Robin J. Spencer

Nature of the renal injury following total renal ischemia in man.

The effects of total renal ischemia (TRI) of 15-87 min duration due to suprarenal clamping of the aorta were studied in 15 mannitol-treated patients undergoing abdominal aortic surgery. 15 patients undergoing similar surgery but requiring only infrarenal clamping served as controls. 1-2 h following TRI, GFR was reduced to only 39% of that in controls, 23 +/- 5 vs. 59 +/- 7 ml/min (P less than 0.001). This could not be ascribed to impaired renal plasma flow (RPF), which was mildly reduced to 331 +/- 71 and was not different from the value in controls, 407 +/- 66 ml/min. However, impaired PAH extraction (43 +/- 7%) and isosthenuria, not present in controls, suggest a primary role for tubular injury in lowering GFR at this time. 24 h following TRI, the GFR remained depressed below controls, 45 +/- 8 vs. 84 +/- 8 ml/min (P less than 0.005), while the transglomerular sieving of neutral dextrans was significantly enhanced (radius interval, 24-40 A). A theoretical analysis of transcapillary solute exchange revealed that these findings could be largely explained by a selective reduction of either RPF (-61%) or of transmembrane hydraulic pressure difference (-18%) below control values. Alternately, a combination of these two factors with changes of smaller magnitude could explain the findings. In contrast, a selective increase in oncotic pressure or decrease of the glomerular ultrafiltration coefficient could be excluded as a cause of hypofiltration 24 h after TRI. These observations lead us to suggest that the transient azotemia observed following TRI is due to a self-limited injury to the nephron that is identical to that seen in overt and sustained forms of acute renal failure.

The diuretic properties of dopamine in patients after open-heart operation.

Dopamine and dobutamine were administered to 12 patients who had undergone open cardiac operations. To eliminate the effects of variation in systemic blood flow upon renal function the drug infusion rates were adjusted to achieve equal cardiac outputs. Under conditions of equivalent systemic pressure and flow, dopamine (5.0 ± 1 μg · kg-1 · min-1) and dobutamine (3.5 ± 1.8 μg · kg-1 · min-1) had similar effects upon glomerular filtration rate (90 ± 29 vs. 83 ± 27 ml · min-1 · 1.73 m-2) and effective renal plasma flow (375 ± 119 vs. 357 ± 126 ml · min-1 · 1.73 m-2). However, dopamine administration resulted in a significantly greater diuresis (2.8 ± 2.7 vs. 1.0 ± 0.3 ml/min), natriuresis (0.32 ± 0.39 vs. 0.07 ± 0.10 mEq Na+/min), and kaliuresis (0.15 ± 0.06 vs. 0.10 ± 0.03 mEq K+/min) (P < 0.05). In patients with modest depression of cardiac performance and renal vasoconstriction, dopamines selective renal vasodilator effects were not evident. Furthermore, these data suggest that dopamine inhibits tubular solute reabsorption directly. Thus, the diuresis and natriuresis that frequently accompany dopamine administration may occur independently of any effects of dopamine upon renal blood flow.

Glomerular and tubular function in non-oliguric acute renal failure

Glomerular and tubular function were evaluated in 30 non-oliguric patients with increasing azotemia following open heart surgery. Fractional clearances (theta) of test solutes relative to that of inulin were determined. In 16 patients, theta dextran (radius 22 to 30 A) exceeded unity, a finding attributed to inulin backleak through necrotic tubules. These patients were classified as having acute renal failure; 14 subsequently required dialysis. In the remaining patients (N = 14), theta dextran was normal. These patients were considered to have prerenal failure; all recovered spontaneously. clearance of inulin (Cin) was lower in acute renal failure than in prerenal failure (12 +/- 2 versus 18 +/- 2 ml/min/1.73 m2; p less than 0.025). The apparent difference in glomerular filtration rate when Cin is used as an index was abolished, however, when Cin in acute renal failure was corrected for tubule backleak of inulin. In acute renal failure, fractional clearance of p-aminohippurate (theta PAH) was 7.1 +/- 1.0, and fractional excretion of potassium (FEk) was 160 +/- 18 percent. These findings strongly suggest that secretory ability in both proximal and terminal tubule augments, respectively, is preserved in acute renal failure. Compared with prerenal failure, the urine-to-plasma inulin ratio was lower (U/Pin = 10 +/- 1 versus 25 +/- 4; p less than 0.005) and FENa was higher (FENa = 5.1 +/- 1.5 versus 0.5 +/- 1.0 percent; p less than 0.01) in acute renal failure.

Effect of the intra-aortic balloon pump upon postoperative renal function in man.

Fifty-seven postoperative cardiac surgical patients receiving intra-aortic balloon pump (IABP) support were selected for detailed hemodynamic and renal function measurements on the basis of depressed cardiac and/or renal function. Eleven patients developed acute renal failure while receiving maximal IABP support and 10 during, or after withdrawal of IABP support. To define further the relationship between IABP support and renal function, 17 patients underwent simultaneous assessment of hemodynamic and renal function under varying conditions of IABP support. These studies, performed just before IABP withdrawal, demonstrated slight, clinically insignificant, improvement in hemodynamic and renal function with increased IABP support. Arterial pressure recordings, performed above and below the intra-aortic balloon in 8 patients, revealed no significant pressure gradient across the balloon whether single- or double-chambered. In addition, the balloon pulse waveform was always evident in the femoral artery. Importantly, the intra-aortic balloon did not interfere demonstrably with renal function, nor did it decrease renal perfusion pressure, in spite of its suprarenal position. Therefore, improvement in systemic perfusion from IABP support in the early postoperative period will result in improved renal perfusion.

The Renal Effects of Sodium Nitroprusside in Postoperative Cardiac Surgical Patients

Sodium nitroprusside (SNP) is frequently used to control hypertension and/or improve systemic blood flow following cardiac operations. Although SNP causes renal vasodilation when infused into isolated kidneys, the reported effects of SNP on renal vascular resistance and blood flow in intact animals and humans have varied. To define the effects of SNP in postoperative cardiac surgical patients, renal clearances and hemodynamics were measured in seven patients within 24 hours of coronary bypass grafting. Studies were delayed until patients were stabilized and had rewarmed following operation. Following baseline measurements (off SNP), SNP infusion was used to lower mean arterial pressure to 85 torr. Pulmonary wedge pressure was maintained by appropriate fluid therapy, and the measurements repeated 1 h later. SNP administration resulted in equivalent decreases in renal (−31 per cent), pulmonic (−29 per cent) and systemic (−33 per cent) vascular resistance. Notwithstanding the decrease in arterial pressure (109 ± 14 to 91 ± 9 torr, P < 0.01), renal blood flow increased by 20 per cent (653 ± 193 to 792 ± 210 ml min−1 1.73 m−2, P < 0.02), in direct proportion to the increase in cardiac index (2.5 ± 0.4 to 3.0 ± 0.31 · min−1·m−2, P <0.01). Thus, in postoperative cardiac surgical patients, SNP administration can be expected to improve renal blood flow, so long as left artrial hypotension is avoided, and the decline in systemic arterial pressure is not excessive. The improvement in renal blood flow achievable with SNP may be critical for patients with severly depressed left ventricular function in whom severe depression of renal blood flow may occur as an antecedent to acute renal failure.