Urinary vanin-1, tubular injury, and graft failure in kidney transplant recipients.

We investigated whether urinary vascular non-inflammatory molecule-1 (vanin-1), a promising early-onset tubular injury marker, correlates with other established tubular injury markers and is associated with graft failure in kidney transplant recipients (KTR). We measured 24 h urinary vanin-1 excretion in 656 KTR (age 53 ± 13 years, 43% female, estimated glomerular filtration rate (eGFR) 53 ± 21 mL/min/1.73 m2) who had undergone kidney transplantation ≥ 1 year. The median 24 h urinary vanin-1 excretion was 145 [51-331] pmol/24 h. 24 h urinary vanin-1 excretion correlated weakly but significantly with other tubular injury markers (ρ = 0.14, p < 0.001 with urinary liver-type fatty acid binding protein, ρ = 0.13, p = 0.001 with urinary post-translationally modified fetuin-A protein, and ρ = 0.10, p = 0.011 with plasma neutrophil gelatinase-associated lipocalin) and with eGFR (ρ = - 0.13, p = 0.001). During a median follow-up of 7.4 [4.9-8.0] years, 94 (14%) KTR developed death-censored graft failure. In multivariable Cox regression analyses, 24 h urinary vanin-1 excretion was not associated with an increased risk of death-censored graft failure (adjusted hazard ratio [95% confidence interval] = 0.96 [0.86-1.07], p = 0.5). In conclusion, our findings do not support the role of urinary vanin-1 as a biomarker of graft failure after kidney transplantation.

Urinary Post-Translationally Modified Fetuin-A Protein Is Associated with Increased Risk of Graft Failure in Kidney Transplant Recipients.

INTRODUCTION: Urinary fetuin-A has been identified as a biomarker for acute kidney injury and is proposed as a biomarker for early detection of kidney function decline. We investigated whether fetuin-A could serve as a marker of graft failure in kidney transplant recipients (KTRs). METHODS: Data of KTR with a functioning graft ≥1 year that were enrolled in the TransplantLines Food and Nutrition Biobank and cohort study were used. Graft failure was defined as the need for re-transplantation or (re-)initiation of dialysis. Urinary fetuin-A was measured using an enzyme-linked immunosorbent assay kit that detected post-translationally modified fetuin-A in the urine (uPTM-FetA). In the main analyses, 24h uPTM-FetA excretion was used. In the sensitivity analyses, we excluded the outliers in 24h uPTM-FetA excretion, and we used uPTM-FetA concentration and uPTM-FetA concentration indexed for creatinine instead of 24h uPTM-FetA excretion. RESULTS: A total of 627 KTRs (age 53 ± 13 years, 42% females) were included at 5.3 (1.9-12.2) years after transplantation. The estimated glomerular filtration rate (eGFR) was 52 ± 20 mL/min/1.73 m2 and uPTM-FetA excretion was 34 (17-74) µg/24 h. During a median follow-up of 5.3 (4.5-6.0) years after baseline measurements, 73 (12%) KTRs developed graft failure. The association of 24h uPTM-FetA excretion with increased risk of graft failure was not constant over time, with increased risk only observed after 3 years from baseline measurements, independent of potential confounders including kidney function and 24 h urinary protein excretion (hazard ratio per doubling of 24h uPTM-FetA excretion = 1.31; 95% confidence interval = 1.06-1.61). This finding was robust in the sensitivity analyses. CONCLUSIONS: Our findings suggest that uPTM-FetA can be used as a marker for early detection of graft failure in KTR. Further studies are needed to confirm our findings.

Urinary Fetuin-A Fragments Predict Progressive Estimated Glomerular Filtration Rate Decline in Two Independent Type 2 Diabetes Cohorts of Different Ethnicities.

INTRODUCTION: There is a great clinical need for novel markers to predict kidney function decline in patients with type 2 diabetes. We explored the potential of posttranslationally modified fetuin-A fragments in urine (uPTM-FetA) as such a marker. METHODS: We included patients with type 2 diabetes from two independent, nonoverlapping prospective cohort studies. A cut-off for uPTM-FetA, measured via ELISA method, was determined using the Youden index in the primary cohort of patients with type 2 diabetes from Taiwan. Kidney endpoint was defined as an estimated glomerular filtration rate (eGFR) decline ≥30% from baseline, reaching of an eGFR <15 mL/min/1.73 m2, or a need of renal replacement therapy. Prospective associations were assessed in Cox regression models. All analyses were replicated in a cohort of patients with type 2 diabetes from the Netherlands. RESULTS: In total, 294 patients with type 2 diabetes (age 61 ± 10 years, 55% male, eGFR 88 ± 16 mL/min/1.73 m2) were included in the primary cohort. During a follow-up of median 4.6 years, 42 participants (14%) experienced the kidney endpoint. Using the defined cut-off, a high uPTM-FetA was associated with a higher risk of renal function decline (Plog-rank < 0.0001). This association was similar in subgroups depending on albuminuria. This association remained, independent of age, sex, baseline eGFR, albuminuria, HbA1c, and other potential confounders (HR: 9.94; 95% CI: 2.96-33.40; p < 0.001 in the final model). Analyses in the validation cohort (376 patients with type 2 diabetes, age 64 ± 11 years, 66% male, eGFR 76 ± 24 mL/min/1.73 m2) using the same cut-off yielded similar results. CONCLUSION: uPTM-FetA was independently associated with kidney function decline in patients with type 2 diabetes validated in a 2-cohort study. The significant additive predictive power of this biomarker from conventional risk factors suggests its clinical use for renal function progression in patients with type 2 diabetes.

Long-term systolic blood pressure variability independent of mean blood pressure is associated with mortality and cardiovascular events: A systematic review and meta-analysis.

The association between long-term systolic blood pressure variability (SBPV) and cardiovascular (CV) outcomes after being adjusted with mean blood pressure (BP) is questionable. This systematic review aims to evaluate the associations between mean BP adjusted long-term SBPV and CV outcomes. A systematic search was conducted on PubMed, Scopus, and Science Direct on January 4, 2023. A total of 9,944,254 subjects from 43 studies were included in this meta-analysis. Long-term SBPV increased the risk of all-cause mortality (HR 1.21 [95%CI 1.16-1.25], I2=100%), CV mortality (HR 1.10 [95%CI 1.07-11.4], I2 = 90%), MACE (HR 1.10 [1.07-1.13], I2 = 91%), cerebrovascular stroke (HR 1.22 [1.16-1.29], I2=100%), and myocardial infarction (HR 1.13 [95%CI (1.07-1.19)], I2=91%). European populations generally had higher risk compared to other continents. In conclusion, long-term SBPV is associated with all-cause mortality, CV mortality, MACE, MI, and stroke. Poor outcomes related to long-term SBPV seem more dominated by cerebrovascular than coronary events.

Comparison of different scoring systems for predicting in-hospital mortality for patients with Fournier gangrene.

PURPOSE: To compare different scoring systems for predicting in-hospital mortality in patients with Fournier gangrene (FG). METHODS: A comprehensive literature search was performed to find all scoring systems that have been proposed previously as a predictor for in-hospital mortality in patients with FG. Data of all patients with FG who were hospitalized in one of Indonesia's largest tertiary referral hospitals between 2012 and 2022 were used. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the scoring systems. RESULTS: Ten scoring systems were found, i.e., Fournier's Gangrene Severity Index (FGSI), Uludag FGSI, simplified FGSI, NUMUNE Fournier score (NFS), Laboratory Risk Indicator for Necrotizing Fasciitis, age-adjusted Charlson comorbidity index, sequential organ failure assessment (SOFA), quick SOFA, acute physiology and chronic health evaluation II, and surgery APGAR score (SAS). Of 164 FG patients included in the analyses, 26.4% died during hospitalization. All scoring systems except SAS could predict in-hospital mortality of patients with FG. Three scoring systems had areas under the ROC curve (AUROC) higher than 0.8, i.e., FGSI (AUROC 0.905, 95% confidence interval (CI) 0.860-0.950), SOFA (AUROC 0.830, 95% CI 0.815-0.921), and NFS (AUROC 0.823, 95% CI 0.739-0.906). Both FGSI and SOFA had sensitivity and NPV of 1.0, whereas NFS had a sensitivity of 0.74 and an NPV of 0.91. CONCLUSION: This study shows that FGSI and SOFA are the most reliable scoring systems to predict in-hospital mortality in FG, as indicated by the high AUROC and perfect sensitivity and NPV.

Diagnostic performance of calf circumference, SARC-F, and SARC-CalF for possible sarcopenia screening in Indonesia.

Asian working group for sarcopenia (AWGS) recently introduced "possible sarcopenia" diagnosis for early identification of sarcopenia in the primary healthcare. For initial screening, 3 modalities, i.e. calf circumference (CC) measurement, strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) questionnaire, and a combination of both (SARC-CalF), are recommended. However, no validation study has been done until now. Therefore, this study aims to evaluate the diagnostic performance of the recommended screening modalities using data from Indonesia. This cross-sectional study included subjects aged ≥ 60 years old who visited primary healthcare in Surabaya, Indonesia. The diagnosis of possible sarcopenia was confirmed with hand-grip strength and repeated chair stand test. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. Among 266 subjects, 186 (70%) were diagnosed with possible sarcopenia. Using the recommended cut-off, the area under the curve, sensitivity, and specificity were 0.511, 48.39% and 53.75% for CC, 0.543, 8.60% and 100% for SARC-F, and 0.572, 19.35% and 95% for SACRC-CalF. Our findings indicate that the diagnostic performance of the recommended screening modalities is poor. Multicenter studies from different areas in Indonesia should be done to confirm these findings.

Plasma endotrophin, reflecting tissue fibrosis, is associated with graft failure and mortality in KTRs: results from two prospective cohort studies.

BACKGROUND: Fibrosis is a suggested cause of graft failure and mortality among kidney transplant recipients (KTRs). Accumulating evidence suggests that collagen type VI is tightly linked to fibrosis and may be a marker of systemic fibrosis and ageing. We studied whether plasma endotrophin, a pro-collagen type VI fragment, is associated with graft failure and mortality among KTRs. METHODS: In cohort A (57% male, age 53 ± 13 years), we measured plasma endotrophin in 690 prevalent KTRs ≥1 year after transplantation. The non-overlapping cohort B included 500 incident KTRs with serial endotrophin measurements before and after kidney transplantation to assess trajectories and intra-individual variation of endotrophin. RESULTS: In cohort A, endotrophin was higher in KTRs compared with healthy controls. Concentrations were positively associated with female sex, diabetes, cardiovascular disease, markers of inflammation and kidney injury. Importantly, endotrophin was associated with graft failure {hazard ratio [HR] per doubling 1.87 [95% confidence interval (CI) 1.07-3.28]} and mortality [HR per doubling 2.59 (95% CI 1.73-3.87)] independent of potential confounders. Data from cohort B showed that endotrophin concentrations strongly decrease after transplantation and remain stable during post-transplantation follow-up [intra-individual coefficient of variation 5.0% (95% CI 3.7-7.6)]. CONCLUSIONS: Plasma endotrophin is strongly associated with graft failure and mortality among KTRs. These findings suggest a key role of abnormal extracellular matrix turnover and fibrosis in graft and patient prognosis among KTRs and highlight the need for (interventional) studies targeting the profibrotic state of KTRs. The intra-individual stability after transplantation indicates potential use of endotrophin as a biomarker and outcome measure of fibrosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT02811835.

Prevalence and risk factors for disability in leprosy patients in Indonesia during the post-elimination era.

Leprosy has been nationally eliminated in Indonesia, but it continues to be a public health problem, with disability contributing to the disease burden. Disability caused by leprosy often results in stigmatization, leading to decreased quality of life. This was a retrospective cross-sectional study using secondary data from primary healthcare centers in one of the districts in the region with the highest number of leprosy patients in Indonesia. All leprosy patients between 2016-2022 were included. Among 189 leprosy patients (mean age 46 years old, 65.6% male), 19% had grade 1 disability and 29.6% had grade 2 disability. Duration of disease, nerve enlargements, leprosy reactions, and symmetric lesions were identified as risk factors for both grade 1 and 2 disability. Being male and having a positive smear test was associated with a higher risk of only grade 2 disability. Disability due to leprosy is still prevalent in the post-elimination era despite the decline in new leprosy cases. Improvement in early case detection and prevention of disability are still needed in the post-elimination era.

Pressure Injury Management in Critically Ill Patients with COVID-19 in a Makeshift Hospital in Indonesia: A Report of Two Cases.

ABSTRACT: Patients who are critically ill with COVID-19 need ventilation support in the ICU. However, ICU patients are at higher risk of developing a pressure injury (PI). Unfortunately, PI prevention is not optimally implemented in Indonesia, especially in the makeshift hospitals created during the COVID-19 pandemic. Here, the authors report two cases of critically ill patients with COVID-19 who developed large sacral PIs during hospitalization in a makeshift hospital in Indonesia. The first patient developed a stage 3, 7 × 7-cm sacral PI on the 14th day of hospitalization. The second patient developed a stage 4, 12 × 8-cm sacral PI on the 16th day of hospitalization. Both patients had elevated d-dimer levels and used a noninvasive ventilator for 1 week. The wounds were treated with surgical debridement, silver hydrogel dressing, and hydrocolloid dressing and complemented with static air mattress overlay. The authors recommend that in situations where there is a shortage of healthcare workers, the government should provide pressure-redistribution devices and silicone foam dressings for all critically ill patients to prevent PI development and lighten the workload of healthcare workers.

Weak Expression of Terminal Complement in Active Antibody-Mediated Rejection of the Kidney.

Background: The role of the complement system in antibody-mediated rejection (ABMR) is insufficiently understood. We aimed to investigate the role of local and systemic complement activation in active (aABMR). We quantified complement activation markers, C3, C3d, and C5b-9 in plasma of aABMR, and acute T-cell mediated rejection (aTCMR), and non-rejection kidney transplant recipients. Intra-renal complement markers were analyzed as C4d, C3d, C5b-9, and CD59 deposition. We examined in vitro complement activation and CD59 expression on renal endothelial cells upon incubation with human leukocyte antigen antibodies. Methods: We included 50 kidney transplant recipients, who we histopathologically classified as aABMR (n=17), aTCMR (n=18), and non-rejection patients (n=15). Results: Complement activation in plasma did not differ across groups. C3d and C4d deposition were discriminative for aABMR diagnosis. Particularly, C3d deposition was stronger in glomerular (P<0,01), and peritubular capillaries (P<0,05) comparing aABMR to aTCMR rejection and non-rejection biopsies. In contrast to C3d, C5b-9 was only mildly expressed across all groups. For C5b-9, no significant difference between aABMR and non-rejection biopsies regarding peritubular and glomerular C5b-9 deposition was evident. We replicated these findings in vitro using renal endothelial cells and found complement pathway activation with C4d and C3d, but without terminal C5b-9 deposition. Complement regulator CD59 was variably present in biopsies and constitutively expressed on renal endothelial cells in vitro. Conclusion: Our results indicate that terminal complement might only play a minor role in late aABMR, possibly indicating the need to re-evaluate the applicability of terminal complement inhibitors as treatment for aABMR.

Mental health and health-related quality of life among healthcare workers in Indonesia during the COVID-19 pandemic: a cross-sectional study.

OBJECTIVES: Healthcare workers (HCWs) are the front lines during the COVID-19 pandemic. They are more exposed to COVID-19 than other professions. Studies from other countries have shown that the mental health and health-related quality of life (HRQoL) of HCWs were affected during this pandemic. However, studies on mental health in Indonesia remain scarce and no study has evaluated the HRQoL among HCWs. Thus, this study was designed to explore the mental health status and HRQoL among HCWs in Indonesia. DESIGN: This was a cross-sectional study. SETTING: This was an open online survey in Indonesia conducted from December 2020 to February 2021. PARTICIPANTS: This study involved HCWs who worked during the COVID-19 pandemic. Of the 502 respondents who accessed the online questionnaire, 392 were included in the analysis. OUTCOMES: Mental health status was measured using the 21-item Depression, Anxiety and Stress Scale and HRQoL was measured using the second version of the 12-item Short-Form Health Survey (SF12v2). RESULTS: The prevalence of depression, anxiety and stress among HCWs was 29.4%, 44.9% and 31.8%, respectively. Using the SF12v2 questionnaire, 354 (90.3%) HCWs were found to have impaired physical component and 156 (39.8%) HCWs have impaired mental component. CONCLUSION: The prevalence of mental health problems among HCWs was high in Indonesia. HRQoL, particularly the physical component, was affected in most HCWs. Thus, policymakers should give more attention to the mental health and HRQoL of HCWs during the COVID-19 pandemic.

Pretransplant endotrophin predicts delayed graft function after kidney transplantation.

Delayed graft function after kidney transplantation is common and increases morbidity and health care costs. There is evidence that endotrophin, a specific fragment of pro-collagen type VI, promotes the inflammatory response in kidney diseases. We tested the hypothesis that pretransplant endotrophin in kidney transplant recipients may be associated with the risk of delayed graft function. Pretransplant plasma endotrophin was assessed using an enzyme-linked immunosorbent assay in three independent cohorts with 806 kidney transplant recipients. The primary outcome was delayed graft function, i.e., the necessity of at least one dialysis session within one-week posttransplant. In the discovery cohort median pretransplant plasma endotrophin was higher in 32 recipients (12%) who showed delayed graft function when compared to 225 recipients without delayed graft function (58.4 ng/mL [IQR 33.4-69.0]; N = 32; vs. 39.5 ng/mL [IQR 30.6-54.5]; N = 225; P = 0.009). Multivariable logistic regression, fully adjusted for confounders showed, that pretransplant plasma endotrophin as a continuous variable was independently associated with delayed graft function in both validation cohorts, odds ratio 2.09 [95% CI 1.30-3.36] and 2.06 [95% CI 1.43-2.97]. Pretransplant plasma endotrophin, a potentially modifiable factor, was independently associated with increased risk of delayed graft function and may be a new avenue for therapeutic interventions.

Gastric perforation mimicking ST-segment elevation myocardial infarction.

ST-elevation myocardial infarction (STEMI) is one of the medical emergencies in cardiology with high morbidity and mortality rate which requires rapid response. In elderly patients, its presenting symptoms may be atypical which may cause the diagnosis of MI to be delayed or missed. Therefore, ST-segment elevation on ECG has become the main instrument for initial diagnosis. However, there are a variety of conditions mimicking the ECG changes of STEMI. We report a case of 70-year-old patient with acute peritonitis and pneumoperitoneum secondary to gastric perforation with dynamic ECG changes mimicking anteroseptal STEMI. After the surgery, the ECG dynamically reverted to normal. He was then discharged after 4 days without any remaining symptoms. Misinterpretation of ECG findings may lead to unnecessary aggressive intervention, costly management strategies and delay in appropriate treatment.

Electrocardiographic abnormalities among late-stage non-dialysis chronic kidney disease patients.

OBJECTIVES: Cardiovascular disease (CVD) complication is common among chronic kidney disease (CKD) patients. Thus, knowledge about CVD and ECG abnormalities in CKD are essential due to progressive nature of the disease and increased risk of sudden cardiac death. This study aims to scrutinize the ECG abnormalities among nondialysis late-stage CKD patients. METHODS: A descriptive observational study was conducted at Dr. Soetomo General Hospital, Surabaya, Indonesia. Subjects were hospitalized patients with late-stage CKD between 1 January and 31 December 2019, who were consulted at the department of cardiology and vascular medicine during their initial admission at emergency room. ECG interpretation for this study was done by qualified cardiologist. RESULTS: There were 191 patients included in this study. Mean ages were 52.2 ± 11.8 years old and 51% were males. Total 143 (74.9%) patients had anemia, 111 (58.1%) had hypertension and 75 (39.3%) had type 2 diabetes mellitus. Mean serum creatinine was 10.5 ± 8.0 mg/dL. There were 176 (92.1%) patients with at least one form of ECG abnormalities. Prolonged QTc interval (36.6%), fragmented QRS complex (29.8%), poor R wave progression (24.6%), peaked T wave (22.0%) and left ventricular hypertrophy (16.7%) were the most common abnormalities. CONCLUSIONS: ECG abnormalities are common among nondialysis late-stage CKD patients. Given the fact that long-term CKD influences the pathogenesis cardiovascular diseases and substantial cardiovascular mortality, there is a need to screen Indonesian CKD patients who are at risks of getting earlier complications.