred following SARS-CoV-2 infection. The review was registered in PROSPERO database (CRD42023407786). Two further cases are reported. The mean age of SARS-CoV-2 infection-associated ANCA-GN was 48 ± 19 years. Fifty-six percent of patients showed positivity for myeloperoxidase (MPO)-ANCA. Among tested patients, 36
Introduction:The potential value of serum galactomannan index (GMI) in monitoring treatment response in patients with fungal peritonitis who are receiving peritoneal dialysis (PD) was assessed in the present study. Methods:The study included all Thailand fungal PD-related infectious complications surveillance (MycoPDICS) DATA study participants who had timely PD catheter removal and availability of both baseline and ≥2 subsequent serum GMI measurements after starting antifungal therapy (if available). Serum GMI was assessed by direct double-sandwich enzyme-linked immunosorbent assay with reference to positive and negative control samples. Comparisons of categorical variables among groups were analyzed by Fisher's exact test for categorical data and the Wilcoxon rank-sum test for continuous variables. Mortality outcomes were analyzed by survival analyses using Kaplan-Meier curves with Log-rank test. Results:Seventy-six (46%) of 166 participants from 21 PD centers between 2018 and 2022 were included. The median age was 58 (50-65) years, and a half of the patients (50%) had type II diabetes. Nineteen (25%) and 57 (75%) episodes were caused by yeast and mold, respectively. Death occurred in 11 (14%) patients at 3 months, and no differences were observed in demographics, laboratories, treatment characteristics, or in baseline serum GMI between those who died and those who survived. Serum GMI progressively declined over the follow-up period after the completion of treatment. Patients who died had significantly higher posttreatment serum GMI levels and were more likely to have positive GMI after treatment. Conclusion:Serum GMI is an excellent biomarker for risk stratification and treatment response monitoring in patients on PD with fungal peritonitis.