Light chains are a ligand for megalin

Klassen, R. Bryan; Allen, Patricia; Batuman, Vecihi; Crenshaw, Kimberly; Hammond, Timothy G.

doi:10.1152/japplphysiol.01090.2003

Cited by 80 publications

(62 citation statements)

References 24 publications

(50 reference statements)

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“…This is likely to reflect divergent tubular handling of polyclonal and monoclonal FLC. Proximal tubular reabsorption of proteins is mediated by megalin-cubulin receptor endocytosis, which has a limited capacity and differential affinity for individual proteins (26,27). Accordingly, the concentration of a monoclonal FLC in the urine will depend on the serum FLC concentration, the degree of albuminuria (reflective of glomerular damage from the monoclonal protein), the degree of tubular damage (reflective of monoclonal tubular disease), and the affinity of tubular receptors for that individual FLC.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Assessment of Serum and Urinary Polyclonal Free Light Chains in Patients with Chronic Kidney Disease

Hutchison¹,

Harding²,

Hewins³

et al. 2008

Clinical Journal of the American Society of Nephrology

311

233

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Results: Serum and FLC concentrations increased progressively with CKD stage (both P < 0.001) and strongly correlated with markers of renal function, including cystatin-C (: R ‫؍‬ 0.8, P < 0.01; and : R ‫؍‬ 0.79, P < 0.01). Urinary FLC concentrations varied significantly between disease groups (: P < 0.001; : P < 0.005) and also rose significantly with increasing CKD stage (both FLC P < 0.0001). Urinary FLC concentrations were positively correlated with their corresponding serum concentration (: R ‫؍‬ 0.63; : R ‫؍‬ 0.65; both P < 0.001) and urinary albumin creatinine ratio (: R ‫؍‬ 0.58; : R ‫؍‬ 0.65; both P < 0.001). The proportion of patients with abnormally high urinary FLC concentrations rose with both the CKD stage and the severity of albuminuria.Conclusions: This study demonstrates significant abnormalities of serum and urinary polyclonal FLC in patients with CKD. These data provide the basis for studies that assess the contribution of polyclonal FLC to progressive renal injury and systemic inflammation in patients with kidney disease.

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Section: Discussionmentioning

confidence: 99%

Quantitative Assessment of Serum and Urinary Polyclonal Free Light Chains in Patients with Chronic Kidney Disease

Hutchison¹,

Harding²,

Hewins³

et al. 2008

Clinical Journal of the American Society of Nephrology

311

233

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“…3 the impact of charge 46 and blood pressure 47 may influence the presence of FLC in urine, adding to the subjective nature of the electrophoretic assessment and making these cut-offs somewhat subjective. sFLC assessment can also be affected by renal function, with a proportional increase of kappa over lambda FLC concentrations as renal function deteriorates that may result in a shift in the sFLCκ/λ ratio.…”

mentioning

confidence: 99%

Comparison of serum free light chain and urine electrophoresis for the detection of the light chain component of monoclonal immunoglobulins in light chain and intact immunoglobulin multiple myeloma

et al. 2015

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“…It is a ligand of the glycoprotein receptor for cubilin and megalin in the proximal renal tubule and for THP in the distal tubule and is seen as a low abundance protein within human urine. 19,20 These light chains were exclusively seen from stents in our encrustation cohort and may be a reflection of increased host cell response to ureteroscopic manipulation or stent trauma. Alpha-1 antitrypsin is a 52-kDa plasma glycoprotein important for the protection of tissues from proteolytic enzymes.…”

mentioning

confidence: 78%

Presence of Five Conditioning Film Proteins Are Highly Associated with Early Stent Encrustation

Canales

Higgins

Markowski

et al. 2009

Journal of Endourology

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Purpose: Ureteral stents are susceptible to biofilm formation and crystal deposition, especially in stone formers. To identify proteins responsible for this accumulation, we compared conditioning film proteomes obtained from human ureteral stents with and without encrustation. Materials and Methods: Twenty-seven Bard InlayÔ hydrophilic ureteral stents were removed after ureteroscopy. Stent encrustation was quantified by visual analog score 0 (none) to 4 (heavy) and further categorized as nonencrusted (scores 0 and 1; n ¼ 22) or encrusted (scores 2, 3, and 4; n ¼ 5). Stent conditioning film was sampled and digested with trypsin, and peptide tandem mass spectrometry data were acquired using liquid chromatography. After protein identification, unconditional exact tests were used to compare categorical variables versus encrustation outcome. Stone analysis and follow-up metabolic urine profiles were examined to identify additional risk factors for stent encrustation. Results: More than 300 unique proteins with >95% confidence were identified. Proteins a-1 anti-trypsin, Ig kappa, IgH G1, and histone H2b and H3a were found to be highly associated with stent encrustation ( p < 0.05), while Tamm-Horsfall protein and histone H2a were found to have a marginal association ( p < 0.1). Patients with early stent encrustation were more likely to have mixed stone analysis ( p ¼ 0.03) and low urinary volumes ( p < 0.01). Conclusion: Immunoglobulins and Tamm-Horsfall protein are common urinary proteins that appear to nonselectively bind early onto ureteral stent surfaces. Histones, nuclear DNA-condensing proteins, likely contribute to stent encrustation because of their unique net positive charge and may represent a potential clinical target for encrustation prevention.

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Light chains are a ligand for megalin

Abstract: Light chains are a ligand for megalin.

Cited by 80 publications

References 24 publications

Quantitative Assessment of Serum and Urinary Polyclonal Free Light Chains in Patients with Chronic Kidney Disease

Quantitative Assessment of Serum and Urinary Polyclonal Free Light Chains in Patients with Chronic Kidney Disease

Comparison of serum free light chain and urine electrophoresis for the detection of the light chain component of monoclonal immunoglobulins in light chain and intact immunoglobulin multiple myeloma

Presence of Five Conditioning Film Proteins Are Highly Associated with Early Stent Encrustation

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