Albumin concentration in the Bowman's capsule: Multiphoton microscopy vs micropuncture technique

Abstract

To the Editor: In their recent report, Russo et al.1.Russo L.M. Sandoval R.M. McKee M. et al.The normal kidney filters nephrotic levels of albumin retrieved by proximal tubule cells: retrieval is disrupted in nephrotic states.Kidney Int. 2007; 71: 504-513Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar measured glomerular albumin filtration in the rat using multiphoton microscopy. They estimated that, under normal condition, albumin filtration is more that 50 times greater than that previously reported with a calculated albumin sieving coefficient (glomerular sieving coefficient) of 0.02–0.04. Assuming that normal plasma albumin concentration in glomerular capillaries is 3.0–3.5 g/dl, one can calculate an expected albumin concentration in the Bowman's capsule in the range of 600–1400 μg/ml. As pointed out also in the commentary of Gekle,2.Gekle M. Renal albumin handling: a look at the dark side of the filter.Kidney Int. 2007; 71: 479-481Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar these values are in great contrast to those previously reported in the literature and obtained by micropuncture technique. Owing to technical difficulties, there are only a few sets of data on albumin ultrafiltrate concentration in the literature, and among them the most careful evaluation is considered that of Tojo and Endou.3.Tojo A. Endou H. Intrarenal handling of proteins in rats using fractional micropuncture technique.Am J Physiol. 1992; 263: F601-F606PubMed Google Scholar Using a sophisticated double pipette technique, they estimated a mean value of Bowman's capsule albumin concentration of 23 μg/ml, and a corresponding glomerular sieving coefficient of 0.00062. Recently, Lazzara and Deen4.Lazzara M.J. Deen W.M. Model of albumin reabsorption in the proximal tubule.Am J Physiol Renal Physiol. 2007; 292: F430-F439Crossref PubMed Scopus (56) Google Scholar reviewed available evidence for glomerular permselective function and concluded that albumin concentration in glomerular ultrafiltrate in normal condition must range from 20 to 30 μg/ml. Thus, the debate on the effective amount of glomerular albumin filtration is still open.2.Gekle M. Renal albumin handling: a look at the dark side of the filter.Kidney Int. 2007; 71: 479-481Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar This is an important issue, since the filtered proteins across the glomerular membrane are involved in the mechanisms leading to kidney disease progression.5.Remuzzi G. Benigni A. Remuzzi A. Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes.J Clin Invest. 2006; 116: 288-296Crossref PubMed Scopus (484) Google Scholar In addition, the beneficial effect of angiotensin antagonism in proteinuric renal diseases is linked to amelioration of glomerular membrane permselective properties.6.Remuzzi A. Gagliardini E. Sangalli F. et al.ACE inhibition reduces glomerulosclerosis and regenerates glomerular tissue in a model of progressive renal disease.Kidney Int. 2006; 69: 1124-1130Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar In the past, we performed a series of micropuncture experiments in non-proteinuric female MWF rats, with surface glomeruli, to collect ultrafiltrate from the Bowman's capsule (using an oil drop to stop proximal tubule fluid flow). In that occasion, we measured albumin concentration by a sensitive enzyme-linked immunoassay. Although we performed these measurements in only three animals, we believe that they can be of interest in the actual debate on the effective amount of albumin filtration at glomerular level. From a total number of 12 collections of Bowman's capsule fluid, lasting 10 min in average, we calculated a mean albumin filtration of 0.34±0.28 pg/min and a concentration of 10.7±4.9 μg/ml (as shown in Figure 1). Our observation would support the hypothesis of a low albumin concentration in the Bowman's capsule and in the early proximal tubule, in line with previous micropuncture measurements.3.Tojo A. Endou H. Intrarenal handling of proteins in rats using fractional micropuncture technique.Am J Physiol. 1992; 263: F601-F606PubMed Google Scholar In addition, as pointed out in the commentary of Gekle,2.Gekle M. Renal albumin handling: a look at the dark side of the filter.Kidney Int. 2007; 71: 479-481Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar our data would indicate that the observation of Russo et al.1.Russo L.M. Sandoval R.M. McKee M. et al.The normal kidney filters nephrotic levels of albumin retrieved by proximal tubule cells: retrieval is disrupted in nephrotic states.Kidney Int. 2007; 71: 504-513Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar may be affected by technical problems, such as low signal-to-noise ratio of fluorescent albumin in the proximal tubule.