Urinary albumin and transferrin as early diagnostic markers of chronic kidney disease

Maeda, Hiroshi; Sogawa, Kazuyuki; Sakaguchi, Kazuko; Abe, Saori; Sagizaka, Wataru; Mochizuki, Shunsuke; Horie, Waka; Watanabe, Toshifumi; Shibata, Y.; Satoh, Mamoru; Sanda, Akihiro; Nomura, Fumio; Suzuki, Jun

doi:10.1292/jvms.14-0427

Cited by 26 publications

(21 citation statements)

References 18 publications

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“…We also found evidence suggesting PH1-CKD glomerular injury, including upregulated transferrin and -microalbumin. 28 Although, we found some similar Ur-PRO patterns in PH1 and IHC for PROs known to be incorporated into COM stone organic matrix, we also observed divergent profiles between IHC and PH1 that we had hypothesized. Hence, an increased presence of Ur-PROs indicative of toxic injury and cell death added relevant data regarding patterns of compensatory and protective mechanisms that are driven by co-existing high UrOx and declining eGFR as PH1-CKD progresses.…”

Section: Discussionmentioning

confidence: 50%

Assessment of Urine Proteomics in Type 1 Primary Hyperoxaluria

et al. 2016

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Background: Primary hyperoxaluria type 1 (PH1) and idiopathic hypercalciuria (IHC) are stone-forming diseases that may result in the formation of calcium (Ca) oxalate (Ox) stones, nephrocalcinosis, and progressive chronic kidney disease (CKD). Poorer clinical outcome in PH1 is segregated by the highest urine (Ur)-Ox (UrOx), while IHC outcomes are not predictable by UrCa. We hypothesized that differences would be found in selected Ur-protein (PRO) patterns in PH1 and IHC, compared to healthy intra-familial sibling controls (C) of PH1 patients. We also hypothesized that the PRO patterns associated with higher UrOx levels would reflect injury, inflammation, biomineralization, and abnormal tissue repair processes in PH1. Methods: Twenty four-hour Ur samples were obtained from 3 cohorts: PH1 (n = 47); IHC (n = 35) and C (n = 13) and were analyzed using targeted platform-based multi-analyte profile immunoassays and for UrOx and UrCa by biochemical measurements. Results: Known stone matrix constituents, osteopontin, calbindin, and vitronectin were lowest in PH1 (C > IHC > PH1; p < 0.05). Ur-interleukin-10; chromogranin A; epidermal growth factor (EGF); insulin-like growth factor-1 (IGF-1), and macrophage inflammatory PRO-1α (MIP-1α) were higher in PH1 > C (p = 0.03 to p < 0.05). Fetuin A; IGF-1, MIP-1α, and vascular cell adhesion molecule-1 were highest in PH1 > IHC (p < 0.001 to p = 0.005). Conclusion: PH1 Ur-PROs reflected overt inflammation, chemotaxis, oxidative stress, growth factors (including EGF), and pro-angiogenic and calcification regulation/inhibition compared to the C and IHC cohorts. Many of the up- and downregulated PH1-PROs found in this study are also found in CKD, acute kidney injury, stone formers, and/or stone matrices. Further data analyses may provide evidence for PH1 unique PROs or demonstrate a poorer clinical outcome.

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Section: Discussionmentioning

confidence: 50%

Assessment of Urine Proteomics in Type 1 Primary Hyperoxaluria

et al. 2016

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“…In contrast, L‐FABP excretion reflects the tubular response due to ischemia and oxidative stress, and increases from the early stages of pathological events before structural damage of the glomerular, tubular, and both cells . Other biomarkers, such as urinary albumin and N ‐acetyl‐β‐ d ‐glucosaminidase (NAG), are used to diagnose early stages of AKI and CKD in cats. However, urinary albumin and NAG increase with progression of glomerular and tubular injuries, respectively.…”

Section: Discussionmentioning

confidence: 99%

Renal expression and urinary excretion of liver‐type fatty acid‐binding protein in cats with renal disease

Katayama

Ohata

Miyazaki

et al. 2020

Veterinary Internal Medicne

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Background Liver‐type fatty acid‐binding protein (L‐FABP) is a biomarker for early detection of renal disease in humans. Liver‐type fatty acid‐binding protein is cytotoxic oxidation products secreted from proximal tubules under ischemia and oxidative stress. Objective To examine renal expression and quantify urinary excretion of L‐FABP in catswith renal disease. Animals One hundred and thirty‐four client‐owned cats including 34 cats with serum creatinine (sCre) values >1.6 mg/dL and 10 other cats that died in clinics. Methods Tissue expressions of L‐FABP were examined by reverse transcription polymerase chain reaction and Western blotting. Urinary L‐FABP (uL‐FABP) and serum L‐FABP (sL‐FABP) levels were determined by enzyme‐linked immunosorbent assay. Anti‐liver‐type fatty acid‐binding protein antibody immunostained renal sections. Results Feline kidneys express L‐FABP. Strong L‐FABP signals were observed in the lumens of proximal tubular cells in 5 cats with high uL‐FABP excretion, but not in 5 cats with low uL‐FABP excretion. In 9 normal cats, uL‐FABP index was <1.2 μg/g urinary creatinine (uCre). High uL‐FABP indexes (>10.0 μg/g uCre) were detected in 7 of 100 cats with low sCre (<1.6 mg/dL) and 18 of 44 cats with high sCre (>1.6 mg/dL). There was a weak correlation between L‐FABP index and sCre, serum symmetric dimethylarginine (SDMA), or blood urea nitrogen (BUN), and these correlation coefficients were increased by analyzing only data of cats with sCre >1.6 mg/dL. There was a weak correlation between u L‐FABP index and sL‐FABP in all tested cats, but not in cats with high sCre. Conclusions and Clinical Importance This study demonstrates correlations between L‐FABP and current renal biomarkers for chronic kidney disease in cats, such as sCre and SDMA. Liver‐type fatty acid‐binding protein may be a potential biomarker to predict early pathophysiological events in feline kidneys.

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“…Pyometra caused transient albuminuria that significantly decreased or returned to values not significantly different from healthy dogs after ovariohysterectomy . Cats with stage I CKD had significantly higher concentrations of uAlb than normal cats, and uAlb concentration had higher sensitivity and specificity for detection of CKD compared with plasma creatinine …”

Section: Renal Biomarkers: Urinementioning

confidence: 97%

Renal biomarkers in domestic species

Hokamp

Nabity

2016

Veterinary Clinical Pathol

133

147

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Current conventional tests of kidney damage and function in blood (serum creatinine and urea nitrogen) and urine (urine protein creatinine ratio and urine specific gravity) are widely used for diagnosis and monitoring of kidney disease. However, they all have important limitations, and additional markers of glomerular filtration rate and glomerular and tubular damage are desirable, particularly for earlier detection of renal disease when therapy is most effective. Additionally, urinary markers of kidney damage and function may help localize damage to the affected portion of the kidney. In general, the presence of high- and intermediate-molecular weight proteins in the urine are indicative of glomerular damage, while low-molecular weight proteins and enzymes in the urine suggest tubular damage due to decreased reabsorption of proteins, direct tubular damage, or both. This review aims to discuss many of these new blood and urinary biomarkers in domestic veterinary species, focusing primarily on dogs and cats, how they may be used for diagnosis of renal disease, and their limitations. Additionally, a brief discussion of serum creatinine is presented, highlighting its limitations and important considerations for its improved interpretation in domestic species based on past literature and recent studies.

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Urinary albumin and transferrin as early diagnostic markers of chronic kidney disease

Cited by 26 publications

References 18 publications

Assessment of Urine Proteomics in Type 1 Primary Hyperoxaluria

Assessment of Urine Proteomics in Type 1 Primary Hyperoxaluria

Renal expression and urinary excretion of liver‐type fatty acid‐binding protein in cats with renal disease

Renal biomarkers in domestic species

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