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1018 URINARY KIDNEY INJURY MOLECULE-1 (KIM-1) IN THE ASSESSMENT OF ACUTE KIDNEY INJURY IN PATIENTS WITH CIRRHOSIS
POSTERS 02d. CIRRHOSIS AND ITS COMPLICATIONS: HEPATORINAL SYNDROME AND ASCITES
1018 URINARY KIDNEY INJURY MOLECULE-1 (KIM-1) IN THE ASSESSMENT OF ACUTE KIDNEY INJURY IN PATIENTS WITH CIRRHOSIS R. Barreto1 , C. Fagundes1 , R. Moreira1 , E. Rodriguez1 , R. Cela1 , E. Sola` 1 , I. Graupera1 , X. Ariza1 , G. Pereira1 , M. Morales2,3,4 , 2,3,4 W. Jimenez ´ , M. Guevara1 , V. Arroyo1 , P. Gines ` 1 . 1 Liver Unit, Hospital Cl´ınic, University de Barcelona, IDIBAPS, CIBERehd, 2 Centro Diagnostico Biomedica, IDIBAPS, Insititud d’Investigacions Biom`ediques August Pi i Sunyer, 3 Biochemistry and Molecular Genetics Dept, Centro de Investigaci´ on Biom´edica en Red de Enfermedades Hep´ aticas y Digestivas (CIBEReHD), 4 Biochemistry and Molecular Genetics Dept, Hospital Clinic, University of Barcelona, Barcelona, Spain E-mail: [email protected] KIM-1 is a protein that is expressed in the kidney in the presence of tubular damage. Studies in the general population of hospitalised patients have shown that measurement of urine KIM-1 concentration (u-KIM-1) is useful to differentiate between acute kidney injury (AKI) caused by tubular damage and kidney injury due to pre-renal causes. So far, there have been no studies reported assessing the potential usefulness of u-KIM-1 in the assessment of AKI in patients with cirrhosis. Aim: To investigate the usefulness of urinary KIM-1 levels in the differential diagnosis of acute kidney injury in cirrhosis. Patients and Methods: 265 patients consecutively admitted for complications of cirrhosis were prospectively evaluated. AKI was defined using the Acute Kidney Injury Network criteria and patients were classified into 4 groups according to the cause of impairment of kidney function: pre-renal (pAKI), Hepatorenal Syndrome (HRS), intrinsic tubular damage (iAKI), and miscellaneous causes. KIM-1 was measured in urine using ELISA (Quantikine Human KIM-1, R&D Systems). Results: One-hundred of the 265 patients (38%) developed AKI. Contrary to the expected results, u-KIM-1 values in patients with AKI were not significantly different from those in patients without AKI (n = 165) (3.8 ng/mL (2.0–6.4) vs 3.4 ng/mL (1.6–6.8) [median and interquartile range], p = 0.342). In addition u-KIM-1 was not useful in differentiating the cause of AKI (pAKI (n = 25): 3.9 (1.3–5.0); HRS (n = 36): 4.3 (2.9–8.0); iAKI (n = 15): 2.4 (1.5–3.8) and miscellaneous (n = 24): 4.3 (1.6–11) ng/mL, p = 0.229). The urinary concentration of KIM-1 in patients with compensated cirrhosis (without AKI) was much higher than that in a group of healthy volunteers matched by age and sex (3.6 ng/mL (1.7–6.7) vs 0.8 ng/mL (0.6–1.1), respectively; p < 0.001), which suggests the existence of an overexpression of KIM-1 in the kidneys of patients with cirrhosis independent of the presence of tubular damage. Conclusions: Contrary to what has already been reported in the general population, measurement of urinary KIM-1 levels in patients with cirrhosis is not useful in either determining the presence or the cause of acute kidney injury. Physicians caring for patients with cirrhosis should be aware that cirrhosis increases the urinary levels of KIM-1.
1019 URINARY NGAL IS USEFUL TO PREDICT CAUSE AND SEVERITY OF KIDNEY FUNCTION IMPAIRMENT AND IS A PROGNOSTIC MARKER IN PATIENTS HOSPITALIZED FOR COMPLICATIONS OF CIRRHOSIS R. Barreto1 , C. Fagundes1 , R. Moreira1 , E. Rodriguez1 , R. Cela1 , S. Elsa1 , I. Graupera1 , X. Ariza1 , G. Pereira1 , M. Morales2,3,4 , 2,3,4 E. Poch5 , W. Jimenez ´ , M. Guevara1 , V. Arroyo1 , P. Gines ` 1 . 1 Liver Unit, Hospital Cl´ınic, University de Barcelona, IDIBAPS, CIBERehd, 2 Centro Diagnostico Biomedica, IDIBAPS, Insititud d’Investigacions Biom`ediques August Pi i Sunyer, 3 Biochemistry and Molecular Genetics Dept, Centro de Investigaci´ on Biom´edica en Red de Enfermedades Hep´ aticas y Digestivas (CIBEReHD), 4 Biochemistry and Molecular Genetics Dept, Hospital Clinic, University of Barcelona, 5 Nephrology Unit, Hospital Clinic de Barcelona, Barcelona, Spain E-mail: [email protected] NGAL is expressed in the kidney as a consequence of tubular damage. Measurement of NGAL in urine (u-NGAL) in the general population of patients at hospital admission is useful to determine the cause of acute kidney injury and in-hospital mortality. Limited information exists regarding u-NGAL in cirrhosis. Aim: To investigate whether u-NGAL is useful in determining the cause and severity of impairment in kidney function and prognosis in hospitalized patients with cirrhosis. Methods: Prospective study of 265 consecutive patients admitted for complications of cirrhosis. Impairment of kidney function was evaluated with the Acute Kidney Injury (AKI) criteria and classified into 4 groups according to the cause: pre-renal (pAKI), Hepatorenal Syndrome (HRS), tubular damage or intrinsic (iAKI), or miscellaneous. NGAL was measured in urine at admission using ELISA (Bioporto, DK). Results: One-hundred of the 265 patients (38%) had AKI at admission or developed it early after admission. Overall, patients with AKI showed higher levels of u-NGAL compared with those without AKI (73 (33–203) vs 32 (15–82) mg/g creatinine [median and interquartile range]; p = 0.001). Patients with i-AKI had the highest levels, followed by patients with HRS, while patients with p-AKI and those with miscellaneous causes had values similar to those of patients without AKI. The best cut-off value to distinguish i-AKI from other causes was 195 [AUC: 0.86 (0.75–0.98)]. Using the median value in the whole series (44 mg/gr creatinine) as cut-off value, the majority of patients with HRS or iAKI (86%) belonged to this group. A high level of u-NGAL (>44 mg/gr creatinine) was associated with more frequent progression of AKI, greater need for dialysis, and, most importantly, higher mortality or transplantation rate both in hospital and at 3 months (23% and 51%, respectively, compared with 8% and 24% in patients with low levels of uNGAL, p < 0.01). u-NGAL was an independent predictive factor of mortality together with serum bilirubin, serum sodium, and hepatic encephalopathy. Conclusions: Measurement of urine NGAL in patients admitted for complications of cirrhosis is useful not only to help establish the cause and severity of impairment of kidney function but also as prognostic marker.
Journal of Hepatology 2013 vol. 58 | S409–S566
S419
1018 URINARY KIDNEY INJURY MOLECULE-1 (KIM-1) IN THE ASSESSMENT OF ACUTE KIDNEY INJURY IN PATIENTS WITH CIRRHOSIS R. Barreto1 , C. Fagundes1 , R. Moreira1 , E. Rodriguez1 , R. Cela1 , E. Sola` 1 , I. Graupera1 , X. Ariza1 , G. Pereira1 , M. Morales2,3,4 , 2,3,4 W. Jimenez ´ , M. Guevara1 , V. Arroyo1 , P. Gines ` 1 . 1 Liver Unit, Hospital Cl´ınic, University de Barcelona, IDIBAPS, CIBERehd, 2 Centro Diagnostico Biomedica, IDIBAPS, Insititud d’Investigacions Biom`ediques August Pi i Sunyer, 3 Biochemistry and Molecular Genetics Dept, Centro de Investigaci´ on Biom´edica en Red de Enfermedades Hep´ aticas y Digestivas (CIBEReHD), 4 Biochemistry and Molecular Genetics Dept, Hospital Clinic, University of Barcelona, Barcelona, Spain E-mail: [email protected] KIM-1 is a protein that is expressed in the kidney in the presence of tubular damage. Studies in the general population of hospitalised patients have shown that measurement of urine KIM-1 concentration (u-KIM-1) is useful to differentiate between acute kidney injury (AKI) caused by tubular damage and kidney injury due to pre-renal causes. So far, there have been no studies reported assessing the potential usefulness of u-KIM-1 in the assessment of AKI in patients with cirrhosis. Aim: To investigate the usefulness of urinary KIM-1 levels in the differential diagnosis of acute kidney injury in cirrhosis. Patients and Methods: 265 patients consecutively admitted for complications of cirrhosis were prospectively evaluated. AKI was defined using the Acute Kidney Injury Network criteria and patients were classified into 4 groups according to the cause of impairment of kidney function: pre-renal (pAKI), Hepatorenal Syndrome (HRS), intrinsic tubular damage (iAKI), and miscellaneous causes. KIM-1 was measured in urine using ELISA (Quantikine Human KIM-1, R&D Systems). Results: One-hundred of the 265 patients (38%) developed AKI. Contrary to the expected results, u-KIM-1 values in patients with AKI were not significantly different from those in patients without AKI (n = 165) (3.8 ng/mL (2.0–6.4) vs 3.4 ng/mL (1.6–6.8) [median and interquartile range], p = 0.342). In addition u-KIM-1 was not useful in differentiating the cause of AKI (pAKI (n = 25): 3.9 (1.3–5.0); HRS (n = 36): 4.3 (2.9–8.0); iAKI (n = 15): 2.4 (1.5–3.8) and miscellaneous (n = 24): 4.3 (1.6–11) ng/mL, p = 0.229). The urinary concentration of KIM-1 in patients with compensated cirrhosis (without AKI) was much higher than that in a group of healthy volunteers matched by age and sex (3.6 ng/mL (1.7–6.7) vs 0.8 ng/mL (0.6–1.1), respectively; p < 0.001), which suggests the existence of an overexpression of KIM-1 in the kidneys of patients with cirrhosis independent of the presence of tubular damage. Conclusions: Contrary to what has already been reported in the general population, measurement of urinary KIM-1 levels in patients with cirrhosis is not useful in either determining the presence or the cause of acute kidney injury. Physicians caring for patients with cirrhosis should be aware that cirrhosis increases the urinary levels of KIM-1.
1019 URINARY NGAL IS USEFUL TO PREDICT CAUSE AND SEVERITY OF KIDNEY FUNCTION IMPAIRMENT AND IS A PROGNOSTIC MARKER IN PATIENTS HOSPITALIZED FOR COMPLICATIONS OF CIRRHOSIS R. Barreto1 , C. Fagundes1 , R. Moreira1 , E. Rodriguez1 , R. Cela1 , S. Elsa1 , I. Graupera1 , X. Ariza1 , G. Pereira1 , M. Morales2,3,4 , 2,3,4 E. Poch5 , W. Jimenez ´ , M. Guevara1 , V. Arroyo1 , P. Gines ` 1 . 1 Liver Unit, Hospital Cl´ınic, University de Barcelona, IDIBAPS, CIBERehd, 2 Centro Diagnostico Biomedica, IDIBAPS, Insititud d’Investigacions Biom`ediques August Pi i Sunyer, 3 Biochemistry and Molecular Genetics Dept, Centro de Investigaci´ on Biom´edica en Red de Enfermedades Hep´ aticas y Digestivas (CIBEReHD), 4 Biochemistry and Molecular Genetics Dept, Hospital Clinic, University of Barcelona, 5 Nephrology Unit, Hospital Clinic de Barcelona, Barcelona, Spain E-mail: [email protected] NGAL is expressed in the kidney as a consequence of tubular damage. Measurement of NGAL in urine (u-NGAL) in the general population of patients at hospital admission is useful to determine the cause of acute kidney injury and in-hospital mortality. Limited information exists regarding u-NGAL in cirrhosis. Aim: To investigate whether u-NGAL is useful in determining the cause and severity of impairment in kidney function and prognosis in hospitalized patients with cirrhosis. Methods: Prospective study of 265 consecutive patients admitted for complications of cirrhosis. Impairment of kidney function was evaluated with the Acute Kidney Injury (AKI) criteria and classified into 4 groups according to the cause: pre-renal (pAKI), Hepatorenal Syndrome (HRS), tubular damage or intrinsic (iAKI), or miscellaneous. NGAL was measured in urine at admission using ELISA (Bioporto, DK). Results: One-hundred of the 265 patients (38%) had AKI at admission or developed it early after admission. Overall, patients with AKI showed higher levels of u-NGAL compared with those without AKI (73 (33–203) vs 32 (15–82) mg/g creatinine [median and interquartile range]; p = 0.001). Patients with i-AKI had the highest levels, followed by patients with HRS, while patients with p-AKI and those with miscellaneous causes had values similar to those of patients without AKI. The best cut-off value to distinguish i-AKI from other causes was 195 [AUC: 0.86 (0.75–0.98)]. Using the median value in the whole series (44 mg/gr creatinine) as cut-off value, the majority of patients with HRS or iAKI (86%) belonged to this group. A high level of u-NGAL (>44 mg/gr creatinine) was associated with more frequent progression of AKI, greater need for dialysis, and, most importantly, higher mortality or transplantation rate both in hospital and at 3 months (23% and 51%, respectively, compared with 8% and 24% in patients with low levels of uNGAL, p < 0.01). u-NGAL was an independent predictive factor of mortality together with serum bilirubin, serum sodium, and hepatic encephalopathy. Conclusions: Measurement of urine NGAL in patients admitted for complications of cirrhosis is useful not only to help establish the cause and severity of impairment of kidney function but also as prognostic marker.
Journal of Hepatology 2013 vol. 58 | S409–S566
S419