The effect of bromhexine on albumin excretion in insulin dependent diabetes.

The effect of the mucolytic agent bromhexine, 72 mg daily for one month, on albumin excretion in insulin dependent diabetes was investigated in a double-blind, randomised, cross-over, placebo-controlled study. Nine patients with normal albumin excretion [overnight albumin excretion rate 3.2 (2.1-8.8) micrograms/min.; mean (range)], six with microalbuminuria [36 (22-95) micrograms/min.] and six with macroalbuminuria [321 (201-1215) micrograms/min.] participated. Albumin excretion was similar after treatment with bromhexine and placebo in all 3 groups [normoalbuminurics 3.6 (1.7-13.5) versus 3.3 (1.9-13.2) micrograms/min.; microalbuminurics 40 (20-128) versus 37 (20-103); macroalbuminurics 396 (247-2160) versus 443 (292-2592)]. Excretion of beta 2-microglobulin and creatinine clearance were identical at the end of each treatment. Blood glucose control and blood pressure remained constant throughout the study in the 3 groups. We conclude that bromhexine 72 mg daily for 1 month had no effect on albumin excretion in IDDM patients with normal and pathological albuminuria.

The effect of bromhexine on experimentally induced diabetic nephropathy.

Diabetes was induced in male Wistar rats by a single i.v. injection of streptozotocin (40 mg/kg). Animals were treated with bromhexine at 2 dose levels (2.5 mg/kg/day and 25 mg/kg/day) for 13 months thereafter and compared to non-diabetic controls and untreated diabetic animals. Renal pathology showed a significant increase in glomerular volume and basement membrane thickening in untreated diabetic animals. The higher dose bromhexine treated diabetic animals showed a significant decrease in glomerular volume as compared with diabetic animals not given bromhexine.

Carbohydrate-containing materials in urine from normal and diabetic subjects.

1. Abnormalities in glycoprotein metabolism are believed to play a role in diabetic microangiopathy. We have therefore measured the urinary excretion of carbohydrate-containing materials in normal and diabetic subjects. 2. Diabetic subjects were found to excrete excessive quantities of such material, which may parallel the increases observed in plasma and structural glycoproteins found in previous studies. 3. Systemic administration of a synthetic derivative of vasicine, which is known to affect mucus glycoprotein, was shown to restore these elevated urinary concentrations seen in diabetic subjects to values close to normal, but his drug had no significant effect on urinary concentrations of such materials in normal subjects.

Pharmacological mechanisms of analgesic nephropathy.

The situation in the experimental field is unresolved; too many factors require clarification before the critical experiment can be conducted to settle the matter once and for all. However, as there is now plentiful evidence to convince any reasonable physician that commonly available analgesics, when abused, carry a significant health risk, one may resonably ask whether any further experimental evidence is needed? The object of this review is in no sense divisive, i.e., by pointing out discrepancies in the available data to thereby cloud the issue rather than resolve them. The problem of abuse lies properly in the field of public health education, and the first step to this would surely be an appropriate worning on the packaging of all commonly used analgesics. For future research, however, government health authorities should be guided in their preclinical testing requirements for mild antiinflammatory analgesics, and enough is now known to draw up guidelines for good laboratory practice in this field.