Extended spectrum beta-lactamases A. Beta-lactam antibiotics a. d. Mechanism of resistances B. Beta-lactamases a. b. Extended spectrum beta-lactamases (ESBL) c. Non-TEM, non-SBV ESBL d. Inhibitor Resistant TEM (IRT) C. Definition, classification and properties of ESBL D. Epidemiology and risk factors E. Laboratory detection and identification of ESBLs
Detection of Chronic Kidney Disease* using eGFR
(estimated Glomerular Filtration Rate)
Why are we changing from Cockcroft-Gault eGFR to MDRD eGFR?
The Cockcroft-Gault formula and Modification of Diet in Renal Disease (MDRD) formula are both
equations to derive an estimated creatinine clearance based on clinical and laboratory parameters. The
Cockcroft-Gault formula requires a weight for the calculation and this means it cannot be generated by
the labs. Weight can also be problematic as an ideal, rather than an actual body weight should be used.
Using the actual weight, in people with BMI above ideal can result in over estimation of serum creatinine.
The MDRD eGFR, which does not require a weight is likely to be closer, if not slightly underestimate
creatinine clearance. The MDRD equation is more easily automated by the labs.
How does eGFR get ordered?
eGFR will be available as a "Request Test" only. Physicians, Diabetes Centres and allied health
professionals who currently order serum creatinine can order this test by requesting eGFR in the "Other
Test" section of the lab requisition. Diabetes Centres can order eGFR according to the recommendations
of the Nova Scotia Renal Program (NSRP) algorithm, Detection, Monitoring & Referral of Chronic Kidney
Disease using eGFR.
When will eGFR reporting be available?
eGFR will be available in most District Health Authorities within the next year. Availability is based on the
lab being able to measure a standardized creatinine. As the report becomes available in your district
notification will be provided by the NSRP. The DCPNS Registry will be adjusted at the same time to
reflect the MDRD eGFR formula.
What does this mean for the Creatinine Clearance data the DCPNS has collected
You will most likely find that for patients who are above their ideal BMI, the MDRD formula will reveal a
lower Creatinine Clearance than the Cockcroft-Gault formula. Since serial measures (measures over
time) are most important, we encourage tracking of these newer values as before (see algorithm for
interpretation of test results and recommended actions).
*Note: Those with values less than 60 mL/min/1.73m2 confirmed over a three-month period have what is
now being called "Chronic Kidney Disease" or CKD. This is the most appropriate terminology to describe
What should the patients be told by the Diabetes Centre staff about their specific eGFR
The Diabetes Centre should provide the results to the family/referring physician who can then interpret
and explain these to the patient in the proper context of other health considerations. If a patient asks
about his/her results, it may be appropriate to say, "We have conducted routine tests to assess your
kidneys. It appears that you may have a decrease in your kidney function that may or may not be related
to your diabetes. Your doctor will explain what these results mean to you".
At any point, are there other actions (other than the "Treat to Target") that should be
taken with any of the eGFR values?
Some medications such as NSAIDs may require adjustment, for further information please contact the
family / referring physician to determine the best course of action.
In the case of Metformin, the following guidelines may be helpful, (see Table 2 for stages
• Metformin is contraindicated and should be discontinued in stages 4 & 5 of chronic kidney disease (eGFR < 30) or hepatic failure.2, 3 • Metformin may be continued in patients with stage 3 chronic kidney disease in stable condition with continued monitoring for deterioration of kidney function. 3 The Cockcroft-Gault formula should be used to determine appropriate dosing. • Metformin should be stopped if there are acute changes in renal function or during periods of illness that could precipitate such changes (e.g. gastrointestinal upset or dehydration) or cause hypoxia (i.e. cardiac or respiratory failure)3. For any other information relating to Metformin please contact your local physician. When is immediate referral to a Nephrologist warranted?
The decision to refer should be made by the family/referring physician because other conditions may
warrant an earlier referral (e.g., anemia, acidosis, etc.). The following guidelines should be considered:
• eGFR less than 30 mL/min/1.73m2 measured on at least 2 occasions.
• Atypical features: hematuria, systemic disease, rapidly rising creatinine, or increased creatinine
greater than 30% after ACEi or ARB. • Nephrotic syndrome: greater than 3.5 g per day proteinuria or albumin to creatinine ratio (ACR) greater than 200. When should eGFR be interpreted with caution?
• Extremes of body habitus such as BMI greater than 35, cachexia (significant loss of muscle mass)
and people with amputations. In these cases, as with all eGFR values, tracking of serial measurements becomes most important in determining stability or progression of kidney function. When is eGFR not valid?
eGFR is validated for patients with stable kidney function and should not be used in the following
• Unstable or rapidly changing creatinine values such as intercurrent illness or hospitalization
• In children under the age of 18†† • When adjusting doses of medications eliminated by the kidneys † In the case of pregnancy, the 24 hour urine collection would be recommended †† In the case of children, seek the opinion of a pediatric nephrologist to see if the 24-hour urine collection or nuclear medicine GFR is recommended. Understanding / measuring albumin in the urine.
Albumin in the urine is a marker of both progression of kidney disease; as well as increased risk of
cardiovascular events. First morning urine samples correlate the best with 24 hour urine collections.
Patients with diabetes should have yearly random urine samples for albumin to creatinine ratio (ACR).
ACR can be repeated to determine if albumin excretion is increasing or decreasing. Targeting a decrease
in albumin of at least 30-50% has shown to be protective in decreasing progression of both kidney and
cardiovascular disease. ACR should be ordered if routine urinalysis is positive for protein.
Table 1. Stages of classic diabetic nephropathy according to urinary albumin level 2
Urine dipstick for protein
for albumin* (mg/day)
< 2.8 (women) Microalbuminuria Negative 2.0 – 20.0 (men) 2.8 – 28.0 (women) Overt nephropathy > 20.0 (men) (Macroalbuminuria) > 28.0 (women) >93.3 (women) * Values are for urinary albumin, not total urinary protein, which will be higher than urinary albumin levels. ACR results may be elevated with conditions other than diabetic nephropathy.2 Table 2. Classification of the stages of chronic kidney disease* ,3, 4
Glomerular filtration rate,
Kidney damage † with normal or increased glomerular filtration rate Kidney damage † with mild decreased glomerular filtration rate Moderately decreased glomerular filtration rate Severely decreased glomerular filtration rate < 15 (or dialysis) * Kidney damage or glomerular filtration rate less than 60 mL/min/1.73m2 for 3 or more months. † Pathologic abnormalities or markers of damage, including persistent proteinuria, abnormalities in urine sediment (persistent presence of erythrocytes, erythrocyte casts, leukocytes or leukocyte casts) or abnormal results in imaging studies (evidence of scarring or small kidneys on ultrasound or bilateral cystic changes consistent with polycystic kidney disease). References:
1 Levey AS, Eckardt KU, Tsukamoto Y, et al. Definition and classification of chronic kidney disease: a
position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney International.
2 Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes
Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada.
Can J Diabetes. 2008; 32 (suppl1):S127 -S215.
3 Canadian Society of Nephrologists 2008 Clinical Recommendations
4 K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and
stratification. AM J Kidney Dis 2002:39 (Suppl 1):S1-266.
The NSRP would like to acknowledge and thank the many contributors and reviewers for their comments
This document is intended to serve as a guide and cannot replace clinical judgment. The recommendations may be inappropriate for specific clinical situations. When in doubt, please consult a nephrologist. For more information, contact:
Nova Scotia Renal Program Bethune Building, Room 539 1276 South Park Street Halifax, Nova Scotia B3H 2Y9 Phone: (902) 473 5656 Fax: (902) 425 1752 Email: [email protected]
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