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Notice of the change to the equation used to calculate estimate glomerular filtration rate (eGFR) across UHB on November 22nd 2021

On 22.11.201, the formula to calculate eGFR at UHB will be changed from MDRD to CKD-EPI. This is in line with long standing NICE guidance. This is a more accurate equation to estimate GFR. This will not affect the management of patients and should not lead to a major eGFR change on an individual patient basis. As per NICE guidance, it is no longer necessary to correct for ethnicity.

 

Further information

At present, eGFR is calculated at UHB using the MDRD equation. This equation was based upon measurements in patients with established renal disease. It uses creatinine, sex, age, and the ethnicity of the patient to estimate the GFR.  The group that developed the MDRD equation subsequently developed the CKD-EPI equation using data from patients who had normal and impaired renal function. Like MDRD, the original CKD-EPI equation used creatinine, sex, age, and the ethnicity of the patient to estimate the GFR however recent NICE guidance has recommended that ethnicity is no longer used. CKD-EPI is thought to reflect renal function better than the MDRD equation. Compared to measured GFR, performance of the two equations are similar when GFR is < 60 mL/min/1.73 m2 with the MDRD equation underestimating GFR at levels > 60 mL/min/1.73 m2 when compared to the CKD-EPI equation. It is thought that the impact on patient management will be minimal however there is a possibility that CKD classifications could change due to CKD-EPI more closely reflecting the ‘true’ GFR. NICE has recommended using the CKD-EPI equation to calculate eGFR since 2014 with ethnicity removal outlined this year.

There is no change to specimen requirements or test requesting.

For clinical queries relating to this change please contact Professor Paul Cockwell (This email address is being protected from spambots. You need JavaScript enabled to view it.). For laboratory queries please contact Dr Alex Lawson (This email address is being protected from spambots. You need JavaScript enabled to view it.).

 

References

Chronic kidney disease: assessment and management. NICE guideline [NG203]

https://www.nice.org.uk/guidance/ng203/resources/chronic-kidney-disease-assessment-and-management-pdf-66143713055173

UK Kidney Association The rationale for removing adjustment for ethnicity from eGFR creatinine and recommendations for implementation of the change in practice

https://ukkidney.org/sites/renal.org/files/guidelines/Rationale_and_recommendations_for_implementation_NICE%20CKD%20Guideline%202021.pdf

Original CKD-EPI Paper – Comparison of MDRD and CKD-EPI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763564/pdf/nihms132246.pdf

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Porphyria Screens

The laboratory performs a urine porphyrin screen in house whilst blood samples (required for latent porphyria or cutaneous porphyria) and all samples from known porphyria patients are referred to a specialist laboratory. The sample required and interpretation depends upon the clinical scenario;

  • ? acute porphyria in a symptomatic patient: Send urine to lab for a porphyrin screen (PBG and total urine porphyrin). A negative PBG screen in a symptomatic patient excludes an acute porphyria as the cause of the symptoms.
  • ? acute porphyria in an asymptomatic patient (or >3 days post-symptoms): Send urine to lab for a porphyrin screen (PBG and total urine porphyrin) and an EDTA blood to refer to a specialist laboratory to rule out latent/resolving porphyria.
  • ? bullous porphyria (skin fragility): Send urine to lab for a porphyrin screen (PBG and total urine porphyrin). A negative total urine porphyrin excludes porphyria as a cause of skin fragility.
  • ? acute photosensitivity (EPP): Send EDTA blood to lab for referral to a specialist laboratory.
  • Asymptomatic patient with a family history of porphyria: Send urine, blood & faecal samples to QEHB laboratory for referral to a specialist laboratory.

All samples for porphyria investigations must be protected from the light otherwise there are a risk of a false negative result. Clinical details MUST be provided with a request for investigation of porphyria. This is to enable appropriate investigation and reporting by both QEHB lab and the specialist laboratories.

In the event of a positive or equivocal urine porphyrin screen, additional samples (EDTA blood/faeces) may be requested for referral to a specialist laboratory.

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Therapeutic Drug Monitoring (TDM)

A TDM service is provided in the department of Clinical Biochemistry for some of the drugs requiring regular monitoring. Please check the time at which a sample should be collected as failure to collect the blood at the appropriate time will make it impossible to compare the measured concentration with an accepted therapeutic range. Assays are of little use under these conditions.

The monitoring of valproic acid is not recommended because of the poor correlation between plasma levels and therapeutic effect. The duty biochemist must be contacted to discuss its measurement for any other purpose.

Any request for urgent therapeutic drug analysis that is not provided by Clinical Biochemistry must be discussed with the Duty Biochemist, or when out-of-hours with the duty Biomedical Scientist who may ask you to discuss this with the Duty Consultant. In some circumstances additional discussion with a pharmacist is required. Some specimens requiring analysis out-of-hours may need to be sent to the Toxicology unit at City Hospital and if you organise this without consulting the Pharmacy department you will incur charges to the trust that will not be the responsibility of Clinical Biochemistry.

Overdoses/Drug Screens

Samples for a 'Drug Screen' are analysed at the Regional Toxicology Laboratory (RTL) at City Hospital. A request for a "drug screen" or ‘unknown drug’ requires:-

  • At least 10 mL of urine in plain tube (NOT containing boric acid).  A green top (Lithium heparin anticoagulant) tube filled with blood.  Detailed patient information.
  • Clinical condition e.g. coma grade, fitting etc.
  • Current known prescribed drugs.
  • Overdose drug(s) if known.
  • Urine specimen type e.g. voided or catheter.

Blood samples taken for a ‘Drug Screen’ are of little use unless there is prior knowledge of the agent ingested. Discuss whether a blood sample is of use with the duty biochemist or duty consultant (via the out-of-hours Biomedical Scientist). Paracetamol, salicylate and lithium measurements are available on a 24 hr basis. All requests for other ingested drugs must be discussed with the Poisons Unit and Regional Toxicology Laboratory and samples sent only by prior arrangement. Any samples requiring urgent analysis at the Regional Toxicology Laboratory will require direct dispatch to that laboratory and must not be sent to the Clinical Biochemistry department. Charges realised by these analysis will be forwarded to the relevant division.

Antibiotics

Amikacin, gentamycin, tobramycin and vancomycin are measured in Clinical Biochemistry but clinical advice is given from Microbiology. For patients with liver or renal impairment, advice on antibiotic dosage is available from Clinical Microbiology.

Assays for other antimicrobials including flucytosine, teicoplanin and streptomycin are available from Microbiology after prior consultation with the Clinical Microbiologist.

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Management of the Menopause

The menopausal transition is best diagnosed on clinical grounds. Endocrine investigation may be helpful where the pattern of age, menstrual history and features of oestrogen deficiency are unusual.

Please indicate the woman’s date of birth, recent menstrual pattern and date of last menstrual period/day of cycle on which the blood sample was collected. A rise in follicle stimulating hormone (FSH) is the earliest sign of the approaching menopause. Measurement of serum FSH is the recommended first investigation if biochemical confirmation is necessary. The measurement of luteinising hormone (LH), oestradiol or progesterone is not appropriate. A serum FSH in the reference range for the follicular phase does not exclude the perimenopause.

Hormone Replacement Therapy

HRT when prescribed (orally or transdermally) for the relief of menopausal symptoms does not require endocrine monitoring. Where there is unexpected failure of treatment, for example due to non-compliance or malabsorption, investigation may be useful. Different formulations of HRT may or may not be detected by oestradiol assays. Please indicate on the request form the HRT preparation prescribed.

The main indication for measuring oestradiol in women on HRT is in those receiving implants containing oestradiol. Early replacement of the implant may result in accumulation of oestradiol. Monitoring of serum oestradiol before the implant is replaced has been recommended to avoid supraphysiological concentrations. Sometimes testosterone implants are used in HRT. Measurement of testosterone in an analogous fashion to oestradiol may help to assess whether a further implant may be necessary.

 

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