Extraglomerular Changes

In advanced stages of nephropathy several structural compartments in the kidney display distinct abnormalities. The hyalinosis of efferent and afferent arterioles was described a long time ago. Increase in the interstitial tissue has in fact been incriminated as a very important determinant of the late fall in renal function [16]. Some information on these structures during earlier phases of nephropathy has been obtained in recent years.

Semi-quantitative studies of the hyalinosis of arterioles have dealt with a very broad clinical range. The results showed that the score of arteriolar lesions correlated with the severity of glomerulopathy and interstitial expansion and also with renal function [17]. Clearly in this composite picture with affection of all compartments it is not possible to determine which is the most important in terms of the further progression of nephropathy, in particular since abnormalities in one compartment may be very closely and causally related to that in others.

In quantitative ultrastructural studies the composition of arteriolar walls was estimated in NA and MA IDDM patients and in controls [18]. All of the patients had clinical blood pressure within the normal range. Increased matrix per media was found in afferent and efferent arterioles in the MA patients, showing that matrix abnormalities have developed in this location at the earliest stage of nephropathy. The matrix/media volume fraction of the afferent arterioles correlated with glomerular parameters, both BMT and matrix/glomerular volume fraction. Quantitative data are now available in one follow-up study, before and after antihypertensive treatment [19]. At baseline highly significant alterations were present in afferent and efferent arterioles. In the follow-up period of 2,5 years a moderate progression was observed in matrix/media volume fraction in afferent arterioles, but no significant worsening in the efferent arterioles. After 8 years a large increase in the matrix/media volume fraction both in the afferent and the efferent arterioles (p<0.001) and a decline in the endothelial cell thickness was found. The arteriolar parameters correlated with AER and inversely with GFR [20].

Another structural change has recently been demonstrated in young Type 1 patients with MA. The volume of the juxta-glomerular apparatus is increased compared with that in non-diabetic controls. Furthermore, also the size expressed relative to glomerular volume, is increased. The interrelationship with functional variables, whether causative or consequent, is not known at the present time [21]. However, after a follow-up of 8 years the JGA-size remained stable, but decreased relative to the glomerular size [22]. The connection between the changes in the afferent and the efferent arterioles, the JGA and possibly the RAS-system, may explain the haemodynamic changes found in early nephropathy [14].

Interstitial expansion is a companion of advanced glomerulopathy and vasculopathy. The interstitium expressed as fraction of cortical space has been shown to correlate with AER and creatinine clearance, as well as with glomerular and arteriolar changes, considering a wide range of functional impairment [17]. We estimated the interstitial volume fraction in the MA patients with low grade albuminuria, and found that it was increased compared to controls already in this early phase [6]. A positive correlation with the degree of glomerulopathy was found, indicating parallel or maybe even interactive processes.

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