The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes.

BACKGROUND In an attempt to reduce late referral and to improve the care of patients with chronic kidney disease (CKD), different organizations have issued guidelines on when to refer patients to the nephrologist. Most suggest referral of patients with a GFR below 60 ml/min/1.73 m2, and demand referral if the GFR is below 30 ml/min/1.73 m2. It is recommended to use the abbreviated MDRD equation to estimate GFR. This formula is, however, sensitive to the creatinine assay methodology. In addition, the impact of the implementation of such guidelines on the nephrology practice has never been evaluated. This study (i) identifies the true burden of CKD in a population and simulates the effects of a 100% implementation of the guidelines on the nephrology work load, and (ii) evaluates the validity of the estimated GFR using the abbreviated MDRD formula when routinely provided. METHODS Different laboratories (both hospital and private) in our region were asked to report on all the serum creatinine values performed during the first week of December 2004. If patients had more than one determination, only the lowest serum creatinine value was retained. Patients already known to a nephrology unit were not included. GFR was calculated using the abbreviated MDRD, using the serum creatinine as reported by these laboratories, or after correction to the MDRD-standard using different published equations. RESULTS 20,108 patients, with a mean age of 53.4+/-16.2 years, 48% females, had at least one serum creatinine determination in the observation period. According to the K/DOQI CKD classification, 20.2, 1.6 and 0.8% of females and 13.3, 1.6 and 0.6% of males were in stage 3, 4 and 5, respectively, when the abbreviated MDRD formula was used with the serum creatinine value as reported by the laboratories. Important differences in classifications were obtained when the different correction formulae for creatinine were applied. According to the current recommendations, this would lead to a mandatory referral of 1650-2400 CKD stage 4 patients per 100 000 inhabitants and a suggested referral of another 4100-15 360 CKD stage 3 patients per 100,000 inhabitants to a nephrology unit. CONCLUSION Implementation of the current guidelines for referral of CKD patients to nephrologists would lead to an overload of the nephrology care capacities. Large differences in estimated GFRs with different corrections for serum creatinine are observed, resulting in important CKD classification differences. Standardization of serum creatinine assays is mandatory before guidelines, and especially the routine provision of the estimated GFR by the abbreviated MDRD formula, can be implemented in clinical practice.

[1]  L. Stevens,et al.  Measurement of kidney function. , 2005, The Medical clinics of North America.

[2]  Philip D. Harvey,et al.  Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38 , 1998, BMJ.

[3]  G. Eknoyan,et al.  Estimating the prevalence of low glomerular filtration rate requires attention to the creatinine assay calibration. , 2002, Journal of the American Society of Nephrology : JASN.

[4]  A. Marchal,et al.  Comparaison des méthodes de dosage de la créatinine sérique , 2001 .

[5]  W. van Biesen,et al.  The pattern of referral of patients with end-stage renal disease to the nephrologist--a European survey. , 1999, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[6]  F. Dekker,et al.  When to initiate dialysis: effect of proposed US guidelines on survival , 2001, The Lancet.

[7]  G. Eknoyan,et al.  Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). , 2005, Kidney international.

[8]  Ethan M Balk,et al.  K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[9]  A. Murray,et al.  Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. , 2005, Journal of the American Society of Nephrology : JASN.

[10]  W. van Biesen,et al.  The Role of Peritoneal Dialysis as the First-Line Renal Replacement Modality , 2000, Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis.

[11]  Z. Massy,et al.  Chronic kidney disease as cause of cardiovascular morbidity and mortality. , 2005, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[12]  K Doqi,et al.  clinical practice guidelines for chronic kidney disease : evaluation, classification, and stratification , 2002 .

[13]  F. Kronenberg,et al.  Predictive performance of renal function equations for patients with chronic kidney disease and normal serum creatinine levels. , 2002, Journal of the American Society of Nephrology : JASN.

[14]  R. Vanholder,et al.  Reevaluation of formulas for predicting creatinine clearance in adults and children, using compensated creatinine methods. , 2003, Clinical chemistry.

[15]  Charles E. McCulloch,et al.  CHRONIC KIDNEY DISEASE AND THE RISKS OF DEATH, CARDIOVASCULAR EVENTS, AND HOSPITALIZATION , 2004 .

[16]  L. Hunsicker Emerging trends for prevention and treatment of diabetic nephropathy: blockade of the RAAS and BP control. , 2004, Journal of managed care pharmacy : JMCP.

[17]  A. Levey,et al.  A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation , 1999, Annals of Internal Medicine.

[18]  G. Beck,et al.  Dietary protein restriction and the progression of chronic renal disease: what have all of the results of the MDRD study shown? Modification of Diet in Renal Disease Study group. , 1999, Journal of the American Society of Nephrology : JASN.

[19]  D. Tompkins,et al.  An automated dry-slide enzymatic method evaluated for measurement of creatinine in serum. , 1983, Clinical Chemistry.

[20]  S. Hallan,et al.  Validation of the Modification of Diet in Renal Disease formula for estimating GFR with special emphasis on calibration of the serum creatinine assay. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[21]  M. Jadoul,et al.  Influence of a pre-dialysis education programme (PDEP) on the mode of renal replacement therapy. , 2005, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[22]  Feng Lin,et al.  The Incidence of End-Stage Renal Disease Is Increasing Faster than the Prevalence of Chronic Renal Insufficiency , 2004, Annals of Internal Medicine.

[23]  Raymond Vanholder,et al.  The burden of kidney disease: improving global outcomes. , 2004, Kidney international.

[24]  L. Brion,et al.  The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. , 1987, Pediatric clinics of North America.

[25]  S. Yusuf,et al.  Renal Insufficiency as a Predictor of Cardiovascular Outcomes and the Impact of Ramipril: The HOPE Randomized Trial , 2001, Annals of Internal Medicine.

[26]  M. Schreiber,et al.  Preliminary findings from the National Pre-ESRD Education Initiative. , 2000, Nephrology news & issues.

[27]  D. Siscovick,et al.  Cystatin C and the risk of death and cardiovascular events among elderly persons. , 2005, The New England journal of medicine.

[28]  M. Kornitzer,et al.  The Belgian Interuniversity Research on Nutrition and Health (B.I.R.N.H.): general introduction. For the B.I.R.N.H. Study Group. , 1989, Acta cardiologica.

[29]  P. Houillier,et al.  Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function. , 2005, Journal of the American Society of Nephrology : JASN.

[30]  G. Bakris,et al.  Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. , 2000, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[31]  Bruce H. R. Wolffenbuttel,et al.  Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy , 2000, The Lancet.

[32]  Tom Greene,et al.  Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.