Glomerular filtration surface in type I diabetes mellitus

Abstract

Previously we have shown that relative glomerular mesangial expansion was an important correlate of renal dysfunction in diabetes. To extend the understanding of structural functional relationships, 37 patients with type I diabetes mellitus for 5 to 33 years were studied with multiple creatinine clearance (Ccr), urinary albumin excretion, and blood pressure measurements, and percutaneous renal biopsies. Glomerular volume and percent sclerosed glomeruli were determined; quantitative stereology was performed to determine relative glomerular structural parameters. Per glomerulus we calculated mesangial volume and capillary filtration surface and per patient we estimated capillary filtration surface. Capillary filtration surface per glomerulus or per patient were highly predictive of Ccr (r = +0.78, r = +0.79, P less than 0.001). There was a significant but weak relationship between Ccr and mesangial volume. However, mesangial volume and glomerular volume together were highly predictive of both Ccr and filtration surface. Mesangial volume was increased and filtration surface decreased in the hypertensive patients and the patients with urinary albumin excretion less than 250 mg/24 hr. Thus, it appears that mesangial expansion within a relatively large glomerulus has less influence on filtration than does a similar increase in mesangial volume within a smaller glomerulus. There is a striking relationship between glomerular filtration rate and filtration surface in diabetes throughout the range from hyperfiltration to significant hypofiltration.

Leucocyte Na+/H+ antiport activity in Type 1 (insulin-dependent) diabetic patients with nephropathy

“…Diabetic subjects who subsequently develop nephropathy have severe mesangial expansion with a progressive decline in glomerular filtration rate as the filtration surface area is gradually reduced [39]. It is uncertain whether the membrane transport defect we have described is a marker for the tendency for mesangial expansion to occur, for only 30% of Type 1 diabetic patients develop nephropathy.…”

Juxtaglomerular apparatus T-cell infiltration affects glomerular structure in Type 1 diabetic patients

“…Regardless of the mechanism(s), the structural changes associated with JGA T-cell infiltration could be protective of the glomerulus. Ultimately, loss of filtration surface as a consequence of mesangial expansion is an important mechanism of GFR loss in diabetic nephropathy [30]. Thus, the increased filtration surface in JGA T-cell positive patients could provide a greater safety margin as mesangial expansion occurs [30].…”

“…Ultimately, loss of filtration surface as a consequence of mesangial expansion is an important mechanism of GFR loss in diabetic nephropathy [30]. Thus, the increased filtration surface in JGA T-cell positive patients could provide a greater safety margin as mesangial expansion occurs [30]. It is possible that this is reflected in the higher AER in the T-cell negative group.…”

“…It is conceivable that T-cell infiltration of the JGA can ultimately lead to reduced JGA endocrine and paracrine function, as is true of parallel phenomena in islet, thyroid and other endocrine tissues in the course of diabetic polyendocrinopathy [26,27,28,29,30], and that this could explain the variability found in response to RAS blockade among Type 1 diabetic patients [33].…”

Are glomerular volume differences between type 1 and type 2 diabetic patients pathologically significant?

“…However, we do not believe this explains the contrasting results. The Minneapolis Group have shown that there is no difference in MGV in normotensive compared with hypertensive type 1 patients [29] and Table 3 (S. M. Mauer, unpublished data). Thus, it is possible that some factor other than blood pressure influences the increase in MGV in the type 2 diabetic patients.…”