The Concordance between Patients’ Renal Replacement Therapy Choice and Definitive Modality: Is It a Utopia?

IntroductionIt is desirable for patients to play active roles in the choice of renal replacement therapy (RRT). Patient decision aid tools (PDAs) have been developed to allow the patients to choose the option best suited to their individual needs.ResultsPatients included in this study: 1044. Of these, 569 patients used PDAs and had made a definitive choice by the end of registration. A total of 88.4% of patients chose dialysis [43% hemodialysis (HD) and 45% peritoneal dialysis (PD)] 3.2% preemptive living-donor transplant (TX), and 8.4% conservative treatment (CT). A total of 399 patients began RRT during this period. The distribution was 93.4% dialysis (53.6% HD; 40% PD), 1.3% preemptive TX and 5.3% CT. The patients who followed the EP changed their mind significantly less often [kappa value of 0.91 (95% CI, 0.86–0.95)] than those who did not follow it, despite starting unplanned treatment [kappa value of 0.85 (95% CI, 0.75–0.95]. A higher agreement between the final choice and a definitive treatment was achieved by the EP and planned patients [kappa value of 0.93 (95% CI, 0.89–0.98)]. Those who did not go through the EP had a much lower index of choosing PD and changed their decision more frequently when starting definitive treatment [kappa value of 0.73 (95% CI, 0.55–0.91)].ConclusionsFree choice, assisted by PDAs, leads to a 50/50 distribution of PD and HD choice and an increase in TX choice. The use of PDAs, even with an unplanned start, achieved a high level of concordance between the chosen and definitive modality.     

Comparison of Early versus Late Below Knee Amputation After Trauma With Standardized Prosthetic Care

BackgroundHigh energy, lower extremity trauma is associated with longstanding pain and functional limitations. The clinical decision to proceed with early amputation or limb salvage is often controversial. This study was designed to compare differences in complications, costs, and clinical outcomes of below knee amputation (BKA) performed early after injury or after attempted limb salvage in a hospital with standardized prosthetic care following amputation.MethodsThis is a retrospective comparative study of subjects who underwent BKA for a traumatic injury at a single level 1 trauma center and received standardized prosthetic care from a single manufacturer from 1999-2016 with minimum 2-year post-amputation follow up. Outcomes collected included demographics, surgical management, unplanned re-operations, and hospital and prosthetic cost data 2 years from time of injury.ResultsOverall, 79 subjects met criteria. Early amputation (EA) was defined by median duration between injury and amputation (6 weeks) with 41 subjects in the EA group and 38 subjects in the late amputation (LA) group. Subjects in the EA group were more likely to have open fractures, high energy mechanism, and less likely to have medical comorbidities. Post-amputation infection was common in both groups (17/41 (42%) vs 17/38 (45%), p=0.77). Subjects undergoing EA were more likely to require unplanned post-amputation revision, 22/41 (54%) versus 10/38 (27%), p=0.017. Hospital costs and prosthetics/orthotics costs from the time of injury to two years following amputation were comparable, with mean hospital EA costs $136,044 versus LA costs $125,065, p=0.38. Mean prosthetics/orthotics costs of EA subjects were $33,252 versus LA costs $37,684, p=0.59.ConclusionUnplanned post-amputation revision surgeries were more common when BKA was performed early after trauma. Otherwise, outcomes and cost were comparable when amputation was performed early versus late. Level of Evidence: IV     

可溶性细胞间粘附分子在慢性肾脏病中的变化

目的:研究慢性肾病(CKD)患者血清可溶性细胞粘附分子-1(soluble intercellular adhesionmolecule-1,sICAM)的变化与临床意义。方法:用双抗体夹心ELISA方法,对52例CKD患者及20例健康对照人群的sICAM-1水平进行检测分析。52例CKD患者中,其中27例为CRF血液透析患者;25例肾功能正常CKD患者。结果:CKD组患者sICAM-1水平明显高于对照组(105.42±61.95)(P<0.01);肾功能正常CKD组和CKD-CRF组sICAM-1水平均显著高于对照组(P<0.01);CRF组sICAM-1水平明显低于肾功能正常CKD组(P<0.01);但高于对照组(84.80±19.61/164.08±70.66/54.61±5.48)(P<0.01)。结论:sICAM-1水平在慢性肾脏病中明显升高,CRF组病人sICAM-1水平低于CKD肾功能正常患者,提示透析过程中可能有sICAM溢出,吸附并丢失入透析液中(1),或可能是肾纤维化为主的病变使sICAM-1表达下降。     

Acute and chronic arterial and venous effects of captopril in congestive cardiac failure.

OBJECTIVE--To determine whether captopril alters peripheral venous tone in patients with congestive cardiac failure. DESIGN--Open study of patients at start of captopril treatment and three months later. SETTING--A hospital gamma camera laboratory. PATIENTS--16 Men with congestive cardiac failure in New York Heart Association class II or III, aged 57-73. INTERVENTIONS--Patients were initially given 500 micrograms sublingual glyceryl trinitrate followed by 25 mg oral captopril. The study was then repeated after three months'' captopril treatment. MAIN OUTCOME MEASURES--Previously validated non-invasive radionuclide techniques were used to measure changes in central haemodynamic variables and peripheral venous volumes in the calf. RESULTS--After 25 mg captopril there were falls in blood pressure and relative systemic vascular resistance and increases in cardiac index and left ventricular ejection fraction. This was accompanied by a 16% increase in peripheral venous volume (95% confidence interval 13.4% to 18.4%, p less than 0.01), which compared with an 11% increase after 500 micrograms glyceryl trinitrate (10% to 12%, p less than 0.01). Eleven patients were restudied after three months'' continuous treatment with captopril. The resting venous volume was higher than it had been initially, by about 10%, and increased by a further 8.4% after 25 mg captopril (5.4% to 11.4%, p less than 0.05). CONCLUSIONS--Captopril is an important venodilator. Venous and arterial dilatation are produced short term and during long term treatment.     

Unplanned cancer presentation in patients with psychiatric disorders: A nationwide register-based cohort study in Denmark

Unplanned presentation in the cancer pathway is more common in patients with psychiatric disorders than in patients without. More knowledge about the risk factors for unplanned presentation could help target interventions to ensure earlier diagnosis of cancer in patients with psychiatric disorders. This study aims to estimate the association between patient characteristics (social characteristics and coexisting physical morbidity) and cancer diagnosis following unplanned presentation among cancer patients with psychiatric disorders. We conducted a population-based register study including patients diagnosed with cancer in 2014–2018 and also registered with at least one psychiatric disorder in the included Danish registers (n = 26,005). We used logistic regression to assess patient characteristics associated with an unplanned presentation. Almost one in four symptomatic patients (23.6 %) with pre-existing psychiatric disorders presented unplanned in the cancer trajectory. Unplanned presentation was most common for severe psychiatric disorders, e.g. organic disorders and schizophrenia. Old age, male sex, living alone, low education, physical comorbidity, and non-attendance in primary care were associated with increased odds of unplanned presentation. In conclusion, several characteristics of patients with pre-existing psychiatric disorders were associated with unplanned presentation in the cancer trajectory; for some groups more than 40 % had an unplanned presentation. This information could be used to design targeted interventions for patients with pre-existing psychiatric disorders to ensure earlier diagnosis of cancer in this population.     

Thiazolidinediones and Risk of Long-Term Dialysis in Diabetic Patients with Advanced Chronic Kidney Disease: A Nationwide Cohort Study

Thiazolidinediones (TZDs) reduce urinary albumin excretion and proteinuria in diabetic nephropathy. The effect of TZDs on hard renal outcome in diabetic patients with chronic kidney disease (CKD) is unknown. We investigate the association of TZDs and risk of long-term dialysis or death in diabetic patients with advanced CKD. The nationwide population-based cohort study was conducted using Taiwan’s National Health Insurance Research Database. From January 2000 to June 2009, 12350 diabetic patients with advanced CKD (serum creatinine levels greater than 6 mg/dL but not yet receiving renal replacement therapy) were selected for the study. We used multivariable Cox regression models and a propensity score-based matching technique to estimate hazard ratios (HRs) for development of long-term dialysis and the composite outcome of long-term dialysis or death for TZD users (n=1224) as compared to nonusers (n=11126). During a median follow-up of 6 months, 8270 (67.0%) patients required long-term dialysis and 2593 (21.0%) patients died before starting long-term dialysis. Using propensity score matched analysis, we found TZD users were associated with a lower risk for long-term dialysis (HR, 0.80; 95% confidence interval [CI], 0.74-0.86) and the composite outcome of long-term dialysis or death (HR, 0.85; 95% CI, 0.80-0.91). The results were consistent across most patient subgroups. Use of TZDs among diabetic patients with advanced CKD was associated with lower risk for progression to end-stage renal disease necessitating long-term dialysis or death. Further randomized controlled studies are required to validate this association.     

Cardiac Troponin I in Non- Acute Coronary Syndrome Patients with Chronic Kidney Disease

Objective

The aim of this study was to assess the results of troponin I (cTnI) in non- acute Coronary Syndrome (ACS) patients with chronic kidney disease (CKD). We also examined the risk factors for elevated cTnI in non-ACS patients with CKD and whether stage 5 CKD modifies the associations of elevated cTnI and the risk factors in non-ACS patients with CKD.

Methods

A retrospective study was performed. Logistic regression models were used.

Results

293 non-ACS patients with CKD were included in the current study. 43.34% non-ACS patients with CKD have an elevated cTnI level and 5.12% have an elevated cTnT level in MI range. In CKD patients without ACS and heart failure, only 26.03% (38/146) patients have an elevated cTnT level. In adjusted analyses, age, diastolic blood pressure and congestive heart failure is associated with an elevated cTnI level in non-ACS patients with CKD. Congestive heart failure is associated with an elevated cTnI level in non-ACS patients with CKD (OR 2.30, 95% CI 1.08,4.88, P=0.03). Stage 5 CKD does not modify the association of congestive heart failure and an elevated cTnI level.

Conclusion

43.34% non-ACS patients with CKD and 26.03% CKD patients without ACS and congestive heart failure have an elevated cTnI level. Congestive heart failure is associated with an elevated cTnI level in non-ACS patients with CKD. Stage 5 CKD does not modify the association of congestive heart failure and an elevated cTnI level.     

Outcome of renal replacement treatment in patients with diabetes mellitus.

OBJECTIVE--To compare the outcome of renal replacement treatment in patients with diabetes mellitus and in non-diabetic patients with end stage renal failure. DESIGN--Retrospective comparison of cases and matched controls. SETTING--Renal unit, Western Infirmary, Glasgow, providing both dialysis and renal transplantation. PATIENTS--82 Diabetic patients starting renal replacement treatment between 1979 and 1988, compared with 82 matched non-diabetic controls with renal failure and 39 different matched controls undergoing renal transplantation. MAIN OUTCOME MEASURES--Patient characteristics, history of smoking, prevalence of left ventricular hypertrophy and myocardial ischaemia at start of renal replacement treatment; survival of patients with renal replacement treatment and of patients and allografts with renal transplantation. RESULTS--The overall survival of the diabetic patients during the treatment was 83%, 59%, and 50% at one, three, and five years. Survival was significantly poorer in the diabetic patients than the controls (p less than 0.001). Particularly adverse features for outcome at the start of treatment were increasing age (p less than 0.01) and current cigarette smoking (relative risk (95% confidence interval) 2.28 (0.93 to 4.84), p less than 0.05). Deaths were mainly from cardiac and vascular causes. The incidence of peritonitis in patients on continuous ambulatory peritoneal dialysis was the same in diabetic patients and controls (49% in each group remained free of peritonitis after one year), and the survival of renal allografts was not significantly worse in diabetic patients (p less than 0.5). CONCLUSIONS--Renal replacement treatment may give good results in diabetic patients, although the outlook remains less favourable than for non-diabetic patients because of coexistent, progressive vascular disease, which is more severe in older patients.     

Features of uremic neuropathy in long-term dialysis

In order to assess the influence of long term hemodialysis on progression of uraemic neuropathy (UN), 16 different electroneurographic (ENG) parameters on 158 dialysis patients were performed. The ENG parameters were compared in three groups of patients of different dialysis age. Group I: high dialysis age (HDA) comprising of, 31 patients being more than 10 years on dialysis; Group II: intermediate dialysis age (IDA) comprising of 53 patients between 5 and 10 years on HD and group III: low dialysis age (LDA) comprising of 74 patients being less than 5 years on dialysis. The influence of sex and age was also analyzed. All sixteen tested parameters were altered in uremic patients when compared to 140 healthy controls (p < 0.01). HDA pts compared to LDA pts and the older group versus the younger had 11 and 9 out of 16 ENG parameters significantly worsened, respectively (p < 0.01). The most profound and reproducible lesion was in prolongation of evoked potential of tibialis posterior and peroneus nerve (FWt, HWt, FWp). HDA, especially after 10 yrs and the age but not the sex is clearly associated with a further progression of UN. However, for unknown reasons, the progression of UN in dialyzed patients is not followed by a parallel worsening of clinical symptoms (p > 0.05).     

Unplanned Excision of Extremity Soft Tissue Sarcoma in Korea: A Nationwide Study Based on a Claims Registry

Unplanned excision of extremity soft tissue sarcoma (STS) is common and has detrimental effects not only on patients’ oncologic outcomes but also on functional and economic issues. However, no study has analyzed a nationwide population-based database. To estimate the incidence and treatment pattern of unplanned excision in extremity STS in the Korean population, a nationwide epidemiologic study was performed using the Korean Health Insurance Review and Assessment Service database, a centralized nationwide healthcare claims registry of Korea that covers the entire Korean population. Among 1,517 patients with extremity STS in the 4-year study period, 553 (36.5%) underwent unplanned excision (unplanned group). About 80% of unplanned excisions were performed in tertiary or general hospitals. Of the unplanned group, 240 (43.4%) underwent re-excision with or without radiation therapy and/or chemotherapy, and 51 (9.2%) did not undergo re-excision but were treated with radiation therapy and/or chemotherapy; whereas, 262 (47.4%) did not undergo any further treatment following unplanned excision. This study is the first nationwide population-based study on the unplanned excision of extremity STS. The results may have implications in establishing preventive or therapeutic measures to reduce the burden of unplanned excision of extremity STS.     

What happens to defaulters from a diabetic clinic?

The annual rate at which patients defaulted from follow up at the Wolverhampton diabetic clinic between 1971 and 1981 was 4.1% overall and 3.5% in white patients. In 1982 a study was started to discover what happened to white patients, born after 1919, who defaulted from the hospital clinic. There were 162 defaulters, of whom 19 had died. Of the remaining 143 patients, 19 were attending another hospital diabetic clinic, 22 had moved out of the area, and 28 refused to participate in the study. Seventy four agreed to participate: 39 were treated with diet, 15 with oral hypoglycaemic agents, and 20 with insulin. They were matched for sex, age, treatment, and duration of diabetes with patients attending the clinic. Non-insulin dependent defaulters were significantly more overweight at diagnosis (40% v 25%; p less than 0.05) and remained more obese. They developed significantly higher diastolic blood pressure (94 v 86 mm Hg; p less than 0.02) and higher haemoglobin A1 (HbA1) concentrations (11.7% v 8.4%; p less than 0.01). They had significantly more neuropathy at reassessment (15 v 6 out of 54; p less than 0.05) and a greater incidence of new retinopathy (p less than 0.02), which correlated with their higher diastolic blood pressures (p less than 0.01) and HbA1 concentration (p less than 0.02). In defaulters who were treated with insulin only the prevalence of neuropathy was significantly different from that in controls (p less than 0.05). Defaulters received minimal medical supervision and suffered greater morbidity than regular attenders at the clinic.     

The reliability of ten-meter sprint time using different starting techniques

Acceleration is an important factor for success in team-sport athletes. The purpose of this investigation was to compare the reliability of 10-m sprint times when using different starting techniques. Junior male rugby players (n = 15) were tested for speed over 10 m on 2 different testing sessions. Three trials of 3 different starting techniques (standing, foot, and thumb starts) were assessed. Despite large differences in the time taken to perform 10-m sprints from different starts, there was minimal difference in the typical error (approximately 0.02 seconds, or <1%) between the 3 different starts. There was a small, 0.02 +/- 0.02 second, decrease (p = 0.05) in sprint time between sessions for the foot start. For all starting techniques, the magnitude of error (typical error) was greater than the smallest worthwhile change (<0.01 second), indicating that acceleration over 10 m measured by photocells only has a marginal chance of reliably detecting a change of sufficient magnitude to be worthwhile in practical terms. However, by accounting for the smallest worthwhile change and typical error, it is possible to establish the probability an individual has had a worthwhile change in sprint performance. Coaching and sports-science practitioners can use a variety of sprint-start techniques shown to have small typical errors (<1%); however, the results from the different starting technique are not interchangeable.     

Plasma Free Metanephrine and Normetanephrine Levels are Increased in Patients with Chronic Kidney Disease

ObjectivePatients with impaired renal function, particularly those on dialysis, frequently exhibit high blood pressure and hemodynamic instability, which often lead to pheochromocytoma assessment. Our objective was to assess plasma free metanephrine (MN) and normetanephrine (NMN) in chronic kidney disease patients (CKD) with or without dialysis.MethodsIn this prospective observational study we performed enzyme-linked immunosorbent assays (ELISAs) to evaluate plasma free MN and NMN in 48 CKD patients (15 with stage 3-5 CKD without dialysis, 26 on hemodialysis [HD], and 7 continuous ambulatory peritoneal dialysis [CAPD]), 30 patients with histologically proven pheochromocytoma, and 43 hypertensive patients. Adrenal masses were ruled out by abdominal computed tomography (CT) scans in all CKD and control hypertensive patients.ResultsAll 3 CKD groups (HD, CAPD, and CKD without dialysis) had significantly higher plasma free MN and NMN levels than the control hypertensive group (P < .0055). HD and CAPD patients had significantly lower plasma free NMN (P < .0055), but free MN levels were not significantly different than those observed in pheochromocytoma patients. In patients with HD, CAPD, and CKD without dialysis, plasma free MN and NMN were higher than manufacturer’s upper limits of normal in 57.7% and 28.5%, 13.3% and 61.5%, and 85.7% and 26.6%, respectively. Regression models showed that the number of dialysis years was significantly correlated with plasma free MN (r = 0.615, P < .001) but not free NMN.ConclusionPlasma free MN and NMN levels are frequently elevated in CKD patients, particularly in those on dialysis. Plasma free MN levels significantly overlap with the range in pheochromocytoma patients and correlate with the number of years on dialysis. (Endocr Pract. 2014;20:139-144)     

New markers of apoptosis in children on chronic dialysis

Enhanced apoptosis is characteristic for chronic kidney disease (CKD). A specific type of apoptosis, anoikis, is connected with the extracellular matrix turnover and cell detachment. Although E-cadherin, extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase (MMP)-8 may play an important role in this process, they have not been analyzed in any nephrological aspect, either in CKD. The aim of study was to evaluate the serum concentrations of E-cadherin, EMMPRIN and their potential regulators (MMP-8, MMP-7, TIMP-1, TIMP-2), with relevance to apoptosis/cell damage markers (sFas, sFasL, Hsp27), in children with CKD. 39 CKD children stages 3–4, 26 CKD children stage 5 still on conservative treatment, 19 patients on hemodialysis (HD), 22 children on automated peritoneal dialysis (APD) and 30 controls were examined. Serum concentrations of those parameters were assessed by ELISA. Median E-cadherin, EMMPRIN and MMP-8 values were significantly increased in patients on dialysis versus those in pre-dialysis period and versus controls. The highest values were noticed in the HD subjects. Regression analysis revealed that EMMPRIN and MMP-8 predicted various apoptosis markers, whereas E-cadherin turned out the best predictor of both apoptosis (Hsp27, sFas, sFasL) and matrix turnover (MMP-7, TIMP-1, TIMP-2) indexes in dialyzed patients. Children with CKD are prone to E-cadherin, EMMPRIN and MMP-8 elevation, aggravated by the dialysis commencement and most evident on hemodialysis. Correlations between parameters suggest their role as indexes of apoptosis in children on dialysis. E-cadherin seems the most accurate marker of anoikis in this population.     

Use of Chronic Kidney Disease to Enhance Prediction of Cardiovascular Risk in Those at Medium Risk

Based on global cardiovascular (CV) risk assessment for example using the Framingham risk score, it is recommended that those with high risk should be treated and those with low risk should not be treated. The recommendation for those of medium risk is less clear and uncertain. We aimed to determine whether factoring in chronic kidney disease (CKD) will improve CV risk prediction in those with medium risk. This is a 10-year retrospective cohort study of 905 subjects in a primary care clinic setting. Baseline CV risk profile and serum creatinine in 1998 were captured from patients record. Framingham general cardiovascular disease risk score (FRS) for each patient was computed. All cardiovascular disease (CVD) events from 1998–2007 were captured. Overall, patients with CKD had higher FRS risk score (25.9% vs 20%, p = 0.001) and more CVD events (22.3% vs 11.9%, p = 0.002) over a 10-year period compared to patients without CKD. In patients with medium CV risk, there was no significant difference in the FRS score among those with and without CKD (14.4% vs 14.6%, p = 0.84) However, in this same medium risk group, patients with CKD had more CV events compared to those without CKD (26.7% vs 6.6%, p = 0.005). This is in contrast to patients in the low and high risk group where there was no difference in CVD events whether these patients had or did not have CKD. There were more CV events in the Framingham medium risk group when they also had CKD compared those in the same risk group without CKD. Hence factoring in CKD for those with medium risk helps to further stratify and identify those who are actually at greater risk, when treatment may be more likely to be indicated.     

Left Ventricular Global Longitudinal Strain (GLS) Is a Superior Predictor of All-Cause and Cardiovascular Mortality When Compared to Ejection Fraction in Advanced Chronic Kidney Disease

BackgroundEchocardiographic global longitudinal strain (GLS) is increasingly recognised as a more effective technique than conventional ejection fraction (EF) in detecting subtle changes in left ventricular (LV) function. This study investigated the prognostic value of GLS over EF in patients with advanced Chronic Kidney Disease (CKD).MethodsThe study included 183 patients (57% male, 63% on dialysis) with CKD stage 4, 5 and 5Dialysis (D). 112 (61%) of patients died in a follow up of 7.8 ± 4.4 years and 41% of deaths were due to cardiovascular (CV) disease. GLS was calculated using 2-dimensional speckle tracking and EF was measured using Simpson’s biplane method. Cox proportional hazard models were used to assess the association of measures of LV function and all- cause and CV mortality.ResultsThe mean GLS at baseline was -13.6 ± 4.3% and EF was 45 ± 11%. GLS was a significant predictor of all-cause [Hazard Ratio (HR) 1.09 95%; Confidence Interval (CI) 1.02–1.16; p = 0.01] and CV mortality (HR 1.16 95%; CI 1.04–1.30; p = 0.008) following adjustment for relevant clinical variables including LV mass index (LVMI) and EF. GLS also had greater predictive power for both all- cause and CV mortality compared to EF. Impaired GLS (>-16%) was associated with a 5.6-fold increased unadjusted risk of CV mortality in patients with preserved EF.ConclusionsIn this cohort of patients with advanced CKD, GLS is a more sensitive predictor of overall and CV mortality compared to EF. Studies of larger populations in CKD are required to confirm that GLS provides additive prognostic value in patients with preserved EF.     

A Systematic Review and Meta-Analysis of Utility-Based Quality of Life in Chronic Kidney Disease Treatments

Background

Chronic kidney disease (CKD) is a common and costly condition to treat. Economic evaluations of health care often incorporate patient preferences for health outcomes using utilities. The objective of this study was to determine pooled utility-based quality of life (the numerical value attached to the strength of an individual''s preference for a specific health outcome) by CKD treatment modality.

Methods and Findings

We conducted a systematic review, meta-analysis, and meta-regression of peer-reviewed published articles and of PhD dissertations published through 1 December 2010 that reported utility-based quality of life (utility) for adults with late-stage CKD. Studies reporting utilities by proxy (e.g., reported by a patient''s doctor or family member) were excluded.In total, 190 studies reporting 326 utilities from over 56,000 patients were analysed. There were 25 utilities from pre-treatment CKD patients, 226 from dialysis patients (haemodialysis, n = 163; peritoneal dialysis, n = 44), 66 from kidney transplant patients, and three from patients treated with non-dialytic conservative care. Using time tradeoff as a referent instrument, kidney transplant recipients had a mean utility of 0.82 (95% CI: 0.74, 0.90). The mean utility was comparable in pre-treatment CKD patients (difference = −0.02; 95% CI: −0.09, 0.04), 0.11 lower in dialysis patients (95% CI: −0.15, −0.08), and 0.2 lower in conservative care patients (95% CI: −0.38, −0.01). Patients treated with automated peritoneal dialysis had a significantly higher mean utility (0.80) than those on continuous ambulatory peritoneal dialysis (0.72; p = 0.02). The mean utility of transplant patients increased over time, from 0.66 in the 1980s to 0.85 in the 2000s, an increase of 0.19 (95% CI: 0.11, 0.26). Utility varied by elicitation instrument, with standard gamble producing the highest estimates, and the SF-6D by Brazier et al., University of Sheffield, producing the lowest estimates. The main limitations of this study were that treatment assignments were not random, that only transplant had longitudinal data available, and that we calculated EuroQol Group EQ-5D scores from SF-36 and SF-12 health survey data, and therefore the algorithms may not reflect EQ-5D scores measured directly.

Conclusions

For patients with late-stage CKD, treatment with dialysis is associated with a significant decrement in quality of life compared to treatment with kidney transplantation. These findings provide evidence-based utility estimates to inform economic evaluations of kidney therapies, useful for policy makers and in individual treatment discussions with CKD patients.     

Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease

Background

The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population.

Objective

To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality.

Methods

Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3–5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed.

Results

GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3–5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32–14.2; p = 0.016).

Conclusion

Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3–5 patients.     

Effect of dialysis on oxidative stress in uraemia

It has been postulated that dialysis of patients with chronic renal failure (CRF) is associated with increased lipid peroxidation which may contribute to vascular and other complications of the syndrome. In the present study, a specific and precise technique [ferrous oxidation in xylenol orange (FOX) assay] was used to measure plasma lipid hydroperoxides (ROOHs) in three groups of uraemic patients. Patients were either studied before starting dialysis (n = 12) or on continuous ambulatory peritoneal dialysis (CAPD, n = 12) or haemodialysis (HD, n = 36) and compared to healthy controls (n = 20). Plasma ROOHs were markedly elevated in HD patients compared with the controls (7.01 +/- 2.9 microM versus 4.25 +/- 2.05 microM; P < 0.005, Mann-Whitney test). Plasma ROOH concentrations in the CAPD patients were increased but not significantly higher than controls (5.36 +/- 3.56 microM versus 4.25 +/- 2.05 microM). By contrast, no differences in ROOH levels were found between controls and predialysis patients. There was no difference in plasma thiobarbituric acid reactive substances (TBARS) between control and the three CRF groups. Absolute and cholesterol standardised plasma alpha-tocopherol levels were lower in the patients (whether they were on dialysis or not) than in the controls (18.62 +/- 6.88 microM versus 22.73 +/- 5.33 microM; P < 0.01 and 1.99 +/- 1.88 microM/mM versus 5.25 +/- 1.0 microM/mM; P < 0.0005, respectively). This study provides direct evidence that enhanced oxidative stress in CRF patients is related to the dialysis treatment rather than the disease itself. Further studies will be necessary to establish the relationships between plasma measures of oxidative stress and cardiovascular complications in CRF patients under dialysis and whether treatment with antioxidants may reduce oxidative stress or reverse adverse effects associated with dialysis.     

Trefoil Factor 1 Excretion Is Increased in Early Stages of Chronic Kidney Disease

Chronic kidney disease (CKD) is associated with high morbidity and mortality. In many patients CKD is diagnosed late during disease progression. Therefore, the implementation of potential biomarkers may facilitate the early identification of individuals at risk. Trefoil factor family (TFF) peptides promote restitution processes of mucous epithelia and are abundant in the urinary tract. We therefore sought to investigate the TFF peptide levels in patients suffering from CKD and their potential as biomarkers for CKD. We analysed TFF1 and TFF3 in serum and urine of 115 patients with CKD stages 1–5 without dialysis by ELISA. 20 healthy volunteers served as controls. Our results showed, that urinary TFF1 levels were significantly increased with the onset of CKD in stages 1–4 as compared to controls and declined during disease progression (p = 0.003, < 0.001, 0.005, and 0.007. median concentrations: 3.5 pg/mL in controls vs 165.2, 61.1, 17.2, and 15.8 pg/mL in CKD 1–4). TFF1 and TFF3 serum levels were significantly elevated in stages 3–5 as compared to controls (TFF1: p < 0.01; median concentrations: 12.1, 39.7, and 34.5 pg/mL in CKD 3–5. TFF3: p < 0.001; median concentrations: 7.1 ng/mL in controls vs 26.1, 52.8, and 78.8 ng/mL in CKD 3–5). TFF3 excretion was increased in stages 4 and 5 (p < 0.001; median urinary levels: 65.2 ng/mL in controls vs 231.5 and 382.6 ng/mL in CKD 4/5; fractional TFF3 excretion: 6.4 in controls vs 19.6 and 44.1 in CKD 4/5). ROC curve analyses showed, that monitoring TFF peptide levels can predict various CKD stages (AUC urinary/serum TFF > 0.8). In conclusion our results show increased levels of TFF1 and TFF3 in CKD patients with a pronounced elevation of urinary TFF1 in lower CKD stages. Furthermore, TFF1 and TFF3 seems to be differently regulated and show potential to predict various CKD stages, as shown by ROC curve analysis.