Evaluation of kidney function in chronic kidney Disease

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Slide 1 : Evaluation of kidney function in chronic kidney disease Salwa Ibrahim, MD MRCP (London) Professor of Nephrology Cairo University
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Slide 3 : CAD is caused by various disease pathology including chronic allograft nephropathy, chronic CNI toxicity, BKV and recurrence of original kidney disease So far, renal biopsy with IF, c4d staining, E/M examination remain the Gold standard technique to diagnose the exact cause of CAD
Slide 4 : GFR is best indicator of kidney function
Slide 5 : How to Assess GFR The best filtration marker should not be protein bound; is freely filtered by the glomerulus, is without any tubular secretion, is not metabolized by the kidney The gold standard has been polysaccharide called inulin but it requires injection and complex collection protocol Alternatives include radionuclides like 125I –iothalamate and Cr-EDTA are labor intensive procedures and too costly for routine use
Slide 6 : Estimation of GFR is the best marker of Kidney function
Slide 7 : Prediction Equations for GFR Estimation Physicians should estimate the level of GFR from prediction equation that takes into account serum creatinine and the following variables Age Gender Race Body size The modification of diet in renal disease study (MDRD) and Cockcroft-Gault equations provide useful estimates of GFR in Adults (Level A recommendation)
Slide 8 : Prediction equations recommended by NKF
Slide 9 : Cockcroft-Gault formulae The equation was derived from a study carried in 1973 out on predominantly hospitalized white men, with creatinine clearance values from 30-130ml/min/ Was validated against creatinine clearance which is known to overestimate inulin clearance and vary from day to day by 10-20% The results of CG formulae are not corrected for body surface area
Slide 10 : The MDRD study Equation The equation is derived from the MRDR study conducted on 1628 CKD cases GFR was assessed using I-iothalamate and single measurement of plasma creatinine 4-variable version including age, gender, plasma creatinine and race and results were expressed as per 1.73 m2 of body surface area
Slide 11 : It was developed on a large database containing persons with CKD More accurate and precise than CG equation for persons with a GFR less than 90 ml/minute/1.73 m2 It correlates better with GFR measured by radioisotope assessment It does not require height or weight Advantages of MDRD study equation
Slide 12 : Limitations of The MDRD Equation It has not been validated in patients younger than 18 or older than 70 years It tends to underestimates GFR at higher ranges of kidney function. i.e. higher than 60 ml/min/1.73m2 Clinical conditions in which it may be necessary to measure GFR by clearance methods include Extremes of age and weight severe malnutrition Disease of skeletal muscle
Slide 13 :
Slide 14 : The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Equation The CKD-EPI developed and validated a new equation designed to match the accuracy of the MDRD equation at GFR <60 ml/min/1.73 m2, and to offer greater accuracy at higher GFR, minimizing the over diagnosis of CKD with the MDRD equation The new CKD equation was developed from 8254 data points from six studies and four clinical populations
Slide 15 : The CKD-EPI equation was as accurate as the MDRD Study equation in the subgroup with estimated GFR less than 60 and more accurate in the subgroup with estimated GFR greater than 60mL/min per 1.73 m2 mL/min per 1.73 m2
Slide 16 : Implications The CKD-EPI equation yields a lower estimated prevalence of chronic kidney disease than the MDRD Study equation primarily because of a lower estimated prevalence of stage 3 disease The CKD-EPI equation yields a prevalence of chronic kidney disease of 23.2 million approximately 3 million fewer than that yielded by the MDRD Study equation
Slide 17 : Limitations of CKD-EPI Equation A single equation is unlikely to work equally well in all populations Few participants had a higher GFR and relatively few participants were older than 70 years or of racial minorities other than black The equation does not overcome the limitations of serum creatinine as an endogenous filtration marker. All creatinine-based equations should be used with caution in people with abnormally high or low muscle mass
Slide 18 : Serum creatinine concentration Serum creatinine is affected by factors other than GFR such as creatinine secretion There is a wide range for serum creatinine in normal persons This wide range means that GFR must decline to half the normal level before serum creatinine rises above the upper limit In the elderly, serum creatinine does not reflect age related decline in GFR because of a concomitant age-related decline in muscle mass
Slide 19 : The relationship between serum creatinine and GFR is parabolic at high levels of GFR, large changes in GFR is reflected by a very small changes in serum creatinine, lately the opposite is true
Slide 20 : Different factors can alter serum creatinine without changing GFR
Slide 21 : NKF recommends the use of GFR rather than serum creatinine
Slide 22 : 24-h urine creatinine clearance It was regarded as sensitive tool of assessment of kidney function Now is not recommended because of Inconvenience of timed urine collection Failure to collect urine sample Tubular secretion of creatinine overestimating GFR in CKD Creatinine clearance
Slide 23 : Serum cystatin C Cystatin C was found to be superior to serum creatinine in predicting renal function The lack of international standardized calibrator and the increased costs limits its use
Slide 24 : Assessment of Proteinuria The ADA and NKF recommend assessment of proteinuria by measuring the ratio of protein/albumin to creatinine in an untimed urine specimen It corrects variation in hydration and is more convenient than 24 hour urine collection
Slide 25 : Although GFR declines with aging, It is debated whether it is truly physiological or pathological process Age adjusted reference intervals have not been recommended It is generally recommended to caution the interpretation of eGFR values in the range of 45-59ml/min/1.73 m2 in people over 70 GFR predication in the elderly
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Slide 27 : Reduced renal function with eGFR < 60 ml/min was seen in 53% Normal creatinine was seen in 41% of those with renal impairment , CG formula underestimated GFR
Slide 28 : NKF Recommendations The working group has concluded that it is currently premature to recommend age-related decision points for eGFR. It is appropriate to advise medical practitioners that people aged >70 years, an eGFR in the range of 45-59ml/min/1.73m2 if stable over time and not associated with other evidence of kidney damage, may be interpreted as consistent with a typical eGFR for this age group
Slide 29 : The drawbacks of CKD staging system Using eGFR has substantial drawbacks. The essential problem is eGFR is derived from serum creatinine which is affected by many variables including muscle mass Recent estimates of CKD claim that 26.3 millions (13%) of adult Americans suffer CKD One third of these CKD patients lack albuminuria which is a recognized marker of kidney injury
Slide 30 : Is there a clinical benefit to labeling every person with an isolated eGFR<60 ml/min/1,73m2 with a disease
Slide 31 : Go et al, 2004 found no increased risk of mortality for an eGFR of 45-59 ml/min/1.73m2
Slide 32 : Subjects with stage 3 CKD without albuminuria had CV risk comparable to subjects without CKD
Slide 33 : Summary NKF recommended the use of eGFR to assess kidney function in CKD Prediction equations such as CG formula and MDRD equation have some drawbacks and limitations Serum creatinine is not accurate to assess kidney function in CKD There are no data to confirm the association between low GFR and CVS and overall mortality in elderly in absence of albuminuria

 


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