Edmund J. Lamb

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.

Prediction of ESRD and Death Among People With CKD: The Chronic Renal Impairment in Birmingham (CRIB) Prospective Cohort Study

Background Validated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD). Study Design Prospective cohort study with validation in a separate cohort. Setting & Participants Cox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (mean follow-up, 6.0 years) in 382 patients with stages 3-5 CKD not initially on dialysis therapy in the Chronic Renal Impairment in Birmingham (CRIB) Study. Resultant risk prediction equations were tested in a separate cohort of 213 patients with CKD (the East Kent cohort). Factors 44 baseline characteristics (including 30 blood and urine assays). Outcomes ESRD and all-cause mortality. Results In the CRIB cohort, 190 patients reached ESRD (12.1%/y) and 150 died (6.5%/y). Each 30% lower baseline estimated glomerular filtration rate was associated with a 3-fold higher ESRD rate and a 1.3-fold higher death rate. After adjustment for each other, only baseline creatinine level, serum phosphate level, urinary albumin-creatinine ratio, and female sex remained strongly (P < 0.01) predictive of ESRD. For death, age, N-terminal pro-brain natriuretic peptide, troponin T level, and cigarette smoking remained strongly predictive of risk. Using these factors to predict outcomes in the East Kent cohort yielded an area under the receiver operating characteristic curve (ie, C statistic) of 0.91 (95% CI, 0.87-0.96) for ESRD and 0.82 (95% CI, 0.75-0.89) for death. Limitations Other important factors may have been missed because of limited study power. Conclusions Simple laboratory measures of kidney and cardiac function plus age, sex, and smoking history can be used to help identify patients with CKD at highest risk of ESRD and death. Larger cohort studies are required to further validate these results.

The influence of a cooked-meat meal on estimated glomerular filtration rate

Background: Chronic kidney disease (CKD) is an important but under-recognized condition. Recent national guidelines have recommended that biochemistry laboratories report estimated GFR (eGFR) to improve diagnosis of CKD and facilitate disease staging and management. Previous reports have suggested that intake of large amounts of cooked meat can lead to a significant increase in serum creatinine concentration. Methods: Participants (n = 32), consisting of 17 healthy volunteers and 15 outpatients, were recruited. Measurement of serum creatinine (kinetic Jaffe method, enzymatic, isotope-dilution mass spectrometry [IDMS]) and cystatin C, and calculation of eGFR were carried out before (i) and after a meal containing cooked meat (ii) and a meat-free meal (iii). Results: Following intake of cooked meat, median serum creatinine concentration (kinetic Jaffe) increased from 80.5 µmol/L preprandially to 101.0 µmol/L 1-2 h postprandially (P<0.0001), and 99.0 µmol/L 3-4 h postprandially (P<0.0001). Median eGFR decreased from 84.0 mL/min/1.73 m2 preprandially to 59.5 mL/min/1.73 m2 1-2 h postprandially (P<0.0001), and 64.0 mL/min/1.73m2 3-4 h postprandially (P<0.0001). Consumption of non-meat-containing meals had little impact on serum creatinine (kinetic Jaffe) and eGFR. Changes in serum creatinine were similar using all three methods, and cystatin C concentration was generally uninfluenced by food intake. Conclusions: Intake of cooked meat has a significant effect on serum creatinine concentration and eGFR. Misclassification of CKD is possible if measurements are made after meals containing cooked meat. Clinicians should ensure that CKD classification is based on samples taken in the appropriate conditions: either fasting or after avoidance of cooked meat on the day of sampling. National guidelines which overlook this factor should be revisited.

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.

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.

Cystatin C improves the detection of mild renal dysfunction in older patients

Background: Conventional estimates of glomerular dysfunction, including serum creatinine and creatinine clearance, are inadequate in older people. In this study we have compared the diagnostic accuracy of a novel test of kidney disease, cystatin C, against these markers in older patients with a range of renal function. Methods: Fifty-three patients (mean age 79.6 years, range 69-92 years) with a variety of medical diagnoses were recruited via outpatient clinics. Exclusion criteria included active rheumatoid disease, known current malignancy, renal replacement therapy/renal transplantation and cognitive impairment. 51Cr-EDTA was used as the reference method against which the other markers of glomerular filtration rate were compared using regression analyses. Results: The best fit with glomerular filtration rate was given by Cockcroft and Gault calculated clearance (R 2 = 0.83), followed by serum cystatin C (R 2 = 0.79), serum creatinine (R 2 = 0.76) and creatinine clearance (R 2 = 0.73). The accuracy for glomerular filtration rate prediction was poor for all markers. Serum cystatin C detected nearly all patients with mild renal impairment whereas serum creatinine only detected half of these cases. Regression modelling predicted that the upper limit of normal for serum cystatin C would be exceeded as glomerular filtration rate fell below 64 mL/min/1.73 m2, compared with 44 mL/min/1.73 m2 for serum creatinine. Conclusion: Serum cystatin C is a simple and sensitive screening test for kidney dysfunction in older people.

Topiramate increases biochemical risk of nephrolithiasis

The incidence of renal stone disease in patients receiving topiramate (TopamaxTM) 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.

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.

Relationship of Serum Cystatin C to Peritoneal and Renal Clearance Measures in Peritoneal Dialysis: A Cross-sectional Study

BACKGROUNDnClinical management of peritoneal dialysis patients includes assessments of peritoneal and renal clearances of the low-molecular-weight endogenous solutes creatinine and urea. Cystatin C is a low-molecular-weight protein used as a glomerular filtration rate marker. We investigated whether serum cystatin C concentration is related to peritoneal and renal clearances of creatinine and urea.nnnSTUDY DESIGNnCross-sectional study.nnnSETTING & PARTICIPANTSn119 patients undergoing peritoneal dialysis in a single dialysis unit.nnnPREDICTORnPeritoneal, renal, and total clearance of urea as Kt/V(urea) and creatinine as weekly creatinine clearance (C(Cr)). Residual renal function (RRF) as the average of renal clearances of urea and creatinine.nnnOUTCOMES & MEASUREMENTSnSerum concentrations of cystatin C measured by using a particle-enhanced nephelometric immunoassay.nnnRESULTSnSerum cystatin C concentration was related inversely to RRF (Spearman rank correlation coefficient [r(s)] = -0.65; P < 0.001), total weekly C(Cr) (r(s) = -0.52; P < 0.001), and total Kt/V(urea) (r(s) = -0.23; P = 0.01). In a multiple regression model, weight, normalized protein catabolic rate, and RRF had independent effects on serum cystatin C concentrations. Additional multiple regression models showed that only the renal components of Kt/V(urea) and weekly C(Cr) contributed to serum cystatin C concentrations.nnnLIMITATIONSnAbsence of reference GFR method.nnnCONCLUSIONSnSerum cystatin C concentrations reflect predominantly renal, not peritoneal, clearance. Serum cystatin C measurement may be a simple and practical alternative to measurement of RRF.

UK Renal Registry 11th Annual Report (December 2008): Chapter 10 Biochemistry profile of patients receiving dialysis in the UK in 2007: national and centre-specific analyses

Introduction: The UK Renal Association Clinical Practice Guidelines include clinical performance measures for biochemical parameters in dialysis patients [1]. The UK Renal Registry (UKRR) annually audits dialysis centre performance against these measures as part of its role in promoting continuous quality improvement. Methods: Cross sectional performance analyses were undertaken to compare dialysis centre achievement of clinical audit measures for prevalent haemodialysis (HD) and peritoneal dialysis (PD) cohorts in 2007. The biochemical variables studied were phosphate, adjusted calcium, parathyroid hormone, bicarbonate and total cholesterol. In addition longitudinal analyses were performed (2000–2007) to show changes in achievement of clinical performance measures over time. Results: Serum phosphate was between 1.1–1.8 mmol/L in 53% of HD and 64% of PD patients. Since 2003 there has been annual improvement in phosphate control for both HD and PD patients, largely through a reduction in phosphate >1.8 mmol/L. PD patients this year also showed a reduction in the percentage with a low phosphate. Adjusted calcium was between 2.2–2.6 mmol/L in 73% of HD and 78% of PD patients. Parathyroid hormone was between 16–32 pmol/L in 25% of HD and 27% of PD patients. The audit measure for bicarbonate was achieved in 71% of HD and 50% of PD patients. There was inter-centre variation for all variables studied. Conclusions: The UKRR consistently demonstrates inter-centre variation in achievement of biochemical clinical audit measures. Understanding the causes of this variation is an important part of improving the care of dialysis patients in the UK.