Estimating glomerular filtration rate: comparison of the CKD-EPI and MDRD equations in a large UK cohort with particular emphasis on the effect of age.

BACKGROUND: The chronic kidney disease (CKD)-Epidemiology Collaboration (CKD-EPI) equation was developed to address the underestimation of measured glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) equation at levels >60 mL/min/1.73 m(2). AIM: To assess the impact of the CKD-EPI equation on the estimation of GFR in a large adult UK population (n = 561,400), particularly looking at the effect of age. DESIGN: Serum creatinine results (ID-MS-aligned enzymatic assay) were extracted from the pathology database during 1 year on adult (≥ 18 years) patients from primary care. METHODS: The first available creatinine result from 174,448 people was used to estimate GFR using both equations and agreement assessed. RESULTS: Median CKD-EPI GFR was significantly higher than median MDRD GFR (82 vs. 76 mL/min/1.73 m(2), P < 0.0001). Overall mean bias between CKD-EPI and MDRD GFR was 5.0%, ranging from 13.0% in the 18-29 years age group down to -7.5% in those aged ≥ 90 years. Although statistically significant at all age groups the difference diminished with age and the agreement in GFR category assignment increased. Age-adjusted population prevalence of CKD Stages 3-5 was lower by CKD-EPI than by MDRD (4.4% vs. 4.9%). CONCLUSION: CKD-EPI produces higher GFR and lower CKD estimates, particularly among 18-59 year age groups with MDRD estimated GFRs of 45-59 mL/min/1.73 m(2) (Stage 3A). However, at ages >70 years there is very little difference between the equations, and among the very elderly CKD-EPI may actually increase CKD prevalence estimates.

Renal tubular proteinuria in patients with irritable bowel syndrome.

OBJECTIVE: Irritable bowel syndrome (IBS) is a common condition that is poorly understood. We have previously demonstrated tubular protinuria in patients with inflammatory bowel disease. This study examined whether tubular proteinuria was a feature of IBS. METHODS: Eighty control subjects (male:female, 28:52; age range 20-65 years) and 21 patients with IBS (male:female, 9:12; age range 16-64 years) (not significant) were recruited. Patients with known renal disease, hypertension, diabetes or microbiological evidence of urinary infection were excluded. The IBS patients all fulfilled the ROME II criteria. None had preceding gastroenteritis. Urinary alpha1-microglobulin (alpha1-M) was measured in a second-voided morning urine sample and corrected for urinary concentration by measurement of creatine. Blood samples were analysed for haematochemical indices including C-reactive protein. Statistical analysis was by unpaired t test. RESULTS: None of the IBS patients were reclassified with inflammatory bowel disease over a 5-year follow up period. All had normal haematochemical parameters. Mean +/- standard deviation urinary alpha1-M concentrations were significantly higher in IBS patients than controls (IBS patients, 1.17 +/- 0.65 mg/mmol; controls, 0.75 +/- 0.36 mg/mmol; P < 0.01) and exceeded 1.5 mg/mmol (the upper reference limit) in seven patients. There was no difference in urinary alpha1-M concentrations in the diarrhoea-predominant and constipation-predominant groups (mean +/- standard deviation, 1.342 +/- 0.65 versus 0.76 +/- 0.48 mg/mmol; P = 0.062). CONCLUSIONS: Urinary alpha1-M concentration is commonly increased in IBS, suggesting the presence of renal proximal tubular injury.

Stability of parathyroid hormone ex vivo in haemodialysis patients.

BACKGROUND: The stability of parathyroid hormone (PTH) in blood ex vivo is a significant practical problem for laboratories and clinicians. Several studies have suggested that PTH is more stable in blood collected into a potassium edetate (EDTA) preservative. METHODS: To confirm that this was applicable to renal dialysis patients using our assay (Nichols chemiluminescence), we examined PTH stability in 13 patients with end-stage renal failure using three different blood collection tubes. RESULTS: PTH remained stable in EDTA plasma for up to 48 h at room temperature. PTH was significantly reduced in serum collected into plain tubes after 2 h, and after 4 h in serum collected into serum separator tubes, at room temperature. CONCLUSION: In the assessment of renal osteodystrophy, the use of EDTA plasma can confer significant benefit, especially in busy laboratories where rapid frozen separation of blood may be hard to achieve.

Metabolic bone disease is present at diagnosis in patients with inflammatory bowel disease.

AIM: To establish whether bone disease is present at diagnosis in inflammatory bowel disease and to identify contributory metabolic abnormalities. METHODS: Newly diagnosed patients with inflammatory bowel disease (19 males, 15 females; mean age, 44 years; range, 17-79 years; 23 ulcerative colitis, 11 Crohn's disease) were compared against standard reference ranges and a control group with irritable bowel syndrome (eight males, 10 females; mean age, 40 years; range, 19-64 years). Bone mineral density (g/cm2, dual-energy X-ray absorptiometry: lumbar spine and femoral neck) and biochemical bone markers were measured. RESULTS: Femoral neck bone mineral density, T- and Z-scores (mean +/- s.d., respectively) were lower in inflammatory bowel disease patients than in irritable bowel syndrome controls (0.78 +/- 0.12 vs. 0.90 +/- 0.16, P = 0.0046; - 0.88 +/- 0.92 vs. 0.12 +/- 1.17, P = 0.0018; - 0.30 +/- 0.89 vs. 0.61 +/- 1.10, P = 0.0030). Lumbar spine bone mineral density and T-scores were also significantly lower in patients than controls (0.98 +/- 0.15 vs. 1.08 +/- 0.13, P = 0.0342; - 1.05 +/- 1.39 vs. - 0.14 +/- 1.19, P = 0.0304). Compared with controls, the urinary deoxypyridinoline : creatinine ratio was increased (7.66 vs. 5.70 nmol/mmol, P = 0.0163) and serum 25-hydroxy vitamin D was decreased (18.7 vs. 28.5 micro g/L, P = 0.0016); plasma osteocalcin and serum parathyroid hormone did not differ (P > 0.05). CONCLUSIONS: The bone mineral density is reduced at diagnosis, prior to corticosteroid treatment, in both Crohn's disease and ulcerative colitis. Our data suggest that this is attributable to increased resorption rather than decreased bone formation.

Renal tubular injury is present in acute inflammatory bowel disease prior to the introduction of drug therapy.

BACKGROUND: 5-aminosalicylic acid (5-ASA) has been associated with renal complications in inflammatory bowel disease. Renal function is typically monitored using serum creatinine; however, significant disease may predate increases in creatinine. AIMS: To identify whether markers of early renal disease (urinary albumin, alpha-1-microglobulin [alpha-1-M] and N-acetyl-beta-D-glucosaminidase [NAG], and serum cystatin C) are useful in the assessment of renal function in inflammatory bowel disease patients receiving 5-ASA. METHODS: Twenty-one patients with a new diagnosis of inflammatory bowel disease were investigated. Samples were taken at diagnosis, and at 3-monthly intervals after the commencement of 5-ASA, for 1 year. RESULTS: Mean creatinine clearance was 100 mL/min and did not change following treatment. Inflammatory bowel disease was not associated with albuminuria. Urinary N-acetyl-beta-D-glucosaminidase and alpha-1-microglobulin at diagnosis were increased in 10 (48%) and 11 (52%) patients, respectively: treatment was not associated with consistent changes in urinary protein excretion. There was a significant correlation between cystatin C and creatinine clearance both at diagnosis (r=-0.533, P=0.0275) and combining the initial and follow-up data (r=-0.601, P < 0.01), but not between creatinine and creatinine clearance (P > 0.05). CONCLUSIONS: Tubular proteinuria is an extra-intestinal manifestation of inflammatory bowel disease irrespective of 5-ASA treatment. Tubular proteins are not useful predictors of an adverse renal response to 5-ASA. Serum cystatin C may be an improved marker of glomerular filtration rate in this setting.

Thyroid function tests: often justified in the acutely ill.

It is claimed that inappropriate requesting of thyroid function tests (TFTs) is common in acutely ill patients. Consecutive inpatient TFTs (n = 129) were assessed in relation to clinical history and common symptoms and signs of thyroid disease. Requests were justified in 69% of cases, most commonly on the basis of atrial fibrillation and/or tachycardia. There were no clear reasons for requesting TFTs in the remaining cases, although the yield of abnormal results in these patients was similar to that in those with justified requests. Thyroid stimulating hormone (TSH) concentration was increased (median 7.5 mU/L, range 4.8-38.6 mU/L) in 22 patients, six of whom had biochemical and/or clinical evidence of hypothyroidism (previously undiagnosed) and five of whom had pre-existing hypothyroidism. Of the remaining 11 patients with increased TSH levels, three were confirmed to have compensated hypothyroidism; non-thyroidal illness (NTI) (including the effect of drugs) accounted for four cases. In four patients (one of whom died during the admission) follow-up was not possible. Of six patients with reduced TSH concentration (range <0.05-0.35 mU/L), one was thyrotoxic on carbimazole, one was receiving thyroxine for hypothyroidism, one had NTI and three were lost to follow-up (two of whom died during their admission). Manifestations of thyroid disease are protean and often subtle, and TFTs are thus clinically justified in many unwell inpatients. Although NTI contributes to some cases of abnormal TSH levels, a significant number of TFT abnormalities are consistent with underlying thyroid abnormality requiring investigation/treatment.

Spuriously elevated plasma calcitonin in a patient with a thyroid nodule not associated with medullary thyroid carcinoma.

An increase in plasma calcitonin concentration is widely regarded as a specific and sensitive indication of underlying medullary thyroid carcinoma (MTC). We present a case in which the association of increased plasma calcitonin concentration and a thyroid nodule was not due to MTC. Subsequent measurement of plasma calcitonin by a variety of methods highlighted the variability that exists in calcitonin measurement and the potential for clinically misleading results. The rationale for investigation and treatment of MTC, including a recommendation to screen all patients with thyroid nodules using plasma calcitonin measurement, is based on the use of specific two-site calcitonin assays which are not universally used in the UK or USA.

Alkaline phosphatase activity measurement in the UK by AMP-buffered methods: an appraisal of current practice.

Most UK clinical laboratories use alkaline phosphatase (ALP) methods similar to that proposed by the International Federation of Clinical Chemistry (IFCC), based on the use of 2-amino-2-methyl-1-propanol (AMP) buffer. We present evidence of significant differences in results produced by apparently similar commercial ALP methods using an AMP buffer. We compared Bayer DAX, Dade Dimension and Boehringer Mannheim Hitachi 717 methods. Boehringer and Dade results were higher than Bayer results (Bland and Altman analysis, log transformed data): Boehringer (+23.0%, limits of agreement 1.16-1.31 times Bayer); Dade (+21.9%, limits of agreement 1.13-1.32 times Bayer). Biases were predominantly due to differences in reagents rather than analyser characteristics. Compared to a reagent system prepared exactly as described by the IFCC, Bayer was sub-optimal and Dade and Boehringer methods produced results higher than the IFCC method. Reference ranges and results on patients' samples by the various methods showed large differences but no clinically significant difference was observed in external quality assessment schemes either between Bayer and Boehringer or against method means. Apparently similar methods produce different results in patients' sera: external quality assessment schemes are not useful in highlighting these differences.