Concerns about KIM-1 as a urinary biomarker for acute tubular necrosis (ATN)

Abstract

To the Editor: In a recent issue of Kidney International, Han et al1.Han W.K. Bailly V. Abichandani R. et al.Kidney injury molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury.Kidney Int. 2002; 62: 237-244Abstract Full Text Full Text PDF PubMed Scopus (1174) Google Scholar, regarding kidney injury molecule-1 (KIM-1) as a urinary biomarker for human proximal tubule injury, requires clarification. First, the selection of biopsied patients with putative acute tubular necrosis (ATN) is problematic. The authors include “ischemia” with minimal change, interstitial nephritis, and membranous nephropathy [with nonsteroidal anti-inflammatory drugs (NSAIDs)] and state that all patients had a confirmed pathologic diagnosis of ATN. Interstitial nephritis, membranous nephropathy (with NSAIDs), and minimal change disease are not commonly associated with ATN. Even in renal biopsies done within days after transplantation, changes of overt tubular necrosis are usually very limited2.Rosen S. Heyman S.N. Difficulties in understanding human “acute tubular necrosis”: Limited data and flawed animal models.Kidney Int. 2001; 60: 1220-1224Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar. Second, the expression of KIM-1 in these patients' biopsies, as illustrated in Figure 1B of Han et al's article, is in the proximal convoluted tubules (S1/S2) not the pars recta (S3), the tubule in which KIM-1 has been demonstrated in experimental ischemia reflow1.Han W.K. Bailly V. Abichandani R. et al.Kidney injury molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury.Kidney Int. 2002; 62: 237-244Abstract Full Text Full Text PDF PubMed Scopus (1174) Google Scholar. Furthermore, there are no biopsy controls from patients that the authors did not consider to have ATN. Third, the control group for urinary KIM-1 concentration was much younger than patients with ATN. The urine collections occurred at various times in relationship to peak creatinine and levels of KIM-1 were “normalized” for this variation. Can one correct for incremental differences in KIM-1 excretion without extensive data concerning the pattern of excretion of this protein? Interestingly, the patient who underwent repair of an aortic aneurysm (represented in Figure 4 of Han et al's article) had very high levels of urinary KIM-1 without clinical ATN. Finally, the patients considered to have contrast nephropathy have limited KIM-1 excretion consistent with the experimental contrast nephropathy model showing predominantly distal nephron injury2.Rosen S. Heyman S.N. Difficulties in understanding human “acute tubular necrosis”: Limited data and flawed animal models.Kidney Int. 2001; 60: 1220-1224Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar. This underscores the limitation of KIM-1 as a marker for ATN that may involve nephron segments other than the proximal tubule.