Effects of traumatic hypovolemic shock on renal function

Renal and systemic hemodynamic evaluations were made in 16 patients within 12- to 72-hr after injury in an effort to determine the effects of severe traumatic hypovolemic shock on renal function. Eleven patients were again studied in the convalescent period. All patients had stable vital signs at time of renal evaluation and no patient received vasopressors or diuretics within 24 hr of study.The early postresuscitative period was associated with a significant reduction in effective renal plasma flow, true renal plasma flow, true renal blood flow, renal oxygen consumption, and the percentage of renal blood flow compared to the total cardiac output; renal vascular resistance, osmolar clearance, and sodium clearance were increased at this time. The glomerular filtration rate, extracellular fluid space, cardiac output, and total peripheral resistance remained normal.All abnormal renal parameters returned to normal with convalescence except in those patients who developed nonoliguric renal failure which was associated with a persistant decrease in glomerular filtration rate and effective renal plasma flow during convalescence.The clinical significance of these findings including the roles of loop diuretics and vasodilators are discussed.     

Renal function in experimentally induced acute pancreatitis in dogs: How it is affected by the nephrotoxic substance in pancreatic exudate from ascitic fluid

Renal failure occurring in dogs during experimental acute pancreatitis and the effect on renal function of intravenous injections of ascitic fluid which accumulated during the acute pancreatitis were studied. Five hours after the induction of acute pancreatitis, the accumulation of 200 to 400 ml of ascitic fluid, and an elevation in hematocrit as well as a decreased mean arterial pressure were observed, which suggested hypovolemia due to plasma loss. At the same time, the renal blood flow, glomerular filtration rate, and urinary output decreased significantly. Hypovolemia was observed to be the main cause of renal failure in accordance with previous reports. When the sterile ascitic fluid was injected into healthy dogs, temporary hypotension was observed without changes in the hematocrit. However, the renal blood flow, glomerular filtration rate and urinary output decreased, together with an elevation in renal vascular resistance, even after the hypotension had returned to normal. This study shows that renal failure associated with acute pancreatitis occurred mainly as a direct result of hypovolemia but also that the sterile ascitic fluid contained nephrotoxic substances which were suspected to be unrelated to vasoactive substances or protease. Their removal is therefore necessary for the treatment and prevention of renal failure complicating acute pancreatitis.     

Renal function in experimentally induced acute pancreatitis in dogs: how it is affected by the nephrotoxic substance in pancreatic exudate from ascitic fluid

Renal failure occurring in dogs during experimental acute pancreatitis and the effect on renal function of intravenous injections of ascitic fluid which accumulated during the acute pancreatitis were studied. Five hours after the induction of acute pancreatitis, the accumulation of 200 to 400 ml of ascitic fluid, and an elevation in hematocrit as well as a decreased mean arterial pressure were observed, which suggested hypovolemia due to plasma loss. At the same time, the renal blood flow, glomerular filtration rate, and urinary output decreased significantly. Hypovolemia was observed to be the main cause of renal failure in accordance with previous reports. When the sterile ascitic fluid was injected into healthy dogs, temporary hypotension was observed without changes in the hematocrit. However, the renal blood flow, glomerular filtration rate and urinary output decreased, together with an elevation in renal vascular resistance, even after the hypotension had returned to normal. This study shows that renal failure associated with acute pancreatitis occurred mainly as a direct result of hypovolemia but also that the sterile ascitic fluid contained nephrotoxic substances which were suspected to be unrelated to vasoactive substances or protease. Their removal is therefore necessary for the treatment and prevention of renal failure complicating acute pancreatitis.     

Lithium clearance in patients with chronic renal diseases.

The clearance of lithium was analyzed in relation to the glomerular filtration rates and the effective renal plasma flow in 41 patients with renal disease and variable degree of renal functional impairment and in 40 normal subjects. In the patients, there was on average a 35% decrease of glomerular filtration rates (109 +/- 64 [SD] ml/min) and renal plasma flow (490 +/- 275 ml/min) and a 25% decrease of lithium clearance (22 +/- 12 ml/min); the lithium clearance correlated closely with the glomerular filtration rates and renal plasma flow (r = 0.69; p less than 0.001). The absolute proximal reabsorption of fluid was decreased by 38% (89 +/- 56 ml/min) while the distal absolute reabsorption of sodium (21 +/- 12 ml/min) was unchanged. Individual values of fractional proximal or distal reabsorption as related to glomerular filtration rates or renal plasma flow were equally distributed between normal and renal subjects, except in the presence of a severe renal function impairment, where both variables decreased exponentially. This suggests that in renal failure, sodium balance is maintained by a proportional decrease of proximal and distal sodium reabsorption in relation to glomerular filtration. Only in the presence of severe renal failure (GFR less than 30 ml/min) both variables are concomitantly readjusted to lower values.     

Renal blood flow in acute epidemic nephritis (nephropathia epidemica of Scandinavia).

Different haemodynamic and functional parameters were studied in 5 cases of acute epidemic nephritis with uraemia using nephroangiography and dye-dilution measurements combined with determination of extraction ratio and clearance for 51Cr-EDTA and PAH. In the acute phase, with greatly reduced renal function, increased vascular resistance was noted in spite of the vasodilatation observed in the renal artery out to and including the interlobular arteries. Moreover, angiography revealed enlarged kidneys with an increase in the thickness of the cortex and reduced cortical contrast accumulation. The renal blood flow, which was normal or slightly reduced initially, increased during convalescence, and renal function returned to normal. The investigation indicated that a primary vascular lesion in glomerular to postglomerular capillaries gives rise to pronounced interstitial oedema, which, probably as a result of secondary tubular compression, may be the cause of the rapidly developing renal failure.     

Amlodipine therapy corrects renal abnormalities encountered in the hypertensive state

Calcium antagonists may increase glomerular filtration rate and renal plasma flow by antagonizing the intrarenal effects of angiotensin II and/or norepinephrine. We prospectively studied the effects of amlodipine, a once-a-day dihydropyridine calcium channel antagonist, in 19 patients with essential hypertension. Studies were performed after 4 weeks of placebo and 6 weeks of amlodipine therapy, and included the assessment of systolic and diastolic BP, renal clearances of inulin and p-aminohippurate, and determination of body fluid composition. Systolic and diastolic BPs were reduced following 6 weeks of amlodipine monotherapy. In spite of significant decreases in mean arterial pressure, there were increases in inulin clearance (+ 13%), and p-aminohippurate clearance (+ 19%). Filtration fraction was not changed. Renal vascular resistance was decreased (-25%). Total blood volume, extracellular fluid volume, and total body water and body weight were not changed. We conclude that amlodipine therapy has the potential to reverse renal abnormalities encountered in the hypertensive state.     

The kidney in malaria: Renal and systemic haemodynamics

Summary: Renal and systemic haemodynamic alterations in malaria vary with the severity of infection. In mild malaria there is no change in renal and systemic haemodynamics. In moderate infection hypervolaemia, increased cardiac index and decreased, systemic vascular resistance are noted. the renal blood flow and glomerular filtration rate are decreased, accompanied by an increase in plasma arginine vasopressin, norepinephrine and renin activity. Yet in some patients only plasma arginine vasopressin and blood volume are increased while renal and systemic haemodynamics are normal. In severe infection blood volume is either normal or decreased; the cardiac index and systemic vascular resistance are normal, while the renal blood flow and glomerular filtration rate are markedly decreased, leading to renal failure.     

Renal physiology: blood flow,glomerular filtration and plasma clearance

The homeostatic and excretory functions of the kidney are dependent on its perfusion, totalling 20–25% of cardiac output, and the process of glomerular ultrafiltration. Renal blood flow (RBF) is directly proportional to the trans-renal gradient which is autoregulated across a mean arterial pressure of 50–150 mmHg in a normotensive person. Selective molecular filtration in the glomerulus is achieved by the glomerular filtration barrier and is related to the size, shape and electrical charge of molecules. The process of ultrafiltration is determined by the balance between hydrostatic and colloid osmotic pressures in the glomerular capillary and Bowmans's space, and is affected by renal plasma flow, altered surface area and changes in afferent and efferent renal arteriole vascular resistance. The phenomenon of renal plasma flow autoregulation minimizes changes in the volume of ultrafiltration through myogenic and tubuloglomerular feedback mechanisms. Glomerular filtration rate can be measured using exogenous inulin, or estimated (eGFR) from creatinine clearance, several equations can be used to calculate eGFR but their limitations in estimating the true excretory function of the kidney need to be taken into consideration.     

Renal handling of beta-2-microglobulin, amylase and albumin in acute pancreatitis.

The renal handling of beta-2-microglobulin, amylase and albumin was studied in patients with acute pancreatitis. The data were compared with results obtained from patients with glomerular proteinuria and from patients with tubular proteinuria. Initially during acute pancreatitis, the clearance ratio (clearance protein/clearance creatinine) for beta-2-microglobulin was increased dramatically (77-fold) compared to normals. After four to seven days this ratio had fallen and was elevated only 7-fold. The corresponding figures for amylase were 3.3 and 1.8 times and for albumin 9 and 5 times respectively. In glomerular disease, the clearance ratios for beta-2-microglobulin, amylase and albumin were increased 6, 1.1, and 154 times and in tubular disease 448, 1.1, and 28 times, respectively. The electrophoretic pattern of the urinary proteins during pancreatitis was mostly normal. In a few cases, slight tubular proteinuria was noticed. Amylase activity in serum and urine from patients with pancreatitis was found to sediment, (S20,W = 4.6) in a sucrose gradient, identical to amylase from normal serum and urine. The marked increase in the excretion of beta-2-microglobulin probably reflects interference of the kidney function at the proximal tubular level. Determinations of this protein in urine may be of value in studies of kidney dysfunction that can accompany pancreatitis.     

Renal physiology: blood flow,glomerular filtration and plasma clearance

The kidney depends on its blood flow (20–25% cardiac output) and glomerular ultrafiltration (20% renal plasma flow) to perform it's homoeostatic and excretory functions. More than 90% of blood flow serves the cortex. Selectivity of molecular filtration in the glomerulus is related to molecular size, shape and electrostatic charge of molecules, and structure of the glomerular filtration barrier with its negatively charged glycoproteins. Ultrafiltration is determined by the balance between hydrostatic and colloid osmotic pressures (Starling forces) in the glomerular capillary and Bowman's space. It is influenced by changes in renal plasma flow, altered surface area and changes in vascular resistance afforded by afferent and efferent arterioles (mediated by sympathetic nerve activity, vasoconstrictors and vasodilators). Autoregulation of renal plasma flow minimizes changes in volume of ultrafiltration (hence, filtered load) through myogenic and tubuloglomerular feedback mechanisms. Renal clearance measurements have practical application in terms of assessing renal plasma flow and glomerular filtration rate (creatinine, inulin) along with some other measurements but all have their limitations.     

Comparative renal effects of midazolam and thiopental in humans

Midazolam is a water-soluble benzodiazepine whose quick onset after intravenous injection, short duration of action, absence of venous irritation, and mild cardiovascular and respiratory effects suggest its use for induction of anesthesia. The renal effects of midazolam-N2O-O2 anesthesia, as determined by renal clearance of injected inulin and para-aminohippuric acid (PAH), in hydrated ASA Class I-II surgical patients (N = 8) were compared in a double-blind fashion with a similar group of patients (N = 9) anesthetized with thiopental-N2O-O2. Except for glomerular filtration rate, there were no significant changes in any of the measured variables (blood pressure, effective renal plasma flow, renal blood flow, and renal vascular resistance). The per cent reduction in glomerular filtration rate in patients given thiopental differed significantly from that in patients given midazolam. This study suggests that midazolam, as opposed to thiopental, offers minimal advantage in maintaining renal performance at least during the period of anesthetic administration.     

Protein-induced glomerular hyperfiltration: role of hormonal factors

High protein diets acutely elevate the glomerular filtration rate. To characterize this response we administered 1 g of protein/kg body weight as a beef steak meal to nine, healthy male subjects and measured glomerular filtration rate (inulin clearance), renal plasma flow (p-amino hippurate clearance), plasma renin activity, aldosterone and plasma and urinary catecholamines. The subjects ingested the meal on three separate days and were pretreated with either placebo, 50 mg indomethacin (to inhibit renal prostaglandin synthesis), or 10 mg enalapril (to inhibit angiotensin II synthesis). Following placebo treatment protein feeding significantly increased the glomerular filtration rate, from a pre-meal level of 101 +/- 7 ml/min/1.73 m2 to a post-meal level of 130 +/- 6 ml/min/1.73 m2, P less than 0.005. A parallel rise in renal plasma flow and a fall in renal vascular resistance were noted. Indomethacin pretreatment attenuated the increase in glomerular filtration rate following the protein meal, 105 +/- 6 ml/min/1.73 m2 pre-meal level to 118 +/- 4 ml/min/1.73 m2 post-meal, P greater than 0.1. Enalapril pretreatment had no significant effect on protein-induced glomerular hyperfiltration. Protein feeding following placebo increased plasma aldosterone concentration while the concentrations were unchanged in the studies where enalapril or indomethacin was administered. Protein feeding following placebo or indomethacin did not alter plasma renin activity while plasma renin activity rose following enalapril administration. Urinary norepinephrine excretion rose while plasma norepinephrine concentration was unchanged in all three study groups. A decrease in urinary dopamine excretion was also noted four hours after the protein meal was ingested.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal function and hemodynamics during prolonged isoflurane-induced hypotension in humans

The effect of isoflurane-induced hypotension on glomerular function and renal blood flow was investigated in 20 human subjects. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and para-aminohippurate (PAH) clearance, respectively. Anesthesia was maintained with fentanyl, nitrous oxide, oxygen, and isoflurane. Hypotension was induced for 236.9 +/- 15.1 min by increasing the isoflurane inspired concentration to maintain a mean arterial pressure of 59.8 +/- 0.4 mmHg. GFR and ERPF decreased with the induction of anesthesia but not significantly more during hypotension. Postoperatively, ERPF returned to preoperative values, whereas GFR was higher than preoperative values. Renal vascular resistance increased during anesthesia but decreased when hypotension was induced, allowing the maintenance of renal blood flow. We conclude that renal compensatory mechanisms are preserved during isoflurane-induced hypotension and that renal function and hemodynamics quickly return to normal when normotension is resumed.     

Chronic effects of tertatolol on renal function in hypertensive patients with mild chronic renal failure.

To assess the potential benefit of drug-induced renal haemodynamic changes in patients with chronic renal failure, we have evaluated the effects of the beta-blocking agent tertatolol on blood pressure, glomerular filtration rate, and renal plasma flow. Inulin and PAH clearances were performed before and after 3 months treatment and oral tertatolol, 5 mg daily in eight hypertensive patients with moderate chronic renal failure. After 3 months of treatment, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) increased significantly by 10% and 13% respectively, whereas renal vascular resistance decreased by 16% and the filtration fraction was unchanged. These results indicate that tertatolol possesses novel renal haemodynamic properties in hypertensive patients with chronic renal failure. However, the long-term benefit of such a therapy is yet to be confirmed.     

Effects of the somatostatin analogue octreotide on renal function in conscious diabetic rats.

BACKGROUND: Studies performed during the last decade have indicated that growth hormone (GH) and insulin-like growth factors (IGFs) may mediate the early renal changes in diabetes mellitus, i.e. hypertrophy and hyperfiltration. This and other observations have led to the suggestion that GH/IGF inhibitors, such as long-acting somatostatin analogue (e.g. octreotide and lanreotide), may be useful in order to inhibit or prevent development of long-term diabetic complications. METHODS: The present study examined the acute and chronic effects of octreotide on renal function following induction of streptozotocin (STZ)-diabetes in rats. The studies were carried out in conscious, non-fasted diabetic animals. RESULTS: Chronic administration of octreotide for 7 days, from onset of diabetes, prevented the decrease of effective renal vascular resistance (ERVR), and the increases in filtration fraction (FF), glomerular filtration rate (GFR), and absolute proximal tubular fluid reabsorption (APR) induced by diabetes. The renal hypertrophy was only partially prevented. In the acute study, similar changes were observed in effective renal plasma flow (ERPF) and ERVR but FF increased and GFR remained unaltered. CONCLUSIONS: Chronic but not acute treatment with octreotide prevented the renal hyperfiltration caused by diabetes. This effect is most likely due to an increase in afferent arteriolar resistance.     

Elevated intra-abdominal pressure and renal function.

The effect of increased intra-abdominal pressure on cardiac output and renal function was investigated using anesthetized dogs into whom inflatable intraperitoneal bags were placed. Hemodynamic and renal function measurements were made at intra-abdominal pressures of 0, 20, and 40 mmHg. Renal blood flo and glomerular filtration rate decreased to les than 25% of normal when the intra-abdominal pressure was elevated to 20 mmHg. At 40 mmHg intra-abdominal pressure, three dogs became anuric, and the renal blood flow and glomerular filtration rate of the remaining dogs was 7% of normal, while cardiac output was reduced to 37% of normal. Expansion of the blood volume using Dextran-40 easily corrected the deficit in cardiac output, but renal blood flow and glomerular filtration rate remained less than 25% of normal. Renal vascular resistance increased 555% when the intra-abdominal pressure was elevated from 0 to 20 mmHg, an increase fifteen-fold that of systemic vascular resistance. This suggests that the impairment in renal function produced by increased intra-abdominal pressure is a local phenomenon caused by direct renal compression and is not related to cardiac output.     

Renal hemodynamics during separate and combined infusion of amino acids and dopamine

Healthy volunteers (N = 9) and patients with varying degrees of renal insufficiency (N = 36) were given a low dose of dopamine and/or amino acids intravenously during a simultaneous measurement of the glomerular filtration rate and the effective renal plasma flow. Dopamine infusion led to a rise in the glomerular filtration rate and a fall in the filtration fraction. Infusion of amino acids was accompanied by an increase in the glomerular filtration rate while the filtration fraction remained unchanged or increased slightly. The highest values for the glomerular filtration were obtained during the combined infusion of amino acids and dopamine. A reserve in filtration capacity was not or hardly present in patients with moderate (GFR 30 to 90 mliter/min/1.73 M2) to severe (GFR less than 30 mliter/min/1.73 M2) renal insufficiency. We conclude that dopamine decreases total renal vascular resistance while amino acids mainly reduce the tone of afferent arterioles. As amino acids and dopamine seem to be additive in their effects on the glomerular filtration rate, we recommend the combined infusion of these two stimuli to measure renal reserve filtration capacity.     

The effect of diuretics on systemic and renal hemodynamics in patients with renal insufficiency

Diuretics have been used in acute renal failure in an attempt to increase urine flow and ameliorate the reduction in glomerular filtrate rate. A beneficial response occurs in some experimental models of acute renal failure when diuretics are administered prophylactically or very early in the course of renal failure and may require a renal vascular bed capable of responding partially, at least, to vasodilating stimuli. In chronic renal insufficiency the most important indications for diuretic use are for the treatment of systemic hypertension and for the correction of the congested state. However, the precise effect of diuretic therapy under these conditions is unpredictable and dependent on the functional state of the renal vessels. Diuretic administration may at times prove detrimental, resulting in a deterioration of glomerular filtration rate. In hemodynamically unstable conditions the slow removal of extracellular fluid by continuous arteriovenous hemofiltration may prove preferable to diuretic administration or standard forms of dialysis.     

Progressive glomerular sclerosis in experimental antiglomerular basement membrane glomerulonephritis

A model of chronic progressive glomerular sclerosis in experimental antiglomerular basement membrane (anti-GBM) glomerulonephritis was developed in Wistar rats. Wistar rats given the accelerated form of anti-GBM anti-body glomerulonephritis initially developed significant proteinuria and renal insufficiency associated primarily with a decrease in glomerular filtration rate (GFR) with normal renal clearance of para-aminohippuric acid and with markedly reduced filtration fraction. The glomerular functional abnormalities were associated with marked glomerular hypercellularity due to leukocytic infiltration as well as proliferation of intrinsic glomerular cells with crescent formation. Late in the course of the disease, by day 21, GFR had fallen further, associated with a parallel decrease in the clearance of para-aminohippuric acid and a normal filtration fraction. At this stage, glomerular hypercellularity had diminished and was replaced by glomerular sclerosis. The model appears to be a reproducible form of chronic glomerulosclerosis and demonstrates that the chronic phase of glomerular basement membrane (GBM) glomerulonephritis is distinctly different from that of the acute phase. It provides a controllable setting to study the glomerular sclerotic process independent of the initial inflammatory changes.     

Renal involvement in subjects with peripheral atherosclerosis

BACKGROUND: Ischemic nephropathy is an important cause of renal failure in western countries. Subclinical renal function abnormalities may exist in patients with extrarenal atherosclerosis, and may precede the onset of overt ischemic nephropathy. METHODS: To assess the impact of extrarenal atherosclerosis on the kidney, we evaluated renal function in 89 subjects with differing degrees of peripheral atherosclerosis, without manifest clinical or laboratory signs of ischemic nephropathy and renovascular hypertension. All laboratory testing, ultrasonography with Doppler analysis for the localization of peripheral vascular disease (carotid and lower limb arteries), and non-invasive evaluation of renal function by radionuclide studies of renal plasma flow (MAG3 clearance) and glomerular filtration (DTPA clearance), as well as total, LDL and HDL cholesterol, and triglycerides were determined; smoking habit was recorded. By combining sonographic data on arterial tree stenosis (ATS), the subjects were grouped according to the atherosclerotic vascular damage (ATS involvement). RESULTS: Despite no change in plasma creatinine and DTPA clearance (from 91.58+/-26.53 mL/min/1.73 m2 to 93.47+/-24.82), MAG3 clearance progressively declined with the severity of vascular damage (from 244.86+/-60.60 mL/min/1.73 m2 to 173.59+/-58.74). Stepwise multiple regression analysis indicated that MAG3 clearance was best explained by ATS involvement (standardized beta coefficient -0.40; p<0.001), smoking habit (-0.34; p= 0.004), and serum LDL-cholesterol (-0.24; p<0.035). CONCLUSIONS: The renal hemodynamic profile in atherosclerotic patients might constitute functional evidence of the silent phase of ischemic renal disease. The findings suggest that renal function should be carefully assessed in patients with extrarenal atherosclerosis, particularly in those with classic cardiovascular risk factors.