Glomerular filtration rate as a putative ‘surrogate end‐point’ for renal transplant clinical trials in children

Pediatric Transplantation - Tập 7 Số 1 - Trang 18-24 - 2003
Guido Filler1, Richard Browne, Mouin G. Seikaly
1Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Canada

Tóm tắt

Abstract: Only with prospective randomized controlled trials is it possible to evaluate the several immunosuppressive regimens available to renal allograft recipients. Commonly used surrogate markers of clinical outcome, such as patient and graft survival, are constantly improving. Current immunosuppressive protocols have improved 1‐yr graft survival to over 90%. The small differences in graft survival among the various immunosuppressive regimes require large patient cohorts in order to establish statistical significance. Such studies are often difficult to conduct in a timely manner, particularly in children. This necessitates the search for better surrogate markers sensitive enough to detect differences in smaller cohorts and in a shorter period of time. While the degree of fibrosis in transplant biopsies might well predict long‐term graft survival, protocol biopsies are expensive, invasive, and unpopular among clinicians. In native kidneys, glomerular filtration rate (GFR) closely correlates with disease progression and interstitial fibrosis and appears to be well positioned as a less invasive surrogate marker for long‐term outcome. Nonetheless, the ideal marker for GFR remains obscure. Serum creatinine has several major drawbacks, making it a poor predictor of GFR. This review discusses the several methods used to estimate or measure GFR with emphasis on 125I‐iothalamate clearance and serum cystatin C (cys‐C). Of all the serum markers, cys‐C is the most reliable and the most promising. However, cys‐C and other endogenous markers cannot replace the diagnostic sensitivity and reliability of radiolabeled markers of GFR such as 125I‐iothalamate in renal transplant clinical trials. Unfortunately, clearance of most radiolabeled markers of GFR including 125I‐iothalamate remain costly and time consuming.

Từ khóa


Tài liệu tham khảo

10.1097/00000658-195809000-00004

10.1016/S0140-6736(78)91970-0

Ferguson R., 1994, Acute rejection episodes‐best predictor of long‐term primary cadaveric renal transplant survival, Clin Transplant, 8, 328

10.1007/s00467-001-0795-9

10.1016/S0197-2456(01)00153-2

10.1002/bjs.1800830813

10.1038/ki.1990.182

10.1038/ki.1985.205

Smith HW, 1951, The Kidney: Structure and Function in Health and Disease, 63

10.1172/JCI100206

10.3181/00379727-32-7564P

Smith HW., The Kidney: Structure and Function in Health and Disease, 39

10.1016/S0140-6736(66)90946-9

Levey AS., 1989, Use of glomerular filtration rate to assess the progression of renal disease, Semin Nephrol, 9, 370

10.1016/S0046-8177(70)80061-2

10.1016/S0041-1345(02)03128-7

Tejani A, 2002, Calculated creatinine clearance (CCC) as the most promising candidate surrogate end point for clinical trials, Am J Transplant, 2, 256

10.1053/ajkd.2000.8237

10.1136/bmj.293.6541.234

10.1016/S0022-5347(17)37891-6

10.3109/00365519009089148

10.1038/ki.1993.125

Russell CD., 1993, Optimum sample times for single‐injection, multi‐sample renal clearance methods, J Nucl Med, 34, 1761

10.1136/adc.47.254.613

10.1016/S0272-6386(84)80026-8

10.1038/ki.1973.127

10.1093/ajcn/37.3.478

10.1016/S0031-3955(16)36251-4

Lwong MBL, 1985, Lack of evidence that formula‐derived creatinine clearance approximates glomerular filtration rate in pediatric intensive care population, Clin Nephrol, 24, 285

Levey AS, 1989, Creatinine filtration, secretion and excretion during progressive renal disease. Modification of Diet in Renal Disease (MDRD) Study Group, Kidney Int Suppl, 27, S73

10.1172/JCI104929

10.1172/JCI100691

Horio M, 1996, Comparison of Jaffe rate assay and enzymatic method for the measurement of creatinine clearance, Nippon Jinzo Gakkai Shi, 38, 296

10.1016/S0022-3476(84)80488-6

Proficiency Testing Survey, 1995, Creatinine, 29

Travis LB, 1977, Simultaneous iothalamate, creatinine and urea clearances in children with renal disease, Pediatrics, 59, 219, 10.1542/peds.59.2.219

10.1146/annurev.me.39.020188.002341

Shah BV, 1992, Spontaneous changes in the rate of decline in reciprocal serum creatinine: errors in predicting the progression of renal disease from extrapolation of the slope, J Am Soc Nephrol, 2, 1186, 10.1681/ASN.V271186

10.1097/00007890-199001000-00018

10.1016/S0272-6386(86)80107-X

10.1159/000180580

10.2165/00003088-198308040-00007

10.7326/0003-4819-130-6-199903160-00002

10.1016/S0140-6736(69)90752-1

10.7326/0003-4819-113-7-501

10.3109/00365518909105415

10.1007/s004670050195

10.1007/BF00866485

Lwong MBL, 1985, Lack of evidence that formula‐derived creatinine clearance approximates glomerular filtration rate in pediatric intensive care population, Clin Nephrol, 24, 285

10.1159/000184483

Jung M, 1994, Niedermolekulare Proteine im Serum als Marker der glomerulären Filtrationsrate: Cystatin C, α-1-Mikroglobulin und β-2-Mikroglobulin. Lab Med, 18, 461

10.3109/00365519709084595

10.1038/ki.1995.40

Kyhse‐Anderson J, 1994, Serum cystatin C, determined by a rapid, automated particle‐enhanced turbidimetric method, is a better marker than serum creatinine for glomerular filtration rate, Clin Chem, 40, 1921, 10.1093/clinchem/40.10.1921

10.1007/BF00856641

10.1111/j.1365-2141.1983.tb02158.x

10.1159/000188621

Filler G, 1997, Are cystatin C and β2‐microglobulin better markers than serum creatinine for prediction of a normal glomerular filtration rate in pediatric subjects?, Clin Chem, 43, 1077, 10.1093/clinchem/43.6.1077

10.1007/s004670050646

10.1007/s004670050419

10.3181/00379727-107-26569

10.1093/glycob/7.4.499

10.1093/clinchem/45.4.567

Giessing M., 1999, Beta‐trace protein as indicator of glomerular filtration rate, Urology, 54, 940

Filler G, 2002, Beta-trace protein, cystatin C, beta(2)-microglobulin and creatinine compared for detecting impaired glomerular filtration rate in children Clin Chem, 48, 729

10.1007/BF00863432

Levey AS, 1993, Glomerular filtration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes Control and Complications Trial Research Group, J Am Soc Nephrol, 4, 1159, 10.1681/ASN.V451159

10.1053/ajkd.1998.v32.pm9669421

10.1016/S0272-6386(97)90488-1

Seikaly MG, 1998, Glomerular filtration rate in children following renal transplantation, Pediatr Transplant, 2, 231

Thông tin
Thông tin xuất bản

Pediatric Transplantation

Tập 7 Số 1

18-24

Thông tin tác giả