Abstract Background Existing screening methods for TB involve trade-offs among sensitivity, specificity and cost. Recent advances mean that dual-energy X-ray is more sensitive and only slightly more costly than conventional chest X-ray and could be a high-performing alternative for TB screening, particularly if associated computer-aided diagnostic (CAD) software were developed. Methods Existing data on sensitivity,specificity and cost were used for six screening methods (sputum testing, conventional chest X-ray with and without CAD software, dual-energy X-ray with and without CAD software, and nucleic acid amplification testing (NAAT), used in various sequences. Cost and effectiveness of 20 different screening pathwayswere examined using data for Pakistan. Monte-carlo based sensitivity analysis focused on parameters for dual-energy X-ray. Results Sputum followed by NAAT is the best pathway when government budgets are low, and NAAT alone is the best when budgets are unlimited. With intermediate budgets, pathways including dual-energy X-ray dominate those including conventional X-rays, particularly if CAD software is developed for dual-energy X-ray. Conclusions Dual-energy X-ray can be a valuable addition to the screening options for TB. Our study provides different TB screening options for policy makers and TB program managers, which could be used as a guide for planning and implementation of TB screening programs.
OBJECTIVE:In this study, we trace the changes in the clinical and histological pattern of IgA nephritis (IgAN) in Singapore as it has evolved over 4 decades and compare the clinical, demographic, histological, and renal outcome of patients with IgAN from the 1st decade and the 4th decade.MATERIALS AND METHODS:This is a retrospective study of all histologically proven IgAN diagnosed between 1976 and 2018. Clinical, laboratory, and histological characteristics between the 1st and the 4th decade, including treatment which could influence the disease progression and renal outcome of these two groups, were compared. We used the Oxford classification to compare the renal biopsy changes for these 2 decades as we were able to retrieve 125 renal biopsy tissues for the 1st cohort of IgAN studied in the 1970s for the comparative study.RESULTS:The commonest clinical presentation throughout the first 3 decades was asymptomatic hematuria and proteinuria (63, 52, and 49%, respectively). In the 4th decade, nephrotic syndrome (31%) was the commonest followed by asymptomatic hematuria and proteinuria (30%), hypertension (21%), and chronic renal failure (11%). The data showed that treatment can modify the Oxford MEST - Crescent scores. Renin-angiotensin system (RAS) blockers modified the S scores, immunosuppressants modified the T and C scores, and combination therapy with RAS blockers and immunosuppressants modified the E, S, and T scores.CONCLUSION:The Oxford MEST classification offers a robust and expressive classification for early and late disease progression with respect to the development of end-stage renal disease (ESRD). E and S seem to be indices of continuing disease activity with progressive glomerulosclerosis, probably still amenable to therapy, but T was a predictive indicator for those destined for ESRD and no longer amenable to therapy.
RATIONALE:Hyperammonemia encephalopathy is a rare but severe complication that has been reported in association with the use of sunitinib, a tyrosine kinase inhibitor. We report here a unique case of a patient with end stage renal disease that was initiated on sunitinib for metastatic renal cell carcinoma.PATIENT CONCERNS:A 65-year-old man with end stage renal disease on maintenance conventional hemodialysis and had concomitant stable Child-Pugh class B liver cirrhosis consequent of hepatitis C infection was started on sunitinib for metastatic renal cell carcinoma. He developed confusion few weeks after starting therapy with no other indication of worsening liver dysfunction otherwise.DIAGNOSIS:He was later diagnosed with hyperammonemia encephalopathy.INTERVENTIONS:His treatment was discontinued and reinitiated at a lower dose after recovery and titrated according to tolerance. As ammonia is a very low molecular weight molecule and is cleared well with diffusive clearance, we intensified his dialysis regimen by increasing intensity for each session and frequency per week.OUTCOMES:With this change in dialysis regimen, patient was able to continue treatment with sunitinib.LESSONS:Clinicians prescribing sunitinib should be vigilant to monitor for this complication in patients receiving sunitinib, apart from the more usual presentation of hepatotoxicity. We found that a more intensive hemodialysis regimen consisting of 4× a week conventional high-flux hemodialysis (HD) can permit the continuation of treatment with sunitinib in an end stage renal disease (ESRD) patient with Child-Pugh class B liver cirrhosis.
Objective: This study on the prevalence of diabetic nephropathy (DN) and coexistence of non-diabetic renal disease (NDRD) in a cohort of 255 non-insulin-dependent diabetes mellitus (NIDDM) patients aims to determine the value of performing renal biopsies in these patients and elucidate the factors which could affect their progression to end-stage renal disease (ESRD). Methods: Among 255 NIDDM patients, 93 had DN alone, 69 had NDRD alone, and the remaining 93 had DN plus NDRD (mixed group). The indications for renal biopsy were based on clinical suspicion of superimposed NDRD, including heavy or rapidly increasing proteinuria, renal impairment even though diabetes is of relatively short duration, rapidly declining renal function, and presence of hematuria with dysmorphic red blood cells suggesting presence of glomerulonephritis. Results: The following were predictors of ESRD: high systolic BP at biopsy, longer duration of diabetes, heavy proteinuria, and presence of diabetic retinopathy. Comparing patients in the NDRD group with the DN group and the mixed group, the NDRD group had lower serum creatinine and higher eGFR with lower urinary proteinuria and higher serum albumin at presentation and on follow-up. Kimmelstiel-Wilson nodules were associated with a poorer prognosis leading to a higher occurrence of ESRD among patients with DN. Conclusion: Renal biopsy is of value in indicating the prognosis of NIDDM patients with DN based on the diabetic lesions. For NIDDM patients with atypical course and suspicion of associated NDRD, a renal biopsy would enable us to diagnose the underlying NDRD and offer appropriate therapy. Most nephrologists would consider renal biopsy for an NIDDM patient based on clinical indications like atypical clinical course and suspicion of an associated NDRD, but they would not perform a routine renal biopsy like for a CKD patient, unless it is for a research indication.
Plasma galectin-3 (pG3) regulates inflammation. B-type natriuretic peptide (BNP), high-sensitivity Troponin I (hsTnI), and pG3 concentrations are elevated in chronic kidney disease (CKD) patients. The associations of pG3 with hsTnI/BNP are unclear. We explored the relationship of hsTnI and BNP with pG3 in Asian CKD patients and healthy controls. We retrieved prospectively collected frozen plasma samples from 163 stable CKD patients and 105 healthy controls. BNP, hsTnI and pG3 were assayed. pG3 was assessed for associations with age, gender, ethnicity, blood pressures; height, weight, body mass index (BMI), previously diagnosed CKD, diabetes, hypertension, coronary artery disease, estimated glomerular filtration rate (eGFR); C-reactive protein, beta-trace protein, 24 h urine protein, serum albumin, uric acid and cystatin C. We created two models predicting pG3 using multiple linear regression. Akaike Information Criterion (AIC) was used for comparison. Significance was taken at P < 0.05. CKD versus healthy participants: mean BMI (28.2 vs. 24.9 kg/m2), median serum creatinine (159 vs. 69 µmol/L; 1.8 vs. 0.78 mg/dL), median eGFR (49 vs. 104 mL/min/1.73m2), median pG3 (29.4 vs. 15.4 ng/mL), median BNP (136 vs. 23 pg/mL), and median hsTnI (12.5 vs. 2.6 pg/mL). By univariate analysis, all variables are associated with pG3 except weight, gender and diagnosis of cerebrovascular or peripheral vascular diseases. A parsimonious model selected for hsTnI, BMI, serum albumin, cystatin C and eGFR (AIC = 77.6). BNP and hsTnI are associated with pG3 in Asian CKD patients. hsTnI is a better predictor of pG3.
This review of 3,289 native kidney biopsies over the past four decades in Singapore documents the changing pattern of biopsy-proven glomerulonephritis (GN) from that of a third world country to that of a developed nation. In the lst decade, mesangial proliferative GN was the most common form of primary GN, similar to the Asian region. In the 2nd decade. the percentage of mesangial proliferative GN decreased, but membranous GN became more common, as was seen in China and Thailand. In the 3rd decade, focal segmental glomerulosclerosis (FSGS) and membranous nephropathy continued to rise. but it was only recently, in the 4th decade, that FSGS prevalence increased dramatically. although membranous nephropathy continues to increase in some Asian countries. In the last decade in Singapore, Malaysia. and Japan, prevalence of IgA nephritis has decreased but remains the most common GN. The percentage of FSGS continues to increase in many countries like in Italy, United States of America, United Kingdom. China, and Malaysia. We surmise that socioeconomic factors play significant roles in the evolution of the renal biopsy pattern.
Background : Chronic kidney disease (CKD) is associated with fluid retention, which increases total body water (TBW) and leads to changes in intracellular water (ICW) and extracellular water (ECW). This complicates accurate assessments of body composition. Analysis of bioelectrical impedance may improve the accuracy of evaluation in CKD patients and multiple machines and technologies are available. We compared body composition by bioimpedance spectroscopy (BIS) against multi-frequency bioimpedance analysis (BIA) in a multi-ethnic Asian population of stable, non-dialysis CKD patients. Methods : We recruited 98 stable CKD patients comprising 54.1% men and 70.4% Chinese, 9.2% Malay, 13.3% Indian, and 8.2% other ethnicities. Stability was defined as no variation in serum creatinine > 20% over three months. Patients underwent BIS analyses using a Fresenius body composition monitor, while BIA analyses employed a Bodystat Quadscan 4000. Results : Mean TBW values by BIS and BIA were 33.6 ± 7.2 L and 38.3 ± 7.4 L; mean ECW values were 15.8 ± 3.2 L and 16.9 ± 2.7 L; and mean ICW values were 17.9 ± 4.3 L and 21.0 ± 4.9 L, respectively. Mean differences for TBW were 4.6 ± 1.9 L (P < 0.001), for ECW they were 1.2 ± 0.5 L (P < 0.001), and for ICW they were 3.2 ±1.8 L (P < 0.001). BIA and BIS measurements were highly correlated: TBW r = 0.970, ECW r = 0.994, and ICW r = 0.926. Compared with BIA, BIS assessments of fluid overload appeared to be more associated with biochemical and clinical indicators. Conclusion : Although both BIA and BIS can be used for body water assessment, clinicians should be aware of biases that exist between bioimpedance techniques. The values of body water assessments in our study were higher in BIA than in BIS. Ethnicity, sex, body mass index, and estimated glomerular filtration rate were associated with these biases.
Objective: The pattern of glomerulonephritis (GN) in Singapore is compared with that of 19 other countries to review changing trends in the evolution of GN in Asian, Eastern, and Western countries. Method: Three thousand two hundred and eighty-nine renal biopsies in Singapore were reviewed and compared with that of 19 other countries. Results: IgA nephritis is on the decline in many countries, including Singapore, though it still remains the commonest GN in Singapore. Membranous GN that if used to be more frequently present in Western countries has also declined though it continues a rising trend in countries such as Singapore and China. Worldwide, the frequency of focal sclerosing glomerulosclerosis (FSGS) continues to increase in many countries, but in some countries, the frequency is still low with mesangiocapillary GN remaining indigenous. Conclusion: Urbanization and socioeconomic changes and less exposure to parasitic and other infestations have transformed Singapore’s pattern, which is tending toward that of more developed countries. Antigenic exposure due to lifestyle changes, environmental, and industrial pollution are significant contributory factors that affect the evolutionary trend of GN in many countries. The rising trend in the frequency of FSGS may reflect aging and obesity.
The National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines recommended the Modification of Diet in Renal Disease study equation for estimating glomerular filtration rate (GFR) for the classification of CKD, but its accuracy was limited to North American patients with estimated GFR <60 mL/min per 1.73 m2 body surface area of European (White) or African (Black) descent. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) developed another equation for estimating GFR, derived from a population that included both participants without kidney disease and with CKD. But many ethnicities were inadequately represented. The International Society of Nephrology, Kidney Disease Improving Global Outcomes committee promulgated clinical practice guidelines, which recommended the CKD-EPI equation. Investigators in Asia subsequently assessed the performance of these GFR estimating equations-the Modification of Diet in Renal Disease study equation, the CKD-EPI equation (creatinine only), and the CKD-EPI equations (creatinine and cystatin C). In this review, we summarize the studies performed in Asia on validating or establishing new Asian ethnicity GFR estimating equations. We included both prospective and retrospective studies which used serum markers traceable to reference materials and focused the review of the performance of GFR estimation by comparisons with the GFR estimations obtained from the CKD-EPI equations.
500 A vast majority of patients with end-stage renal disease (ESRD) starts dialysis sub-optimally in an unplanned manner (1). These patients either present late or have an acute or unexpected deterioration of renal function resulting in the urgent need for dialysis. Consequently, 60 – 70% of patients who progress to ESRD do not have a functioning access at the time of dialysis initiation. Hemodialysis (HD) through a central venous catheter (CVC) is the default dialysis modality for such patients (1). In spite of the fact that starting HD with a CVC is independently associated with increased mortality, high rates of bacteremia, and increased hospitalization rates (2,3), peritoneal dialysis (PD) is rarely considered a practical option for urgent initiation of dialysis. Inability to create rapid PD access, lack of standards and protocols, worries about catheter leakages, relative ease of CVC insertion, and physicians’ preferences are the usual stumbling blocks. A majority of such patients subsequently stays on HD, as PD is rarely presented as an option once HD therapy is established, even to the patients who would otherwise have been considered excellent candidates for PD. As a result, the number of patients on PD remains unacceptably low worldwide (4). In Singapore, the percentage of ESRD patients on PD has steadily declined, from over 20% in 2002 to less than 15% in 2014 (5). Regardless of the method of PD catheter insertion (surgical, peritoneoscopic, or percutaneous), a waiting period of 2 to 4 weeks is usually recommended before dialysis initiation. This break-in period is considered vital to minimize the risk of catheter-related complications, especially the pericatheter or incisional leaks. Dialysate leakage has been reported in 15% to 37% of PD patients and is most common within 2 weeks of PD catheter insertion with conventional PD initiation (6,7). Urgent-start PD, defined as the initiation of dialysis using a modified prescription within 2 weeks of PD catheter insertion, is increasingly viewed as a practical and suitable option for ESRD patients who need to start dialysis urgently (6,7,8). Initiation of PD, even in late-presenting patients, can result in a reduced number of subsequent procedures, better preservation of residual renal function, better quality of life, and reduced overall cost of dialysis (9,10). Recent studies have shown that PD is a safe and efficient alternative to HD in acute unplanned dialysis settings. There is no significant difference in patient survival between the 2 modalities. The incidence of dialysis-related complications, especially bacteremia, is much lower in PD than in HD patients (11). Others have shown comparable outcomes and complication rates between urgentand elective-start PD (12). However, urgent-start PD has its unique logistical requirements. A successful urgent-start PD program requires the establishment of specific infrastructure, protocols, and clinical pathways involving multiple healthcare professionals and support staff. In this article, we describe our experience of developing an urgent-start PD program in a Singapore center. We believe that our urgent-start PD program can serve as a framework to develop similar services in other centers in our region. Before July 2015, all our incident PD patients were planned. All PD catheters were placed by urologists, predominantly using the laparoscopic method. Peritoneal dialysis training was typically started 2 to 4 weeks after catheter insertion. All patients needing urgent initiation of dialysis received HD through a CVC. An urgent-start PD program was initiated in July 2015 involving a lead urgent-start PD nephrologist, an interventional nephrologist certified to place percutaneous PD catheters under fluoroscopic guidance, a lead urgent-start PD nurse and a PD coordinator. In the planning phase, a comprehensive outline of the program was developed. The logistical, operational, and staffing requirements were identified. The essential elements included an adequate outpatient space and beds to provide low-volume PD exchanges; a mechanism to ensure rapid PD catheter insertions; a suitable number of PD nurses to supervise low-volume PD exchanges in both inpatient and outpatient settings; a dedicated outpatient clinic for rapid assessments and follow-up of patients; and a PD coordinator to streamline the pathway. Details of specific equipment and supplies required such as PD catheters, transfer sets, PD solutions, and PD catheter insertion set were specified. Nursing support was secured by providing education about urgent-start PD and involving them in the design of protocols and policies to assist in the management of urgent-start PD patients. Medical social worker support was ensured for fast-tracked financial assistance for patients entering the program on short notice. Detailed workflows, protocols, and urgent-start PD prescriptions were developed. A comprehensive framework for patient monitoring and followup was established to ensure patient safety (supplementary online material). A business case was then presented to the hospital’s senior management. The potential benefits to the patients and the institution were highlighted, including the possible reduction in the use of CVC and related blood stream infections, reduced hospitalizations, decreased length of stay, increased patient choice and satisfaction, increased PD uptake, and reduced dialysis cost to the patients and institution. An interventional nephrology program for percutaneous insertion of PD catheters under fluoroscopic guidance was developed to ensure rapid and timely placement of PD Supplemental material available at www.pdiconnect.com DESCRIPTION OF AN URGENT-START PERITONEAL DIALYSIS PROGRAM IN SINGAPORE
INTRODUCTION A complex relationship exists between chronic kidney disease-mineral and bone disorder (CKD-MBD) and adverse outcomes among dialysis patients. This study aimed to report the prevalence of CKD-MBD and examine the impact of achieving target CKD-MBD parameters on morbidity and mortality one year after peritoneal dialysis (PD) initiation.METHODS In this retrospective cohort study, patients electively initiated on PD were followed up for one year. Laboratory parameters were collected and the prevalence of CKD-MBD 4-6 months after PD initiation was determined based on the Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Linear regression and Cox proportional hazards model were used to evaluate the effects of achieving CKD-MBD targets 4-6 months after PD initiation on hospitalisation, the incidence of peritonitis or exit-site infections (ESIs), and mortality at one year.RESULTS The prevalence of CKD-MBD among the 86 patients in this study was 86.0% (KDOQI) and 54.7% (KDIGO). There was no significant difference in hospitalisation duration between patients who achieved targets and those who did not. Patients who failed to meet all the KDIGO CKD-MBD or calcium serum targets had a higher incidence of peritonitis or ESI. A trend toward shorter time to death was observed among patients who failed to meet the KDIGO phosphorus serum targets.CONCLUSION There was moderate (KDIGO) to high prevalence (KDOQI) of CKD-MBD among the patients. Achievement of all the KDIGO CKD-MBD or calcium serum targets was associated with reduced peritonitis or ESI, while achievement of the KDIGO phosphorus serum targets was associated with improved survival.
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.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.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.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.
INTRODUCTION Clinical practice guidelines recommend different levels of dietary protein intake in predialysis chronic kidney disease (CKD) patients. It is unknown how effectively these recommendations perform in a multi-ethnic Asian population, with varied cultural beliefs and diets. We assess the profi le of protein intake in a multi-ethnic Asian population, comparing healthy participants and CKD patients. MATERIALS AND METHODS We analysed the 24-hour urine collections of the Asian Kidney Disease Study (AKDS) and the Singapore Kidney Function Study (SKFS) to estimate total protein intake (TPI; g/day). We calculated ideal body weight (IDW; kg): 22.99 × height2 (m). Standard statistical tests were applied where appropriate, and linear regression was used to assess associations of continuous variables with protein intake. RESULTS There were 232 CKD patients and 103 healthy participants with 35.5% diabetics. The mean TPI in healthy participants was 58.89 ± 18.42 and the mean TPI in CKD patients was 53.64 ± 19.39. By US National Kidney Foundation (NKF) guidelines, 29/232 (12.5%) of CKD patients with measured glomerular filtration rate (GFR) <25 (in mL/min/1.73 m2) had a TPI-IDW of <0.6 g/kg/day. By Caring for Australasians with Renal Impairment (CARI) guidelines, 76.3% (177/232) of CKD patients had TPI-IDW >0.75g/kg/ day. By American Dietetic Association (ADA) guidelines, 34.7% (44/127) of CKD patients with GFR <50 had TPI-IDW between 0.6 to 0.8 g/kg/day. Only 1/6 non-diabetic CKD patients with GFR <20 had a protein intake of between 0.3 to 0.5 g/kg/day. A total of 21.9% (25/114) of diabetic CKD patients had protein intake between 0.8 to 0.9 g/kg/day. CONCLUSION On average, the protein intake of most CKD patients exceeds the recommendations of guidelines. Diabetic CKD patients should aim to have higher protein intakes.
Background . The use of spot urine protein to creatinine ratios in estimating 24 hr urine protein excretion rates for diagnosing and managing chronic kidney disease (CKD) predated the standardization of creatinine assays. The comparative predictive performance of spot urine ratios and 24 hr urine collections (of albumin or protein) for the clinical outcomes of CKD progression, end-stage renal disease (ESRD), and mortality in Asians is unclear. We compared 4 methods of assessing urine protein excretion in a multiethnic population of CKD patients. Methods . Patients with CKD (n=232) provided 24 hr urine collections followed by spot urine samples the next morning. We created multiple linear regression models to assess the factors associated with GFR decline (median follow-up: 37 months, IQR 26–41) and constructed Cox proportional-hazards models for predicting the combined outcome of ESRD and death. Results . The linear regression models showed that 24 hr urine protein excretion was most predictive of GFR decline but all other methods were similar. For the combined outcomes of ESRD and death, the proportional hazards models had similar predictive performance. Conclusions . We showed that all methods of assessments were comparable for clinical end-points, and any method can be used in clinical practice or research.
Introduction: Bioimpedance spectroscopy measures overhydration (OH), which is used to manage hypertension in non-Asian dialysis patients. OH is calculated from equations derived from populations including chronic kidney disease (CKD) patients on dialysis. It is unclear if this applies to managing hypertension in Asian patients. Objective: We examined the cross-sectional association of OH with systolic (SBP) and diastolic (DBP) blood pressures in a population of Asianpredialysis CKD and dialysis patients. Methods: We prospectively recruited 352 patients (59.4% male, Chinese 65.3%, mean age 61.8 ± 10.7 years, 46 on dialysis; 52%, 84.4%, and 25.9% with previously diagnosed diabetes, hypertension, and coronary artery disease, respectively). They underwent bioimpedance spectroscopy with the Fresenius Body Composition Monitor (BCM). Standard statistical tests and linear regression were used to correlate SBPand DBP (mmHg) with OH. Results: Overall, averageSBP was 140 ± 22, DBP was 74 ± 11, and median OH was 1.0L (IQR: 0.2–2.0). Non-dialysis CKD patients had mean SBP of 139 ± 20, DBP74 ± 11, and median OH of 1.0L (IQR: 0.1–1.9). By linear regression, SBP was associated with OH, SBP = 137.8 + 1.39 × OH (p = 0.0496); but DBP was not associated with OH. Patients on dialysis had mean SBP of 146 ± 30, DBP 76 ± 13, and median OH of 1.6L (IQR: 0.35–2.6). By linear regression, SBP was associated with OH, SBP = 130.3 + 8.8 × OH (p < 0.001); but DBP was not associated with OH. Conclusions: The Fresenius BCM overhydration indicator is associated with SBP in Asian predialysis CKD and dialysis patients, and may be useful in guiding antihypertensive therapy in Asians.
Introduction: This is a report of a clinical trial on the therapeutic efficacy and safety of combined aliskiren and losartan (an angiotensin II receptor blocker (ARB)) versus aliskiren alone and ARB alone in non-diabetic chronic kidney disease (CKD) over a 3-year period. Materials and methods: This was a randomised trial in 155 patients with non-diabetic CKD comparing aliskiren (150 mg/day) ( n =52) versus losartan (100 mg/day) ( n =52) and the third group aliskiren (150 mg/day) combined with losartan (100 mg/day) ( n =51). The trial utilised primary renal end points of eGFR <15 ml/min or end-stage renal failure. Results: All three groups had significant reduction of proteinuria ( p <0.001 for all). The changes in eGFR, total urinary protein from baseline to each year were not significantly different between the three therapeutic groups. Conclusion: This study in non-diabetic CKD patients showed that combination therapy with aliskiren and ARB was as efficacious as aliskiren alone and ARB alone. There was one patient who developed a non-fatal stroke in the combined aliskiren and ARB group while the other two groups had none.
INTRODUCTION Clinical practice guidelines recommend using creatinine-based equations to estimate glomerular filtration rates (GFRs). While these equations were formulated for Caucasian-American populations and have adjustment coefficients for African-American populations, they are not validated for other ethnicities. The Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) recently developed a new equation that uses both creatinine and cystatin C. We aimed to assess the accuracy of this equation in estimating the GFRs of participants (healthy and with chronic kidney disease [CKD]) from a multiethnic Asian population. METHODS Serum samples from the Asian Kidney Disease Study and the Singapore Kidney Function Study were used. GFR was measured using plasma clearance of 99mTc-DTPA. GFR was estimated using the CKD-EPI equations. The performance of GFR estimation equations were examined using median and interquartile range values, and the percentage difference from the measured GFR. RESULTS The study comprised 335 participants (69.3% with CKD; 38.5% Chinese, 29.6% Malays, 23.6% Indians, 8.3% others), with a mean age of 53.5 ± 15.1 years. Mean standardised serum creatinine was 127 ± 86 μmol/L, while mean standardised serum cystatin C and mean measured GFR were 1.43 ± 0.74 mg/L and 67 ± 33 mL/min/1.73 m2, respectively. The creatinine-cystatin C CKD-EPI equation performed the best, with an estimated GFR of 67 ± 35 mL/min/1.73 m2. CONCLUSION The new creatinine-cystatin C equation estimated GFR with little bias, and had increased precision and accuracy in our multiethnic Asian population. This two-biomarker equation may increase the accuracy of population studies on CKD, without the need to consider ethnicity.
To the Editor: We read with great interest the article by Astor et al.,1.Astor B.C. Muth B. Kaufman D.B. Pirsch J.D. Hofmann R.M. Djamali A. Serum β2-microglobulin at discharge predicts mortality and graft loss following kidney transplantation.Kidney Int. 2013; 84: 810-817Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar which reported that serum β2-microglobulin (β2-M) at discharge is a potent predictor of long-term mortality and graft loss in kidney transplant recipients. Although considered a limitation of the study, nevertheless it is impressive that only one measurement of serum β2-M and serum creatinine at discharge could strongly predict outcomes over a median follow-up period over 5 years. This study is the first to demonstrate an association between serum β2-M and long-term outcomes in kidney transplant recipients. It is interesting that, about three decades ago, other workers2.Schweizer R.T. Moore R. Bartus S.A. Bow L. Hayden J. Beta 2-microglobulin monitoring after renal transplantation.Transplant Proc. 1981; 13: 1620-1623PubMed Google Scholar,3.Ahlmein J. Studies of serum beta-2-microglobulin in the initial post-operative period after clinical transplantation.Scand J Urol Nephrol. 1980; 54: 145-149Google Scholar including ourselves4.Woo K.T. Lee E.J.C. Lau Y.K. Lim C.H. Beta-2-microglobulin in the assessment of renal function of the transplanted kidney.Nephron. 1985; 39: 223-227Crossref PubMed Scopus (15) Google Scholar reported that serum β2-M used alone or with urine β2-M and SUR (serum-to-urine β2-M ratio) appears to be a useful index for assessment of renal allograft function as well as for detection of potential renal damage. In 1983, Edwards et al.5.Edwards L.C. Helderman J.H. Hamm L.L. Ludwin D. Gailunas Jr, P. Hull A.R. Noninvasive monitoring of renal transplant function by analysis of beta-2-microglobulin.Kidney Int. 1983; 23: 767-770Abstract Full Text PDF PubMed Scopus (35) Google Scholar reported that serum β2-M levels measured up to 48h before a rise in serum creatinine were accurate in predicting or diagnosing rejection in 91% of all patients. Increased serum β2-M levels may reflect either increased synthesis and/or defect of glomerular filtration. Increased urinary excretion reflects primarily defective tubular reabsorption and/or possible increased filtered load. In the case of the transplanted kidney, this increased urinary β2-M excretion would probably indicate proximal tubular damage due to transplant rejection. The elegant study by Astor et al.1.Astor B.C. Muth B. Kaufman D.B. Pirsch J.D. Hofmann R.M. Djamali A. Serum β2-microglobulin at discharge predicts mortality and graft loss following kidney transplantation.Kidney Int. 2013; 84: 810-817Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar could have yielded even more intriguing information if β2-M levels had been obtained from both the urine and the serum and the SUR had been calculated. We are in agreement with Astor et al.1.Astor B.C. Muth B. Kaufman D.B. Pirsch J.D. Hofmann R.M. Djamali A. Serum β2-microglobulin at discharge predicts mortality and graft loss following kidney transplantation.Kidney Int. 2013; 84: 810-817Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar that elevated serum β2-M can be a useful prognostic marker. This is based on our earlier work on immunoglobulin A (IgA) nephritis, which reported that patients with IgA nephritis with glomerular sclerosis have higher levels of serum β2-M, which were correlated with severe proteinuria and intensity of IgA staining on immunofluorescence.6.Woo K.T. Tan Y.O. Yap H.K. Lau Y.K. Tay J.S.H. Lim C.H. Beta-2 microglobulin in mesangial IgA nephropathy.Nephron. 1984; 37: 78-81Crossref PubMed Scopus (7) Google Scholar
Survival differences with hemodialysis (HD) or peritoneal dialysis (PD) in patients with end-stage renal disease (ESRD) may vary substantially according to demographics or comorbidities [ [1] Vonesh E.F. Snyder J.J. Foley R.N. Collins A.J. The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis. Kidney Int. 2004; 66: 2389-2401 Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar ]. In that regard, intra-dialytic hypotension can induce myocardial stunning that contributes to heart failure in HD patients [ [2] Burton J.O. Jefferies H.J. Selby N.M. McIntyre C.W. Hemodialysis-induced cardiac injury: determinants and associated outcomes. Clin J Am Soc Nephrol. 2009; 4: 914-920 Crossref PubMed Scopus (516) Google Scholar ], and may be detrimental to ESRD patients with concomitant ischemic cardiomyopathy (ICMP). However, PD obviates the need for a high-flow arteriovenous fistula and allows gradual daily ultrafiltration, both likely favorable for patients with ICMP. Consequentially, PD may be associated with lower risk of congestive heart failure (CHF) compared with HD [ [3] Trespalacios F.C. Taylor A.J. Agodoa L.Y. Bakris G.L. Abbott K.C. Heart failure as a cause for hospitalization in chronic dialysis patients. Am J Kidney Dis. 2003; 41: 1267-1277 Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar ]. These theoretical assumptions may influence modality selection in favor of PD, in incident dialysis patients with ESRD and ICMP, and warrant detailed examination. Accordingly, we aim to evaluate 2-year patient-centered outcomes in this cohort with respect to initial dialysis modality. We hypothesize that patients on PD (versus HD) will experience less major adverse cardiac events (MACE), hospitalization days, and mortality over 2 years from dialysis initiation.
INTRODUCTION Clinical practice guidelines recommend using creatinine-based equations to estimate glomerular filtration rates (GFRs). While these equations were formulated for Caucasian-American populations and have adjustment coefficients for African-American populations, they are not validated for other ethnicities. The Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) recently developed a new equation that uses both creatinine and cystatin C. We aimed to assess the accuracy of this equation in estimating the GFRs of participants (healthy and with chronic kidney disease [CKD]) from a multiethnic Asian population. METHODS Serum samples from the Asian Kidney Disease Study and the Singapore Kidney Function Study were used. GFR was measured using plasma clearance of 99mTc-DTPA. GFR was estimated using the CKD-EPI equations. The performance of GFR estimation equations were examined using median and interquartile range values, and the percentage difference from the measured GFR. RESULTS The study comprised 335 participants (69.3% with CKD; 38.5% Chinese, 29.6% Malays, 23.6% Indians, 8.3% others), with a mean age of 53.5 ± 15.1 years. Mean standardised serum creatinine was 127 ± 86 μmol/L, while mean standardised serum cystatin C and mean measured GFR were 1.43 ± 0.74 mg/L and 67 ± 33 mL/min/1.73 m2, respectively. The creatinine-cystatin C CKD-EPI equation performed the best, with an estimated GFR of 67 ± 35 mL/min/1.73 m2. CONCLUSION The new creatinine-cystatin C equation estimated GFR with little bias, and had increased precision and accuracy in our multiethnic Asian population. This two-biomarker equation may increase the accuracy of population studies on CKD, without the need to consider ethnicity.