Effects of short-term glycemic control, low protein diet and administration of enalapril on renal hemodynamics and protein permselectivity in type 2 diabetic patients with microalbuminuria

Tohoku J Exp Med. 1999 Oct;189(2):117-33. doi: 10.1620/tjem.189.117.


To determine whether each of glycemic control (GC), low protein diet (LPD) or administration of angiotensin converting enzyme inhibitor (ACEI) has beneficial effects on diabetic nephropathy through the different mechanisms, changes in charge and size selectivity of glomerulus and renal hemodynamics were analyzed in microalbuminuric type 2 diabetic patients after additive combination therapy (first period: GC only, second period: GC-LPD, third period: GC+LPD+ACEI). To detect improvement of the impairments of glomerular charge selectivity and size selectivity, changes in the ratio of the renal clearance of two plasma proteins with similar molecular radii and different isoelectric points (pIs) (ceruloplasmin and IgG: CRL/IgG) and changes in the ratio of the renal clearance of two plasma proteins with similar pIs and different molecular radii (alpha2-macroglobulin and albumin: alpha2/Alb) were examined before and after each therapy. Creatinine clearance decreased significantly in the first and third periods although slight but not significant decrease was detected in the second period. Filtration fraction was significantly decreased only in the third period. Although renal clearances of Alb, IgG and CRL were decreased in periods of all three therapies, that of alpha2-macroglobulin with a large molecular radius was decreased significantly only after the third therapy. Neither CRL/IgG nor alpha2/Alb changed during these three therapies. These findings suggest that each of three short-term therapies consisting of GC, GC+LPD and GC+LPD+ACEI, reduced proteinuria in microalbuminuric type 2 diabetic patients not through the improvement of renal size and charge selectivities, but through improvement of renal hemodynamics.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Albuminuria / diet therapy
  • Albuminuria / drug therapy
  • Albuminuria / etiology
  • Albuminuria / therapy*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Blood Glucose / analysis*
  • Ceruloplasmin / analysis
  • Ceruloplasmin / chemistry
  • Combined Modality Therapy
  • Comorbidity
  • Creatinine / blood
  • Diabetes Mellitus, Type 2 / diet therapy
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetes Mellitus, Type 2 / therapy*
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / diet therapy
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / therapy*
  • Diet, Protein-Restricted*
  • Enalapril / pharmacology
  • Enalapril / therapeutic use*
  • Female
  • Humans
  • Hypertension / complications
  • Hypoglycemic Agents / therapeutic use
  • Immunoglobulin G / blood
  • Immunoglobulin G / chemistry
  • Insulin / therapeutic use
  • Kidney Glomerulus / drug effects
  • Lipids / blood
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Renal Circulation / drug effects*
  • Serum Albumin / analysis
  • Serum Albumin / chemistry
  • Sulfonylurea Compounds / therapeutic use
  • Treatment Outcome
  • alpha-Macroglobulins / analysis
  • alpha-Macroglobulins / chemistry


  • Angiotensin-Converting Enzyme Inhibitors
  • Blood Glucose
  • Hypoglycemic Agents
  • Immunoglobulin G
  • Insulin
  • Lipids
  • Serum Albumin
  • Sulfonylurea Compounds
  • alpha-Macroglobulins
  • Enalapril
  • Creatinine
  • Ceruloplasmin