Nabumetone, a newer non-steroidal anti-inflammatory drug (NSAID) which preferentially blocks cyclo-oxygenase-2 activity, may be less nephrotoxic than indomethacin. This study tested whether nabumetone has effects different from those of indomethacin on exercise-induced changes in renal function and the renin–aldosterone system. In a randomized fashion, ten subjects were studied after indomethacin (100 mg), nabumetone (1 g) or no medication (control) administered orally at 22.00 hours on the day before each study day, and again at 8.00 hours upon arrival at the laboratory. Renal function was studied at baseline, during graded 20-min exercise sessions at 25%, 50% and 75% of the maximal oxygen uptake rate, and subsequently during two 1-h recovery periods. Heart rate, arterial blood pressure, cardiac output and plasma catecholamines at rest and during exercise were not altered by indomethacin or nabumetone. Indomethacin decreased urinary rates of excretion of 6-oxo-prostaglandin F 1α (6-oxo-PGF 1α ) and thromboxane B 2 in all study periods. Nabumetone decreased 6-oxo-PGF 1α excretion during and after exercise. Excretion rates for PGE 2 did not change. Neither indomethacin nor nabumetone changed baseline values or exercise-induced decreases in renal plasma flow or glomerular filtration rate. Indomethacin, but not nabumetone, decreased sodium excretion, urine flow rate and free water clearance. The renal response to exercise, however, remained unchanged. In contrast with nabumatone, indomethacin decreased the plasma renin concentration. Thus, during exercise, nabumetone may decrease the excretion of 6-oxo-PGF 1α by inhibition of cyclo-oxygenase-1 or by inhibition of specific exercise-induced activation of cyclo-oxygenase-2, or both. None of the drugs changed the renal response to exercise. Inhibition by indomethacin of angiotensin II and thromboxane A 2 synthesis may, during exercise, counterbalance renal vasoconstriction caused by blockade of vasodilatory prostaglandins.

1. Renal haemodynamics, lithium and sodium clearance were measured in 14 patients treated with recombinant interleukin-2 for metastatic renal cell carcinoma. 2. Patients were studied before and after 72 h of continuous intravenous infusion of recombinant interleukin-2 (18×10 6 i.u.·24 h -1 ·m -2 ) and 48 h post therapy. Cardiac output was measured by impedance cardiography. Effective renal plasma flow and glomerular filtration rate were determined by the renal clearances of 131 I-hippuran and 99m Tc-diethylenetriaminepenta-acetic acid (DTPA) respectively. Renal clearance of lithium ( C Li ) was used as an index of proximal tubular outflow. 3. Treatment caused a transient decrease in mean arterial blood pressure and systemic vascular resistance, but cardiac output remained unchanged. Renal blood flow decreased and renal vascular resistance increased during and after treatment. Sodium clearance decreased from 1.10 (0.63/1.19) ml/min to 0.17 (0.18/0.32) ml/min ( P = 0.003). Glomerular filtration rate remained unchanged, whereas the median C Li decreased from 26 (17/32) ml/min to 17 (10/21) ml/min ( P = 0.008). Calculated absolute proximal reabsorption rate of water increased from 63 (40/69) ml/min to 71 (47/82) ml/min ( P = 0.04). The urinary excretion rate of thromboxane B 2 and the ratio between excretion rates of thromboxane B 2 and 6-keto-prostaglandin-F 1α increased by 98% ( P = 0.022) and 175% ( P = 0.022) respectively. 4. The study suggests a specific recombinant interleukin-2-induced renal vasoconstrictor effect. Changes in renal prostaglandin synthesis may contribute to the decrease in renal blood flow. The lithium clearance data suggest that an increased proximal tubular reabsorption rate may contribute to the decreased sodium clearance during recombinant interleukin-2 treatment.

1. The present randomized, double-blind cross-over study compared endogenous and exogenous lithium clearance ( C Li ) for estimation of the effect of dopamine on tubular sodium reabsorption. Twelve normal, salt-repleted male subjects were investigated on three different occasions with either placebo or 450 mg or 600 mg of lithium given in random order at 22.00 hours. After an overnight fast, renal clearance studies were performed during a 1 h baseline period and subsequently during the second hour of an infusion of 3 μg min −1 kg −1 of dopamine. 2. Baseline values of endogenous C Li and fractional excretion of lithium (FE Li ) [27.0 (23.5–30.5) ml/min and 24.2 (203–28.2)% (means with 95% confidence interval)] were lower than exogenous values [lithium, 450 mg: 32.7 (29.9–35.4) ml/min ( P < 0.05) and 27.4 (25.2–29.6)% ( P < 0.05); lithium, 600 mg: 33.4 (29.2–37.6) ml/min ( P < 0.05) and 28.6 (26.3–31.0)% ( P < 0.01)]. Both test doses of lithium increased the baseline sodium clearance ( C Na ), but glomerular filtration rate and urine flow rate remained unchanged. 3. Dopamine increased C Na to similar values on the three study days. C Li increased to 40.9 (35.5–46.5) ml/min (endogenous lithium, P < 0.001), 43.2 (40.8–45.6) ml/min (450 mg of lithium, P < 0.01) and 44.9 (41.3–48.4) ml/min (600 mg of lithium, P < 0.001), respectively. FE Li increased to 32.2 (27.5–37.0)% ( P < 0.01), 35.4 (33.0–37.7)% ( P < 0.01) and 35.9 (32.8–38.9)% ( P < 0.01), respectively. Values during dopamine infusion did not differ significantly. 4. The lower baseline values of endogenous C Li and FE Li compared with exogenous values suggest that C Li in humans depends on the plasma concentrations of lithium. However, the effect of dopamine on C Li and FE Li was expressed to the same extent with endogenous and exogenous lithium, indicating that the two methods are interchangeable for estimation of dopamine-induced changes in tubular function.

1. Previous histological studies have demonstrated partial reinnervation of the human transplanted kidney. However, it remains unknown whether this reinnervation is of any functional significance. 2. The effects of noradrenaline infusion (2 μgh −1 kg −1 ) and lower body negative pressure (−27 mmHg) on renal haemodynamics, sodium excretion and tubular function were investigated in 25 renal transplant recipients and 10 normal subjects. Sixteen of the transplant recipients had all been transplanted for more than 27 months, and nine had all been transplanted for less than 2 months. 3. After an overnight fast, the subjects were water-loaded, and clearance studies were performed with a 1 h baseline period, a 1 h period with noradrenaline infusion, another 1 h baseline period, and a final 1 h period with lower body negative pressure. 4. During noradrenaline infusion the relative decrease in effective renal plasma flow, glomerular filtration rate and clearance of lithium and sodium was significantly more pronounced in the long-term transplanted patients than in the control subjects. 5. Lower body negative pressure only depressed the glomerular filtration rate significantly in the control subjects. Further, the relative decrease in effective renal plasma flow and clearance of lithium and sodium was significantly greater in the control subjects than in the two groups of transplanted patients. 6. The present study thus demonstrated that in short- and long-term transplanted kidneys in man, supersensitivity to circulating noradrenaline and an inadequate response to lower body negative pressure was present. This strongly suggests that the human transplanted kidney remains functionally denervated.

1. The effect of a single dose of lithium on renal function before and during intravenous infusion of dopamine (3 μg min −1 kg −1 ) was investigated in 12 healthy males. In a double-blind and randomized design, 450 mg or 600 mg of lithium carbonate or placebo was administered orally at 22.00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1 h baseline period and three 1 h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 ± 0.35 ml/min, but with lithium it increased to 1.25 ± 0.44 ( P < 0.001) and 1.17 ± 0.46 ml/min ( P < 0.01) after 450 and 600 mg, respectively. Urine flow rates were unchanged compared with placebo. Lithium did not significantly affect glomerular filtration rate, but both doses slightly increased effective renal plasma flow by 7% ( P < 0.05) and 10% ( P < 0.01), respectively. 3. The maximal natriuretic and diuretic effects of dopamine were not reduced by lithium, but the percentage increases in sodium clearance were significantly diminished after 450 mg ( P < 0.01) and 600 mg ( P < 0.001) of lithium. Lithium had no effect on dopamine-induced changes in effective renal plasma flow, glomerular filtration rate or osmolal clearance. Neither lithium nor dopamine influenced plasma concentrations of renin, aldosterone or atrial natriuretic peptide. 4. In conclusion, single test doses of lithium, as normally used in lithium clearance studies, increase baseline values of sodium clearance and effective renal plasma flow. Although these effects of lithium do not reduce the maximal renal responses to low-dose dopamine, they result in an underestimation of the percentage increase in sodium excretion.