Relationships among diabetes, microalbuminuria, and ACE inhibition.

Increasing worldwide rates of diabetes mellitus, combined with the significant micro- and macrovascular complications that accompany the disease, point to a heightened need to develop simple, rational strategies to protect against end-organ damage, particularly diabetic nephropathy. Although simple strategies do exist, i.e., early diagnosis of microalbuminuria (MAU) followed by nephroprotective therapy with angiotensin-converting enzyme (ACE) inhibitors, the use of these techniques should be increased. This is especially true for primary care physicians, who will continue to handle the majority of diabetic patients. To combat the underuse of this dual approach, this article reviews a stepwise approach to identifying early MAU so that therapeutic measures can be undertaken before the disorder progresses to diabetic nephropathy and, consequently, to end-stage renal disease in the majority of patients. Once a diagnosis of MAU is made, a variety of trials have demonstrated that ACE inhibitor therapy should be considered the standard therapy to retard worsening albuminuria and subsequent renal disease. ACE inhibitors can retard the progression of microalbuminuria and can lower the percentage of patients who progress to end-stage renal disease and death. Significant data indicate that ACE inhibitors should be used in MAU diabetics regardless of the level of blood pressure. In particular, the ACE inhibitor fosinopril may offer advantages because of its dual route of elimination, thus simplifying dosing in renally impaired patients. The newly developed angiotensin II receptor antagonists should be considered in patients intolerant to ACE inhibitors because of the similar effect on the interruption of the renin-angiotensin system.

Renal and extrarenal use of glutamine in normal and acidotic dogs.

The total body clearance of glutamine in five normal and four acidotic dogs was estimated from the kinetics of disappearance from the blood of 14C-[U]-L-glutamine administered in a central vein as a single bolus. The disappearance curve was analyzed as reflecting a biexponential phenomenon with both a mixing and a metabolism component occurring, respectively, in the extracellular (mixing) and intracellular compartment (metabolism). The apparent total body metabolism of glutamine (total body clearance x arterial concentration) was compared with the renal use of this aminoacid as directly determined by renal A-V differences and blood flow. It was demonstrated that the renal use of glutamine represents between 13% and 25% of the total body use, and was increased by acidosis, which did not change significantly the overall rate of synthesis or use.