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Leptin, the gene product of the ob gene, is important in the control of appetite in rodents and may have an important role in humans. The clearance of leptin from the circulation is unknown. As the leptin receptor is present in the kidney, we evaluated the role of the kidney in removing circulating leptin in humans. We measured leptin in aortic and renal vein plasma in 8 patients with intact renal function and 6 patients with impaired renal function who were undergoing elective cardiac catheterization. Renal blood flow was measured in all patients to calculate net mass balance across the kidney. In patients with intact renal function there is net renal uptake of 12% of circulating leptin, whereas in patients with renal insufficiency there is no renal uptake of leptin. In a separate cohort of 36 patients with end-stage renal failure on hemodialysis, peripheral leptin levels factored for body mass index was increased by > fourfold as compared to a group of healthy controls (N = 338). In addition, plasma leptin is not cleared by hemodialysis with a modified cellulose membrane. Additional studies are required to evaluate the role of leptin in mediating the anorexia of uremia.

The present study was designed to test whether altered renovascular reactivity is associated with the increased risk of radio-contrast nephropathy (RCN) in diabetics. We studied 50 patients (24 diabetics, 26 nondiabetics) with chronic renal insufficiency undergoing cardiac catheterization. Patients were randomized to receive either saline, or one of three renal vasodilator/diuretic drugs--dopamine, atrial natriuretic peptide (ANP), or mannitol--by intravenous infusion during cardiac catheterization. Renal blood flow (RBF) was measured by thermodilution at various time points during cardiac catheterization. RCN was defined as an increase in PCr of at least 25% over baseline within 48 hours of cardiac catheterization. Baseline PCr and creatinine clearance were similar in diabetics and nondiabetics (2.6 +/- 0.2 mg/dl vs. 2.4 +/- 0.1 mg/dl, and 32 +/- 3 ml/min vs. 34 +/- 3 ml/min, respectively), but baseline RBF was significantly lower in diabetics (154 +/- 21 ml/min/kidney vs. 277 +/- 36 ml/min/kidney, P < 0.05). Diabetic patients exposed to the three vasodilator/diuretic drugs had the greatest increase in RBF throughout cardiac catheterization. The incidence of RCN among the diabetics receiving those drugs was 83%, 83% and 75%, in the dopamine, ANP and mannitol groups, respectively. In contrast, among the nondiabetics in each of those groups the incidence of RCN was zero (all P < 0.05, diabetics vs. nondiabetics). In the saline control group the rates of RCN in the diabetics and nondiabetics were 43% and 38%, respectively (NS). In conclusion, the increased risk of RCN among diabetics was associated with exaggerated renovascular reactivity: baseline vasoconstriction and enhanced vasodilation with vasodilator/diuretic drugs. These same drugs, however, reduced the risk of RCN in nondiabetic patients.

Radiocontrast-induced nephropathy (RCIN) is a common cause of acute renal failure in hospitalized patients. Renal vasoconstriction figures prominently in the proposed pathogenesis of RCIN based on animal experiments. Prior human studies examining renal hemodynamic changes after contrast medium (CM) injection are inconclusive. No previous study of animals or humans has established a relationship between CM-associated renal hemodynamic changes and the subsequent development of RCIN. In the present study, we examined the renal hemodynamic effects of CM in patients at high risk of RCIN. In addition, we related those effects to the subsequent development of RCIN. Using renal vein thermodilution catheters, we measured renal blood flow (RBF) in 12 patients with chronic renal failure [serum creatinine (SCr) greater than or equal to 159 mumol/liter] during ionic CM injection for cardiac catheterization. We made measurements at the start of the procedure (t = 0), before the ventriculogram (t = 5), after the ventriculogram (t = 15), and after the coronary angiogram (t = 65). We measured SCr at t = 0 and again 24 and 48 hours later. Mean RBF for the group tended to increase after the ventriculogram, and increased significantly by t = 65 (P less than 0.005 vs. t = 0). When examined by individual patient, RBF fell below baseline in three patients (30%) at t = 15, but rose above baseline again by t = 65. Only one patient (8.3%) had a fall in RBF below baseline at t = 65. RCIN (defined as an increase in SCr greater than or equal to 25% above baseline) developed in six patients (50%) within 48 hours.(ABSTRACT TRUNCATED AT 250 WORDS)