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Background & Aims Diabetes Mellitus is the most common cause of end-stage kidney disease (ESKD) in Singapore. ESKD patients have high disease burden and are at increased risk of recurrent hospitalizations, including fluid overload. This study aimed to characterize the risk factors associated with readmissions for fluid overload that will identify high-risk hospitalizations for interventions to reduce readmissions. Methods Retrospective cohort study of all hospitalizations for fluid overload in adults with diabetes and ESKD on dialysis in SingHealth hospitals between 2018 and 2021. Fluid overload was defined by discharge codes for fluid overload, heart failure, pulmonary edema, and generalized edema until 30th December 2022. Multivariable Cox regression analysis using the Prentice, Williams and Peterson Total Time (PWP-TT) model was performed for the outcomes of readmissions for fluid overload within 30 days and 90 days of discharge. Results Among 3234 hospitalizations for fluid overload, readmission for fluid overload within 30-day and 90-day occurred in 585 (18.1%) and 967 (29.9%) hospitalizations, respectively. Ischemic heart disease, peripheral vascular disease and lower hemoglobin level were independently associated with readmissions for fluid overload within 30 and 90 days. Additionally, heart failure, hemodialysis (compared to peritoneal dialysis) and lack of statin at discharge were associated with increased 90-day readmission risk. Conclusion Modifiable (hemoglobin level, statin use) and non-modifiable factors (ischemic heart disease, peripheral vascular disease and heart failure) influenced the risk of readmission for fluid overload. These results may guide risk stratification and inform targeted interventions to reduce avoidable, unplanned readmissions for recurrent fluid overload among individuals with diabetes and ESKD., (The Author(s). Published by S. Karger AG, Basel.)

With the exponential surge in patients with coronavirus disease 2019 (COVID-19) worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multicenter projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online-generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multicenter collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: To evaluate the mid-term outcomes of regular surveillance venography with or without percutaneous transluminal angioplasty (PTA) in haemodialysis patients presenting with central venous occlusive disease., Materials and Methods: A single-centre retrospective analysis of haemodialysis patients who presented with central vein occlusion (CVO) and central vein stenosis (CVS) between January 2008 and December 2011 was performed. CVO and significant CVS were defined as 100% and >50% luminal narrowing, respectively. Upon successful angioplasty on first presentation, patients were followed up with regular surveillance venography within 3-6 months of the intervention and were re-treated when a significant stenosis or occlusion was demonstrated. Data on patient's demographics, comorbidities, presenting symptoms, type of upper limb dialysis access, lesion characteristics and complications were collected. Technical success, primary patency and primary assisted patency were analysed., Results: Thirty-five patients with CVO and 77 patients with CVS were enrolled. The technical success of initial PTA was 77% and 73% for the CVO and CVS groups, respectively. The primary patency at 3 months was 65% and 55% for the CVO group and CVS group, respectively ( P = 0.32). The primary assisted patency at 1 year was 88% and 99% for the CVO group and CVS group, respectively ( P = 0.009). At 2 years, the primary assisted patency were 77% and 90%, respectively ( P = 0.07). There was significant difference in the overall primary assisted patency ( P = 0.048) between the CVO and CVS groups., Conclusion: CVOs are more difficult to treat than CVS. High primary assisted patency rates can be achieved with surveillance venography, albeit at the expense of increased number of interventions. Further cost effectiveness studies need to be performed to study the true benefit of our surveillance programme.

Introduction:: Hemodialysis is the main modality of renal replacement therapy in Singapore. However, a majority of the patients in Singapore are initiated on hemodialysis via a catheter. This study examines the complication rates and factors predicting catheter-related bloodstream infections and mortality rates in patients who were initiated on hemodialysis at our institution., Methods:: This is a single-center retrospective analysis of incident hemodialysis patients who were initiated on renal replacement therapy between 1 January 2010 and 31 December 2012. Catheter-related bloodstream infection risk factors, organisms, and associated mortality were analyzed., Results:: The catheter-related bloodstream infection and exit site infection incidence rates were 0.75 and 0.50 per 1000 catheter days, respectively. The mean duration to first catheter-related bloodstream infection episode was 182.47 ± 144.04 catheter days. Prolonged catheter duration was found to be a risk factor for catheter-related bloodstream infection. Compared to patients initiated on dialysis via arteriovenous fistula, initiation of dialysis via catheter is strongly associated with increased mortality (6.0% vs 14.5%; p = 0.02). In particular, the presence of diabetes mellitus and development of catheter-related bloodstream infection was associated with increased mortality ( p = 0.04 and 0.05, respectively). In addition, patients who began hemodialysis before being seen by a nephrologist were associated with decreased mortality (3.4% vs 13.0%; p = 0.03)., Conclusion:: In conclusion, prolonged duration of catheter insertion is found to be a risk factor for catheter-related bloodstream infection in hemodialysis patients, and its development is associated with increased mortality. Early referral to a nephrologist and creation of arteriovenous fistula in pre-end-stage renal disease patients are pivotal in improving the outcomes of patients.

Background: In 1985 we reported that 11% of a cohort of 151 patients with IgA nephritis (IgAN) had developed end-stage renal disease (ESRD) after a follow-up period of 5 years. 15 years later, 35% had developed ESRD., Methods: We retrieved 125 stored renal biopsy paraffin blocks of the original cohort. From these, 102 patients were included in the present study and scored according to the Oxford classification as 21 specimens with less than 8 glomeruli were excluded and in 2 others, tissue samples were too tiny for a re-block. ESRD was ascertained by linking the study cohort to the Singapore Renal Registry at the National Registry of Diseases Office., Results: Renal survival curves for each of the Oxford MEST lesions: endocapillary proliferation (E) (p < 0.04), segmental glomerulosclerosis (S) (p < 0.05), tubular atrophy/interstitial fibrosis (p < 0.0001) were significantly associated with ESRD. Mesangial hypercellularity, less commonly associated with progressive chronic kidney disease (CKD) in the study, was independently associated with ESRD at 30 years (p < 0.03). In this cohort, E and S were associated with lower eGFR at presentation and doubling of serum creatinine in the first 5 years. This study's initial 5 years was representative of the "natural history" of IgAN since no renin-angiotensin system (RAS) blockers or immunosuppression were administered. This represents the early phase of disease progression. E and S may be considered "early disease activity predictors"., Conclusion: Mesangial hypercellularity and tubular atrophy/interstitial fibrosis (M1 and T1/T2 lesion) of the Oxford classification independently predicted long term ESRD.
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Background: Epstein-Barr virus-associated smooth muscle tumors (EBV SMT) in adult kidney transplant recipients (KTR) are rare. The aims of this study are to document the clinical features, types of treatment given, and outcomes of KTR with EBV SMT in our institution., Methods: Sixteen patients were identified from our institution's databases. Patients' survival, tumor outcome, and graft survival were compared between patients who remained on cyclosporine-based immunosuppressant and those who converted to sirolimus-based therapy., Results: The median time of diagnosis was 9.4 yr after kidney transplantation, and majority of the patients had multifocal disease at the time of diagnosis. Overall, the patient survival rate was 75% over a mean follow-up period of five yr. Two patients with non-functioning allograft at the time of diagnosis of EBV SMT were excluded from the treatment outcome analysis. Comparing the sirolimus (n = 7) vs. cyclosporine groups (n = 7), patient survival rate was 100% vs. 42.9% (p = 0.08), graft survival 71.4% vs. 28.7% (p = 0.53), and disease-free status 42.9% vs. 14.3% (p = 0.73), respectively., Conclusion: Surgical resection in combination with decreasing immunosuppression or conversion to sirolimus appears to be effective in the treatment of EBV SMT in KTR., (© 2013 John Wiley & Sons A/S.)

Background and Aims: Individuals are prone to disease because of certain disease-susceptible genes. The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D), the angiotensinogen (AGT) gene, M235T, and the angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasians and Japanese patients have reported contradictory results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese subjects to assess their clinical impact., Methods: Genotyping was performed with DNA isolated from peripheral leucocytes, polymerase chain reaction amplification of the polymorphic sequence, restriction enzymes digestion, and separation and identification of DNA fragments. Clinical data at renal biopsy and final status on renal function were determined from patients' records., Results: Comparing all IgAN patients with controls, AGT and ATR genotype distributions were similar, whereas there was a significant increase in the ACE DD genotype (P < 0.05). When comparing patients with end-stage renal failure (IgAN-ESRF) and those without (IgAN-nonESRF), there was no difference among the three gene polymorphisms. In contrast, there were significant differences in higher male prevalence (P < 0.05), increased serum creatinine at presentation (P < 0.05), more sclerosis (P < 0.01) and higher tubulointerstitial lesion score (P < 0.001) in the IgAN-ESRF group., Conclusion: Among the ACE, AGT and ATR gene polymorphisms, only the DD genotype may predispose the individual to IgAN in the Chinese population. None are significant for prognosticating ESRF.

Background/methods: Molecular Adsorbent Recirculating System (MARS) was used in three consecutive critically ill patients at the Singapore General Hospital with advanced malignancy and acute liver failure (ALF). Case 1 was a male patient with hepatocellular carcinoma (HCC) for which initial right hepatectomy was followed by left hepatectomy 5 months later for recurrent HCC. The postoperative course following second surgery was complicated by severe methicillin-resistant Staphylococcus aureus (MRSA) sepsis, mild azotaemia and subacute cholestatic liver failure. MARS was used thrice in this patient. Case 2 was a female patient with advanced acute lymphoblastic leukaemia (ALL) with post bone marrow transplantation (BMT) acute haemolytic-uraemic syndrome (HUS) secondary to cyclosporin A (Cy A), cytomegalovirus (CMV) infection, severe nosocomial pneumonia, acute renal failure (ARF) treated with continuous haemofiltration and acute veno-occlusive disease resulting in Budd-Chiari syndrome. The latter precipitated ALF. MARS was instituted twice. Case 3 was a male patient with advanced, refractory Hodgkin's disease previously treated with multiple courses of chemotherapy. ALF developed secondary to acute viral hepatitis B flare. He was given a trial of MARS once in the ICU. All the three patients eventually died., Results: Mean MARS intradialytic systemic pressures were as follows: systolic pressure range was 95 +/- 17 to 128 +/- 17 mmHg and diastolic pressure range was 51 +/- 5 to 67 +/- 7 mmHg. Pressure at albumin dialysate exit point from dialyser 1 (Ae) ranged from 253 +/- 11 to 339 +/- 15 mmHg and that at albumin dialysate entry point into dialyser 1 (Aa) ranged from 142 +/- 11 to 210 +/- 6 mmHg. Ultrafiltration (UF) was 633 +/- 622 mL over mean treatment duration of 6.3 +/- 0.9 h with a total heparin dose of 1583 +/- 817 IU. Coagulation status pre- and 6-h post-MARS was similar: aPTT (P=0.116) and platelet count (P=0.753). There were no bleeding complications or circuit thromboses. MARS had a significant de-uraemization effect (pre- and post-MARS serum creatinine and urea: P=0.046 and 0.028, respectively) but did not significantly attenuate blood lactate, ammonia or total bilirubin levels. Albumin dialysate (Ae - Aa) urea and creatinine concentrations appeared to be sharply attenuated after 6 h of MARS. In contrast, the removal of total bilirubin by albumin dialysate from the blood compartment appeared to plateau after 4 h of continuous MARS operation., Conclusions: MARS was well-tolerated in critically ill patients with advanced and complicated cancer. Low-dose heparin was safe and did not compromise MARS circuit integrity. Although MARS had a significant de-uraemization effect, this appeared to be limited by the duration of MARS operation. Our data suggested that such a limit was reached earlier for total bilirubin. More data are needed to confirm the present findings and further delineate the saturation limit of MARS for different toxins that accumulate in ALF. This would affect the optimal duration of MARS therapy.

Objective: Dihydropyrimidine dehydrogenase (DPD) catalyzes the degradation of thymine, uracil, and the chemotherapeutic drug 5-Fluorouracil. In general reverse-phase high pressure liquid chromatography is the standard method for separating 5-[2-(14)C]Fluorouracil and 5-[2-(14)C]Fluoro-5,6-dihydrouracil. However, the use of 100% aqueous solution (as HPLC mobile phase) may collapse the C-18 bonded phase and result in a retention time shift. The aim of this study is to develop a rapid, reproducible, sensitive method for screening partial DPD deficiency in healthy volunteers., Design and Methods: The activity of DPD was measured using 5-[2- (14)C]Fluorouracil (5-[2-(14)C]FUra) followed by separation of substrate and product 5-[2-(14)C]FUraH(2) with a 15 x 4.6 mm I.D., 5 microm particle size (d(p)) porous graphitic carbon (PGC) column (Hypercarb(R)) and HPLC with online detection of the radioactivity. This was standardized using the protein concentration of the cytosol (NanoOrange(R) Protein Quantitation)., Results: Complete baseline separation of 5-[2-(14)C]Fluorouracil (5-[2-(14)C]FUra) and 5-[2-(14)C]Fluoro-5,6-dihydrouracil (5-[2-(14)C]FUraH(2)) was achieved using a porous graphitic carbon (PGC) column. The detection limit for 5-[2-(14)C]FUraH(2) was 0.4 pmol., Conclusions: By using linear gradient separation (0.1% Trifluoroacetic acid [TFA] in water to 100% Methanol) protocols in concert with PGC columns (Hypercarb(R)), we have demonstrated that a PGC column has a distinct advantage over C-18 reverse phase columns in terms of column stability (pH 1-14). This method provides an improvement on the specific assay for DPD enzyme activity. It is rapid, reproducible and sensitive and can be used for routine screening for healthy and cancer patients for partial and profound DPD deficiency before treatment with 5- FUra.

Objective: To study the anti-proliferative effect of Dipyridamole (anti-platelet), Dipyridamole with Warfarin, and Warfarin (anticoagulant) alone, in human endothelial cells in vitro., Design and Methods: Human endothelial cells were harvested from umbilical cords. Primary cultures were usually successful. However, subculture yields were usually contaminated with smooth muscle cells. We have developed an improved method for the isolation of endothelial cells by using Collagenase II, coating the culture flask with fibronectin and using serum-free media. The endothelial cells were characterised by anti-PECAM-1/PE (CD31) using Flow Cytometry with viability of 95% after trypsinization with 0.05% Trypsin and 1 mM EDTA. Growth and proliferation studies were performed in vitro in the presence of 5 microM Dipyridamole, 5 microM Dipyridamole with 5 microM Warfarin, 5 microM Warfarin alone by cell counts, (3)H-thymidine and (3)H-leucine incorporation., Results: The incorporation of (3)H-Leucine at day 6 in each test condition revealed no significant change. Control 12678 +/- 2968 CPM, Dipyridamole 8698 +/- 189 CPM, Dipyridamole and Warfarin 7541 +/- 413 CPM, and Warfarin alone 10711 +/- 732 CPM. With the incorporation of (3)H-Thymidine, Dipyridamole alone as well as Dipyridamole with Warfarin reduced the basal proliferation rates significantly when compared to controls. Control 14355 +/- 4441 CPM, Dipyridamole 1100 +/- 152 CPM (p<0.05), Dipyridamole with Warfarin 1092 +/- 272 CPM (p<0.05). Warfarin alone did not reduce proliferation significantly 12870 +/- 2677 CPM (NS)., Conclusions: We have developed a method to isolate pure endothelial cells from human umbilical cords using Serum-Free Media (SFM). EC with high purity was characterised by anti-PECAM-1/PE (CD31) using Flow Cytometry. Dipyridamole at a concentration of 5 microM inhibited the proliferation of endothelial cells at day 6 by 93%. These techniques can be used for routine analysis and proliferation studies.

Preoperative localisation procedures in primary hyperparathyroidism have been associated with advantages like decreased operative dissection, shorter operating time and in some series, lower morbidity and mortality. However, successful identification of parathyroid glands exceeding 90% is achievable at surgery without preoperative localisation studies. Sixty-nine patients who underwent parathyroidectomy at the Department of Surgery, Singapore General Hospital, between March 1990 and July 1996 were analysed to determine the role of preoperative localisation techniques. Preoperative localisation of parathyroid glands consisted of computed tomographic (CT) scan in 66.7% of patients, technetium99 sestamibi scan in 23.2%, ultrasound in 15.9% and angiographic localisation in 4.3% of the patients. In the 28 end stage renal failure patients who were operated for progressive renal osteodystrophy, 6 had preceding renal transplants. The success of identifying parathyroid glands at operation in these 28 patients was independent of CT scan findings. CT scan was correct in only 6% of patients while surgical exploration had a success rate of 100%. Of the 41 patients with primary hyperparathyroidism, the success of CT scan in identifying enlarged parathyroid glands was 41.4% compared to 91.6% via surgical exploration. Furthermore, CT scan was not able to discriminate between superior and inferior parathyroid glands. Preoperative Tc-99m sestamibi scan and ultrasound correctly localised pathologic parathyroid gland in 40% and 18.2% of the patients, respectively. Therefore, the use of preoperative imaging to localise parathyroid glands before the intended exploration was found not to be useful in our series.