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 effects of candesartan on diabetes glomerulopathy: a double-blind, placebo-controlled trial.

Our objective was to study the effects of candesartan on diabetic glomerulopathy in young normoalbuminuric and normotensive patients with type 1 diabetes in a double-blind, placebo-controlled trial. In 13 patients aged 24 years at baseline, we evaluated blood pressure, kidney biopsies and kidney function tests at baseline and after 5 years of treatment. Kidney biopsies were examined with light and electron microscopy, glomerular filtration rate and effective renal plasma flow determined with inulin and para-aminohippuric acid clearances. Two patients in the placebo group needed antihypertensive treatment because they developed microalbuminuria and/or hypertension, but no patient in the candesartan group did. A significant reduction in mesangial matrix volume and mesangial volume occurred in the candesartan group, although changes in morphological parameters were similar between groups. Office blood pressure was significantly lower in the candesartan group at follow-up than in the placebo group. Deterioration in morphological parameters observed in earlier studies of our patients did not become worse during treatment with candesartan or placebo. The effects of candesartan, with reduction in morphological parameters and lowering of blood pressure, might influence future treatment of glomerulopathy in type 1 diabetes patients.

Presence and specificity of tumor associated lymphocytes from ascites fluid in prostate cancer.

BACKGROUND: In the present study, we had the rare opportunity to study immunological responses of TAL from ascites fluid in a patient with hormone-refractory prostate cancer. METHODS: We evaluated tumor antigen-specific T-cell responses, induced by either prostate specific antigen (PSA) pulsed dendritic cells (DCs) or PSA peptides, in TAL and peripheral blood lymphocytes. RESULTS: DC stimulation with PSA protein induced recognition of naturally processed PSA epitopes by both blood and ascites T cells. In contrast, only ascites T cells recognized the PSA-3 peptide, after stimulation with PSA-pulsed DCs or peptides. Finally, although IFNgamma secreting T cells were detectable in both blood and ascites by ELISPOT, multiplex cytokine assay detected the presence of predominantly Th2 cytokines. CONCLUSIONS: Although tumor antigen-specific TAL were detected in ascites fluid, these cells were producing immunosuppressive cytokines which may contribute to tumor escape from recognition and/or destruction by the immune system.

Nondipping and its relation to glomerulopathy and hyperfiltration in adolescents with type 1 diabetes.

OBJECTIVE: To determine whether there is a relation between dipping/nondipping status and end-organ damage (measured as renal glomerulopathy) and long-term renal function in order to predict the development of nephropathy in normoalbuminuric patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Analysis of renal biopsy and ambulatory blood pressure measurements was done in relation to renal function tests performed during a 10-year period. Forty unselected patients (16 girls), with a mean age of 17.7 years and a mean duration of 10.7 years, were studied. The renal biopsies were examined by electron microscopy. Ambulatory blood pressure was monitored (Space Labs 90 207). Systolic nondippers were defined as a <7%, diastolic nondippers as a <14%, and mean arterial blood pressure (MAP) nondippers as a <12% fall in blood pressure during the night. Renal function was evaluated every other year by clearances of inulin (glomerular filtration rate [GFR]) and para-amino hippurate (effective renal plasma flow [ERPF]), and filtration fraction (GFR/ERPF) was calculated. Overnight urinary albumin excretion rate and long-term mean HbA(1c) were measured. RESULTS: MAP (27% of the patients) and diastolic nondippers (12%) had a significantly thicker basement membrane; larger mesangial matrix volume fraction; and higher long-term GFR, nighttime heart rate, and mean HbA(1c) than dippers. CONCLUSIONS: Nondipping status was related to more renal morphological changes and long-term hyperfiltration in normoalbuminuric adolescents and young adults, despite a short duration of type 1 diabetes. Nondipping status may be an early predictor of later nephropathy.