In Reply

Abstract

Dr Diskin quips that the chronic kidney disease (CKD) tests would never meet the gold or tobacco currency standards as quoted by the late economist John Kenneth Galbraith. While we agree with Dr Diskin that the assessment of albuminuria or urine sediment “after football practice” has limitations, we maintain that this diagnostic test, like all diagnostic tests in medicine, must be considered within the clinical context for appropriate interpretation. The evidence supporting the use of urinary albumin-creatinine ratio and estimated glomerular filtration rate (GFR) tests for targeted populations at increased risk for CKD is strong.1National Kidney FoundationK/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.Am J Kidney Dis. 2002; 39: S1-S266PubMed Google Scholar, 2Levey A.S. Eckardt K.U. Tsukamoto Y. Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).Kidney Int. 2005; 67: 2089-2100Crossref PubMed Scopus (2448) Google Scholar, 3Stevens L.A. Coresh J. Greene T. Assessing kidney function - measured and estimated glomerular filtration rate.N Engl J Med. 2006; 354: 2473-2483Crossref PubMed Scopus (2264) Google Scholar The urinary total protein or albumin-creatinine ratio tests provide a reasonable estimate of the 24-hour excretion and are easier to obtain in practice.1National Kidney FoundationK/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.Am J Kidney Dis. 2002; 39: S1-S266PubMed Google Scholar, 2Levey A.S. Eckardt K.U. Tsukamoto Y. Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).Kidney Int. 2005; 67: 2089-2100Crossref PubMed Scopus (2448) Google Scholar, 4Ginsberg J.M. Chang B.S. Matarese R.A. Garella S. Use of single voided urine samples to estimate quantitative proteinuria.N Engl J Med. 1983; 309: 1543-1546Crossref PubMed Scopus (618) Google Scholar The urinary albumin-creatinine ratio greater than 30 mg/g is associated with kidney damage due to diabetes, glomerular diseases and hypertension, and faster disease progression in both diabetic and nondiabetic kidney disease. Moreover, albuminuria is a continuous variable risk factor for cardiovascular events, beginning at levels below this threshold. We agree with Dr Diskin that the assessment of albuminuria or urine sediment “after football practice” has limitations, as noted in the list of conditions, including exercise, associated with transient albuminuria in the position paper.We also agree with Dr Diskin that serum creatinine, as he states, is not GFR, but is related to the reciprocal of GFR. The GFR estimate is attractive conceptually as an approximation of measured kidney function. The GFR estimate is more accurate than serum creatinine alone because it accounts in part for variations in serum creatinine due to differences in creatinine generation related to age, sex, and race. An estimated GFR less than 60 mL/min/1.73 m2(1 mL/s/1.73 m2) is associated with an increased risk of kidney failure, CKD complications, hospitalization, cardiovascular events, and death.What alternative tests for CKD does Dr Diskin pose? The evidence he cites uses inulin clearance, a test that cannot be widely implemented even in research studies in the United States as it is not currently approved by the US Food and Drug Administration for use in humans. Other exogenous filtration markers are available but are also too complex to use in routine practice. A 24-hour urine collection for measurement of creatinine clearance has important limitations, primarily collection errors and also overestimation of clearance, a result of tubular secretion of creatinine. Indeed, in the Modification of Diet in Renal Disease (MDRD) Study, the GFR estimate correlated better with measured GFR than did the measured 24-hour creatinine clearance.5Levey A.S. Bosch J.P. Lewis J.B. Greene T. Rogers N. Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.Ann Intern Med. 1999; 16: 461-470Crossref Scopus (12880) Google Scholar For these reasons, the 24-hour urine collection for measurement of creatinine clearance is no longer recommended to routinely assess kidney function. It is useful as a confirmatory test for patients with usual body habitus or diet.3Stevens L.A. Coresh J. Greene T. Assessing kidney function - measured and estimated glomerular filtration rate.N Engl J Med. 2006; 354: 2473-2483Crossref PubMed Scopus (2264) Google Scholar Understanding the strengths and limitations of targeted CKD testing in the clinical context is critical for appropriate implementation.1National Kidney FoundationK/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.Am J Kidney Dis. 2002; 39: S1-S266PubMed Google Scholar, 2Levey A.S. Eckardt K.U. Tsukamoto Y. Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).Kidney Int. 2005; 67: 2089-2100Crossref PubMed Scopus (2448) Google Scholar, 3Stevens L.A. Coresh J. Greene T. Assessing kidney function - measured and estimated glomerular filtration rate.N Engl J Med. 2006; 354: 2473-2483Crossref PubMed Scopus (2264) Google ScholarDrs Futrakul separate CKD stages 1 and 2 from 3 to 5, noting insensitivity of albuminuria screening for interstitial fibrosis in the earlier stages. Conceptually, this separation is valuable to emphasize evaluation of kidney damage for those with a GFR estimate of 60 mL/min/1.73 m2 or greater. We noted that screening for specific CKD causes, such as interstitial nephritis, requires clinical judgment and may necessitate the use of other tests. The preliminary data of Drs Futrakul in supporting both the use of fractional excretion of magnesium as a marker for early kidney damage and the use of vasodilator therapy to slow the progression of glomerular and diabetic kidney diseases require confirmation before routine clinical application.Promotion of CKD testing for patients with diabetes, hypertension, cardiovascular disease, a family history of CKD, and age greater than 60 years may not be the tobacco or gold standard, but is the public health standard. Perhaps, Galbraith would describe the current resistance to implement CKD tests as outdated “conventional wisdom”6Galbraith J.K. The Affluent Society. The Riverside Press, Cambridge, Massachusetts1958Google Scholar that ignores recent data.Letters to the Editor may be in response to an article that appeared in AJKD no more than 6 months previously, or may concern a topic of interest to current nephrology. The body of the letter should be as concise possible and in general should not exceed 250 words. Up to 10 references and 1 figure or table may be included. There is no guarantee that letters will be published. Letters are subject to editing and abridgment without notice.Letters should be submitted via AJKD’s online manuscript handling site, www.editorialmanager.com/ajkd. More information, including details about how to contact the editorial staff for assistance, is available in the journal’s Information for Authors. Dr Diskin quips that the chronic kidney disease (CKD) tests would never meet the gold or tobacco currency standards as quoted by the late economist John Kenneth Galbraith. While we agree with Dr Diskin that the assessment of albuminuria or urine sediment “after football practice” has limitations, we maintain that this diagnostic test, like all diagnostic tests in medicine, must be considered within the clinical context for appropriate interpretation. The evidence supporting the use of urinary albumin-creatinine ratio and estimated glomerular filtration rate (GFR) tests for targeted populations at increased risk for CKD is strong.1National Kidney FoundationK/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.Am J Kidney Dis. 2002; 39: S1-S266PubMed Google Scholar, 2Levey A.S. Eckardt K.U. Tsukamoto Y. Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).Kidney Int. 2005; 67: 2089-2100Crossref PubMed Scopus (2448) Google Scholar, 3Stevens L.A. Coresh J. Greene T. Assessing kidney function - measured and estimated glomerular filtration rate.N Engl J Med. 2006; 354: 2473-2483Crossref PubMed Scopus (2264) Google Scholar The urinary total protein or albumin-creatinine ratio tests provide a reasonable estimate of the 24-hour excretion and are easier to obtain in practice.1National Kidney FoundationK/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.Am J Kidney Dis. 2002; 39: S1-S266PubMed Google Scholar, 2Levey A.S. Eckardt K.U. Tsukamoto Y. Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).Kidney Int. 2005; 67: 2089-2100Crossref PubMed Scopus (2448) Google Scholar, 4Ginsberg J.M. Chang B.S. Matarese R.A. Garella S. Use of single voided urine samples to estimate quantitative proteinuria.N Engl J Med. 1983; 309: 1543-1546Crossref PubMed Scopus (618) Google Scholar The urinary albumin-creatinine ratio greater than 30 mg/g is associated with kidney damage due to diabetes, glomerular diseases and hypertension, and faster disease progression in both diabetic and nondiabetic kidney disease. Moreover, albuminuria is a continuous variable risk factor for cardiovascular events, beginning at levels below this threshold. We agree with Dr Diskin that the assessment of albuminuria or urine sediment “after football practice” has limitations, as noted in the list of conditions, including exercise, associated with transient albuminuria in the position paper. We also agree with Dr Diskin that serum creatinine, as he states, is not GFR, but is related to the reciprocal of GFR. The GFR estimate is attractive conceptually as an approximation of measured kidney function. The GFR estimate is more accurate than serum creatinine alone because it accounts in part for variations in serum creatinine due to differences in creatinine generation related to age, sex, and race. An estimated GFR less than 60 mL/min/1.73 m2(1 mL/s/1.73 m2) is associated with an increased risk of kidney failure, CKD complications, hospitalization, cardiovascular events, and death. What alternative tests for CKD does Dr Diskin pose? The evidence he cites uses inulin clearance, a test that cannot be widely implemented even in research studies in the United States as it is not currently approved by the US Food and Drug Administration for use in humans. Other exogenous filtration markers are available but are also too complex to use in routine practice. A 24-hour urine collection for measurement of creatinine clearance has important limitations, primarily collection errors and also overestimation of clearance, a result of tubular secretion of creatinine. Indeed, in the Modification of Diet in Renal Disease (MDRD) Study, the GFR estimate correlated better with measured GFR than did the measured 24-hour creatinine clearance.5Levey A.S. Bosch J.P. Lewis J.B. Greene T. Rogers N. Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.Ann Intern Med. 1999; 16: 461-470Crossref Scopus (12880) Google Scholar For these reasons, the 24-hour urine collection for measurement of creatinine clearance is no longer recommended to routinely assess kidney function. It is useful as a confirmatory test for patients with usual body habitus or diet.3Stevens L.A. Coresh J. Greene T. Assessing kidney function - measured and estimated glomerular filtration rate.N Engl J Med. 2006; 354: 2473-2483Crossref PubMed Scopus (2264) Google Scholar Understanding the strengths and limitations of targeted CKD testing in the clinical context is critical for appropriate implementation.1National Kidney FoundationK/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.Am J Kidney Dis. 2002; 39: S1-S266PubMed Google Scholar, 2Levey A.S. Eckardt K.U. Tsukamoto Y. Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).Kidney Int. 2005; 67: 2089-2100Crossref PubMed Scopus (2448) Google Scholar, 3Stevens L.A. Coresh J. Greene T. Assessing kidney function - measured and estimated glomerular filtration rate.N Engl J Med. 2006; 354: 2473-2483Crossref PubMed Scopus (2264) Google Scholar Drs Futrakul separate CKD stages 1 and 2 from 3 to 5, noting insensitivity of albuminuria screening for interstitial fibrosis in the earlier stages. Conceptually, this separation is valuable to emphasize evaluation of kidney damage for those with a GFR estimate of 60 mL/min/1.73 m2 or greater. We noted that screening for specific CKD causes, such as interstitial nephritis, requires clinical judgment and may necessitate the use of other tests. The preliminary data of Drs Futrakul in supporting both the use of fractional excretion of magnesium as a marker for early kidney damage and the use of vasodilator therapy to slow the progression of glomerular and diabetic kidney diseases require confirmation before routine clinical application. Promotion of CKD testing for patients with diabetes, hypertension, cardiovascular disease, a family history of CKD, and age greater than 60 years may not be the tobacco or gold standard, but is the public health standard. Perhaps, Galbraith would describe the current resistance to implement CKD tests as outdated “conventional wisdom”6Galbraith J.K. The Affluent Society. The Riverside Press, Cambridge, Massachusetts1958Google Scholar that ignores recent data. Letters to the Editor may be in response to an article that appeared in AJKD no more than 6 months previously, or may concern a topic of interest to current nephrology. The body of the letter should be as concise possible and in general should not exceed 250 words. Up to 10 references and 1 figure or table may be included. There is no guarantee that letters will be published. Letters are subject to editing and abridgment without notice.Letters should be submitted via AJKD’s online manuscript handling site, www.editorialmanager.com/ajkd. More information, including details about how to contact the editorial staff for assistance, is available in the journal’s Information for Authors. Letters to the Editor may be in response to an article that appeared in AJKD no more than 6 months previously, or may concern a topic of interest to current nephrology. The body of the letter should be as concise possible and in general should not exceed 250 words. Up to 10 references and 1 figure or table may be included. There is no guarantee that letters will be published. Letters are subject to editing and abridgment without notice.Letters should be submitted via AJKD’s online manuscript handling site, www.editorialmanager.com/ajkd. More information, including details about how to contact the editorial staff for assistance, is available in the journal’s Information for Authors. Letters to the Editor may be in response to an article that appeared in AJKD no more than 6 months previously, or may concern a topic of interest to current nephrology. The body of the letter should be as concise possible and in general should not exceed 250 words. Up to 10 references and 1 figure or table may be included. There is no guarantee that letters will be published. Letters are subject to editing and abridgment without notice. Letters should be submitted via AJKD’s online manuscript handling site, www.editorialmanager.com/ajkd. More information, including details about how to contact the editorial staff for assistance, is available in the journal’s Information for Authors. Support: Dr Vassalotti is the Chief Medical Officer of the National Kidney Foundation. Dr Stevens is Program Director, Implementation, at the National Kidney Foundation Center for Guideline Development and Implementation at Tufts-New England Medical Center; Dr Levey is Director of that center and Editor-in-Chief of AJKD. Financial Disclosure: The authors report no financial conflicts of interest with the subject of this reply. Standards and Precision of Thought: What Might Galbraith Say?American Journal of Kidney DiseasesVol. 51Issue 1PreviewIn the midst of the wild currency fluctuations of the early 19th century, London stockbroker David Ricardo, launched one of the most famous careers in economic thought with his uncompromising support of what was soon to be known the world over as the “Gold Standard”: “It is most justly contended that a currency to be perfect should be absolutely invariable…” and that gold, though imperfect, is “the best with which we are acquainted.”1 Most agree that the Gold Standard lasted from 1879 until 1971 when the remaining attenuated version was finally cancelled by Richard Nixon. Full-Text PDF An Innovative Strategy to Effectively Prevent ESRDAmerican Journal of Kidney DiseasesVol. 51Issue 1PreviewWe have read the article from Vassalotti et al1 with great interest. In some types of CKD, only late stages (3 to 5) are recognized due to the insensitivity of microalbuminuria for detection of early stages (1 and 2). In such advanced stages, treatment fails to correct the hemodynamic maladjustment associated with renal microvascular disease—a crucial determinant of renal disease progression.2 We have recently demonstrated that such failure is due to impaired vascular repair, namely deficiencies in angiogenic factors such as endothelial progenitor cells, vascular endothelial growth factor (VEGF), and angiopoietin-1, whereas antiangiogenic factors, namely angiopoietin-2, kinase insert domain receptor (a type III receptor tyrosine kinase encoded by KDR), and endostatin, are enhanced. Full-Text PDF