Urinary Fatty Acids and Liver-Type Fatty Acid Binding Protein in Diabetic Nephropathy

Sasaki, Hiroyo; Kamijo‐Ikemori, Atsuko; Sugaya, Takeshi; Yamashita, Kayoko; Yokoyama, Takeshi; Koike, Jyunki; Sato, Takeo; Yasuda, Takashi; Kimura, Kenjiro

doi:10.1159/000214210

Cited by 54 publications

(49 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The levels of urinary L-FABP were also significantly higher in those with diabetic kidney disease. These results indicate that diabetic patients may be exposed to NEFA overload in the proximal tubules, and this overload contributes to diabetic renal disease [54] . Further research is necessary, in particular on the reason for tubular NEFA overload in diabetic patients and whether this is related to repeated episodes of hypoglycemia.…”

Section: Nefa Cause Direct Tissue Damage Including Myocardial and Kidmentioning

confidence: 77%

“…Liver-type fatty acid binding protein (L-FABP) is a cytoplasmic protein that belongs to a group of molecules that participate in intracellular fatty acid metabolism. In the presence of NEFA overload, there is an up-regulation of L-FABP in proximal tubules, and this apparently represents a protective mechanism to reduce tubular damage [54] . Urinary excretion of L-FABP has been found to be correlated with the severity and progression of diabetic kidney disease [54] .…”

Section: Nefa Cause Direct Tissue Damage Including Myocardial and Kidmentioning

confidence: 99%

See 1 more Smart Citation

Hypoglycemia: A Possible Link between Insulin Resistance, Metabolic Dyslipidemia, and Heart and Kidney Disease (the Cardiorenal Syndrome)

2011

View full text Add to dashboard Cite

Resistance to insulin metabolic signaling in adipose tissue contributes to the lipid abnormalities in obese, hyperinsulinemic, insulin-resistant patients who develop the cardiorenal syndrome. These same metabolic dyslipidemic abnormalities can be found in conditions of caloric energy restriction with decreased adiposity or normal insulin levels, such as anorexia, starvation or non-diabetic kidney disease. In this review, we assess hypoglycemia as an alternative physiological explanation for the biochemical and lipid findings in conditions of insulin resistance (IR). Therefore, PubMed databases were searched for articles on the effect of hypoglycemia and starvation on non-esterified fatty acid (NEFA) elevation and abnormalities in insulin signaling in muscles as well as abnormal kidney metabolism. The search included articles on NEFA and their role in triglyceride (TG) and high-density lipoprotein (HDL) metabolism, as well as kidney and heart disease. Available studies support that hypoglycemia increases NEFA generation from adipose tissue. Elevated levels of NEFA induce increased plasma levels of TG and decreased levels of HDL cholesterol, and may cause direct kidney and myocardial damage. IR of adipose and skeletal muscle tissue, and the elevation in insulin levels in obese, insulin-resistant patients could be explained by an adaptation to their carbohydrate intake. These molecular abnormalities in insulin metabolic signaling can also be found in hypoglycemia or starvation. In conclusion, IR of adipose tissue cannot fully explain the lipid ab- normalities observed in the cardiorenal syndrome. Decreased blood glucose levels (e.g. hypoglycemia) occur frequently in patients at risk for this syndrome. Hypoglycemia-induced increases in NEFA levels can promote lipid abnormalities that contribute to IR and the cardiorenal syndrome.

show abstract

Section: Nefa Cause Direct Tissue Damage Including Myocardial and Kidmentioning

confidence: 77%

Section: Nefa Cause Direct Tissue Damage Including Myocardial and Kidmentioning

confidence: 99%

Hypoglycemia: A Possible Link between Insulin Resistance, Metabolic Dyslipidemia, and Heart and Kidney Disease (the Cardiorenal Syndrome)

2011

View full text Add to dashboard Cite

show abstract

“…FAs are important in mammals as mediators of signal transduction for metabolic regulation and are rarely present in the free state in biological fluids because of their hydrophobic character and cytotoxicity. Overproduction of FFAs induces oxidative stress and production of inflammatory cytokines by increasing mitochondrial reactive oxygen species and subsequently leads to tubulointerstitial damage [20]. It is well established that FFA levels are increased in patients with ADHF and renal ischemia [21].…”

Section: Discussionmentioning

confidence: 99%

Urinary Liver-Type Fatty Acid-Binding Protein Level as a Predictive Biomarker of Acute Kidney Injury in Patients with Acute Decompensated Heart Failure

et al. 2017

View full text Add to dashboard Cite

Background: There are no biological markers to predict the onset of acute kidney injury (AKI) in patients with acute decompensated heart failure (ADHF). Liver-type fatty acid-binding protein (L-FABP) levels are markedly upregulated in the proximal tubules after renal ischemia. We investigated whether urinary L-FABP is a suitable marker to predict AKI in ADHF patients. Methods: We examined 281 consecutive patients with ADHF. Serum creatinine (Cr) and L-FABP levels were measured at admission and 24 and 48 h after admission. Results: AKI developed in 104 patients (37%). Urinary L-FABP levels at admission were significantly higher in patients with AKI than in those without (33.0 vs. 5.2 μg/g Cr; p < 0.001). Multivariate analysis showed that baseline urinary L-FABP level was an independent predictor of AKI in ADHF patients (odds ratio 1.08, 95% confidence interval 1.05-1.12; p < 0.001). Receiver operating characteristic analysis showed that baseline urinary L-FABP level exhibited 94.2% sensitivity and 87.0% specificity at a cutoff value of 12.5 μg/g Cr. Conclusions: Urinary L-FABP level is useful for predicting the onset of AKI in patients with ADHF. The results of our study could help clinicians diagnose AKI in ADHF patients earlier, leading to possible improvements in the treatment of this group of patients.

show abstract

“…Furthermore, the culprit pathogenetic molecule responsible for the initiation and propagation diabetic nephropathy remains unproven and uncertain [39,40,41,42,43,44,45,46,47,48,49,50,51,52,53]. Several independent and often conflicting lines of evidence from both human and experimental studies point to a variety of different pathogenetic mechanisms including oxidative stress, underlying genetic predispositions such as the nonmuscle myosin heavy-chain 9 gene on chromosome 22 or variants at chromosome 6q24–27 among African Americans [39,40,41,42], the production of advanced glycosylation end-products and the interaction of these end-products on the multiligand receptor of the immunoglobulin superfamily receptor for advanced glycation end-products [43,44], a role for intrarenal angiotensin II and/or renin production [45], pathogenetic roles for inflammation [46], lipid toxicity [47,49], podocyte injury and apoptosis [50,51], and chemokine/growth factor release causing renal injury [52,53]. …”

Section: Mechanisms Of Ckd Progression Still Remain Uncertainmentioning

confidence: 99%

Can ACE Inhibitors and Angiotensin Receptor Blockers Be Detrimental in CKD Patients?

Onuigbo

2011

Nephron Clin Pract

View full text Add to dashboard Cite

Current epidemiological data from the USA, Europe, Asia and the Indian subcontinent, Africa, the Far East, South America, the Middle East and Eastern Europe all point to the increasing incidence of renal failure encompassing acute kidney injury (AKI), chronic kidney disease (CKD) and end-stage renal disease (ESRD). While the explanations for these worldwide epidemics remain speculative, it must be acknowledged that these increases in AKI, CKD and ESRD, happening worldwide, have occurred despite the universal application of strategies of renoprotection over the last 2 decades, more especially the widespread use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We note that many of the published large renin-angiotensin-aldosterone system (RAAS) blockade randomized controlled trials, upon which current evidence-based practice for the increasing use of ACEIs and ARBs for renoprotection derived from, have strong deficiencies that have been highlighted over the years. From reports in the literature, there is an increasing association of exacerbations of renal failure with ACEIs and ARBs, more so in the older hypertensive patient, >65 years old. The biological plausibility for ACEI and ARB to protect the kidneys against a background of potential multiple pathogenetic pathways to account for CKD progression appears to be not very defensible. We reviewed the literature along these lines and submit that ACEIs and ARBs often cause unrecognized significant worsening renal failure in CKD patients, sometimes irreversible, and that more caution is required regarding their use, especially in the older hypertensive patients, with likely ischemic hypertensive nephropathy. Given the increasing association of concomitant RAAS blockade with worsening renal failure following exposure to iodinated contrast, during acute illness, in the perioperative period and following lower bowel preparations prior to colonoscopy, we submit that, preferably, ACEIs and ARBs be withheld for 2–4 days prior to or during these clinical scenarios. This represents the concept of renoprevention.

show abstract

Urinary Fatty Acids and Liver-Type Fatty Acid Binding Protein in Diabetic Nephropathy

Cited by 54 publications

References 64 publications

Hypoglycemia: A Possible Link between Insulin Resistance, Metabolic Dyslipidemia, and Heart and Kidney Disease (the Cardiorenal Syndrome)

Hypoglycemia: A Possible Link between Insulin Resistance, Metabolic Dyslipidemia, and Heart and Kidney Disease (the Cardiorenal Syndrome)

Urinary Liver-Type Fatty Acid-Binding Protein Level as a Predictive Biomarker of Acute Kidney Injury in Patients with Acute Decompensated Heart Failure

Can ACE Inhibitors and Angiotensin Receptor Blockers Be Detrimental in CKD Patients?

Contact Info

Product

Resources

About