Urine retinol-binding protein 4: a functional biomarker of the proximal renal tubule.

Measurement of retinol-binding protein 4 in urine (uRBP4) is arguably the most sensitive biomarker for loss of function of the human proximal renal tubule. Megalin- and cubilin-receptor-mediated endocytosis normally absorbs > 99% of the approximately 1.5 g/24 h of protein filtered by the renal glomerulus.

Analysis of molecular forms of urine Retinol-Binding Protein in Fanconi Syndrome and design of an accurate immunoassay.

Background: Retinol-Binding Protein in urine (uRBP), a biomarker for the proximal renal tubular disease of congenital and acquired Fanconi Syndrome (FS) occurs in multiple forms. However these have not had quantitative mass spectrometric (MS) analysis, nor is there a validated assay for defined molecular species of uRBP with linearity on sample dilution.

Methods: A 'Top-down' MS approach identified distinct forms of uRBP differing by only one amino acid.

Characterization of a recurrent in-frame UMOD indel mutation causing late-onset autosomal dominant end-stage renal failure.

Background And Objectives: In a single-center renal clinic, we have established routine mutation testing to diagnose UMOD-associated kidney disease (UAKD), an autosomal dominant disorder typically characterized by gout, hyperuricemia, and renal failure in the third to sixth decades.

Design, Setting, Participants, & Measurements: Four probands and their multigeneration kindreds were assessed by clinical, historical, and biochemical means. Diagnostic UMOD sequencing was performed, and mutant uromodulin was characterized in vitro.

Does oral N-acetylcysteine reduce contrast-induced renal injury in patients with peripheral arterial disease undergoing peripheral angiography? A randomized-controlled study.

The nephroprotective role of N-acetylcysteine (NAC) against contrast-induced nephropathy (CIN) in patients undergoing peripheral arterial angiography remains unclear. A total of 40 patients undergoing peripheral arterial angiography were randomized to receive intravenous (iv) hydration only (group 1) or oral NAC in addition to iv hydration (group 2; ISRCTN: 35882618). Primary outcome was reduction in the elevation of urinary retinol binding protein (RBP), albumin-creatinine ratio (ACR), and serum creatinine (serC).

Remote ischemic preconditioning for renal protection during elective open infrarenal abdominal aortic aneurysm repair: randomized controlled trial.

We aimed to determine whether remote ischemic preconditioning (IP) reduces renal damage following elective open infrarenal abdominal aortic aneurysm (AAA) repair. Sequential common iliac clamping was used to induce remote IP in randomized patients. Urinary retinol binding protein (RBP) and albumin-creatinine ratio (ACR) were measured following induction and 3, 24, and 48 hours postoperatively.

Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study.

Background: Abacavir/lamivudine and tenofovir/emtricitabine fixed-dose combinations are commonly used first-line antiretroviral therapies, yet few studies have comprehensively compared their safety profiles.

Methods: Forty-eight-week data are presented from this multicenter, randomized, open-label study comparing the safety profiles of abacavir/lamivudine and tenofovir/emtricitabine, both administered with efavirenz, in HLA-B*5701-negative HIV-1-infected adults.

Results: Three hundred eighty-five subjects were enrolled in the study.

Remote ischemic preconditioning for renal and cardiac protection during endovascular aneurysm repair: a randomized controlled trial.

Purpose: To report a randomized clinical trial designed to determine if remote ischemic preconditioning (IP) has the ability to reduce renal and cardiac damage following endovascular aneurysm repair (EVAR).

Methods: Forty patients (all men; mean age 76+/-7 years) with abdominal aortic aneurysms averaging 6.3+/-0.

Lysosomal enzymuria is a feature of hereditary Fanconi syndrome and is related to elevated CI-mannose-6-P-receptor excretion.

Background: Lysosomal enzymuria is usually considered to be a non-specific marker of renal injury, but little is known about lysosomal enzyme excretion in renal proximal tubular cell disorders such as the renal Fanconi syndrome (FS). We examined excretion of two lysosomal enzymes and the cation-independent mannose-6-phosphate receptor (CI-MPR) in patients with inherited FS.

Methods: The lysosomal enzyme cathepsin D was measured by ELISA and isolated by pepstatin-agarose affinity chromatography; N-acetyl-beta-d-glucosaminidase (NAG) was assayed colorimetrically, as was the cytosolic enzyme lactate dehydrogenase (LDH).

Does N-acetylcysteine prevent contrast-induced nephropathy during endovascular AAA repair? A randomized controlled pilot study.

Purpose: To examine if N-acetylcysteine (NAC) reduces the incidence of contrast nephropathy during endovascular abdominal aortic aneurysm repair (EVAR) as evidenced by changes in markers of renal function.

Methods: Twenty consecutive men (mean age 72 years, range 65-79) undergoing EVAR were randomized to receive standard intravenous fluid hydration or standard fluid hydration and NAC (600 mg BID orally, 4 doses). Venous blood and urine were collected prior to the procedure and for 5 postoperative days and analyzed blindly for serum creatinine, urinary retinol-binding protein (RBP), and albumin/creatinine ratio (ACR).

Signalling through phospholipase C interferes with clathrin-mediated endocytosis.

We investigated if phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P2) hydrolysis by phospholipase C activation through cell surface receptors would interfere with clathrin-mediated endocytosis as recruitment of clathrin assembly proteins is PtdIns(4,5)P2-dependent. In the WKPT renal epithelial cell line, endocytosed insulin and beta2-glycoprotein I (beta2gpI) were observed in separate compartments, although endocytosis of both ligands was clathrin-dependent as demonstrated by expression of the clathrin-binding C-terminal domain of AP180 (AP180-C). The two uptake mechanisms were different as only insulin uptake was reduced when the mu2-subunit of the adaptor complex AP-2 was silenced by RNA interference.

Quantitative amino acid and proteomic analysis: very low excretion of polypeptides >750 Da in normal urine.

Background: Quantitative data on protein and polypeptide excretion in normal urine are lacking. In Fanconi syndrome, failure of proximal tubular protein reabsorption leads to 'tubular' proteinuria, but little is known about peptide excretion.

Methods: Urine from normal (N=5) and Fanconi patients (Dent's disease, N=2; Lowe syndrome, N=3) was fractionated by size-exclusion chromatography into proteins (>10 kD) and smaller polypeptides.

The urinary proteome in Fanconi syndrome implies specificity in the reabsorption of proteins by renal proximal tubule cells.

Polypeptides present in the glomerular filtrate are almost completely reabsorbed in the first segment of the proximal tubule by receptor-mediated endocytosis; in renal Fanconi syndrome (FS), there is failure to reabsorb many of these polypeptides. We have compared the urinary proteomes in patients with Dent's disease (due to a CLC5 mutation), a form of FS, with normal subjects using three different proteomic methods. No differences in the levels of several plasma proteins were detected when standardized to total protein amounts.

Megalin is essential for renal proximal tubule reabsorption and accumulation of transcobalamin-B(12).

Megalin has previously been shown to bind and mediate endocytosis of transcobalamin (TC)-B(12). However, the physiological significance of this has not been established, and other TC-B(12) binding proteins have been suggested to mediate renal uptake of this vitamin complex. The present study demonstrates by the use of megalin-deficient mice that megalin is, in fact, essential for the normal renal reabsorption of TC-vitamin B(12) and for renal accumulation of this highly conserved vitamin.