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Edmund J Lamb

Publications and source records attributed to Edmund J Lamb.

At least 19 recordsLinked to original sources
PubMed2006

Does the ID-MS traceable MDRD equation work and is it suitable for use with compensated Jaffe and enzymatic creatinine assays?

BACKGROUND: International recommendations suggest that measurement of serum creatinine should be supplemented with an estimate of glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) study equation. One problem has been the lack of standardization of commercially available creatinine assays resulting in varying estimates of GFR. A revision of the MDRD equation offers traceability to a reference method. This study evaluates the use of isotope dilution mass spectrometry (ID-MS), the compensated Jaffe and enzymatic creatinine methods compared with the Beckman CX3 Jaffe assay used to derive the MDRD equation and investigates their impact on GFR estimation using both the original and ID-MS-traceable MDRD equations. METHODS: Serum creatinine was measured in 277 patients by (i) ID-MS, (ii) a Roche enzymatic assay, (iii) a Roche compensated kinetic Jaffe assay and (iv) a Beckman CX3 kinetic Jaffe assay. Estimated GFR was calculated using the MDRD equations. RESULTS: The ID-MS (-7.5%), Roche enzymatic (-8.6%) and compensated kinetic Jaffe (-11.9%) assays were all negatively biased (P < 0.0001) compared with the Beckman CX3 assay, causing predictable, clinically significant, overestimation of GFR when the original MDRD equation is used. This positive bias was reduced (ID-MS 6.7 to 0.4%; enzymatic 8.8 to 3.4%; compensated kinetic Jaffe 13.7 to 7.1%) when GFRs were calculated using the ID-MS-traceable MDRD equation. CONCLUSIONS: Compensated assays that account for non-creatinine chromogen interference produce significantly higher estimates of GFR when using the original MDRD equation. Use of the ID-MS-traceable MDRD equation ameliorates this effect. There is good agreement between estimated GFR derived from the original MDRD equation using Beckman Astra CX3 data and estimated GFR derived from the new ID-MS-traceable MDRD equation using a local ID-MS creatinine assay. This suggests that the ID-MS-traceable MDRD equation may be reliably used with both ID-MS and true ID-MS-traceable creatinine assays without the requirement for standardization to the MDRD laboratory.

Biomarkers↗
PubMed2006

Cardiac troponin T circulates in the free, intact form in patients with kidney failure.

BACKGROUND: The clinical significance of the increased concentrations of cardiac troponins observed in patients with end stage renal disease (ESRD) in the absence of an acute coronary syndrome (ACS) is controversial. One proposed explanation is that immunoreactive fragments of cardiac troponin T (cTnT) accumulate in ESRD. We used gel-filtration chromatography (GFC) to ascertain whether fragments of cTnT, which could cross-react in the commercial diagnostic immunoassay (Roche Diagnostics), were the cause of the increased cTnT in the serum of patients with ESRD. METHODS: We subjected sera from ESRD patients (n = 21) receiving dialysis and having increased cTnT concentrations to size-separation GFC. We detected cTnT in the chromatography fractions by use of the same antibodies used in the commercial assay for serum cTnT. RESULTS: In all patients, cTnT immunoreactivity eluted as a major, homogeneous peak in an identical position between the peaks of serum prolactin [relative molecular mass (Mr) 23,000] and albumin (Mr 67,000): the elution pattern of cTnT in samples obtained from ACS patients was identical to that of the ESRD patients. There was no evidence that low-molecular-mass (Mr < 23,000) cTnT fragments were the cause of the increased cTnT in the patients studied. CONCLUSIONS: The form of cTnT observed in the serum of patients with kidney failure and immunoreactive in the diagnostic assay is predominantly the free intact form, as in patients with ACS. Our data are consistent with the view that circulating cTnT in renal failure reflects cardiac pathology.

Chromatography, Gel↗
PubMed2005

Cardiac troponins and renal function in nondialysis patients with chronic kidney disease.

BACKGROUND: Serum cardiac troponin concentrations are commonly increased in end-stage renal disease (ESRD) in the absence of an acute coronary syndrome (ACS). The data on cardiac troponin I (cTnI) are more variable than those for cardiac troponin T (cTnT). There is little information on cardiac troponin concentrations in patients with chronic kidney disease (CKD) who have not commenced dialysis. METHODS: We studied 222 patients: 56 had stage 3 (moderate CKD); 70 stage 4 (severe CKD); and 96 stage 5 (kidney failure). Patients underwent echocardiography and were followed prospectively for a median of 19 months; all-cause mortality was recorded. RESULTS: Overall, serum cTnT was increased above the 99th percentile reference limit in 43% of all CKD patients studied, compared with 18% for cTnI. Serum cTnT and cTnI concentrations were more commonly increased in the presence of more severe CKD (11 and 6 patients in stage 3, 27 and 8 in stage 4, and 57 and 24 in stage 5 (P < 0.0001 and <0.02, respectively). Among 38 patients with detectable cTnI, 32 had detectable cTnT (r(s) = 0.67; P < 0.0001). There was evidence that decreasing estimated glomerular filtration rate increased the odds of having detectable cTnT (P < 0.001) but not cTnI (P = 0.128). There was no evidence to support an adjusted association of detectable cardiac troponins with increasing left ventricular mass index. Increased cTnT (P = 0.0097), but not cTnI, was associated with decreased survival. CONCLUSIONS: Increased cTnT and cTnI concentrations are relatively common in predialysis CKD patients, in the absence of an ACS, including among those with stage 3 disease. The presence of left ventricular hypertrophy alone does not explain these data. Detectable cTnT was a marker of decreased survival.

Aged↗
PubMed2005

B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CKD: relationship to renal function and left ventricular hypertrophy.

BACKGROUND: Most patients with chronic kidney disease (CKD) develop cardiovascular complications. Natriuretic peptides are novel markers that can be used to identify and monitor heart failure, but the effect of renal disease on these markers is not fully understood. The aim of the present study is to explore the relationship among circulating B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) concentrations and clinical variables in a cohort of patients with CKD. METHODS: Plasma BNP and NT-proBNP concentrations and left ventricular (LV) mass index were measured in 213 predialysis patients with CKD. RESULTS: Plasma BNP and NT-proBNP concentrations increased with declining estimated glomerular filtration rate (GFR; P < 0.0001). Estimated GFR had an independent effect on plasma BNP (P = 0.0028) and, to a greater extent, plasma NT-proBNP (P < 0.0001) concentrations: mean BNP concentration increased by 20.6% per 10-mL/min/1.73 m2 (0.17-mL/s) reduction in estimated GFR compared with 37.7% for NT-proBNP. NT-proBNP/BNP ratio increased with CKD stage (P < 0.0001). Median plasma BNP and NT-proBNP concentrations were greater in patients with LV hypertrophy (P < 0.0001), and LV mass index had an independent effect on both BNP (P = 0.0223) and NT-proBNP (P < 0.0017). CONCLUSION: Estimated GFR and LV mass index have independent effects on both plasma BNP and NT-proBNP concentrations in patients with CKD. NT-proBNP appears to be affected more by declining kidney function, in keeping with the hypothesis that its clearance is predominantly renal. Our data have significant implications for application of these peptides as cardiac biomarkers in patients with CKD.

Aged↗
PubMed2005

Susceptibility of glomerular filtration rate estimations to variations in creatinine methodology: a study in older patients.

BACKGROUND: It is recommended that measurement of serum creatinine should be supplemented with a creatinine-based estimation of glomerular filtration rate (GFR). The influence of creatinine methodology on these estimates is not always appreciated. We have studied differences in creatinine methods and their influence on GFR estimation specifically in older people. METHODS: In all, 46 older patients (mean age 80 y, range 69-92 y) with predominantly mild or moderate kidney disease were studied. Serum creatinine was measured using a rate Jaffe method and two different enzymatic methods. Isotope dilution mass spectrometry served as the reference creatinine method. GFR was estimated using both the Modification of Diet in Renal Disease (MDRD) and Cockcroft and Gault formulae: a 51Cr-EDTA GFR estimation served as the reference GFR method. RESULTS: Both enzymatic methods produced creatinine results that were significantly different (P<0.001) from the reference method. The Jaffe method over- and underestimated creatinine at low and high concentrations, respectively. The most likely explanation for these differences relates to standardization of the assays. Irrespective of creatinine method, the Cockroft and Gault formula tended to underestimate GFR, and the MDRD formula to overestimate GFR. Use of the differing creatinine methods to estimate GFR produced predictable biases of the estimate, with mean GFR estimates varying by 14% across the creatinine methods. CONCLUSION: Estimates of GFR depend critically upon the accuracy and precision of the creatinine measurement used in their calculation.

Aged↗
PubMed2005

Estimating kidney function in adults using formulae.

With increasing emphasis on the earlier detection and management of chronic kidney disease (CKD), estimation of the glomerular filtration rate (GFR) has assumed greater importance. It is accepted that use of serum creatinine concentration alone as a marker of kidney function is inadequate; in particular, it has a poor sensitivity for detecting CKD. International recommendations favour the reporting of creatinine-based estimates of GFR using formulae which also take into account age, gender and other variables that affect the relationship between serum creatinine and GFR: in particular, the four-variable formula derived from the Modification of Diet in Renal Disease study (4-v MDRD) is increasingly being used. We have reviewed the literature supporting the use of this formula compared with the well-established Cockcroft and Gault formula. Overall, evidence supports the use of the 4-v MDRD formula as an improved estimate of GFR in people with moderate/advanced CKD. Neither formula performs well in people with normal and mildly reduced kidney function. However, there remain significant problems with this approach and areas where further research is required. In particular, the widespread adoption of estimated GFR reporting has refocused attention on the limitations of creatinine measurement and highlighted clinical situations in which the formulae are inadequate.

Adult↗
PubMed2004

The significance of serum troponin T in patients with kidney disease: a review of the literature.

The last 10 years have witnessed radical changes in the definition and diagnosis of the acute coronary syndrome (ACS), including myocardial infarction, as a result of the introduction of sensitive and specific markers of myocardial damage, the cardiac troponins. One barrier to the universal acceptance of these markers has been the observation that troponin T (cTnT) concentration is commonly increased in the presence of renal failure. Initially it was believed that this constituted an important false positive limitation of the test. This was confounded by problems with the initial cTnT assay and by the observation that troponin I (cTnI) was generally not increased in these patients. However, it has recently been demonstrated that the prognostic significance of a raised cTnT concentration in patients with a suspected ACS is unaffected by renal impairment. Further, powerful outcome studies are now being reported demonstrating that raised concentrations of serum cTnT are predictive of mortality in haemodialysis patients. This review summarizes our current understanding of the prevalence and significance of raised serum cTnT concentrations in patients with kidney disease and highlights areas where our understanding is incomplete. Evidence suggests that raised troponin concentrations in uraemic patients do indeed reflect myocardial injury. In the future, patients demonstrating this abnormality may be the target for more aggressive cardiac intervention, the advantages of which have been demonstrated in the non-uraemic population.

Acute Disease↗
PubMed2004

Topiramate increases biochemical risk of nephrolithiasis.

The incidence of renal stone disease in patients receiving topiramate (Topamax) is 2-4 times that expected in the background population. This has been attributed to a weak carbonic anhydrase inhibitor effect, but published data are scant. Following three cases of renal stones in patients receiving topiramate, we evaluated biochemical risk for nephrolithiasis in eight further unselected patients. Most patients demonstrated inadequate urinary acidification and hypocitraturia; in some cases citrate was undetectable. Several patients also had other risk factors for nephrolithiasis, including increased urinary sodium, calcium and oxalate excretion. The biochemical changes induced by topiramate appear highly penetrant. Experience with this drug is relatively short-lived and it is being prescribed for long-term use in (often) relatively young patients. This report highlights the significantly increased metabolic risk of stone formation in patients receiving topiramate.

Adult↗
PubMed2003

Kidney function in older people: pathology, assessment and management.

It is commonly not appreciated that kidney failure is predominantly a disease of older people and that the use of renal replacement therapy (RRT) amongst these patients is increasing rapidly. It is still unclear whether the decline in kidney function with increasing age represents pathology or is part of the normal ageing process. Conventional laboratory approaches to the assessment of kidney function in older people are inadequate, but the use of calculated clearance formulae and serum cystatin C can enable the earlier detection of chronic kidney disease (CKD) in this population. This could facilitate treatment aimed at reducing the progression of kidney disease in older people and improved management of its secondary complications.

Aged↗