Because the relationship between serum creatinine and GFR is difficult to to address the issues of variability in creatinine measurement and to develop a. 7) What is the difference between creatinine clearance and GFR? 18) What are the problems associated with the use of serum creatinine as a filtration marker. The following is a list of frequently asked questions pertaining to the current 5) What is the difference between creatinine clearance and GFR? 6) What is the.
Historically, the serum urea concentration was considered a useful biomarker of GFR, but high tubular back diffusion and the dependence on protein intake and hydration made interpretation difficult. The renal clearance of creatinine has a long history as a measure of GFR 5but it was not until the introduction of analytical techniques, based on the original Jaffe chemistry, incorporating continuous-flow dialysis or detergents enabling direct serum measurement that serum creatinine became the almost universal biomarker of choice for GFR 6.
Over the last 40 years, the clinical importance of serum creatinine measurements in diagnosing renal disease and then enabling accurate monitoring of disease progression cannot be over emphasized.
The development of formulae for estimating GFR 7 and disease staging 8 based on serum creatinine reiterate the continuing importance of this biomarker. Why, then, is the professional perception of serum creatinine so negative? Consequently, drugs that inhibit the tubular secretion of creatinine [e. Similar problems of interpretation arise from changes in the creatinine-production rate, with observed increases in response to therapeutics [e.
The vital evidence underlying our negative perception of serum creatinine, however, is the data reported by Shemesh et al. The pressure to change to new serum biomarkers of GFR becomes ever more vocal.
Formal GFR was measured by iohexol clearance. The authors provide a detailed discussion of the limitations of their study, but their conclusions that the 3 biomarkers are equivalent, both in terms of diagnostic performance—even for minor degrees of deterioration of renal function—and in terms of risk prediction for progression, should help to improve our perception of serum creatinine.
Any serum biomarker of GFR must obey the laws of physics: As the GFR declines, the serum concentration should increase. The fact that the relationship between serum concentration and GFR is a reciprocal function explains how the relatively small changes in concentration that occur in the early stages of renal function decline are followed by an accelerating increase.
Consequently, for decades nephrologists in clinical practice have monitored the rate of progression of renal disease in patients by simply plotting the reciprocal of the serum creatinine concentration against time. This reciprocal function is not unique to creatinine but is true for any biomarker of GFR.
The physics is confirmed by Spanaus et al. Further exploration of the discrepancy between our perception of serum creatinine and the conclusions of Spanaus et al. Publications promoting new serum biomarkers of GFR have tended to use ROC curve analysis to demonstrate better, usually only marginally, diagnostic performance; however, diagnosis represents only one of the clinical applications of measuring serum creatinine.
A clinically crucial situation in which creatinine is considered both diagnostically sensitive and reliable is the monitoring of graft function after renal transplantation, for which alterations in the dosing of immunosuppressive drugs are based on small changes in the serum creatinine concentration, usually within the reference interval.
Serum Creatinine and Glomerular Filtration Rate: Perception and Reality
The explanation for the contradiction to our perception lies in an understanding of biological variation, a fundamental concept in clinical chemistry.
The implicit conclusions are that applying a reference interval for serum creatinine is inappropriate, thereby resolving the apparent incongruity of the Shemesh data 12and that longitudinal monitoring of serum creatinine in any individual will ensure early detection of GFR decline and incipient renal disease.
It is recommended to report two values for the estimated GFR, one value if the patient is African American and another value if the patient is not African American.
The reason for this recommendation is that race can be difficult to represent reliably in electronic medical records and it is difficult, even if the race is noted, to know if the patient is of a mixed ethnic background. If the calculated GFR value is less than or equal to 60, it is recommended to report the value rounded to a whole number e. The reason not to report numeric values greater than 60 is because the impact of variability in the creatinine measurement has a progressively greater impact on the variability of the calculated GFR value as the creatinine value becomes smaller corresponding to more normal renal function, and the accuracy of the estimated GFR is poorer at higher GFRs .
Laboratories need to communicate to clinical providers and to pharmacists the clinical issues associated with a creatinine method that is calibrated to be traceable to IDMS. The critical clinical issues are the change in reference range, and the impact on using creatinine and calculated GFR to adjust dosage of nephrotoxic drugs.
Reporting calculated GFR from serum creatinine
The algorithms used to adjust drug dosages are usually based on the Cockcroft-Gault equation or the absolute creatinine value. Because the product labeling for drugs is based on one of these approaches, pharmacists and providers are obliged to use those algorithms.
Consequently, the laboratory must provide information on the magnitude of difference between an IDMS-traceable creatinine result and a result by the former method used by the laboratory. There are two principal approaches to establish traceability to a RMP.
One approach is to measure native clinical samples, using the routine method and using the RMP. The product calibrator s for the routine method is then value assigned to produce results for the native clinical samples that are equivalent to those from the RMP. The other approach to establish the values for the routine method product calibrator s is to use a reference material that is commutable with the native clinical samples between the RMP and the routine method, and which has its value assigned by a RMP.
Reporting calculated GFR from serum creatinine
IVD manufacturers may also need to address imprecision and non-specificity of creatinine methods. IVD manufacturers should provide information to customers regarding the relationship between results from a creatinine method calibrated to be traceable to IDMS and previous conventionally calibrated methods.
This is essential information that the laboratory needs to make available to clinical providers and to pharmacists. In addition, IVD manufacturers should provide educational information to laboratories to assist them in reporting calculated GFR and in the transition from conventionally calibrated to IDMS-calibrated routine methods. IVD manufacturers should communicate with external quality assurance proficiency testing programs to ensure that laboratories participating in those programs are graded appropriately during the transition period from conventionally calibrated to IDMS-calibrated routine methods.
External quality assurance proficiency testing providers should ensure that participants are appropriately graded when there may be a bimodal distribution of results as some laboratories report results using reagent and calibrator inventory that has been conventionally calibrated, while others report results using newer inventory that has IDMS-traceable calibration. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Am J Kidney Dis ; Kidney Disease Outcome Quality Initiative.
Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol ; Performance of the Cockcroft-Gault and modification of diet in renal disease equations in estimating GFR in ill hospitalized patients.
State of the art in accuracy and inter-laboratory harmonization.