Impaired tubule function is found in many acquired and hereditary diseases and this is usually not detected by conventional measures of kidney disease, such as glomerular filtration estimated by serum creatinine. Grossly impaired tubule function can be present, and cause clinical problems, even when glomerular filtration is ‘normal’. Until recently clinical measurement of renal tubule function has been difficult.
Assay of Urine Retinol-Binding Protein 4 (uRBP4), now offers the best Biomarker of the function of the proximal renal tubule.
Since plasma RBP4 filtered by the renal glomerulus is almost completely reabsorbed by the proximal tubules, levels in healthy urine are very low (<3 μg/mmol creatinine). Complete failure of this reabsorption increases this excretion 104-105-fold, causing uRBP4 levels of about 10 mg/mmol creatinine. This is likely the largest range of any tubular biomarker.
When the proximal renal tubule fails to reabsorb salts and water as well as filtered proteins such as RBP4 there is a renal ‘Fanconi Syndrome’. However, most uRBP4 elevations due to tubule damage are seen without the salt, water and acid abnormalities. Failure of reabsorption of RBP4 and other filtered plasma proteins is also termed ‘Tubular’ or ‘Low Molecular Weight’ proteinuria. This distinguishes it from the ‘Glomerular Proteinuria’ of much chronic kidney disease.