Details

Autor(en) / Beteiligte

• Marshall, Sally Margaret

Titel

Albumin Excretion in Diabetes Mellitus

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

1989

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Diabetes mellitus carries a twenty-fold excess mortality for insulin-dependent (IDDM) and two-fold for non-insulin dependent (NIDDM) patients compared with the nondiabetic population. Almost all of this excess is confined to those people who develop persistent proteinuria and is due mainly to cardiovascular and renal disease. In insulin-dependent diabetes, uraemia is common, whilst in non-insulin dependent diabetes, cardiovascular disease accounts for the majority of deaths. Once persistent proteinuria develops, progression of IDDM patients to end-stage renal disease is inevitable. The dip-stick tests classically used to detect proteinuria are insensitive. Sensitive immunoassay techniques have shown that urine from healthy subjects normally contains 20 mg albumin/1. There is thus a large gap between the normal range and pathological proteinuria detected by conventional testing. Diabetic patients may excrete more albumin than normal subjects, but remain dip-stick negative - so called microalbuminuria. Several studies have shown that those IDDM patients with microalbuminuria are the ones who progress to persistent proteinuria, whilst in noninsulin-dependent diabetes, similar levels of albumin excretion are predictive of early death, mainly from cardiovascular disease. The cut-off point of microalbuminuria predicting increased risk is 30 ug/min in a timed overnight urine collection. The predictive power of microalbuminuria is based on albumin excretion rates measured in timed urine collections, which are impractical and open to many sources of error. Measurement of albumin concentration on an aliquot of overnight urine had poor sensitivity and specificity in identifying those patients with AER 30-150 ug/min. However, correction for creatinine excretion improved the value of the test considerably. Thus, an albumin:rcreatinine ratio >3.5 had a sensitivity of 98% and specificity of 69% in predicting AER 30-150 ug/min. Measurement of albumin:creatinine ratio in an aliquot of the first morning urine may thus be an acceptable screening test for microalbuminuria. It is likely that the detection and monitoring of abnormal albumin excretion will become routine in the diabetic clinic. Microbumintest is a commercial reagent tablet which the manufacturers claim will detect albumin concentrations >40 ug/ml. Evaluation of the tablet by 1 operator using 106 urine samples [albumin concentration 34. 5(1.5-149) ug/ml; mean (range)] revealed a sensitivity of 84% and specificity 80%. Eight operators tested 24 urine samples twice. There was a large intra- and interoperator variability. This variability, plus the low sensitivity and specificity, make Microbumintest unsuitable for routine use. The hallmark of diabetic nephropathy is the accumulation of abnormal mucopolysaccharide material in the mesangium and basement membrane. The mucolytic agent bromhexine decreases glomerular volume in experimental diabetes and also decreases the urinary excretion of mucopolysaccharides in IDDM. In a randomised, double-blind, placebo-controlled trial, bromhexine 72 mg daily had no effect on albumin excretion in IDDM patients with normoalbuminuria, microalbuminuria and persistent proteinuria. Growth factors may be involved in diabetic renal hypertrophy. The role of epidermal growth factor (hEGF) has been examined. Albumin and hEGF excretion were measured in 19 healthy adults with normal albumin excretion and 55 diabetic subjects with AER 1.4-879 ug/min. The hEGF:creatinine ratio was decreased in the diabetic subjects with abnormal albumin excretion. There was a significant correlation between hEGF:creatinine and AER (r=-0.49, p=0.02). Thus abnormal albumin excretion is common in diabetes and reflects widespread vascular disease. Identification of patients with abnormal excretion by frequent testing over many years, coupled to aggressive management of the associated abnormalities, may lead to diminution of the excess mortality carried by these patients. (Abstract shortened by ProQuest.)