Risk markers of future microalbuminuria and hypertension based on clinical and morphological parameters in young type 1 diabetes patients.

BACKGROUND: Nephropathy is a severe complication of type 1 diabetes and develops in 30% of patients. Currently, it is not possible to identify young patients at risk prior to the development of microalbuminuria (MA) and/or hypertension (HT). OBJECTIVE: To study predictors of MA and/or HT in young normoalbuminuric (NA) patients with type 1 diabetes. SUBJECTS AND METHODS: Forty-six NA and normotensive (NT) type 1 diabetes patients, regularly followed since onset with checks on metabolic control, kidney function, and MA, were investigated with kidney biopsies and 24-h ambulatory blood pressure measurements (ABPMs) after 10.6 yr of diabetes. The patients were followed another six and a half years with regard to the development of MA and HT. RESULTS: Fifteen patients developed MA and/or HT during follow-up. The strongest risk markers were poor metabolic control after puberty, high day-time systolic blood pressure (BP), and increased BMT at 10 yr, which explained 62% of the outcome for MA and/or HT at 17 yr duration with 77% sensitivity and 65% specificity. The threshold values were long-term postpubertal HbA(1c) > 8.2%, day-time systolic BP > 130 mmHg, and BMT > 490 nm/1.73 m(2). CONCLUSIONS: Normoalbuminuric and NT patients at risk of developing MA and HT could be identified and might benefit from an early start of antihypertensive therapy and improvement of metabolic control.

The course of diabetic glomerulopathy in patients with type I diabetes: a 6-year follow-up with serial biopsies.

Diabetic nephropathy is a severe complication and few studies have described the early morphological changes over time. Two kidney biopsies were performed, within a 6-year interval, in 29 primarily normoalbuminuric patients, aged 24 years at the second biopsy. These were examined with light and electron microscopy. Glomerular filtration rate, and effective renal plasma flow were determined with inulin and para-aminohippurate clearances. Urinary albumin excretion rate and the 24 ambulatory blood pressure were determined. Ten patients had developed microalbuminuria and/or hypertension; of these, six were treated with antihypertensive medication for 2 years or more. Significant increases were found in night time diastolic blood pressure and decreases in systolic and diastolic dipping. The glomerular volume, mesangial volume, mesangial matrix volume fraction and foot process width increased significantly. The group that was treated later for complications had the worst long-term metabolic control, thicker basement membranes and larger mesangial matrix and volume at the first biopsy, than the persistent normoalbuminuric group. During the follow-up, the untreated group with complications and the persistent normoalbuminuric group showed an increase in morphological parameters, whereas no progression occurred in the treated patients who also improved their metabolic control. In conclusion, the morphological parameters deteriorated in the normoalbuminuric patients and in those with complications, but were unchanged in the small antihypertensive-treated group with improved metabolic control.

Ambulatory blood pressure and heart rate in relation to kidney structure and metabolic control in adolescents with Type I diabetes.

AIMS/HYPOTHESIS: To evaluate the relationship between metabolic control, kidney function, ambulatory blood pressure and renal morphology in normoalbuminuric adolescents with Type I (insulin-dependent) diabetes mellitus. METHODS: Metabolic control, clearance of inulin and para-amino hippuric acid, 24 h ambulatory blood pressure and renal biopsies were studied in 41 patients who were 17.8 +/- 0.5 (SEM) years of age and 10.7 +/- 0.5 years after onset of diabetes. RESULTS: Glomerular filtration rate and filtration fraction were higher in diabetic patients than in healthy control subjects. At least one third of the patients had systolic and nocturnal diastolic blood pressures above the 90th centile. Basement membrane thickness was 512 +/- 17 nm, volume fraction of mesangial matrix 10.7 +/- 0.3% and foot process width 415 +/- 6 nm. Nocturnal mean arterial blood pressure, adjusted for body height and gender, correlated directly to the basement membrane thickness, the volume fraction of mesangial matrix and the foot process width. Multiple regression analysis showed that HbA1c, nocturnal heart rate and body height account for 44% of the variations in blood pressure. HbA1c, nocturnal heart rate and body height explained 57% of the variation in basal membrane thickness, and HbA1c, nocturnal heart rate and duration of diabetes explained 43% of Vv(matrix/glom). Actual renal function or urinary albumin excretion rate had no effect. CONCLUSION/INTERPRETATION: Nocturnal heart rate and nocturnal blood pressure, especially the mean arterial blood pressure, seem to be related to glomerulopathy changes in patients in whom persistent microalbuminuria has not yet developed. These findings suggest that a disturbance in sympathovagal balance could have a pathogenic effect.

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

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.