11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Urinary liver-type fatty acid binding protein and chronic kidney disease

      article-commentary
      1 , 2 , 3
      Indian Journal of Nephrology
      Medknow Publications & Media Pvt Ltd

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The number of the dialysis patient increases year by year, with diabetic kidney disease as the main contributor. Therefore, diagnostic markers for predicting the prognosis of early diabetic kidney disease are needed to distinguish patients who are at higher risk of progression to ESRD, start renal protective therapy, and thus decrease the number of patients with ESRD. Urinary albumin has been used not only for diagnosis and categorization of diabetic kidney disease, but also in the evaluation of management strategies. However, several studies showed un-coupling of the development of increased urinary albumin levels and the occurrence of renal dysfunction. Krolewski et al. described normoalbuminuria patients with a baseline glomerular filtration rate over 105 who had early progressive renal dysfunction,[1] indicating that more reliable biomarkers are necessary. In addition to the glomerular changes, tubulointerstitial injury has an important impact on the progression of diabetic kidney disease. Tubular biomarkers may reflect pathophysiological conditions that cannot be detected by measuring urinary albumin. Liver-type fatty-acid binding protein (L-FABP) is expressed in the proximal tubules of the human kidney and participates in fatty acid metabolism. Free fatty acids (FFAs) are bound to albumin, filtered through the glomeruli, and reabsorbed into the proximal tubules. FFAs loaded on the proximal tubules are then bound to L-FABP and transported to mitochondria or peroxisomes, where they are metabolized by β-oxidization.[2] In order to evaluate the dynamics of human L-FABP in kidney disease, transgenic animal model studies were performed.[3] Human L-FABP gene expression in the kidney was found to be up-regulated and urinary excretion of human L-FABP was increased by stress, such as urinary protein overload, tubular stretch, hypertension, ischemia-reperfusion, and toxins that cause tubulointerstitial damage.[3] We speculate that increased urinary L-FABP levels in humans result from up-regulation of L-FABP gene expression in the kidney. The present study[4] is the first to show clinical significance of increased urinary L-FABP during progression of diabetic kidney disease in Indian patients with type 2 diabetes. Urinary L-FABP levels were also higher in normoalbuminuric patients than in control subjects. Similar results were reported in studies of Japanese and European populations.[5 6] In a prospective observational follow-up study of type 1 or type 2 diabetic patients, increased urinary L-FABP levels were found to be associated with progression of diabetic kidney disease.[5 7] These results indicated that urinary L-FABP levels accurately reflected the disease severity and could potentially serve as a clinical marker to identify patients who are likely to experience disease progression. Furthermore, there have been numerous reports of intervention studies in which urinary L-FABP levels correlate with responses to renoprotective treatment.[8] Based on these results, a urinary human L-FABP ELISA kit developed by CMIC Holdings Co. Ltd. (Tokyo, Japan) was authorized as an extracorporeal diagnostic agent, and urinary L-FABP was approved as a tubular injury biomarker in clinical practice by the Ministry of Health, Labour and Welfare in Japan in 2011.[8] Unfortunately, the urinary L-FABP values in this Indian study were measured using a “research use only“ diagnostic kit. Long-term observational studies of type 2 diabetes patients with normoalbuminuria and microalbuminuria have been performed with about 12 years of follow-up.[9] Araki et al. reported recently that increased urinary L-FABP levels were associated with the occurrence of future cardiovascular events, in addition to progression to ESRD, and even in patients with normalbuminuria.[9] Urinary L-FABP may reflect the degree of systemic microcirculation injury and thus be a predictive marker for the onset of cardiovascular disease. A longitudinal study using an authorized urinary human L-FABP ELISA kit with confirmed accuracy is needed to reveal correlations between urinary L-FABP and renal prognosis or the onset of cardiovascular events in Indian subjects with type 2 diabetes.

          Related collections

          Most cited references8

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Early Progressive Renal Decline Precedes the Onset of Microalbuminuria and Its Progression to Macroalbuminuria

          OBJECTIVE Progressive decrease in the glomerular filtration rate (GFR), or renal decline, in type 1 diabetes (T1D) is observed in patients with macroalbuminuria. However, it is unknown whether this decline begins during microalbuminuria (MA) or normoalbuminuria (NA). RESEARCH DESIGN AND METHODS The study group (second Joslin Kidney Study) comprises patients with T1D and NA (n = 286) or MA (n = 248) who were followed for 4–10 years (median 8 years). Serial measurements (median 6, range 3–16) of serum creatinine and cystatin C were used jointly to estimate GFR (eGFRcr-cys) and assess its trajectories during follow-up. RESULTS Renal decline (progressive eGFRcr-cys loss of at least 3.3% per year) occurred in 10% of the NA and 35% of the MA (P < 0.001). In both groups, the strongest determinants of renal decline were baseline serum concentrations of uric acid (P < 0.001) and tumor necrosis factor receptor 1 or 2 (TNFR-1 or -2, P < 0.001). Other significant risk factors included baseline HbA1c, age/diabetes duration, and systolic blood pressure. Relative impacts of these determinants were similar in NA and MA. Renal decline was not associated with sex or baseline serum concentration of TNF-α, IL-6, IL-8, IP-10, MCP-1, VCAM, ICAM, Fas, or FasL. CONCLUSIONS Renal decline in T1D begins during NA and it is determined by multiple factors, similar to MA. Thus, this early decline is the primary disease process leading to impaired renal function in T1D. Changes in albumin excretion rate, such as the onset of MA or its progression to macroalbuminuria, are either caused by or develop in parallel to the early renal decline.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Clinical Significance of Urinary Liver-Type Fatty Acid–Binding Protein in Diabetic Nephropathy of Type 2 Diabetic Patients

            OBJECTIVE Urinary liver-type fatty acid–binding protein (L-FABP) is a promising indicator of tubular but not glomerular damage. The aim of this study was to evaluate the clinical usefulness of urinary L-FABP as a prognostic biomarker in impaired diabetic nephropathy in type 2 diabetes. RESEARCH DESIGN AND METHODS This investigation involved a cross-sectional and longitudinal analysis of the relationship between urinary L-FABP levels and progressive nephropathy. Urinary L-FABP was measured with enzyme-linked immunosorbent assay. In the cross-sectional analysis, the association of urinary L-FABP, with the severity of diabetic nephropathy, was investigated in 140 patients with type 2 diabetes and in 412 healthy control subjects. Of the patients in the former study, 104 have been followed for 4 years. The progression of diabetic nephropathy was defined as progressive albuminuria, end-stage renal disease, or induction of hemodialysis. RESULTS Urinary L-FABP levels were progressively increased in subjects with normo-, micro-, or macroalbuminuria and further increased in patients with end-stage renal disease. In the longitudinal analysis, high urinary L-FABP levels were associated with the increase in albuminuria, progression to end-stage renal disease, or induction of hemodialysis. This was particularly demonstrated in the subgroup of patients without renal dysfunction (n = 59), where high urinary L-FABP levels were associated with the progression of diabetic nephropathy. CONCLUSIONS Urinary L-FABP accurately reflected the severity of diabetic nephropathy in type 2 diabetes, and its level was high in the patients with normoalbuminuria. Moreover, higher urinary L-FABP was a risk factor for progression of diabetic nephropathy.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Urinary Liver-Type Fatty Acid-Binding Protein Predicts Progression to Nephropathy in Type 1 Diabetic Patients

              OBJECTIVE Urinary liver-type fatty acid-binding protein (u-LFABP) is a marker of tubulointerstitial inflammation and has been shown to be increased in patients with type 1 diabetes and is further increased in patients who progress to micro- and macroalbuminuria. Our aim was to evaluate u-LFABP as a predictor of progression to micro- and macroalbuminuria in type 1 diabetes. RESEARCH DESIGN AND METHODS From an inception cohort of 277 patients, u-LFABP, adjusted for urinary creatinine (enzyme-linked immunosorbent assay), was measured in 24-h urine samples from 165 normoalbuminuric patients 9.6 ± 3.5 (mean ±SD) years after onset of type 1 diabetes. The outcome measured was development of persistent micro- or macroalbuminuria or death. RESULTS Patients were followed for a median of 18 (range 1–19) years; 39 progressed to microalbuminuria, 8 of those progressed further to macroalbuminuria, and 24 died. In a Cox regression model, baseline log u-LFABP levels predicted the development of microalbuminuria, adjusted for known risk factors (sex, age, A1C, systolic and diastolic blood pressure, albumin excretion rate, serum creatinine, and smoking) (hazard ratio [HR] 2.3 [95% CI 1.1–4.6]) and log u-LFABP predicted mortality (adjusted HR 3.0 [1.3–7.0]). u-LFABP (above versus below the median) predicted the development of macroalbuminuria (adjusted HR 2.6 [1.2–5.4]). As a continuous variable, u-LFABP tended to predict macroalbuminuria (HR 1.9, P = 0.2), but numbers were small. CONCLUSIONS High levels of the tubular inflammation marker u-LFABP predict the initiation and progression to diabetic nephropathy and all-cause mortality, independent of urinary albumin excretion rate and other established risk factors.
                Bookmark

                Author and article information

                Journal
                Indian J Nephrol
                Indian J Nephrol
                IJN
                Indian Journal of Nephrology
                Medknow Publications & Media Pvt Ltd (India )
                0971-4065
                1998-3662
                Sep-Oct 2015
                : 25
                : 5
                : 263-264
                Affiliations
                [1 ]Department of Internal Medicine, Division of Nephrology and Hypertension, Tokyo, Japan
                [2 ]Department of Anatomy, Division of Nephrology and Hypertension, St. Marianna University School of Medicine, Kanagawa, Japan
                [3 ]Department of Internal Medicine, Tokyo Takanawa Hospital, Tokyo, Japan
                Author notes
                Address for correspondence: Dr. A. Kamijo-Ikemori, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki 216-8511, Japan. E-mail: a2kamijo@ 123456marianna-u.ac.jp
                Article
                IJN-25-263
                4588319
                09c87b52-7582-4194-8514-d956ad27e1f5
                Copyright: © Indian Journal of Nephrology

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                Categories
                Commentary

                Nephrology
                Nephrology

                Comments

                Comment on this article