Central pulse pressure in patients with chronic kidney disease and in renal transplant recipients.

Patients with chronic kidney disease (CKD) and renal transplant recipients (RTR) have increased cardiovascular risk. The value of measuring central pulse pressure (cPP) over brachial pulse pressure (pPP) is not known. Central PP was measured in 597 patients (364 CKD:233 RTR). In multivariate analysis, age and female gender positively correlated with cPP; heart rate and estimated glomerular filtration rate negatively correlated with cPP. Associations for age, heart rate and gender persisted after additional adjustment for pPP and aortic wave reflection. This model accounted for 91% of the variability in cPP, with pPP alone accounting for 74%. Results were similar when both patient groups were analysed separately. A subset of patients with CKD had aortic pulse wave velocity (PWV) and left ventricular mass index (LVMI) measured. There were no differences in the univariate correlations between PWV (r=0.368 vs 0.315; P=0.4) or LVMI (r=0.125 vs 0.163; P=0.7); nor in the multivariate models created for PWV (P=0.1) or LVMI (P=0.1) when either cPP or pPP were used. This study demonstrates that in these patients most of the variability in cPP can be explained by pPP. Additionally, cPP does not appear to provide additional information beyond pPP in determining PWV and LVMI.

Variation between centres in access to renal transplantation in UK: longitudinal cohort study.

OBJECTIVE: To assess whether equity exists in access to renal transplantation in the UK after adjustment for case mix in incident patients with end stage renal disease. DESIGN: Longitudinal cohort study. SETTING: UK Renal Registry and UK Transplant Registry. PARTICIPANTS: All incident renal replacement treatment patients (n=16 202) from 65 renal centres submitting data to the UK Renal Registry between 1 January 2003 and 31 December 2005, followed until 31 December 2008 (or until transplantation or death, whichever was earliest). OUTCOME MEASURES: Proportion of incident dialysis patients at each renal centre who were registered on the national transplant list; time taken to achieve registration; and proportion of patients subsequently transplanted. RESULTS: We found that recipients' age, ethnicity, and primary renal diagnosis were associated with the likelihood of accessing the waiting list or receiving a transplant. After adjustment for case mix, significant inter-centre variability existed in access to the transplant list (change in -2LogL=89.9, df=1, P<0.001), in the time taken to register patients on the waiting list (change in -2LogL=247.4, df=64, P<0.001), in receipt of a renal transplant from a donor after brain stem death (change in -2LogL=15.1, df=1, P=0.001), and in receipt of a renal transplant from a living donor or a donor after cardiac death (change in -2LogL=46.1, df=1, P<0.001). CONCLUSIONS: Significant variation in access to renal transplantation exists between centres within the UK that cannot be explained by differences in case mix.

A method of identifying and correcting miscoding, misclassification and misdiagnosis in diabetes: a pilot and validation study of routinely collected data.

AIMS: Incorrect classification, diagnosis and coding of the type of diabetes may have implications for patient management and limit our ability to measure quality. The aim of the study was to measure the accuracy of diabetes diagnostic data and explore the scope for identifying errors. METHOD: We used two sets of anonymized routinely collected computer data: the pilot used Cutting out Needless Deaths Using Information Technology (CONDUIT) study data (n = 221 958), which we then validated using 100 practices from the Quality Improvement in Chronic Kidney Disease (QICKD) study (n = 760,588). We searched for contradictory diagnostic codes and also compatibility with prescription, demographic and laboratory test data. We classified errors as: misclassified-incorrect type of diabetes; misdiagnosed-where there was no evidence of diabetes; or miscoded-cases where it was difficult to infer the type of diabetes. RESULTS: The standardized prevalence of diabetes was 5.0 and 4.0% in the CONDUIT and the QICKD data, respectively: 13.1% (n = 930) of CONDUIT and 14.8% (n = 4363) QICKD are incorrectly coded; 10.3% (n = 96) in CONDUIT and 26.2% (n = 1143) in QICKD are misclassified; nearly all of these cases are people classified with Type 1 diabetes who should be classified as Type 2. Approximately 5% of T2DM in both samples have no objective evidence to support a diagnosis of diabetes. Miscoding was present in approximately 7.8% of the CONDUIT and 6.1% of QICKD diabetes records. CONCLUSIONS: The prevalence of miscoding, misclassification and misdiagnosis of diabetes is high and there is substantial scope for further improvement in diagnosis and data quality. Algorithms which identify likely misdiagnosis, misclassification and miscoding could be used to flag cases for review.

Validation and utility of a computerized South Asian names and group recognition algorithm in ascertaining South Asian ethnicity in the national renal registry.

BACKGROUND: The UK Renal Registry (UKRR) reports on equity and quality of renal replacement therapy (RRT). Ethnic origin is a key variable, but it is only recorded for 76% patients overall in the UKRR and there is wide variation in the degree of its completeness between renal centres. Most South Asians have distinctive names. AIM: To test the relative performance of a computerized name recognition algorithm (SANGRA) in identifying South Asian names using the UKRR database. DESIGN: Cross-sectional study of patients (n = 27 832) starting RRT in 50 renal centres in England and Wales from 1997 to 2005. METHODS: Kappa statistics were used to assess the degree of agreement of SANGRA coding with existing ethnicity information in UKRR centres. RESULTS: In 12 centres outside London (number of patients = 7555) with 11% (n = 747) self-ascribed South Asian ethnicity, the level of agreement between SANGRA and self-ascribed ethnicity was high (kappa=0.91, 95% CI 0.90-0.93). In two London centres (n = 779) with 21% (n = 165) self-ascribed South Asian ethnicity, SANGRA's agreement with self-ascribed ethnicity was lower (kappa=0.60, 95% CI 0.54-0.67), primarily due to difficulties in distinguishing between South Asian ethnicity and other non-White ethnic minorities. Use of SANGRA increased numbers defined as South Asian from 1650 to 2076 with no overall change in percentage of South Asians. Kappa values showed no obvious association with degree of missing data returns to the UKRR. CONCLUSION: SANGRA's use, taking into account its lower validity in London, allows increased power and generalizability for both ethnic specific analyses and for analyses where adjustment for ethnic origin is important.

Correction of chronic metabolic acidosis for chronic kidney disease patients.

BACKGROUND: Metabolic acidosis is a feature of chronic kidney disease (CKD) due to the reduced capacity of the kidney to synthesise ammonia and excrete hydrogen ions. It has adverse consequences on protein and muscle metabolism, bone turnover and the development of renal osteodystrophy. Metabolic acidosis may be corrected by oral bicarbonate supplementation or in dialysis patients by increasing the bicarbonate concentration in dialysate fluid. OBJECTIVES: To examine the benefits and harms of treating metabolic acidosis in patients with CKD, both prior to reaching end-stage renal disease (ESRD) or whilst on renal replacement therapy (RRT), with sodium bicarbonate or increasing the bicarbonate concentration of dialysate. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library, issue 4 2005), Cochrane Renal Group's specialised register (October 2005), MEDLINE (1966 - October 2005) and EMBASE (1980 - October 2005). SELECTION CRITERIA: Randomised controlled trials (RCTs), crossover RCTs and quasi-RCTs investigating the correction of chronic metabolic acidosis in adults or children with CKD. DATA COLLECTION AND ANALYSIS: Outcomes were analysed using relative risk (RR) and weighted mean difference (MD) for continuous measures. MAIN RESULTS: We identified three trials in adult dialysis patients (n = 117). There were insufficient data for most outcomes for meta-analysis. In all three trials acidosis improved in the intervention group though there was variation in achieved bicarbonate level. There was no evidence of effect on blood pressure or sodium levels. Some measures of nutritional status/protein metabolism (e.g. SGA, NP NA) were significantly improved by correction in the one trial that looked in these in detail. There was heterogeneity of the effect on serum albumin in two trials. Serum PTH fell significantly in the two trials that estimated this, there was no significant effect on calcium or phosphate though both fell after correction. Complex bone markers were assessed in one study, with some evidence for a reduction in bone turnover in those with initial high bone turnover and an increase in low turnover patients. The studies were underpowered to assess clinical outcomes, in the one study that did there was some evidence for a reduction in hospitalisation after correction. AUTHORS' CONCLUSIONS: The evidence for the benefits and risks of correcting metabolic acidosis is very limited with no RCTs in pre-ESRD patients, none in children, and only three small trials in dialysis patients. These trials suggest there may be some beneficial effects on both protein and bone metabolism but the trials were underpowered to provide robust evidence.

Late referral for dialysis: improving the management of chronic renal disease.

BACKGROUND: Timely nephrological referral of patients with chronic renal failure (CRF) is important, but referral at a late stage of disease is common. AIM: To investigate whether late referral of patients is avoidable, and where the missed opportunities lie. DESIGN: Prospective ascertainment of new cases and comprehensive review of pre-end stage history. METHODS: Patients admitted to Bristol and Portsmouth renal units for chronic RRT between June 1997 and May 1998 were identified from computer databases. Data were collected from case notes and hospital records, and a self-administered patient questionnaire. Late referral, defined as dialysis within 4 months of first referral to a dialysing nephrologist, was categorized by algorithm as unavoidable or avoidable. RESULTS: Of 250 patients, 96 (38%) were referred late. Forty-three (45%) had definite avoidable reasons: 35 (37%) with raised serum creatinine for a median 3.7 years (IQR 1.5-8.2) before referral, and eight (8%) with risk factors for renal disease but scant assessment of renal function; 12/43 (31%) had a diagnosis of diabetic nephropathy. Late referred patients were less likely to receive standard renal therapies for chronic renal failure, were in a poorer clinical state at start of RRT, and more often required emergency dialysis, compared to patients referred early. Late referrals were as likely from a hospital as a primary care physician. DISCUSSION: A significant proportion of patients are avoidably referred to a dialysing renal unit at a very late stage. Guidelines on referral should be developed by nephrologists, primary and secondary care physicians, and patient groups, and further research is needed into the cost-effectiveness of early referral strategies.

Endothelial dysfunction in chronic renal failure: roles of lipoprotein oxidation and pro-inflammatory cytokines.

BACKGROUND: Chronic renal failure (CRF) is associated with an increased risk of ischaemic heart disease (IHD), but the mechanisms responsible are controversial. We investigated the relationship of two sets of candidate mechanisms-indices of LDL oxidation and markers of inflammatory activity-with vascular endothelial dysfunction (VED). METHODS: We carried out cross-sectional analysis of 23 dialysed and 16 non-dialysed CRF patients, 28 healthy controls, and 20 patients with stable angina and normal renal function. The following were determined: (i) LDL oxidation by Cu(2+) and ultraviolet light, serum autoantibodies to oxidized LDL (oxLDL); (ii) forearm flow-mediated vasodilatation, plasma concentrations of adhesion molecules, and von Willebrand factor (vWF); and (iii) circulating levels of TNF-alpha and IL-6, C-reactive protein (CRP), and fibrinogen. RESULTS: Endothelium-dependent vasodilatation (EDV) was lower in angina, pre-dialysis, and dialysis CRF patients than in controls (all P<0.005). Compared with controls, vWf (P<0.005) and adhesion molecules (vCAM-1, P<0.005; iCAM-1, P=0.01; E-selectin, P=0.05) were raised in dialysis, and vCAM-1 (P=0.01) in pre-dialysis CRF patients. Dialysed patients had lower HDL cholesterol (P=0.01) and higher triglyceride (P=0.05) than controls, but LDL-oxidation was similar in all groups. Autoantibodies to oxLDL were raised in angina (P<0.005) and pre-dialysis (P=0.006), but were absent in most dialysed patients. Concentrations of IL-6, TNF-alpha, CRP and fibrinogen were elevated in CRF compared with control and angina patients (P<0.005). In the whole population, IL-6 and TNF-alpha correlated negatively with EDV, HDL cholesterol, and positively with triglyceride, blood pressure, vWf, iCAM-1, vCAM-1 and E-selectin (r=-0.43 to +0.70, all P<0.05). CONCLUSIONS: Endothelial dysfunction is unrelated to LDL oxidation, suggesting that LDL oxidation might not be a major cause of VED in CRF. In contrast VED was more severe in CRF than in angina patients and is associated with increased acute-phase proteins and plasma cytokines, demonstrating a chronic inflammatory state. These observations may explain the VED and increased IHD risk of patients with CRF.

Renal complications of jejuno-ileal bypass for obesity.

Jejuno-ileal bypass has until recently been an accepted treatment for refractory morbid obesity. Although hyperoxaluria causing renal tract calculi is a well-recognized complication, we describe eight patients who developed significant renal failure attributable to hyperoxaluria resulting from this procedure, three requiring renal replacement therapy. We review the literature, describing 18 other cases with renal failure, the mechanisms of hyperoxaluria and its treatment. Because reversal of the bypass may result in stabilization or partial improvement of renal function, these patients require long-term follow-up of renal function.

Can the use of low-dose dopamine for treatment of acute renal failure be justified?

The use of dopamine for the prevention and treatment of acute renal failure is widespread. Its use is based on physiology suggesting selective renal vasodilation when it is infused at low dose. This article reviews the available data on the clinical use of dopamine. When used to prevent acute renal failure in high-risk treatments there is no evidence of benefit of dopamine but, given the low incidence of significant renal failure, the studies are underpowered. In treatment of acute renal failure, the quality of the data is poor. Only in one small randomised trial of moderate acute renal failure in patients with malaria was a clinically significant benefit of dopamine shown. The rest of the data, in the form of case series, showed either no benefit of dopamine or small benefits of little clinical significance. Again, these studies are of insufficient power for conclusions to be drawn as to the overall benefits and risks. We conclude that benefits of dopamine use cannot be ruled out by currently available data but its use cannot be advised until trials examining clinically important endpoints in large numbers of patients have been performed.

Calcium phosphate stones during long-term acetazolamide treatment for epilepsy.

We report a case of recurrent renal calculi containing calcium phosphate associated with long-term acetazolamide treatment for epilepsy. Unfortunately, the cause of stone formation was not recognised for many years, by which time irreversible renal damage had occurred.

Calcified plaque is common in the carotid and femoral arteries of dialysis patients without clinical vascular disease.

BACKGROUND: Cardiac and vascular mortality are common in end-stage renal disease (ERSD) and are often attributed to accelerated atherosclerosis. SUBJECTS AND METHODS: We studied 24 non-diabetic ESRD patients without cardiac or vascular disease (M = 12, F = 12) and 24 age-, sex- and race-matched healthy controls. All underwent B-mode ultrasound for carotid and femoral intima media thickness (IMT) and plaque (% stenosis) together with blood pressure (BP), and echocardiograms to determine left ventricular mass. RESULTS: Both BP and mean IMT were similar in patients and controls. However, discrete plaque was present in 71% (17/24) of patients compared with 21% (5/24) of controls (P = 0.001), and % stenosis was greater in patients (carotid 12.2 +/- 11% vs 2.3 +/- 5.9%, P < 0.0004; femoral 16.4 +/- 19.1% vs 3.1 +/- 6.4%, P < 0.003). Plaque was soft/atheromatous in 3 of the 5 controls, but not in any of the 17 patients (P = 0.007), all of whom had calcified lesions. BP and cholesterol were not correlated with IMT or plaque in patients, but in control subjects carotid IMT was correlated with systolic BP (r = 0.66, P < 0.0005) and diastolic BP (r = 0.45, P < 0.03). In patients, the only independent variables related to vascular morphology were serum albumin which was inversely related to IMT (P < 0.03) and to plaque (carotid P < 0.05, femoral P < 0.02) and age, which was related to femoral plaque only (P < 0.04). Left ventricular end-diastolic internal dimension, not LVMI, correlated positively with carotid IMT (P < 0.04). CONCLUSION: Our results show that calcified plaque is common in ESRD patients and hypoalbuminaemia may be an associated factor.