The effectiveness of a psychoeducational intervention on health outcomes of patients undergoing haemodialysis: A randomized controlled trial.

AIM: The aim of this work is to examine the effectiveness of a psychoeducational intervention on self-efficacy (primary outcome), anxiety, depression, treatment adherence, and health-related quality of life (HRQoL) of patients undergoing haemodialysis. METHODS: A two-group randomized controlled trial of 124 patients (65 and 59 patients in the intervention and control groups, respectively) recruited from a tertiary hospital in Singapore was conducted. Data were collected from January 2015 to June 2016. Outcomes were measured at baseline and 1, 3, and 6 months after the intervention. General linear model was used to analyse data. RESULTS: Our findings showed significant group effect on HRQoL (effects of kidney disease on daily life; p = 0.041), time effect on all outcomes (p < 0.05; except for treatment adherence behaviours and HRQoL [burden of kidney disease]), and group * time interaction effect on anxiety (p = 0.040) and depression (p = 0.003), with the intervention group reporting better outcomes. CONCLUSIONS: The positive effects of our intervention on patients' self-efficacy, psychological well-being, treatment adherence attitudes, and HRQoL implied its potential use in dialysis/renal centres to improve patients' self-care and health outcomes.

Going to war on COVID-19: Mobilizing an academic nephrology group practice.

AIM: The COVID-19 pandemic poses unprecedented operational challenges to nephrology divisions in every country as they cope with COVID-19-related kidney disease in addition to regular patient care. Although general approaches have been proposed, there is a lack of practical guidance for nephrology division response in a hospital facing a surge of cases. Here, we describe the specific measures that our division has taken in the hope that our experience in Singapore may be helpful to others. METHODS: Descriptive narrative. RESULTS: A compilation of operational responses to the COVID-19 pandemic taken by a nephrology division at a Singapore university hospital. CONCLUSION: Nephrology operational readiness for COVID-19 requires a clinical mindset shift from usual standard of care to a crisis exigency model that targets best outcomes for available resources. Rapid multi-disciplinary efforts that evolve flexibly with the local dynamics of the outbreak are required.

Health-related quality of life of Asian patients with end-stage renal disease (ESRD) in Singapore.

BACKGROUND: This study aimed to identify factors associated with the health-related quality of life (HRQOL) of multiethnic Asian end-stage renal disease (ESRD) patients treated with dialysis. The role of dialysis modality was also explored. METHODS: Data used in this study were from two cross-sectional surveys of Singaporean ESRD patients on haemodialysis (HD) or peritoneal dialysis (PD). In both surveys, participants were assessed using the kidney disease quality of life (KDQOL) instrument and questions assessing socio-demographic characteristics. Clinical data including co-morbidity (measured by Charlson comorbidity index [CCI]), albumin level, haemoglobin level, and dialysis-related variables (e.g. dialysis vintage and dialysis adequacy) were retrieved from medical records. The 36-item KDQOL (KDQOL-36) was used to generate three summary scores (physical component summary [PCS], mental component summary [MCS] and kidney disease component summary [KDCS]) and two health utility scores (Short Form 6-dimension [SF-6D] and EuroQol 5-dimension [EQ-5D]). Linear regression analysis was performed to examine the association of factors with each of the HRQOL scale scores. RESULTS: Five hundred and two patients were included in the study (mean age 57.1 years; male 52.4 %; HD 236, PD 266). Mean [standard deviation (SD)] PCS, MCS and KDCS scores were 37.9 (9.7), 46.4 (10.8) and 57.6 (18.1), respectively. Mean (SD) health utility score was 0.66 (0.12) for SF-6D and 0.60 (0.21) for EQ-5D. In multivariate regression analysis, factors found to be significantly associated with better HRQOL included: young (<45 years) or old age (>60 years), low CCI (<5), high albumin (≥37 g/l) and high haemoglobin (≥11 g/dl) with PCS; long dialysis vintage (≥3.5 years) with MCS; old age, Malay ethnicity and PD modality with KDCS; low CCI, high albumin and high haemoglobin with EQ-5D and high albumin with SF-6D. CONCLUSIONS: Clinical characteristics are better predictors of HRQOL in ESRD patients than socio-demographics in Singapore. Dialysis modality has no impact on the health utility of those patients.

Native renal cysts and dialysis duration are risk factors for renal cell carcinoma in renal transplant recipients.

Urinary tract cancers are the third most common cancers in renal transplant recipients (RTX). This study examined the impact of dialysis duration and native renal cyst(s) (NRC) on renal cell carcinoma (RCC) occurrence among 1036 RTX followed-up from 1995 to July 2007. Abdominal ultrasonography was planned within 1-month of transplant, then every 5 years, or 2 years if renal cysts developed. Based on presence and time of development of NRC, RTX were grouped into those with no (No-NRC), new (New-NRC), preexisting (Pre-NRC) and time-indeterminate NRC (TI-NRC). Ten asymptomatic RTX were diagnosed with RCC at a median of 5.8 years posttransplant and had 5-year graft and patient survivals of 90% and 100%, respectively, following appropriate therapy. RCC occurred only in Pre-NRC and TI-NRC who had significantly longer dialysis duration than No- or New-NRC (6.7 ± 3.9 and 3.3 ± 3.2 vs. 2.7 ± 3.1 and 2.6 ± 2.4 years, respectively). These results suggest that NRC and increased dialysis duration are risk factors for RCC posttransplant. Since early treatment of RCC gives excellent outcomes, regular ultrasonography performed within a month of transplantation, then every 5 years for those without cysts and every 2 years for those with cysts for early detection of RCC is recommended.

Microbiology of tunnelled catheter-related infections in a multi-ethnic South-east Asian patient population.

INTRODUCTION: Clinical practice guidelines recommend empiric antibiotic therapy for suspected tunnelled haemodialysis catheter-related infections (CRI), and the choice of antibiotics should be adjusted according to the local microbiological profile and antimicrobial sensitivities. We aim to describe the microbiology, antibiotic sensitivities, and clinical outcomes of CRI with tunnelled haemodialysis catheters in a multi-ethnic South-East Asian population. METHODS: Using a prospective vascular access registry, we identified 99 patients who had catheters removed for suspected or confirmed CRI (50.5% male, mean age 56.9 years) from January 1, 2007, till May 2009. We retrospectively retrieved microbiology, mortality and echocardiography data from the hospital electronic databases. RESULTS: There were 115 removal-unique cultures that yielded 75.7% Gram-positive and 24.3% Gram-negative isolates (15 removals were polymicrobial). Organisms isolated were methicillin-resistant Staphylococcus aureus (MRSA) 28.6%, methicillin-sensitive S. aureus 26.5%, coagulase-negative staphylococci 21.4%, Pseudomonas aeruginosa 10.2%, and others. Out of 8 patients who died, 7 had MRSA. Risk factors associated with mortality were Chinese race (p = 0.03), MRSA infection (p < 0.001), and older age (p < 0.001). CONCLUSION: Gram-positive isolates accounted for most tunnelled CRI and MRSA was highly associated with death. In sick patients presenting with suspected CRI, the preferred empiric antibiotic regimen should include agents active against both MRSA and P. aeruginosa.

Beneficial effects of high-dose losartan in IgA nephritis.

AIM: Several short-term studies have reported the efficacy of high-dose ARB in reducing proteinuria in patients with diabetic nephropathy. The benefits of long-term high-dose ARB losartan in IgA nephritis have not been explored. METHOD: This was a 6-year randomized trial in 207 patients with IgA nephritis comparing high-dose ARB (losartan 200 mg/day) with normal dose ARB (losartan 100 mg/day), normal dose ACEI (20 mg/day) and low-dose ACEI (10 mg/day). Multivariate ANOVA was used to test the effect of drug treatment on both eGFR and total urinary protein (TUP). RESULTS: Comparing patients on high-dose ARB (n = 63) with those on normal dose ARB (n = 43), normal dose ACEI (n = 61) and low-dose ACEI (n = 40), patients on high Dose ARB had significantly higher eGFR (p < 0.0005) and lower proteinuria (p < 0.005) at the end of the study. The loss in eGFR was 0.7 ml/min/year for high-dose ARB compared to 3.2 - 3.5 ml/ min/year for the other 3 groups (p = 0.0005). There were more patients on high-dose ARB with improvement in eGFR compared to other 3 groups (p < 0.001). CONCLUSION: Data from this study suggest that high-dose ARB therapy is more efficacious in reducing proteinuria and preserving renal function when compared with normal dose ARB and ACEI. In Year 5, patients on high-dose ARB had a gain in eGFR suggesting that there is possibility of recovery of renal function in these patients on long-term high-dose therapy.

Significant impact of gene polymorphisms on tacrolimus but not cyclosporine dosing in Asian renal transplant recipients.

Calcineurin inhibitors (CNI) are metabolized by cytochrome-P4503A (CYP3A) enzymes and extruded into the intestinal lumen by the drug efflux pump, P-glycoprotein (P-gp). The impact of single nucleotide polymorphisms (SNPs) of genes encoding CYP3A5 and P-gp on CNI dosing was examined among Asian renal transplant recipients. Frequencies of CYP3A5*1 versus *3 and MDR1-C3435T were correlated with tacrolimus (TAC) and cyclosporine (CSA) concentration-to-dose (C/D) ratios. Among 82 recipients (49% male; 88% Chinese), the majority were CYP3A5 expressors (*1*1 and *1*3, 11% and 40%, respectively) and 49% were nonexpressors (*3/*3). The prevalence of MDR-1-C3435T variants was 3435CC (41%), 3435CT (46%), and 3435TT (13%). Among 18 TAC-treated recipients, all receiving Diltiazem (DTZ), the median C/D ratio was lower for CYP3A5 *1/*1 versus *1/*3 versus *3/*3 (1.9, 4.6, and 13.5 ng/mL per 0.1 mg/kg/d, respectively; P = .001). The median C/D ratio was higher for TAC-treated patients with MDR-1-3435CC (14.1, 7.3, and 2.2 ng/mL per 0.1 mg/kg/d for CC, CT, and TT, respectively; P = .023). Neither CYP3A5 nor MDR-1-C3435T variants had an impact on CSA C/D ratios. Thus, CYP3A5 SNP has a significant impact on TAC dosing in Asian renal transplant recipients, which was likely to facilitate TAC metabolism. Although MDR-1-3435CC with higher P-gp expression should experience more TAC efflux and, therefore, lower TAC C/D ratios, all MDR-1-3435CC carriers were CYP3A5 nonexpressors; the latter ultimately contributed to the observed higher TAC C/D ratios in this population. This study advocates starting with a higher TAC dose for CYP3A5 expressors. Coadministration of DTZ may further optimize the TAC level through preferential P-gp binding and CYP3A4 inhibition.

Projecting the Burden of Chronic Kidney Disease in a Developed Country and Its Implications on Public Health.

BACKGROUND: Chronic Kidney Disease (CKD) is a major public health problem worldwide. There is limited literature on a model to project the number of people with CKD. This study projects the number of residents with CKD in Singapore by 2035 using a Markov model. METHODS: A Markov model with nine mutually exclusive health states was developed according to the clinical course of CKD, based on a discrete time interval of 1 year. The model simulated the transition of cohorts across different health states from 2007 to 2035 using prevalence, incidence, mortality, disease transition, and disease detection rates. RESULTS: From 2007 to 2035, the number of residents with CKD is projected to increase from 316,521 to 887,870 and the prevalence from 12.2% to 24.3%. Patients with CKD stages 1-2 constituted the largest proportion. The proportion of undiagnosed cases will decline from 72.1% to 56.4%, resulting from faster progression to higher CKD stages and its eventual detection. CONCLUSION: By 2035, about one-quarter of the Singapore residents are expected to have CKD. National policies need to focus on primary disease prevention and early disease detection to avoid delayed treatment of CKD which eventually leads to end-stage renal disease.

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable maintenance renal transplant patients: pooled results from three international, multicenter studies.

BACKGROUND: Mycophenolate mofetil (MMF) is effective in renal transplant patients but concerns remain over its gastrointestinal (GI) tolerability. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) has been developed with the intention of improving mycophenolic acid-related GI tolerability. METHODS: Data were pooled in a planned analysis of three subprotocols of the myfortic Prospective Multicenter Study (myPROMS). In a 6-month study, efficacy and safety of converting stable renal transplant recipients from MMF to a bioequivalent dose of EC-MPS for mycophenolic acid exposure were evaluated. Treatment efficacy was recorded and graft function was assessed by measuring serum creatinine and estimating creatinine clearance. Adverse events (AEs) and infections were monitored and the incidence of EC-MPS dose changes was recorded. RESULTS: A total of 588 patients were recruited, 564 (96%) of whom completed the study. The rate of treatment failure (defined as biopsy-proven acute rejection, graft loss, or death) was 1.9%, with no episodes of graft loss and only one death reported during the study. Renal function remained stable throughout the trial. EC-MPS was well tolerated; the majority of AEs were mild or moderate in severity. Dose reductions or interruptions were required by 6.3% and 1.9% of patients, respectively. Gastrointestinal AEs occurred in 138 patients (23.5%). The rate of dose adjustment as a result of a GI AE was 2.2%. CONCLUSIONS: Equimolar conversion from MMF to EC-MPS in maintenance renal transplant patients was safe and maintained efficacy.

Long term outcome of renal allografts in patients with immunoglobulin A nephropathy.

Recurrent glomerular disease is an important cause of late allograft loss in renal transplant recipients. Immunoglobulin A nephropathy (IgAN) is a leading cause of end-stage renal disease (ESRD) worldwide and its recurrence has been reported in allografts. The present study examined outcomes following renal transplantation (RTX) in 101 patients with ESRD due to biopsy-proven IgAN, in comparison to non-IgA patients, and evaluated the incidence of recurrence. The study population (mean age 34.8 +/- 7.7 years; males 62.2%; Chinese 88.3%) underwent RTX under CsA immunosuppression between November 1984 and December 2004; as two patients underwent retransplantation during the study period, 103 allografts (56.3% cadaveric) were included for retrospective analysis. At time of analysis on 1 January 2005, 78 (75.7%) renal allografts (IgAN RTX) were functioning, of which 51 (49.5%) had normal serum creatinine, 27 (26.2%) had chronic allograft dysfunction, while 25 had graft losses, either due to patient death with functioning grafts (5.8%) or withdrawal to dialysis (18.5%). Persistent microscopic haematuria, not attributable to other causes or proteinuria > 1 g/day occurred in 42.7% and 13.6% of allografts respectively. Of 29 allografts biopsied for evaluation of proteinuria and/or renal dysfunction post-RTX, 8 (27.6%) had IgAN (overall histological recurrence, 7.8%). Of these, three had graft loss due to recurrent IgAN, three had elevated serum creatinine, while two had normal serum creatinine. Overall five and ten year patient survivals for IgAN RTX were 95.3% and 82.2%, and five and ten year actuarial graft survivals were 82.3% and 67.8% respectively. Five and ten year patient and graft survivals for IgAN RTX were not significantly different from that for non-IgAN RTX. In summary, RTX patients with IgAN have a low incidence of documented histological recurrence and recurrence contributing to graft loss occurs in only 2.9%. These results suggest that RTX is an excellent modality of renal replacement therapy in this population.

3rd College of Physicians' lecture--translational research: From bench to bedside and from bedside to bench; incorporating a clinical research journey in IgA nephritis (1976 to 2006).

Translational research (TR) can be defined as research where a discovery made in the laboratory (bench) can be applied in the diagnosis, treatment or prevention of a disease. Examples of medical discoveries contributing to translational medicine (TM) include the isolation of insulin by Banting (Nobel Laureate, 1923), the discovery of penicillin by Alexander Fleming (Nobel Laureate, 1945) and recently the discovery of the role of bacterium Helicobacter pylori in the causation of gastritis and peptic ulcer by Marshall and Warren (Nobel Laureates, 2005). Clinical research (CR) would be a more appropriate term for the bulk of research work undertaken by doctors. CR embraces both clinical based and laboratory-based research. The terminology "bedside to bench" applies more to CR as opposed to "bench to bedside" in the case of TR. But regardless of who does it, as long as the discovery can be translated to the bedside and results in improvement in patient care it can be considered a contribution to TM. Our work spans a 30-year period, involving laboratory-based research, clinical trials and genomics of IgA nephritis (Nx). This is a series of work to elucidate the pathogensis and therapy of IgANx. Plasma beta-thromboglobulin (BTG) an in-vivo index of platelet aggregation and anti-thrombin III increase due to a constant thrombogenecity resulting from platelet degranulation formed the basis for anti-platelet and low-dose warfarin therapy. A study of the natural history of IgANx revealed 2 courses, a slowly progressive course with end-stage renal failure (ESRF) at 7.7 years and a more rapid course at 3.3 years. Triple therapy (cyclophosphamide, persantin and low-dose warfarin) delayed progression to ESRF by about 8 years and for some patients up to 20 years. Documentation of abnormal suppressor T cell function provided the basis for immune therapy. Four patterns of proteinuria were present in IgANx and it is the quality and not so much the quantity of proteinuria which determined the prognosis. Low molecular weight proteinuria was a bad prognostic marker. A controlled therapeutic trial using ACEI/ATRA showed that therapy decreases proteinuria, improves renal function and converts non-selective to selective proteinuria. Subsequent work confirmed that it was the ATRA, not the ACEI which contributed to improved renal function. Individual anti proteinuria response to ATRA varies depending on ACE gene polymorphism. We found that the II genotype of the ACE gene was renoprotective and patients with this genotype had significantly reduced incidence of ESRF compared to those with the DD genotype. Patients responsive to ATRA therapy can retard progression to ESRF by up to 32 years. Mild renal failure can be reversed with possible regression of glomerulosclerosis because of glomerular remodelling by ATRA.

Compensatory Hypertrophy After Living Donor Nephrectomy.

BACKGROUND: Previous studies have shown that kidney volume enhances the estimation of glomerular filtration rate (eGFR) in kidney donors. This study aimed to describe the phenomenon of compensatory hypertrophy after donor nephrectomy as measured on computerized tomographic (CT) scans. METHODS: An institutional Domain Specific Review Board (DSRB)-approved study involved approaching kidney donors to have a follow up CT scan from 6 months to 1 year after surgery; 29 patients participated; 55% were female. Clinical chart review was performed, and the patient's remaining kidney volume was measured before and after surgery based on CT scans. eGFR was determined with the use of the Modification of Diet in Renal Disease equation. RESULTS: Mean parenchymal volume of the remaining kidney for this population (mean age, 44.3 ± 8.5 y) was 204.7 ± 82.5 cc before surgery and 250.5 ± 113.3 cc after donor nephrectomy. Compensatory hypertrophy occurred in 79.3% of patients (n = 23). Mean increase in remaining kidney volume was 22.4 ± 23.2% after donor nephrectomy in healthy individuals. Over a median follow-up of 52.9 ± 19.8 months, mean eGFR was 68.9 ± 12.4 mL/min/1.73 m(2), with 24.1% of patients (n = 7) in chronic kidney disease grade 3. Absolute and relative change in kidney volume was not associated with sex, race, surgical approach, or background of hypertension (P = NS). There was a trend of decreased hypertrophy with increasing age (P = .5; Spearman correlation, -0.12). CONCLUSIONS: In healthy kidney donors, compensatory hypertrophy of the remaining kidney occurs in 79.3% of the patients, with an average increment of about 22.4%. Older patients may have a blunted compensatory hypertrophy response after surgery.

Outcome of Living Donor Transplant Kidneys With Multiple Arteries.

BACKGROUND: Living donor transplantation (LDT) using kidneys with multiple arteries (MA) has previously been reported to be associated with increased complications and poorer outcomes in recipients. The objective of this study was to investigate outcomes of LDT with MA at the National University Hospital of Singapore, an institution with modest kidney transplant volumes. METHODS: From 2007 to 2014, a total of 109 consecutive living donor kidney transplantations were performed. Of the nephrectomies, 91% were left sided. A total of 19 cases involved MA, of which 7 with small polar vessels (<2 mm) were ligated and 12 were revascularized. Baseline characteristics and outcomes were comparable between donor-recipient pairs with MA and single artery (SA). Both groups had equivalent induction and maintenance immunosuppressive regimens. RESULTS: Mean warm ischemia time (minutes) was similar for kidneys with MA and SA (4.3 ± 3.2 vs 3.9 ± 3.2, P = .38). Operative time (minutes) in the recipients was also equivalent (P > .05) for MA and SA (158 ± 39.2 and 145 ± 57.2, respectively). The MA kidney recipients had a lower estimated glomerular filtration rate (eGFR) on postoperative day 5 compared to SA (56.6 ± 24.2 vs 74.1 ± 35.9 mL/min/1.73 m(2), P = .058). However, eGFR at 1 year was the similar for both groups (64.9 ± 16.2 vs 66.4 ± 18.1 mL/min/1.73 m(2), respectively, P = .76). Delayed graft function rates were 5.6% and 6.6% for MA and SA, respectively (P = .9). There were no surgical complications for LDT recipients within the MA group. Patient and graft survival was 100% in the MA group compared with 98% in the SA group (P > .05). CONCLUSIONS: With current surgical techniques, LDT with MA can achieve equally good functional outcomes at 1 year as SA kidneys, with minimal surgical complications.

Preventing renal transplant failure.

INTRODUCTION: Allograft failure due to immunological or non-immunological causes or a combination and patient death after transplantation are the 2 major causes of renal transplant loss. This paper reviews the various causes of allograft failure and explores strategies for its prevention. RESULTS: Immune mechanisms of renal allograft failure are those mediated by acute and chronic rejection and are initiated by human leukocyte antigen (HLA) disparity between donor and recipient and increased recipient immune responsiveness that results in pre-sensitisation against HLA antigens. Better HLA matching between donor and recipient in both live-donor and cadaveric renal transplant recipients and the use of more potent immunosuppressants has reduced the incidence of acute rejection and resulted in improved overall graft survivals in recent years. However, as the use of more potent immunosuppression increases the risk of infections and malignancy, tailoring therapy by administering more potent immunosuppression to those at higher immunological risk may result in a better balance between the risks and benefits of immunosuppressive therapies. Ischaemia of the donor kidney, calcineurin inhibitor (CNI), mediated nephrotoxicity, reduced renal mass, hypertension, hyperlipidaemia and infections contribute to allograft failure through non-immunological mechanisms. Indeed, any cause of renal injury that results in nephron loss, either immunological or non-immunological, leads to reduced renal mass and initiates further renal damage due to hyperfiltration. Optimising these factors and minimising CNI nephrotoxicity are critical in reducing chronic allograft failure. CONCLUSIONS: Optimising each of these time-dependent and immunosuppressive drug-related factors would allow the maximization of renal allograft function and survival.

Hemodialysis versus Peritoneal Dialysis: A Comparison of Survival Outcomes in South-East Asian Patients with End-Stage Renal Disease.

BACKGROUND: Studies comparing patient survival of hemodialysis (HD) and peritoneal dialysis (PD) have yielded conflicting results and no such study was from South-East Asia. This study aimed to compare the survival outcomes of patients with end-stage renal disease (ESRD) who started dialysis with HD and PD in Singapore. METHODS: Survival data for a maximum of 5 years from a single-center cohort of 871 ESRD patients starting dialysis with HD (n = 641) or PD (n = 230) from 2005-2010 was analyzed using the flexible Royston-Parmar (RP) model. The model was also applied to a subsample of 225 propensity-score-matched patient pairs and subgroups defined by age, diabetes mellitus, and cardiovascular disease. RESULTS: After adjusting for the effect of socio-demographic and clinical characteristics, the risk of death was higher in patients initiating dialysis with PD than those initiating dialysis with HD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.67-2.59; p<0.001), although there was no significant difference in mortality between the two modalities in the first 12 months of treatment. Consistently, in the matched subsample, patients starting PD had a higher risk of death than those starting HD (HR: 1.73, 95% CI: 1.30-2.28, p<0.001). Subgroup analysis showed that PD may be similar to or better than HD in survival outcomes among young patients (≤65 years old) without diabetes or cardiovascular disease. CONCLUSION: ESRD patients who initiated dialysis with HD experienced better survival outcomes than those who initiated dialysis with PD in Singapore, although survival outcomes may not differ between the two dialysis modalities in young and healthier patients. These findings are potentially confounded by selection bias, as patients were not randomized to the two dialysis modalities in this cohort study.

Comparison of the preference-based EQ-5D-5L and SF-6D in patients with end-stage renal disease (ESRD).

OBJECTIVES: The objective of this study was to compare the performance of the 5-level EuroQol 5-dimension (EQ-5D-5L) and the Short Form 6-dimension (SF-6D) instruments in assessing patients with end-stage renal disease (ESRD) in Singapore. METHODS: In a cross-sectional study, ESRD patients attending a tertiary hospital were interviewed using a battery of questionnaires including the EQ-5D-5L, the kidney disease quality of life instrument (KDQOL-36), and questions assessing dialysis history and socio-demographic characteristics. We reviewed patients' medical records for their clinical information. We assessed the construct validity of the EQ-5D-5L and SF-6D index scores and compared their ability to distinguish between patients differing in health status and the magnitude of between-group difference they quantified. RESULTS: One hundred and fifty ESRD patients on dialysis (mean age, 60.1 years; female, 48.7%) participated in the study. Both EQ-5D-5L and SF-6D demonstrated satisfactory known-groups validity; the EQ-5D-5L was more sensitive to differences in clinical outcomes and the SF-6D was more sensitive to differences in health outcomes measured by KDQOL scales. The intraclass correlation coefficient between the measures was 0.36. The differences in the EQ-5D-5L index score for patients in better and worse health status were greater than those measured by the SF-6D index score. CONCLUSIONS: Both EQ-5D-5L and SF-6D are valid instruments for assessing ESRD patients. However, the two preference-based measures cannot be used interchangeably and it appears that EQ-5D-5L would lead to more favorable cost-effectiveness results than SF-6D if they are used in economic evaluations of interventions for ESRD.

Analysis of the interactions of immunosuppressive drugs with cyclosporine in inhibiting DNA proliferation.

Though the high immunosuppressive efficacy of cyclosporine has revolutionized clinical transplantation, renal, hepatic, and neural toxicities limit its therapeutic potential. One approach to this problem is to combine CsA therapy with immunosuppressive agents that act synergistically with it, thereby permitting lower doses and mitigating drug-induced toxicity. The present study examines the in vitro interactions of various immunosuppressive agents--namely, 6-mercaptopurine (6MP), dexamethasone (Dexa), FK506, and Enisoprost (EP)--with CsA. These investigations dissect the impact of the drug combinations in inhibiting 3H-thymidine incorporation into DNA by normal human peripheral blood lymphocytes activated by mitogens or by alloantigens in mixed lymphocyte culture responses. The median-effect equation was used to analyze the dose-effect relationships of immunosuppressive drugs either alone or in combination. The interactions were quantified by calculation of combination indices (CI). CI values less than 1, greater than 1, and equal to 1 represent synergistic, antagonistic, and additive interactions, respectively. In combination with CsA, 6MP showed modest and Dexa profound synergism, while EP displayed modest and FK506 marked antagonism. These findings confirm the clinical impression of in vivo synergism between CsA and Dexa. They suggest that in vitro analysis of drug interactions may distinguish synergistic drug combinations potentially applicable to clinical practice.