Gas chromatographic and gas chromatographic—mass spectrometric analysis of organic acids in plasma of patients with chronic renal failure

We have developed a high-performance liquid chromatography (HPLC) method for assay of hippurate in plasma of patients with renal failure. Hippurate accounts, in part, for the impaired binding of drugs and metabolites to albumin and may cause other disorders in azotemic patients. The method is precise, accurate and reproducible. Among 25 patients with acute and chronic renal failure having serum creatinine in the range of 2.9–43 mg/dl (256–3,801 μmol/l), plasma hippurate ranged from 0.11 to 16.2 mg/dl (6.1–904 μmol/l). Hippurate concentration correlated moderately closely with plasma creatinine, urea and anion gap. Its curvilinear relation to the reciprocal of serum creatinine indicated a proportional decline of GFR and tubular function or the accumulation of inhibitors of the proximal tubular anion secretory pathway. The method should be useful for further studies of abnormal albumin binding as well as other disorders in azotemic patients.

Section: Discussionsupporting

confidence: 93%

Plasma Hippurate in Renal Failure: High-Performance Liquid Chromatography Method and Clinical Application

Igarashi

Gulyassy

Stanfel

et al. 1987

“…To understand kidney failure in order to treat it more effectively, it is important to know whether such a substance is a uraemic toxin responsible for any of the clinical features of the uraemic syndrome. There are many hundreds, possibly thousands, of organic acids present in increased plasma concentrations in urae mia [2], and work has focused on those with known or postulated physiological effects present at substantially elevated levels [3], K A R f F R © 1996 S. Karger AG, Basel C l \ 0028-2766/96/0732-0169$ 10.00/0 E-Mail karger(itfkanscr.ch Fax + 41 61 306 12 34 Much of the clinical morbidity of the uraemic syn drome is the result of neurological abnormalities [4], and substances which contribute to these features are of par ticular importance. Organic acids, for example hippuric acid and indoxyl-3-sulphate, have been studied as poten tial uraemic toxins, but the plasma protein binding of these acids is insufficient to prevent substantial removal by haemodialysis [5,6], The furan dicarboxylic acid 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (5-pro pyl FPA; fig.…”

Section: Introductionmentioning

confidence: 99%

“…Organic acids, for example hippuric acid and indoxyl-3-sulphate, have been studied as poten tial uraemic toxins, but the plasma protein binding of these acids is insufficient to prevent substantial removal by haemodialysis [5,6], The furan dicarboxylic acid 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (5-pro pyl FPA; fig. 1) accumulates in uraemic plasma [2] and is not removed by haemodialysis [6,[7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Hypothesis: Is Accumulation of a Furan Dicarboxylic Acid (3-Carboxy-4-Methyl-5-Propyl-2-Furanpropanoic Acid) Related to the Neurological Abnormalities in Patients with Renal Failure?

Ca²,

We³

1996

The plasma concentrations of a lipophilic furan dicarboxylic acid (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid; 5-propyl FPA), which is highly bound to albumin and not removed by haemodialysis, have been measured in patients with renal impairment who were not dialysis dependent or who were treated by either haemodialysis or peritoneal dialysis. Neurological abnormalities were assessed as absent, moderate, or severe. A relationship was observed between the increasing severity of abnormalities attributable to the uraemic state and the higher plasma concentrations of 5-propyl FPA. There are theoretical grounds for believing that 5-propyl FPA contributes to these neurological abnormalities because of its structure and also because it inhibits the transport of organic acids in the kidney and could do likewise at the blood-brain barrier.

“…The serum levels of CMPF have been quantified by gas chromatography/mass spectrometry [5] and high-perfor mance liquid chromatography (HPLC) [1.3. 6.…”

mentioning

confidence: 99%

Reduced Renal Clearance of Furancarboxylic Acid, a Major Albumin-Bound Organic Acid, in Undialyzed Uremic Patients

Sato¹,

Koyama²,

Miyazaki³

et al. 1996

3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) is accumulated in uremic serum as a major albumin-bound organic acid. We determined both serum and urine levels of total CMPF to calculate renal clearance of CMPF in healthy subjects and undialyzed uremic patients. Urinary excretion of CMPF and renal clearance were significantly decreased in the uremic patients. The relative clearance ratios of CMPF to creatinine were as low as 0.43% in healthy subjects and 0.45% in uremic patients, indicating that only the protein-unbound, free form of serum CMPF (about 0.4%) is ultrafiltrated in the glomeruli and then excreted into urine. In conclusion, CMPF is accumulated in uremic serum as a consequence of its reduced renal clearance. Urinary excretion of CMPF may be explained only by glomerular filtration of free CMPF in the blood.