Kidney morphological changes in relation to long-term renal function and metabolic control in adolescents with IDDM

Abstract

For the past 10-15 years all the children at our unit with insulin-dependent diabetes mellitus have been repeatedly followed-up with renal function tests. Renal biopsy, examined by light and electron microscopy, was included in the follow-up of 36 adolescents and young adults, aged 13-25 years, with a disease duration of 7-19 years. All subjects had undergone at least three renal function tests before biopsy and none had persistent microalbuminuria. Renal function was evaluated as glomerular filtration rate and effective renal plasma flow determined by clearances of inulin and para-amino hippuric acid. Glomerular filtration rate and filtration fraction were increased before and at the time of the biopsy. Glomerular basement membrane thickness (331-858 nm) and mesangial matrix volume fraction (7.4-17.1%) were increased. Long-term hyperfiltration and hyperperfusion before biopsy correlated inversely with mean glomerular volume. Increased filtration fraction before the biopsy correlated directly with mean of all HbA1c (r = 0.485, p< 0.01) and both variables correlated directly with mesangial matrix volume fraction, basement membrane thickness and structural index (r = 0.433, p < 0.01 and r = 0.626, p < 0.001, respectively). Urinary albumin excretion rate correlated directly with foot process width (r = 0.645, p < 0.001). By multiple regression analysis the most important variable for the increase in basal membrane thickness was the metabolic control while the mean of previous filtration fraction was most important for the increase in mesangial matrix volume. In conclusion, although none of the patients showed constant microalbuminuria, early diabetic structural changes were evident with basal membrane thickening and increased mesangial matrix volume. The structural changes related to long-standing hyperfiltration and poor metabolic control.

The Early Natural History of Nephropathy in Type 1 Diabetes

“…There was a trend toward a positive correlation with GBM width; a minor, albeit significant, direct relationship with Vv(Int/cortex); and a weak negative association with Vv(MC/glom). Similar findings of a correlation of HbA 1c with GBM width but not with Vv(Mes/glom) or Vv(MM/glom) in young type 1 diabetic patients have been previously described (23,24,27). Much stronger relationships between glycemia and rates of changes in glomerular structure have been reported in adults with microalbuminuria (27,32).…”

“…They are also consistent with findings of Ellis et al (23) that normoalbuminuric subjects, including prepubertal children with average duration of ϳ8 years, often have GBM thickening and mesangial expansion. Berg et al (24) found greater GBM width and Vv(MM/glom) in 36 normoalbuminuric adolescents compared with control subjects, but Vv(Mes/glom) was not increased.…”

Risk of nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis of type 1 diabetes.

“…Other studies of renal biopsies suggest that levels of urine albumin excretion below the cutoff for MA increase concomitantly with histological changes in renal morphology that are compatible with early diabetic renal injury (15,16). These data, together with our study, suggest that the rate of change of the ACR is a biochemical estimate of the rate of renal morphological changes related to diabetic nephropathy.…”

The clinical significance of hyperfiltration in diabetes

“…It was concluded that previous hyperfiltration may add to the prediction of glomerular morphological changes. Another study was performed in 36 predominantly normoalbuminuric patients with type 1 diabetes, who were aged 13 to 25 years and had disease duration of 7 to 19 years [59]. During the first 10 years of diabetes, GFR was significantly higher than that of control participants, with median GFR peaking at 150 ml min −1 1.73 m −2 at 2 years after diagnosis.…”