Lysine transport in human kidney.

Area of Science:

• Nephrology
• Human Genetics
• Molecular Biology

Background:

• Hereditary disorders of membrane transport can affect amino acid reabsorption in the kidneys.
• Persistent hyperlysinemia with hyperlysinuria indicates an unusual inborn error of amino acid transport.

Purpose of the Study:

• To characterize the renal tubular transport of lysine in a patient with hyperlysinuria.
• To elucidate the kinetic properties of lysine transport systems in the human kidney.

Main Methods:

• Oral lysine loading test (300 mg/kg) in the patient and controls.
• Measurement of plasma and urine concentrations of dibasic amino acids (lysine, arginine, ornithine) and cystine.
• Kinetic analysis of renal transport systems.

Main Results:

• The patient exhibited significantly elevated basal urinary excretion of lysine and other dibasic amino acids.
• Two distinct lysine renal tubular transport systems were identified: a high-affinity system (impaired in the patient) and a low-affinity system (reduced capacity in the patient).
• The patient's high-affinity transport system showed reduced affinity for lysine and impaired transport of other dibasic amino acids, while the low-affinity system had significantly lower capacity for lysine.

Conclusions:

• Human renal tubular lysine transport involves at least two kinetically distinct systems.
• The patient's condition represents a novel defect in the high-affinity transport system for dibasic amino acids, particularly affecting lysine.
• This case underscores the clinical heterogeneity of inherited membrane transport disorders affecting amino acids.