Remission and regression in the nephropathy of type 1 diabetes when blood pressure is controlled aggressively.
BACKGROUND
Diabetic nephropathy is a chronic, progressive kidney disease with a mean rate of decline of in glomerular filtration rate (GFR) of 10 to 12 mL/min/year (natural history). The introduction of aggressive antihypertensive treatment has improved the renal prognosis during the last decades. To examine whether remission and regression of diabetic nephropathy are possible in type 1 diabetic patients, we analyzed data from a prospective observational cohort study that was started in 1983.


METHODS
We measured GFR with a 51Cr-EDTA plasma clearance technique every year for seven years (range 3 to 14 years) in 301 consecutive type 1 diabetic patients with diabetic nephropathy. Diabetic nephropathy was diagnosed clinically if the following criteria were fulfilled: persistent albuminuria> 200 microg/min, presence of diabetic retinopathy, and no evidence of other kidney or renal tract disease. Blood pressure, albuminuria, glycosylated hemoglobin A1c, and serum cholesterol were measured every three to four months during the study. In total, 271 patients received antihypertensive treatment, 179 patients predominantly with angiotensin-converting enzyme inhibitors. Remission was defined as albuminuria <200 microg/min sustained for at least one year and a decrease of at least 30% from preremission levels (surrogate endpoint), and regression as a rate of decline in GFR (DeltaGFR) equal to the natural aging process: < or =1 mL/min/year during the entire observation period (principal end point).


RESULTS
The total number of patients who obtained remission was 92 (31%), with a duration of remission of [median (range)] 3.4 (1.0 to 14.1) years, and regression 67 (22%). The patients were stratified in quintiles by the average value of office mean arterial blood pressure (mean +/- SE): 93 +/- 0.5, 99 +/- 0.2, 103 +/- 0.1, 107 +/- 0.2, and 113 +/- 0.4 mm Hg. The prevalence of patients obtaining remission/regression was 58/42, 33/32, 25/11, 20/20, and 17/7% in each quintile, respectively. Spontaneous remission and regression occurred in 10 and 14 patients from the persistent normotensive group (N = 30), none of whom had ever received antihypertensive treatment. In all 301 consecutive patients, the (mean +/- SE) DeltaGFR was 4.0 +/- 0.2 mL/min/year during the investigation period.


CONCLUSIONS
Our study suggests that aggressive antihypertensive treatment in type 1 diabetic patients can induce remission and regression in a sizable fraction of patients with diabetic nephropathy. Lower arterial blood pressure, reduced albuminuria, and better glycemic control were predictors of regression of diabetic nephropathy.
Hovind
P
P
Steno Diabetes Center, Gentofte, Denmark. phovind@dadlnet.dk
Rossing
P
P
Tarnow
L
L
Smidt
U M
UM
Parving
H H
HH
D000328:Adult; D000419:Albuminuria / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D012075:Remission, Spontaneous
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents