Effect of Diabetes on Renal Medullary Oxygenation During Water Diuresis FRANKLIN H. EPSTEIN, MD 1 ARISTIDIS VEVES, MD 1 POTTUMARTHI V. PRASAD, PHD 2 OBJECTIVE — To study the effect of water diuresis on renal medullary and cortical oxygen- ation in patients with diabetes using blood oxygenation level– dependent magnetic resonance imaging (BOLD MRI). RESEARCH DESIGN AND METHODS — Nine mild diabetic subjects (48  2.7 years of age, six women) and nine nondiabetic subjects of similar age and sex, all without known vascular or renal disease, were studied noninvasively by MRI before and during water diuresis. RESULTS — Water diuresis induced an increase in medullary oxygenation in control sub- jects, producing a decrease in R 2 * (apparent spin-spin relaxation time) of 1.89  0.27 (P  0.01), but no significant change in the group of diabetic subjects. CONCLUSIONS — These findings in middle-aged diabetic subjects, which resembled those previously described in elderly subjects 65 years of age, suggest early impairment of adaptive vasodilatation within the renal medulla in diabetes. Diabetes Care 25:575–578, 2002 T he renal medulla of mammalian kid- neys operates in a state of relative hypoxia compared with other or- gans and with the renal cortex because of the counter-current flow of blood through its looped capillaries, which per- mits the excretion of a concentrated urine (1). The state of oxygenation of renal cor- tex and medulla can be assessed noninva- sively in human subjects using blood oxygenation level– dependent magnetic resonance imaging (BOLD MRI). Normal young men and women exhibit a marked increase in renal medullary oxygenation during water diuresis that is demonstra- ble by this technique (2,3). This adaptive change, which probably reflects an in- crease in medullary capillary blood flow, is attenuated with aging and sup- pressed in young subjects by inhibition of cyclooxygenase (3). Medullary hypoxic injury character- izes the phenomenon of acute renal fail- ure (4), and it was therefore of interest to examine the renal medullary response to water diuresis in patients with diabe- tes—a condition thought to predispose to acute renal failure (5,6). In order to avoid the nonspecific effects of renal scarring resulting from obvious diabetic nephrop- athy to the greatest extent, we selected nine patients with adult-onset diabetes without microalbuminuria, hypertension (blood pressure 150/90 mmHg), or re- nal insufficiency and compared them with nine healthy control subjects. The results suggest a defect in adaptive change in renal medullary oxygenation in dia- betic subjects. RESEARCH DESIGN AND METHODS Study plan To compare responses to water diuresis in subjects with and without diabetes, we recruited nine individuals (six women and three men) 36 – 63 years of age (mean age 48  2.7 years),with mild type 2 di- abetes controlled with diet and oral sulfo- nylurea drugs, and nine healthy individuals (six women and three men) without diabetes, 39 –59 years of age (mean age 51  2.2 years). The mean du- ration of diabetes in the diabetic subjects was 6.5 years (median 7  4.75 years, range 0.1–15). The following exclusion criteria were applied to subjects in all groups: smoking any amount of cigarettes during the previous 6 months, cardiovas- cular disease (coronary artery disease, ar- rhythmia, or congestive heart failure), history of stroke or transient ischemic at- tack, peripheral vascular disease (symp- toms of claudication and/or absence of peripheral pulses), chronic renal disease, severe dyslipidemia (triglycerides 600 mg/dl or cholesterol 300 mg/dl), or any other serious chronic disease requir- ing active treatment. Subjects were also excluded if they were on any of the fol- lowing medications: any type of anti- hypertensive, lipid-lowering agent, glucocorticoid, antineoplastic agent, psy- choactive agent, or bronchodilator. In ad- dition, diabetic patients with proliferative retinopathy, peripheral somatic neuropa- thy, and/or insulin or troglitazone therapy were excluded from the study. In all sub- jects, the medical history (aside from dia- betes) was essentially negative, arterial blood pressure was 150/90 mmHg, a complete blood count and urinalysis was normal, and the serum creatinine concen- tration was 1.2 mg per 100 ml. The ex- cretion of microalbumin was 200/g per gram of creatinine in all subjects, and the groups were not significantly different from each other in height or weight. The study was approved by the Committee on ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● From the 1 Department of Medicine, Beth Israel Deaconess Medical Center, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts; and the 2 Department of Radiology, Beth Israel Deaconess Medical Center, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts. Address correspondence and reprint requests to Dr. F. H. Epstein, Beth Israel Deaconess Medical Center East, 330 Brookline Ave., Dana 517, Boston, MA 02215. E-mail: fepstein@caregroup.harvard.edu. Received for publication 21 May 2001 and accepted in revised form 4 September 2001. Abbreviations: BOLD, blood oxygenation level dependent; MRI, magnetic resonance imaging; NO, nitric oxide; PGE 2 , prostaglandin E 2 . A table elsewhere in this issue shows conventional and Syste `me International (SI) units and conversion factors for many substances. Pathophysiology/Complications O R I G I N A L A R T I C L E DIABETES CARE, VOLUME 25, NUMBER 3, MARCH 2002 575