Response to the draft entitled: “Designed to Tackle Renal Disease in Wales: A
National Service Framework”
This response is made on behalf of the Standing Specialist Advisory Group in Clinical
Chemistry (SSAGCC).
Secretary:
Dr D A Hullin
Department of Clinical Biochemistry
Royal Glamorgan Hospital
Ynysmaerdy
Llantrisant
CF72 8XR
This response is made following the suggested format of response as indicated in the
draft NSF (pages 5-6). When questions are posed for which the SSAGCC has no
collective specific response then this is stated as such.
Consultation Questions
1.
Do you agree with the standards we have chosen?
In principle we agreed with the standards chosen. However, from a laboratory stand
point there are significant issues of detail with regard to the application of standards:
Children’s Standard 2 (page 40)
a) Serum Creatinine measurement. Interpretation (1 [a] ).
Published historical reference intervals for serum creatinine in children exist but
the applicability with respect to a standardized creatinine measurement
methodology remains unknown. Pathology laboratories are not currently in a
position to provide validated standardized normal serum creatine reference
intervals (see also page 56 paragraph 4). Laboratories will need to standardize to
an isotope dilution mass spectrometry (ID-MS) measurement of creatinine.
b) Estimated GFR in children is proposed to be measured by either the Schwartz
Haycock or Counaghan Barratt formulae (page 40 1 [a] ).
The Schwartz Haycock formula was published in 1976 based on Technicon
methodology (details unspecified) published in 1963 by the now defunct
Technicon Corporation. Within the publication the methodology is not detailed
but is believed to be a blanked Jaffé end point assay. The applicability of the
formula is to age groups 6/12 to 20 years, and a total of 186 individuals were
studied across the whole age-range. The formula requires the provision of an
accurate height measurement – information not normally and reliably supplied to
laboratories.
The Counaghan Barratt formula was published also in 1976. The age group
studied was 2 months to 14 years and a total of 186 individuals provided data.
The methodology was again Technicon based (believed to be blanked end-point
Jaffé but in this case with prior removal of interfering chromogens in a sub-group
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analysis, with subsequent blind application of the derived correction factor within
the whole group). The formula also requires the provision of an accurate height
measurement.
The SSAGCC do not believe that laboratories will be in a position to apply either
formula because height measurement is unlikely to be provided reliably. The
SSAGCC also advise that both such formulae be examined with respect to
standardized ID-MS based serum creatinine measurements, and modified
accordingly.
c) Reference (page 40 1 [c] ) is made to children at risk of CKD requiring regular
dip-stick urinalysis for protein and haemoglobin, and that protein/creatinine ratio
estimations must be carried out if the dip-stick is positive for protein. This advice
is contrary to that provided in Standard 3 (iii) page 81/82 requiring that
albumin/creatinine ratio is to be adopted as the preferred method (of urine protein
measurement). See also page 56 line 5.
d) The SSAGCC would be concerned if guidance from external bodies (page 41.2
[e], and page 44.1 [d] ) required at present or in future measurements of
biochemical markers of metabolic bone disease, growth and nutrition without
assurance that the necessary funding required to support such measurements was
made available.
Standard 4 (page 44 1 (e) ).
Laboratories in Wales should standardize age-related reference intervals for lipid
measurements in children (total cholesterol, HDL cholesterol and triglycerides).
Resources to enable this standardization should be made available.
Children’s Standard 10 (page 68).
The implication is that a child transforms to an adult (in renal terms) on his/her 18 th
birthday. However, the estimated GFR (eGFR: 4-part MDRD) is only applicable
from age 20 years and above. As already stated laboratories will not be in a position
to supply eGFR using the Schwartz Haycock equation (the only “paediatric” equation
validated to 20 years). Thus there appears to be a 2 year limbo period. Data on the
validity of the 4-part MDRD as applied to the age group 18 to 20 years is required.
Standard 3 Detection of renal disease (page 81).
The Cockcroft Gault equation would be very difficult to implement by laboratories as
a standard for eGFR as it requires an accurate knowledge of the patient’s current
weight, a parameter rarely if ever supplied to the laboratory. The SSAGCC would
advise that the Welsh NSF for Renal Disease standardizes to the 4-part MDRD
equation for universal applicability, as also advised by the Renal Association.
Furthermore the SSAGCC would advise that all laboratories in Wales standardize to
the ID-MS measurement of creatinine and apply the “175” 4-part MDRD equation,
with suitable slope and intercept corrections for specific analyser/chemistry systems.
Without these standardization procedures in advance of implementation differences in
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clinical care based on differences of eGFR estimation across Wales will inevitably
emerge.
Reporting the eGFR (page 81).
Ideally the eGFR should become a specific and separate request allied to the
measurement of serum urea and electrolyte (U&E) profile, rather than an automatic
calculation from that profile. This is to avoid the inappropriate repetitive calculation
of eGFR in the acutely ill patient monitored by frequent serial U&E measurements.
The separation of the reported eGFR from the U&E profile will allow laboratories to
issue cumulative reports of eGFR thus fulfilling the requirement to report “in a format
which allows any measurement to be easily compared to previous results”.
The SSAGCC would also advise that only eGFRs of 89 ml/min/1.73m2 or less are
reported numerically, and that otherwise all results are reported as greater than 90
ml/min/1.73 m2. The suggestion from some quarters that only eGFRs of less than 60
ml/min/1.73m2 be reported should be resisted. Knowledge of deterioration of renal
function within Stage 2 CKD is a requirement of Standard 3,
As it will, in most cases, be impossible for the laboratory to have knowledge of the
ethnic origin of the patient then a standard correction factor would be supplied on all
reports for Afro-American patients, to be subsequently applied by the requesting
physician when required.
The SSAGCC would also advise that laboratories provide, within the report format,
current reference to the Renal Association website to enable ready access to
information to aid interpretation of the reported result.
Reporting of urine protein excretion (pages 81/82).
The SSAGCC is concerned that the NSF advises that the albumin/creatinine ratio be
adopted as the preferred method of protein measurement. Currently methods for
estimating albumin/creatinine ratio are optimized for the measurement of so-called
microalbumin: this is the estimate of albumin excretion in patients developing
nephropathy who are dip-stick negative to proteinuria screening. This measurement is
currently almost exclusively reserved for patients developing diabetic nephropathy.
For laboratories to apply albumin/creatinine ratios as the preferred method for frank
(dip-stick positive) proteinuria would require substantial cost resources to support the
analytical measurements. Currently the absolute cost of a protein/creatine ratio is
£1.11 whereas the cost of an albumin/creatinine ratio is £5.96 (data supplied from
Medical Biochemistry UHW).
Moreover, additional dilution and repeat measurements of albumin for patients with
frank proteinuria would further amplify these costs. Laboratories are not in a position
to absorb such costs without substantial additional resources.
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The SSAGCC for these reasons advises caution in standardizing to albumin/creatinine
ratio and suggests a standardized protein/creatinine ratio be adopted for patients with
CKD with frank proteinuria.
Standard 4 page 83
The Welsh NSF is insufficiently detailed to allow non-specialists an understanding of
necessary required frequency of monitoring of CKD. In such circumstances we
believe that models for monitoring will become based on published UKCKD
guidelines. The SSAGCC is extremely concerned that such applied monitoring will
not be matched with the necessary resources to allow laboratories to provide these
services. Such lack of recognition of the resource implications for laboratories has
been a constant feature of all recent NSF implementations, to the detriment of
laboratory finances.
2.
Do you think they will effectively tackle renal disease in Wales and
improve the quality of renal care?
In essence the SSAGCC do think they will improve the quality of renal care with the
provisos stated in the response to question 1.
3.
Are there any key interventions which you do not consider meet the above
criteria? (criteria are to be clear specific and measurable).
The SSAGCC would refer to the response to question 1 reference Standard 4 page 83.
4.
Do you consider they could be achieved in your area over time?
The SSAGCC response is a collective one covering the whole of Wales: we believe
the standards of care are achievable within a modern resourced health-care system.
5.
Do you have any other comments you would like to make about this
document?
None other than stated in the response to question 1.
6.
How would you like to see the NSF standards document presented?
As one complete publication.
7.
Which of the key interventions do you think will have the biggest impact
on renal disease and the services to diagnose and treat?
The routine reporting of cumulative eGFR.
8.
The key interventions are going to be implemented over time. Which of
the key interventions do you think are the most urgent for
implementation? Please give specific reference
The cumulative eGFR – this defines the categories of CKD.
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9.
What ideas do you have to ensure patients and the Multidisciplinary
Renal Team are involved in influencing implementation, the setting up of
renal networks and the work of the Renal Advisory Group?
The SSAGCC does not have a collective view.
10.
Do you have any ideas about how developments at Welsh Assembly
Government level on renal disease can be communicated to you more
effectively?
The SSAGCC believe communication to laboratories is effectively distributed via the
current advisory structures (WSAC, LSSC, SSAGs).
11.
What ideas do you have to ensure patients can be involved to help
organisations to make their service better?
The SSAGCC has no collective view.
12.
Can you foresee any barriers to the implementation of these standards?
If so, are there any actions which the Welsh Assembly Government
should take to overcome these barriers?
See question 1 response. Clinical biochemistry laboratories are concerned over the
lack of provision of resources for laboratory tests for the implementation of all NSFs.
13.
Are there aspects of implementation process and programmes of action
being developed, there are a series of groups looking at different aspects:
finance, workforce and information.
The SSAGCC strongly believe that laboratory representation is required to consider
the aspects of finance, workforce and information including standardization of
analytical methods, methods of reporting and of quality assurance.
14.
What programmes of action to support implementation do you think are
needed?
The SSAGCC believes that implementation, as relevant to laboratories, is best
achieved using the current advisory structure to establish a realistic timetable matched
with appropriate advanced funding.
15.
How useful is the website to you and your organisation?
The SSAGCC has no collective view.
16.
Could it be improved to meet your and your organisations requirements
more effectively?
The SSAGCC has no collective view.
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17.
What would enable you to share your knowledge and your examples of
best practice with others through the website?
The Clinical Biochemistry laboratories in Wales already share knowledge and best
practice using the Association for Clinical Biochemistry All Wales Clinical Audit
Group. Relevant audit activity could be linked to this group’s website.
18.
Can you think of any important issues we may have missed out?
See Question 1 response with respect to resource implications for Clinical
Biochemistry laboratories.
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