Mechanisms of renin secretion during hemorrhage in the dog.

The importance of renal perfusion pressure (RPP), the sympathetic beta adrenergic nervous system and renal prostaglandins (PG) on renin release during a uniform 15-17% reduction in blood pressure by hemorrhage (HH) was studied systematically in anesthetized dogs. All groups of animals had similar decrements in systemic and renal hemodynamics with HH. In control dogs (n = 7), both plasma renin activity (PRA, 4.1-9.0 ng angiotensin I/ml per h, P < 0.05) and renin secretory rate (RSR, 26-228 ng/ml per h.min, P < 0.005) increased significantly with HH. This increase in renin release during HH was not abolished by any single maneuver alone including beta adrenergic blockade with d,l-propranolol (n = 6), renal PG inhibition with indomethacin (n = 7), or control of RPP (n = 6). However, when beta adrenergic blockade was combined with control of RPP (n = 7) during HH, neither PRA (1.9-2.7 ng/ml per h, NS) nor RSR (16-53 ng/ml per h.min, NS) increased significantly. Similarly, a combination of beta adrenergic blockade and PG inhibition (n = 6) also abolished the increase in PRA (1.5-1.4 ng/ml per h, NS) and RSR (14-55 ng/ml per h.min, NS) during HH despite significant decreases in sodium excretion. Finally, a combination of PG inhibition and RPP control was associated with significant increases in PRA and RSR during HH. These results support a multifactorial mechanism in renin release during HH and implicate both the beta adrenergic receptors, renal baroreceptors, and possibly the macula densa as constituting the primary pathways of renin release during HH of this magnitude. Because either constant RPP or PG inhibition blunted renin release during HH in the setting of beta adrenergic blockade, the present results strongly suggest that the renal baroreceptor, and probably the macula densa mechanism are PG mediated.

Effect of hemodialysis on left ventricular function. Dissociation of changes in filling volume and in contractile state.

Prior studies of the effect of hemodialysis on left ventricular function have not distinguished between the removal of uremic toxins and the change in cardiac filling volume. To separate these effects, left ventricular function was examined by serial echocardiography in five stable hemodialysis patients before and after three different dialysis procedures: (a) hemodialysis with volume Loss, (b) ultrafiltration (volume loss only), and (c) hemodialysis without volume loss. The patients were similarly studied under control conditions and after increased (5 degrees of head-down tilt for 90 min) and decreased (lower body negative pressure) cardiac filling volume. After hemodialysis with volume loss, end-diastolic volume (EDV) decreased from 167 to 128 ml (P less than 0.001) and end-systolic volume (ESV) decreased from 97 to 51 ml (P less than 0.001) without a change in stroke volume (SV). Ejection fraction increased from 42 to 52% (P less than 0.001) and mean velocity of circumferential fiber shortening (VCF) increased from 0.61 to 1.04 circumferences (circ)/s (P less than 0.001). After ultrafiltration, EDV decreased from 167 ml to 124 ml (P less than 0.001) and SV from 73 ml to 39 ml (P less than 0.001), without significant changes in ESV or VCF. In contrast to the maneuvers in which volume loss occurred, after hemodialysis without volume loss ESV decreased from 95 to 66 ml (P less than 0.001) and SV increased from 74 ml to 97 ml (P less than 0.001) without changes in EDV. EF increased from 44 to 59% (P less than 0.001) and VCF increased from 0.64 to 1.26 circ/s (P less than 0.001). Ventricular function curves plotted from data obtained under conditions of altered cardiac filling volume before and after the three dialysis maneuvers demonstrate that ultrafiltration produced a pure Frank-Starling effect, while hemodialysis with or without volume loss produced a shift in the ventricular function curves, which demonstrated an increase in the contractile state of the left ventricle. The changes in left ventricular function produced by regular hemodialysis are the combined effects of a decrease in EDV and an increase in the contractile state of the left ventricle.

Renin expression in renal proximal tubule.

Angiotensinogen, angiotensin-converting enzyme, and renin constitute the components of the renin-angiotensin system. The mammalian renal proximal tubule contains angiotensinogen, angiotensin-converting enzyme, and angiotensin receptors. Previous immunohistochemical studies describing the presence of renin in the proximal tubule could not distinguish synthesized renin from renin trapped from the glomerular filtrate. In the present study, we examined the presence of renin activity and mRNA in rabbit proximal tubule cells in primary culture and renin mRNA in microdissected proximal tubules. Renin activity was present in lysates of proximal tubule cells in primary culture. Cellular renin content in cultured proximal tubule cells was increased by incubation with 10(-5) M isoproterenol and 10(-5) M forskolin by 150 and 110%, respectively. In addition, renin transcripts were detected in poly(A)+ RNA from cultured proximal tubule cells by RNA blots under high stringency conditions. In microdissected tubules from normal rats, renin mRNA was not detectable with reverse transcription and polymerase chain reaction. However, in tubules from rats administered the angiotensinogen-converting-enzyme inhibitor, enalapril, renin was easily detected in the S2 segment of the proximal tubule. We postulate the existence of a local renin-angiotensin system that enables the proximal tubule to generate angiotensin II, thereby providing an autocrine system that could locally modulate NaHCO3 and NaCl absorption.

Dissociation of systemic and renal effects in endotoxemia. Prostaglandin inhibition uncovers an important role of renal nerves.

To elucidate the mechanisms responsible for systemic and renal hemodynamic changes in early endotoxemia, the roles of prostaglandins (PG) and renal nerves were investigated. Endotoxin (E, 3 micrograms/kg i.v.) was given to two groups of anesthetized dogs that had undergone unilateral renal denervation: Group I (n = 9) E only; Group II (n = 11) E + indomethacin (10 mg/kg i.v.) or meclofenamate (5 mg/kg i.v.). A third group of dogs (Group III, n = 5) received indomethacin (10 mg/kg i.v.) only. 1 h after E group I dogs, mean arterial pressure (MAP) decreased from 126 to 94 mm Hg (P less than 0.001), and prostacyclin (6-keto-Fl alpha metabolite, PGI2) increased (from 0.64 to 2.08 ng/ml, P less than 0.005). Glomerular filtration rate (GFR) and renal blood flow (RBF) declined comparably both in innervated and denervated kidneys. In marked contrast, group II dogs had a stable MAP (136-144 mm Hg, NS) and no increase in PGI2 levels. Plasma renin activity (0.7-2.5 ng/ml per h, P less than 0.005) increased, and renin secretion was greater in innervated compared with denervated kidneys (255 vs. 74 U/min, P less than 0.01) in these PG-inhibited dogs. In addition, denervated kidneys in group II dogs had a greater GFR (42 vs. 34 ml/min, P less than 0.01) and RFB (241 vs. 182 ml/min, P less than 0.01) than innervated kidneys after E. Group III animals had no significant changes in systemic or renal hemodynamics, plasma renin activity or PGI2 during the study. These results suggest that PGI2 mediates the systemic hypotension of early endotoxemia in the PG-intact animal. Moreover, PG inhibition uncovers an important effect of E to increase efferent renal nerve activity with a consequent decline in GFR and RBF independent of changes in MAP. Finally, the results demonstrate that renal nerves are important stimuli to renin secretion in early endotoxemia via pathways that are PG-independent.

The role of renal nerves and prostaglandins in control of renal hemodynamics and plasma renin activity during hypotensive hemorrhage in the dog.

The effects of hypotensive hemorrhage (HH) on renal hemodynamics and plasma renin activity (PRA) during prostaglandin (PG) synthesis inhibition were examined in three groups of dogs. In each group of animals arterial blood pressure was lowered by a 30% decrement. In the first group of eight control animals, HH was not associated with a significant change in glomerular filtration rate (GFR, 42-36 ml/min, NS); renal blood flow (RBF) declined significantly, from 234 to 171 ml/min, P < 0.05. In the second group of eight animals, pretreated with RO 20-5720 (RO, 2 mg/kg), a competitive inhibitor of PG synthesis, HH was associated with a significant fall in GFR (43-17 ml/min, P < 0.001) and RBF (195-89 ml/min, P < 0.001). In the third group of eight animals, pretreatment with indomethacin (IN, 10 mg/kg), a chemically dissimilar PG inhibitor, HH was also associated with a significant fall in GFR (38-8 ml/min, P < 0.001) and RBF (150-30 ml/min, P < 0.001). Renal denervation attenuated this renal ischemic effect of HH in the presence of PG inhibition. In the RO group, GFR (34 vs. 17 ml/min, P < 0.005) and RBF (145 vs. 89 ml/min, P < 0.025) were significantly greater in denervated vs. innervated kidneys during HH. Similarly, in animals treated with IN, a significantly higher GFR (28 vs. 8 ml/min, P < 0.005) and RBF (101 vs. 30 ml/min, P < 0.005) occurred in denervated as compared to innervated kidneys during HH. With HH, the increase in PRA in the control group (3.34-11.68 ng/ml per h, P < 0.005) was no different than that observed in the RO group (4.96-18.9 ng/ml per h, P < 0.001) or IN group (4.71-17.8 ng/ml per h, P < 0.001). In summary, the present results indicate that renal PG significantly attenuate the effect of HH to decrease GFR and RBF. Furthermore, renal denervation exerts a protective effect against the enhanced renal ischemic effects which occur in the presence of PG inhibition during HH. Finally, PG inhibition does not alter the effect of HH to cause an increase in PRA.

Therapeutic renal arterial occlusion for elimination of proteinuria: 'medical nephrectomy'.

A patient with severe nephrotic syndrome who was too debilitated to undergo surgical nephrectomies, underwent therapeutic bilateral renal artery occlusion by the selective injection of isobutyl 2-cyanoacrylate into the renal arteries. The therapy resulted in dramatic cessation of urine flow and elimination of proteinuria.

Prescribing medication in long-term dialysis units.

Little information is available regarding the current patterns of medication use in long-term dialysis centers. Therefore, we surveyed the medication records of 1,023 patients undergoing long-term dialysis therapy in 27 dialysis centers. The mean number of medications prescribed per patient was 7.7 +/- 0.54, increasing patient age, increasing duration of dialysis, in-center dialysis, and the presence of underlying diabetic and hypertensive nephropathy were associated with increased frequency of medication use. The use of multiple pharmacologic agents was associated with a high frequency of drug duplication (12%), potential dosage error (9%), potential significant drug interaction (15%), and use of contraindicated drugs (2.5%). A lack of individualization of the use of several pharmacologic agents was apparent. An extreme degree of center variability in drug use was also apparent. Periodic review of medication use should be undertaken in the long-term dialysis setting.

The systemic beta-adrenergic pathway to renin secretion: relationships with the renal prostaglandin system.

The relationship between renin release evoked by circulating beta-agonists and the renal prostaglandin (PG) system is incompletely defined. Thus, we evaluated systemic and renal hemodynamic responses to iv (0.5 micrograms/kg X min) and intrarenal arterial (0.6 micrograms/kg X min) infusions of the beta1-agonist prenalterol (PNL) in four separate groups of anesthetized dogs. Consecutive iv PNL infusions (n = 6) resulted in a reversible decrease in mean arterial pressure (130 to 117 mm Hg; P less than 0.05) and increases in cardiac output (3.93 to 4.90 liters/min; P less than 0.001), PRA (1.96 to 5.12 ng/ml X h; P less than 0.01), and 6-keto-PGF 1 alpha levels (190 to 482 pg/ml; P less than 0.01). The glomerular filtration rate and renal blood flow were modestly, but not significantly, decreased by the PNL infusions. In a second group of dogs, the infusion of the PG synthesis inhibitor indomethacin (IN; 10 mg/kg, iv; n = 7) before the second PNL infusion blunted PG increases but did not significantly modify the systemic or renal hemodynamic responses to PNL. The magnitude of the PRA and renin secretory rate (RSR) increases post-IN administration was similar to control values, but the absolute levels achieved were not as great as before IN infusion. To assess the role of the renal baroreceptor pathway to renin release after PNL, a suprarenal clamp was used to maintain a constant renal perfusion pressure during PNL infusion in a third group of dogs. In this group (n = 5), both PRA and RSR (from innervated and denervated kidneys) increased after PNL infusion, although IN again diminished the maximum PRA and RSR responses observed. Finally, the unilateral intrarenal arterial infusion of PNL in the last group of dogs did not alter PRA, RSR, or renal hemodynamics. These results demonstrate that renin release elicited by a circulating beta-agonist functions independently of PG synthesis, and that the pathway operates via an extrarenal mechanism.

Renin regulation in cultured proximal tubular cells.

Recent studies have documented the presence of a complete renin-angiotensin system in the proximal tubule of the kidney: however, little is known about the regulation of renin in this proximal tubular system. Therefore, we performed the present studies to learn whether the behavior of the renin system in cultured proximal tubule is similar to that of the juxtaglomerular renin system. Basal renin secretion from rabbit proximal tubular cells in primary culture was low and not affected by isoproterenol (10(-5) mol/L), diltiazem (10(-5) mol/L), or a zero-calcium bath (O nmol/L). Only the calcium ionophore A23187 (10(-4) mol/L) significantly reduced renin secretion in these cells (from 2.44 +/- 0.37 to 1.14 +/- O.08 ng angiotensin I/mg protein per hour, P<.05). When the proximal tubular cells were lysed so the effects of the test agents on intracellular renin content could be assessed, isoproterenol caused a significant twofold (107 percent) increase (from 2.02 +/- 0.56 to 4.18 +/- 0.81 ng angiotensin I/mg protein per hour, P<.05), whereas diltiazem, A23187, and zero- and high-calcium baths did not produce a significant change. The effects of these agents on renin mRNA were examined in rabbit and rat proximal tubular cells in primary culture with the use of an S1 nuclease protection assay. Densitometry analysis of renin mRNA and either GAPDH mRNA (rat) or alpha-actin (rabbit) showed no significant alterations in renin mRNA abundance. In summary, these results confirm the presence of renin mRNA in cultured proximal tubular cells and suggest that a low-level, constitutive secretion of renin occurs in this system that is decreased by A23187. Moreover, the results also suggest that proximal tubular renin is regulated, albeit differently from the juxtaglomerular renin system. Finally, short-term increments in proximal tubular renin occur without a change in renin mRNA.

Implications of nonsteroidal anti-inflammatory drug therapy.

This panel considered the clinical implications of nephrotoxicity due to nonsteroidal anti-inflammatory drugs. Although the clinical benefits and safety of these agents are well established, the drugs may adversely affect renal perfusion, electrolyte balance, and blood pressure in susceptible patients. The renal effects of these agents are directly related to their potency in inhibiting renal prostaglandins as reflected by inhibition of urinary prostaglandin excretion; however, none of the nonsteroidal anti-inflammatory drugs is completely free of the risk. Hyperkalemia is the most frequently observed adverse effect, most commonly occurring in patients with diabetes mellitus, patients with mild to moderate renal insufficiency, and patients receiving beta blockers, angiotensin converting enzyme inhibitors, or potassium-sparing agents. Patients at risk for the development of fluid retention and acute reductions in glomerular filtration rate include those with congestive heart failure, systemic lupus erythematosus, chronic glomerulonephritis, or liver failure with ascites, those receiving diuretics, premature infants, and possibly the elderly. Monitoring of serum creatinine and electrolyte levels, blood pressure, and body weight is suggested for susceptible patients receiving these agents.

Gas exchange during dialysis. Contrasting mechanisms contributing to comparable alterations with acetate and bicarbonate buffers.

Although arterial hypoxemia during hemodialysis is common and may contribute to dialysis morbidity, the mechanisms responsible remain uncertain. Additionally, controversy exists as to whether bicarbonate dialysate produces less hypoxemia than acetate dialysate. The short- and long-term effects of acetate dialysate and bicarbonate dialysate on gas exchange were compared in eight stable patients undergoing dialysis using a closed, proportioning system and a double-blind, crossover study design. Dialysate was sampled immediately proximal and distal to the dialyzer to determine its contribution to total carbon dioxide elimination. Ventilatory parameters and blood gas values were measured before dialysis, at one hour, and after dialysis. Arterial oxygen tension fell significantly and comparably at one hour with both dialysates, whereas the alveolar-arterial oxygen gradient increased only slightly. Despite hypoxemia, minute ventilation decreased by 4 to 18 percent, and arterial carbon dioxide tension was unchanged. Although total carbon dioxide elimination was unchanged in all groups, there was a significant decrease in lung total carbon dioxide elimination with acetate dialysate of 9.23 +/- 2.69 to 7.74 +/- 1.57 mmol per minute on Day 1 (mean +/- SD, p less than 0.025) concomitant with a loss of total carbon dioxide into the bath of 2.04 +/- 0.20 mmol per minute, resulting in a significant reduction in respiratory quotient (0.92 +/- 0.07 to 0.75 +/- 0.05, p less than 0.01). In contrast, there was a gain of total carbon dioxide into the blood of 1.64 +/- 0.45 mmol per minute with bicarbonate dialysate, which resulted in an increased pH at one hour compared with acetate dialysate (7.39 +/- 0.04 versus 7.35 +/- 0.03, p less than 0.05). Hypoxemia persisted after dialysis in all groups and was associated with an increased alveolar-arterial oxygen gradient in three of the four groups. It is concluded that transitory hypoventilation contributes to comparable hypoxemia with both acetate and bicarbonate dialysates by different mechanisms. With acetate dialysate, there is a decrease in carbon dioxide load to the lungs, whereas with bicarbonate dialysate, the mechanism responsible appears to be a suppression of respiratory drive resulting from a gain of bicarbonate from the dialysate. Additionally, neither dialysate prevents post-dialysis hypoxemia, which is associated with an increased alveolar-arterial oxygen gradient resulting from a mechanism that remains to be elucidated.

Regulation of the genes for 11beta-hydroxysteroid dehydrogenase type 1 and type 2 in the kidney of the Dahl rat.

BACKGROUND: An isoenzyme of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), 11beta-HSD-2 confers aldosterone specificity on the mineralocorticoid receptor (MR) and is found collocated in renal cortical collecting duct cells with the MR. To investigate whether the salt sensitivity of the Dahl salt-sensitive (S) rat is due to 11beta-HSD deficiency, we measured 11beta-HSD-1 and 11beta-HSD-2 mRNA levels in the kidneys of Dahl-S and Dahl salt-resistant (R) rats. In addition, we studied the effects of gender, age and dietary sodium on expression of mRNA for the two isoforms. S and R rats were placed on low- or high-sodium (HNa) diets and sacrificed after 33 and 115 days. Rat kidney RNA was isolated and 11beta-HSD-1 and 11beta-HSD-2 mRNA levels were measured on Northern filter hybridization using isoform-specific probes. RESULTS: No strain differences were observed in the mRNA expression of the two isoforms of 11beta-HSD under any of the experimental conditions. No gender or age differences were observed in 11beta-HSD-2 mRNA but HNa diet almost doubled 11beta-HSD-2 mRNA (P<0.0009). 11beta-HSD-1 mRNA levels were consistently higher, more than double, in male rats versus females rats (P<0.0001), and in the 115-day-old rats versus the 33-day-old rats (P<0.0001). Dietary sodium intake did not affect 11beta-HSD-1 mRNA levels. CONCLUSIONS: There is no difference in the expression of the two isoforms of 11beta-HSD in the kidneys of the S and R rats, which might explain the salt sensitivity and higher blood pressure of the S rat. Renal 11beta-HSD-1 mRNA levels are higher in male than in female rats, and in the older rats of both strains. In the kidney, the 11beta-HSD-2 gene is regulated by sodium status but is not affected by gender or age.

Effect of sertraline hydrochloride on dialysis hypotension.

Hemodialysis hypotension (HH) is a very common disorder and has a multifactorial etiology. Autonomic dysfunction occurs in up to 50% of patients with end-stage renal disease (ESRD) and plays a key role in HH in some patients. Sertraline hydrochloride, a central nervous system serotonin reuptake inhibitor, has been shown to be an effective treatment of hypotension caused by autonomic dysfunction in disorders such as neurocardiogenic syncope and idiopathic orthostatic hypotension. This study sought to determine whether sertraline was effective in ameliorating HH. A retrospective chart analysis was performed that included nine consecutive patients (aged > or = 54 years, time on hemodialysis > or = 2.2 years) placed on sertraline (50 to 100 mg/d) for depression who also had HH (defined as prehemodialysis systolic blood pressure [SBP] < or = 100 mm Hg, > or = 40 mm Hg decrease in SBP during hemodialysis, SBP <90 mm Hg, any diastolic blood pressure <40 mm Hg, or a decrease in blood pressure-causing symptoms) before treatment with sertraline. The data from a 6-week pre-sertraline period were compared with the data from a 6-week sertraline period (defined as 6 weeks after drug begun). Blood pressure medications were unchanged during the trial period of sertraline. However, nadir mean arterial pressure recorded during a given dialysis session in the pre-sertraline period (55+/-4 mm Hg) was significantly lower than that recorded in the sertraline period (68+/-5 mm Hg; P < 0.05). In addition, the number of hypotensive episodes (same definition as HH) per dialysis session during the sertraline period was significantly lower than that during the pre-sertraline period (mean, 0.6+/-0.2 episodes per session v 1.4+/-0.3 episodes per session; P < 0.005). The number of therapeutic interventions required for hypotension during the sertraline period was also significantly less than that during the pre-sertraline period (mean, 1.7+/-0.8 interventions v 11.0+/-3.0 interventions; P < 0.005). The urea reduction ratio (62.7%+/-4.7% v 63.1%+/-9.3%; P = NS) and hematocrit (28.9%+/-0.8% v 29.5%+/-1.0%; P = NS) did not change significantly. It is concluded that the short-term (6 weeks) use of sertraline hydrochloride reduces HH in some patients with ESRD. A possible mechanism for this effect is sertraline-induced attenuation of the paradoxical sympathetic withdrawal that may underlie HH in some patients with ESRD.

Clinical acute renal failure with nonsteroidal anti-inflammatory drugs.

Under baseline euvolemic conditions, prostaglandins play little to no role in the minute-to-minute regulation of renal function. Where these compounds come to serve a major role is in the setting of a systemic or intrarenal circulatory disturbance. In the setting of a decreased absolute or effective circulatory volume, a number of vasoconstrictor effectors are stimulated whose function is to preserve the systemic circulation. At the same time, these compounds stimulate the synthesis of renal vasodilatory prostaglandins. In turn, prostaglandins oppose the vasoconstrictive effect of these effectors such that the renal circulation remains well-preserved while the rest of the circulation is clamped down. Predictably, inhibition of prostaglandin synthesis would lead to unopposed renal vasoconstriction, resulting in a precipitous decline in renal function. Clinical conditions in which the renal circulation is critically dependent on the effect of vasodilatory prostaglandins include volume depletion, congestive heart failure, and cirrhosis. There are other conditions in which the circulatory volume is normal, but due to the intrarenal generation of vasoconstrictors, the kidney is similarly dependent on vasodilatory prostaglandins. Such conditions include glomerulonephritis and urinary tract obstruction.

Anemia, hypertension, and myocardial dysfunction in end-stage renal disease.

Cardiovascular disease remains the major cause of mortality in patients with end stage renal disease (ESRD). The pathophysiology of cardiac dysfunction in ESRD is complex and not fully understood. However, it appears that the two major determinants of left ventricular (LV) hypertrophy and dysfunction are anemia and hypertension, both of which are very common in ESRD patients. Early and aggressive correction of anemia and hypertension may have a significant impact on cardiac disease in ESRD patients. This article presents a discussion on the management of anemia and hypertension, and the current information available on the pathogenesis and management of LV dysfunction in ESRD.

The outcome of the urban renal patient: the importance of social factors and center effects.

Caring for the urban renal patient can be a challenge to providers for many reasons. Although racial and socioeconomic factors have an impact on the health of this population, one must also consider the effect of the urban environment on the ill, especially those with renal disease. This article reviews the state of health among the poor and nonwhite minorities, who tend to inhabit the urban regions of this country, and then highlights the unique characteristics of those with renal disease. The impact of the Medicare end-stage renal disease (ESRD) program and center-specific quality of care on the outcome of the urban patient with ESRD is explored.

The renal proximal tubule renin-angiotensin system.

In conclusion, a complete RAS is present in the mammalian proximal tubule that is potentially autocrine and paracrine in nature. Maneuvers that stimulate renin in JG cells and renal vasculature appear to also stimulate renin in the proximal tubule. The subcellular localization of the different components and the regulation of this epithelial RAS still remain to be defined. This RAS may be important in regulation of proximal tubule NaCl and NaHCO3 transport. Finally, one can speculate that activation of this RAS may play a pathogenetic role in some patients with essential hypertension and in the hypertension and cyst growth seen in autosomal dominant polycystic kidney disease.

Pulmonary gas exchange during dialysis in patients with obstructive lung disease.

Hypoxemia occurs during routine hemodialysis and may contribute to morbidity, but its cause is not well understood. We reasoned that patients with COPD would be more vulnerable to abnormalities in gas exchange with dialysis. Thus, to investigate the cause of dialysis-related hypoxemia, we measured gas exchange in a group of stable dialysis patients with normal pulmonary function (n = 6) and a group of dialysis patients with COPD (n = 6). Measurements were made predialysis, at 1 h, and postdialysis with both acetate and bicarbonate dialysates. Acetate dialysis decreased PaO2 in normal and COPD patients at 1 h and postdialysis. Acetate-induced hypoxemia was associated with reduced respiratory CO2 excretion and hypoventilation but PaCO2 did not change. This decrease in CO2 excretion resulted from CO2 fixation during acetate metabolism and modest CO2 loss across the dialyzer. Hypoxemia occurred only postdialysis with bicarbonate dialysate in normal and COPD patients. An increased P(A-a)O2 occurred postdialysis with both dialysates, and was most consistently observed in the COPD patients. In summary, at least two mechanisms contribute to dialysis hypoxemia. With acetate dialysate, alveolar hypoventilation from CO2 unloading occurs at 1 h and postdialysis due to acetate metabolism. However, abnormalities in ventilation/perfusion contribute to postdialysis hypoxemia observed with both dialysates. In addition, the decrement in PaO2 associated with dialysis is similar in normal and COPD patients, although preexisting COPD makes postdialysis changes more apparent.

Adrenal insufficiency after unilateral radical nephrectomy.

A case of adrenal insufficiency occurring after unilateral radical nephrectomy is presented. Recommendations for identification and treatment of this condition are discussed.

Effect of atriopeptin III on renin release in vitro.

The ability of atriopeptin III (AP) to directly inhibit renal renin release has not been resolved. This issue was examined in a series of experiments performed in a system of rat renal cortical slices (dry weight 1.91 mg) in which the goal was to explore the effects of AP on renin release induced by cyclic AMP (cAMP)-coupled stimuli or by agents which are believed to decrease intracellular calcium (Cai). Concentration response relationships were initially established for all test agents. The cAMP stimuli utilized were isoproterenol (10(-5) M), forskolin (10(-5) M), and dibutyryl cAMP (3 X 10(-4) M); each of these agents produced a significant increase in renin release in the system (with isoproterenol a 59% increase, with forskolin 37%, and with dibutyryl cAMP 52%). The addition of AP (2.09 X 10(-8) M, a minimum inhibitory concentration derived from preliminary studies) significantly blunted these increases; in the case of the dibutyryl cAMP-stimulated renin release, the inhibition was partial as a significant 25% increase in renin occurred in the presence of AP. The addition of the calcium channel blocking agent diltiazem (10(-4) M) resulted in a significant increase in renin release (364 to 567 ng X mg-1, p less than .05) which was not blocked by the addition of AP. Similarly, TMB-8 (0.6 X 10(-4) M), another agent thought to lower Cai, also resulted in increased renin release (455 to 810 ng X mg-1), p less than .01) which was also unaffected by the addition of the AP. In summary, these results show that AP is capable of partially inhibiting renin release in vitro, particularly renin release coupled to cAMP action. In contrast, renin release induced by a decline in Cai appears to be unaffected by the addition of AP.