Association between Circulating MicroRNAs (miR-21-5p, miR-20a-5p, miR-29b-3p, miR-126-3p and miR-101-3p) and Chronic Allograft Dysfunction in Renal Transplant Recipients.

Chronic allograft dysfunction (CAD) is a major condition affecting long-term kidney graft survival. Serum microRNA (miRNA) has been reported as a biomarker for various conditions of allograft injuries. The upregulation of miR-21 is the best-known miRNA change in graft tissue, urine and plasma. However, the correlation of plasma miR-21 with the severity of CAD remains unclear. In our study, 40 kidney transplantation recipients with late graft survival for more than 10 years were enrolled. The CAD group (n = 20) had either an eGFR between 15 to 60 mL/min or a biopsy-proved chronic allograft nephropathy or rejection. The control group (n = 20) had an eGFR ≥ 60 mL/min without proteinuria and hematuria for a consecutive 3 months before the study. We performed RNA sequencing to profile the miRNAs expression. There were six differentially expressed miRNAs in the CAD group. Among them, miR-21-5p and miR-101-3p were decreased, and miR-20a-5p was increased. We found that miR-21-5p, miR-20a-5p and miR-101-3p all participated in the TGF-beta pathway. We demonstrated that decreased miR-21-5p and miR-101-3p, and increased miR-20a-5p were the novel CAD-associated miRNAs in the TGF-beta pathway. These findings may pave the way for developing early prediction miRNAs biomarkers for CAD, and possibly developing therapeutic tools in the field of kidney transplantation.

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

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

A Fatal Case of Chlorfenapyr Poisoning and the Therapeutic Implications of Serum Chlorfenapyr and Tralopyril Levels.

Chlorfenapyr is a new contact and stomach insecticide derived from natural pyrroles secreted by Streptomyces spp. It is a pro-insecticide and acts after metabolic transformation to its active metabolite tralopyril. Tralopyril is an uncoupler of oxidative phosphorylation in the mitochondria of the target insects and of experiment animals, leading to the disruption of adenosine triphosphate synthesis and death. Several fatal human poisonings had been reported and no blood chlorfenapyr or tralopyril measurements were available. The treatment remains supportive. A 32-year-old healthy man ingested 200 mL of 10% chlorfenapyr as a suicide attempt. Unfortunately, he succumbed at 157 h post-ingestion, shortly after having fever and seizures. His serum level of chlorfenapyr at 4 h post-exposure was 77.4 ng/mL, and was undetectable at 113 and 156 h, respectively. The serum levels of tralopyril were 723.6, 14,179, and 9654.2 ng/mL at 4, 113, and 156 h post-ingestion, respectively. The delay in the rise of serum tralopyril levels was noticeable, which seems to correlate with the patient's signs and symptoms. The information may have therapeutic implications in the management of this deadly poisoning.

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

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

Epidemiology of haemodialysis patients and haemodialysis performance in Nauru.

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

Reducing Waiting Times and Admission Periods through Pre-Admission Testing: A Quality Improvement Study on In-Hospital Renal Biopsy.

Background: Admission for renal biopsy is considered the gold standard for diagnosing kidney disease. However, prolonged waiting times for admission can lead to delayed diagnosis. Despite this issue, there are currently no studies demonstrating how to improve the efficiency of renal biopsy procedures. Methods: We initiated a quality improvement project to implement pre-admission testing (PAT) for renal biopsy from 2016 to 2024 (until 15 April). Our evaluation focused on waiting times for admission, length of admission periods, hospitalization expenses, percentage of cases with no renal biopsy performed, incidence of severe bleeding due to renal biopsy, and percentage of cases with adequate tissue samples obtained. Additionally, we highlighted the time periods during the outbreak of SARS-CoV-2. Results: The highest annual case number was observed in time period 1 (168.3/year). Following the outbreak of SARS-CoV-2, there was a notable decrease in case numbers during time period 2 (119.8), which then increased to 143.0 in time period 3 (post-SARS-CoV-2 era). The mean waiting time was 13.72 ± 40.30 days for time period 1 and 10.00 ± 47.80 days for time period 2, without statistical significance. Following the implementation of PAT, patients now only need to wait approximately 0.76 days for admission, representing a significant reduction in waiting time. Subsequently, following the implementation of PAT, the waiting time decreased significantly to 2.09 ± 2.65 days. Additionally, hospitalization expenses per patient significantly decreased from approximately USD 69.62 ± 97.09 to USD 41.66 ± 52.82. The percentage of missed biopsy is significantly low (p < 0.001). Severe bleeding events (indicated as embolization and blood transfusion) were consistent across the three time periods (p = 0.617). Conclusions: The implementation of PAT can improve the pre-admission process for renal biopsy, resulting in decreased waiting times, fewer missed appointments, shorter admission durations, and reduced hospitalization expenses. We propose implementing PAT for outpatient individuals awaiting in-hospital renal biopsy procedures to mitigate delayed diagnosis, reduce pre-admission waiting periods, and streamline admission processes, thereby enhancing overall patient care efficiency.

Machine Learning Models to Predict the Risk of Rapidly Progressive Kidney Disease and the Need for Nephrology Referral in Adult Patients with Type 2 Diabetes.

Early detection of rapidly progressive kidney disease is key to improving the renal outcome and reducing complications in adult patients with type 2 diabetes mellitus (T2DM). We aimed to construct a 6-month machine learning (ML) predictive model for the risk of rapidly progressive kidney disease and the need for nephrology referral in adult patients with T2DM and an initial estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2. We extracted patients and medical features from the electronic medical records (EMR), and the cohort was divided into a training/validation and testing data set to develop and validate the models on the basis of three algorithms: logistic regression (LR), random forest (RF), and extreme gradient boosting (XGBoost). We also applied an ensemble approach using soft voting classifier to classify the referral group. We used the area under the receiver operating characteristic curve (AUROC), precision, recall, and accuracy as the metrics to evaluate the performance. Shapley additive explanations (SHAP) values were used to evaluate the feature importance. The XGB model had higher accuracy and relatively higher precision in the referral group as compared with the LR and RF models, but LR and RF models had higher recall in the referral group. In general, the ensemble voting classifier had relatively higher accuracy, higher AUROC, and higher recall in the referral group as compared with the other three models. In addition, we found a more specific definition of the target improved the model performance in our study. In conclusion, we built a 6-month ML predictive model for the risk of rapidly progressive kidney disease. Early detection and then nephrology referral may facilitate appropriate management.

Integrated Osteoporosis Care to Reduce Denosumab-Associated Hypocalcemia for Patients with Advanced Chronic Kidney Disease and End-Stage Renal Disease.

The incidence of hypocalcemia is high in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) undergoing denosumab treatment. Since 2018, we have carried out a "multidisciplinary integrated care program for osteoporosis among patients with CKD and ESRD" in our hospital. The aim of this study was to compare the incidence of denosumab-associated hypocalcemia among patients with advanced CKD and ESRD before and after the integrated care program. We retrospectively reviewed the records of patients on their first dose of denosumab treatment from January 2012 to December 2021. A total of 3208 patients were included in our study. Among the 3208 patients, there were 101 dialysis patients, 150 patients with advanced CKD (stage 4 and 5), and 2957 patients with an estimated glomerular filtration rate (eGFR) higher than or equal to 30. The incidence of post-treatment severe hypocalcemia (corrected calcium level less than 7.0 mg/dl) within 30 days was significantly higher in the dialysis and advanced CKD group than in patients with an eGFR higher than or equal to 30 (6.9% vs. 2.0% vs. 0.1%, respectively, p < 0.001). Based on the results of the multivariate regression model, poor renal function (p < 0.05) and lower baseline corrected calcium level (p < 0.05) were associated with severe hypocalcemia within 30 days following the first dose of denosumab treatment. The incidence of post-treatment severe hypocalcemia within 30 days in advanced CKD and dialysis patients was significantly lower after the integrated care program (6.8% vs. 0.8%, p < 0.05). Our study shows that multidisciplinary integrated care may reduce the incidence rate of denosumab-associated severe hypocalcemia among patients with advanced CKD and ESRD.

Quality Improvement Initiatives in Renal Biopsy for Patient-Centered Communication by Shared Decision Making.

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.

Air Pollution Alleviation During COVID-19 Pandemic is Associated with Renal Function Decline in Stage 5 CKD Patients.

Introduction: Air pollution is a novel environmental risk factor for chronic kidney disease (CKD). Air quality improved during COVID-19 lockdowns; however, the effects of these lockdowns on PM2.5 concentrations and renal function remain unclear. Methods: We conducted a retrospective cohort study to compare air pollution and estimated glomerular filtration rate (eGFR) decline in patients with stage 5 CKD between a year-long period of lockdown (2020; n = 724) and a similar period before lockdown (2019, n = 758). Results: Compared with 2019, a 17.5% reduction in the average PM2.5 concentration (from 17.36% to 14.32%; P < 0.001) and a 45.1% reduction (from 20.56% to 11.25%; P < 0.001) in cumulative days with PM2.5 concentration >35 µg/m3 were noted in 2020. Moreover, a 93% reduction in PM2.5 air quality index >150 per station-day (from 0.43% to 0.03%) was observed in 2020. From 2019 to 2020, the yearly incidence of eGFR decline ≥5 mL/min/1.73 m2 decreased by 33.7% (24.6% vs 16.3%; P < 0.001). Similarly, the proportion of patients who started undergoing regular dialysis also decreased by 32.7% in 2020 (from 20.8% to 14.0%; P = 0.001). Conclusion: Our findings suggest that fewer events of renal function decline during the COVID-19 pandemic may be associated with a decline in PM2.5 concentrations, supporting the global strategy of reducing air pollution to prevent CKD progression.

Patterns of biopsy-proven renal diseases in geriatric patients: A single medical center experience.

The elderly population is expanding rapidly, and that has become a major healthcare burden in terms of chronic kidney disease. The distribution patterns of kidney diseases in these elderly patients remain largely unclear. Here, we compared biopsy-based renal disease patterns between elderly and nonelderly patients. We performed a single-center, retrospective study (1992-2008) on biopsy-proven renal diseases to compare results between geriatric patients (age ≥ 65 years; n = 254) and nongeriatric patients (18 ≤ age < 65 years; n = 2592). Renal pathology was interpreted by pathologists based on light microscopy, immunofluorescence, and electron microscopy. The ages of the geriatric and nongeriatric groups were 71.8 ±â€…4.5 (65.1-87.3) and 39.7 ±â€…17.6 (18-64.9) years, respectively, and 74% and 41% of them, respectively, were men. In the geriatric group, the most frequent diagnosis was membranous nephropathy (46.1%), followed by minimal change disease/focal segmental glomerulosclerosis (16.9%), diabetic nephropathy (8.3%), hypertensive nephrosclerosis (7.5%), and IgA nephropathy (5.9%). The geriatric group had more membranous nephropathy and less lupus nephritis and IgA nephropathy than the nongeriatric group. Furthermore, the 5-year survival rate of the geriatric group was significantly low. Our results demonstrated the different distributions of renal biopsy patterns in geriatric patients diagnosed with acute or chronic progressive kidney injury and proteinuria through renal biopsy.

FDG PET/CT images demonstrating Fournier gangrene with bilateral pelvic muscle extension in a patient with recurrent rectosigmoid cancer.

A 71-year-old male patient with Parkinsonism was referred for an F-FDG PET/CT scan for suspicious recurrence of rectosigmoid adenocarcinoma. The FDG PET/CT scan revealed increased FDG uptakes in the lower pelvic region around the wall of the rectal stump, with extension to the bilateral pelvic sidewalls and the right gluteous minimus muscle. In addition, multiple small air bubbles were noted in the lesions on the attenuation CT images. Fournier gangrene was diagnosed. After treatment with intravenous antibiotics and debridement with sigmoidoscopic irrigation, the patient was discharged and remained uneventful during clinical follow-up for 50 days.

FDG PET/CT repeatedly demonstrated hepatic cyst infection in a patient with autosomal dominant polycystic kidney disease.

A 70-year-old man with a history of autosomal dominant polycystic kidney disease was referred for F-FDG PET/CT scans twice at 6-month intervals due to repeated fever with negative conventional imaging studies. The FDG PET/CT scans revealed different hepatic cyst lesions in the 2 scans, with a large infected cyst in the second study. After aspiration and intravenous antibiotics treatment, the patient was discharged and remained uneventful thereafter for 6 months.