The kidney in the graphic arts.
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Anatomy, Artistic↗
Biomedical subjects
S K Mujais
Publications and source records attributed to S K Mujais.
Modulation of renal sodium-potassium-adenosine triphosphatase by aldosterone. Effect of high physiologic levels on enzyme activity in isolated rat and rabbit tubules.
The purpose of this study was to determine the nephron site, time course, and mechanism of mineralocorticoid action on renal tubular Na-K-ATPase in rats and rabbits, without dietary manipulation and by using the natural mineralocorticoid aldosterone. Sustained, high physiologic levels of circulating aldosterone mimicking those produced endogenously during potassium loading or sodium deprivation were provided by constant delivery of the hormone in doses of 5 or 50 micrograms/100 g body wt per 24 h, respectively, from osmotic minipumps implanted subcutaneously. In adrenal-intact rats receiving the 5-microgram dose, aldosterone levels were similar to those seen in animals fed a high K diet and produced a time-dependent increase in Na-K-ATPase activity in the cortical-collecting tubule (CCT) to a level 103% higher than in controls after 7 d (2,007 +/- 178 vs. 989 +/- 72 pmol/mm per h, P less than 0.001); the enzyme activity in the proximal convoluted tubule, medullary thick ascending limb, and the inner stripe of the medullary-collecting tubule did not change significantly. The increment in CCT Na-K-ATPase was larger (142%) in animals receiving for the same period of time the 50-micrograms dose, which produced circulating aldosterone levels similar to those of sodium-deprived rats. A significant stimulation of Na-K-ATPase activity was seen in the CCT of adrenalectomized rats after 24 h of treatment with either dose of the hormone, and at 12 h only in animals receiving the 50 micrograms/100 g per 24 h regimen. To determine whether the enhanced Na-K-ATPase activity produced by aldosterone is due to synthesis of new enzyme units or to alteration in its kinetics, we examined the ouabain-binding capacity and the affinity for Na and K of the enzyme from CCT of rabbits treated with 5 micrograms/100 g body wt per 24 h aldosterone for 3 d. These experiments revealed a parallel increment on Na-K-ATPase activity and specific [3H]ouabain binding in aldosterone-treated rabbits, while the affinity of the enzyme for either sodium or potassium was unaltered. The results of this study indicate that high physiologic levels of aldosterone simulating those measured during K loading or Na deprivation lead to a segment-specific increase in Na-K-ATPase activity in the CCT. This effect was time-and dose-dependent and was due to an increase in the number of active enzyme units. The segmental specificity and time course of the increase in enzyme activity suggest that modulation of Na-K-ATPase by aldosterone plays a role in the chronic adaptation of the CCT to altered availability of sodium and potassium, and therefore in the homeostasis of these cations by the kidney.
Adrenalectomy↗
Relationship between adrenal steroids and renal Na-K-ATPase. Effect of short-term hormone administration on the rat cortical collecting tubule.
Mineralo- and glucocorticoids stimulate renal Na-K-ATPase activity if given over a few days, but their immediate effect on the enzyme (i.e. within the time period required to alter electrolyte transport) remains controversial. We evaluated the short-term (3 h) in vivo effect of physiologic and pharmacologic doses of the natural glucocorticoid (corticosterone) and mineralocorticoid (aldosterone), and of a semisynthetic glucocorticoid (dexamethasone) on Na-K-ATPase activity in cortical collecting tubules microdissected from adrenalectomized rats. This nephron segment was chosen because it is a major target site for both classes of corticoids. Neither corticosterone (0.006, 0.6, and 5 mg/100 g body wt, IM), nor dexamethasone (5 mg/100 g body wt, IM) or aldosterone (10 micrograms and 50 micrograms, IV) altered significantly Na-K-ATPase activity in the cortical collecting tubule of these animals 3 h after administration. These results confirm our previous observations in the mouse, and suggest that the enhancing effect of corticosteroids on the renal enzyme seen after longer intervals represents a secondary phenomenon, possibly related to augmentation of the sodium load presented to the pump.
Adenosine Triphosphatases↗
Course of renal pathology in patients with systemic lupus erythematosus.
Evaluation of the course of lupus nephropathy by serial kidney biopsy in 50 patients revealed a complex pattern of transitions from one histologic class to another. A high rate of transformations (56 percent) was observed, with fewer than half the patients remaining in the original category. Although the general trend was towards transformation to a less severe lesion (WHO classes III and IV transforming into classes II and V), this was certainly not the rule for all individual classes. These transformations were rarely predictable on the basis of available clinical, laboratory, or pathologic information, and were less common in younger patients. These results help clarify the pathologic behavior of lupus nephropathy in the modern therapeutic era and highlight the value of pathologic examination for the planning and evaluation of therapy in selected patients.
Adult↗
Transient renal dysfunction during initial inhibition of converting enzyme in congestive heart failure.
Treatment with captopril in resistant normotensive congestive heart failure is associated with a pronounced reduction in blood pressure, particularly after the first dose. The effects of this reduction on renal function were assessed in 10 patients at the beginning of and during chronic treatment (at one week and three months). Renal plasma flow and glomerular filtration rates were measured by isotope clearance during water diuresis. The first dose of captopril (25 mg) led to a pronounced fall in renal plasma flow and glomerular filtration rates together with a decrease in mean arterial pressure; this fall correlated with baseline plasma renin activity. These changes were paralleled by decreases in water and sodium excretion. In contrast, by the end of the first week of treatment a similar fall in mean arterial pressure occurred together with a pronounced increase in renal plasma flow; the glomerular filtration rate was maintained and there was no decrease in water and sodium excretion. This new response pattern recurred after three months of treatment. The difference in response at different stages of treatment may reflect the balance between the different mechanisms influencing kidney dynamics in heart failure and their alteration by converting enzyme inhibition. The sustained increase in renal plasma flow during chronic treatment with captopril may account for the continued control of heart failure in these patients.
Adult↗
Regulation of renal Na-K-ATPase in the rat. Role of the natural mineralo- and glucocorticoid hormones.
Both mineralo- and glucocorticoids stimulate renal Na-K-ATPase, but their relative role in the regulation of the enzyme remains controversial. In this study we measured Na-K-ATPase activity in the cortical collecting tubule (CCT) of adrenalectomized rats replaced with either the native mineralocorticoid (aldosterone) or glucocorticoid (corticosterone) in doses calculated to yield previously determined physiologic concentrations of these hormones (5 ng X dl-1 and 5 micrograms X dl-1, respectively). This was achieved by continuous delivery of aldosterone (1 microgram X 100 g-1 X d-1) from an osmotic minipump or of corticosterone (2 pellets of 20 mg each), implanted subcutaneously either at adrenalectomy or 7 d later, when Na-K-ATPase activity reached its nadir. Adrenalectomized rats not receiving hormone replacement and adrenal-intact animals served as controls. The CCT was chosen because it contains the highest concentration of binding sites for both hormones. Na-K-ATPase activity declined 52% in the CCT of untreated adrenalectomized rats after 7 d, and remained unchanged thereafter. Physiologic replacement doses of aldosterone prevented this decline and restored the activity of the enzyme after it had been allowed to decrease maximally following adrenal ablation, whereas similar replacement of corticosterone was without effect. These observations suggest that under physiologic conditions Na-K-ATPase in the CCT, a probable target nephron segment of both hormones, is under mineralocorticoid rather than glucocorticoid control.
Adenosine Triphosphatases↗
Predictive value of angiotensin II antagonists in renovascular hypertension.
An angiotensin II antagonist, sarcosine-1, threonine-8 angiotensin II ( [Sar1, Thr8] A II), was infused preoperatively in 14 patients with renal artery stenosis. Postoperative graft patency was documented by renal flow scan in 13 patients. One of these required antihypertensive therapy immediately after surgery, while the other 12 had a significant BP reduction in the first postoperative week (141 +/- 3.7 to 110 +/- 1.6 mm Hg). With longer follow-up, six patients remained normotensive (group 1), while the other six had "residual hypertension" (group 2). There was no significant difference between the two groups as regards age, preoperative BP level, plasma renin activity, blood volume, or response to [Sar1, Thr8] A II. In contrast, clinical signs were most helpful in predicting response to surgery. "Cured" patients had shorter duration of hypertension (less than one year) than patients with residual hypertension, and less impairment of renal excretory function; three patients in group 2 but none in group 1 had a history of malignant hypertension. The decision to operate remains a multifactorial evaluation and cannot be based on results of any single test alone.
Adult↗
Reversal of left ventricular hypertrophy with captopril: heterogeneity of response among hypertensive patients.
Reversal of left ventricular hypertrophy (LVH) has been reported not to occur with all antihypertensive agents. Moreover, a dissociation between blood pressure response to medical therapy and reversal of ventricular hypertrophy has been previously observed. To evaluate the effects of captopril we studied the electrocardiographic (ECG) changes in 26 severe hypertensive patients who received the drug for more than one year. In 14 patients with normal pretreatment ECG, captopril controlled blood pressure effectively [132 +/- 2.9 (SE) to 104 +/- 3.9 mmHg, p less than 0.001], but had no effect on ECG voltage. In 12 patients with pretreatment LVH, two different response patterns were observed despite similar blood pressure control (144 +/- 4.9 to 102 +/- 3.1 mmHg and 148 +/- 7.3 to 109 +/- 7.3 mmHg, p less than 0.001 for both): seven had complete normalization of ECG while five had residual LVH pattern. No significant difference was found between the latter two groups in regard to age, sex, weight, etiology of hypertension, pretreatment ECG voltage, blood pressure, plasma renin activity, duration of treatment and duration of maintained blood pressure control. The reversal of LVH pattern occurred early (between 12 to 16 months) with no overall correlation between lowering of blood pressure and ECG voltage changes. The heterogeneity of response observed in this study suggests that factors other than blood pressure control modify the reversal of cardiac hypertrophy by antihypertensive therapy.
Blood Pressure Determination↗
Nondiabetic renal disease in patients with diabetes mellitus.
Renal diseases other than diabetic nephropathy were found in 10 of 122 diabetic patients who underwent renal biopsy between 1960 and 1982. These diseases included lupus glomerulonephritis, acute post-streptococcal glomerulonephritis, membranoproliferative glomerulonephritis (type I), focal glomerulosclerosis, idiopathic membranous nephropathy, and nonspecific immune complex glomerulonephritides. Because some of these disorders can alter the management and prognosis of renal disease in diabetic patients, the appearance of urinary abnormalities or deterioration in renal function inconsistent with the natural history of diabetic nephropathy raises the possibility of a nondiabetic renal disease and should lead to a more detailed evaluation.
Adult↗
Early diagnosis of pericarditis in acute myocardial infarction.
Pericarditis complicating acute myocardial infarction assumes increasing importance in this era of quantitating infarct size by precordial ST segment mapping. Early recognition of this complication avoids diagnostic and therapeutic errors. In this study we looked for factors that could alert to the early diagnosis of pericarditis, such as ST elevation measured within 24 hours from onset, extent of CPK, LDH, and SGOT elevation, as well as degree of pump dysfunction. ST segment elevation in millimeters on admission seemed to be one factor that was of predictive value in this condition. Pericarditis occurred in three forms: (1) within a few hours from the onset of myocardial infarction and this form seems to carry a high mortality rate; (2) a more common variety occurs within 24 to 72 hours from onset and carries a higher mortality rate than matched controls; and (3) the late syndrome of Dressler's, not observed in our series. Aside from increased incidence of heart failure, other complications of myocardial infarction and the coronary risk factors were not significantly higher in patients with pericarditis. Salicylate treatment offers immediate relief in the majority of patients.
Aspartate Aminotransferases↗
Principles and clinical uses of diuretic therapy.
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Diuretics↗
Heparin free hemodialysis using heparin coated hemophan.
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Adult↗
Tubular CO2 production from glutamine in the rat: segmental profile and modulation.
The present study was designed to test whether tubular carbon dioxide production from the carbon skeleton of uniformly 14C-labelled glutamine exhibits quantitative and qualitative segmental heterogeneity. Our results show that CO2 production from glutamine in the proximal convoluted tubule (PCT) was dependent on substrate concentrations and is saturable at 10(-4) M of glutamine. Glutamine oxidation was demonstrable in all nephron segments examined. The PCT is the quantitatively predominant site of glutamine oxidation. Intermediate nephron segments, however, such as the thick ascending limb (MAL) and the distal convoluted tubule possess a significant capacity for glutamine oxidation, particularly when examined in terms of tubular protein content. Modulation of glutamine oxidation by extracellular pH was segment specific. Stimulation by acidosis and inhibition by alkalosis were observed in the PCT while carbon dioxide production from glutamine in the MAL was pH-insensitive. Glutamine oxidation was closely linked to sodium transport and greatly decreased by inhibition of Na-K-ATPase. In both the PCT and MAL, glutamine oxidation was inhibited by high extracellular potassium concentrations and in the PCT enhanced by extracellular hypokalemia. N-Ethyl maleiamide, an inhibitor of proton ATPase, led to almost complete cessation of CO2 production from the substrate in both PCT and MAL. Acetazolamide, an inhibitor of carbonic anhydrase, led to a partial reduction in carbon dioxide formation in the PCT, but did not affect glutamine oxidation in the MAL. We conclude that segmental qualitative heterogeneity characterizes oxidation of the carbon skeleton of glutamine with proximal segments showing the predictable effects of pH changes and carbonic anhydrase inhibition. The MAL appears to be nonmodulating.
Animals↗
Hypertension in obese patients: hemodynamic and volume studies.
Distinct hemodynamic and volume characteristics have been suggested for established hypertension in severe obesity, namely, a high cardiac output, and expanded blood volume, and a normal peripheral resistance. To evaluate whether hypertension in moderately obese patients represents a separate entity that can be defined by hemodynamic and volume profiles, we studied these in 50 such patients and compared results with those obtained in 59 nonobese essential hypertensives and 25 normal subjects. Both obese and nonobese hypertensives had a normal cardiac index (men, 2.8 +/- 0.1 vs 2.8 +/- 0.09 liter/min/m2; women, 2.9 +/- 0.1 vs 2.8 +/- 0.1 liter/min/m2, respectively) and similarly elevated total peripheral resistance (men, 47.1 +/- 2.3 vs 46.5 +/- 1.9 U . m2; women, 45.0 +/- 2.4 vs 44.0 +/- 1.3 U . m2, respectively) as compared to normals (cardiac index: men, 2.9 +/- 0.09 liter/min/m2, women, 3.4 +/- 0.2 liter/min/m2; total peripheral resistance: men, 29.4 +/- 1.0 U . m2, women, 28.3 +/- 2.8 U. m2). Volume measurements corrected to body surface area showed that both obese and nonobese hypertensive patients had lower blood volume (men, 2.6 +/- 0.05 vs 2.5 +/- 0.05 liter/m2; women, 2.2 +/- 0.05 vs 2.3 +/- 0.05 liter/m2, respectively) than normals (men, 2.9 +/- 0.08 liter/m2; women, 2.5 +/- 0.08 liter/m2). The results of this study suggest that hypertension in moderately obese subjects is similar in its hemodynamic and volume profiles to hypertension in the nonobese and that the presence of obesity does not alter the hemodynamic characteristics of established essential hypertension.
Adult↗
Responses of the stenosed and contralateral kidneys to [Sar1, Thr8] AII in human renovascular hypertension.
To better define the intrarenal hemodynamic effects of angiotensin in human renovascular hypertension, 10 patients underwent renal hemodynamic and functional measurements before and during infusion of a competitive angiotensin analog, [Sar1, Thr8] AII. Eight had technically satisfactory split function studies. Despite a fall in mean arterial pressure (132 +/- 6 to 121 +/- 6 mm Hg, p less than 0.05) and humoral changes consistent with angiotensin-mediated hypertension, the intrarenal effects of this analog were commonly those of an angiotensin agonist, producing vasoconstriction and sodium retention. This was quantitatively greatest in the contralateral kidney, whose preinfusion sodium excretion (86 +/- 30 microEq/min vs 25 +/- 9 microEq/min, p less than 0.02) and glomerular filtration rate (76 +/- 7 ml/min vs 41 +/- 7 ml/min, p less than 0.01) were higher than the stenotic kidney. In some cases, an increase in renal blood flow and rise in sodium excretion were evident during angiotensin blockade, suggesting a tonic intrarenal action of angiotensin. Although renin vein renin values differed markedly between the stenotic and contralateral kidney (ratio = 2.05 +/- 0.30), relative changes in effective renal plasma flow were correlated (r = 0.84: p less than 0.01) during infusion of this analog. These results underscore the differences in sensitivities between vascular beds to the effects of angiotensin II and the major role of the contralateral kidney in renal function and sodium homeostasis in human renovascular hypertension.
Adult↗
Correlation between peritoneal equilibration test and dialysis adequacy and transport test, for peritoneal transport type characterization. Mexican Nephrology Collaborative Study Group.
OBJECTIVE: The aim of this study was to analyze the correlation between the peritoneal equilibration test (PET) and the dialysis adequacy and transport test (DATT) for peritoneal transport type characterization, and the degree of patients' acceptance for each test. DESIGN: Cross-sectional, observational multicenter study. SETTING: Five referral (tertiary) dialysis centers of institutional practice. PATIENTS: The study included 107 adult continuous ambulatory peritoneal dialysis (CAPD) patients with a prescription of four exchanges of 2 L per day, irrespective of age, gender, cause of end-stage renal disease, time on dialysis, nutritional status, or residual renal function. Patients on immunosuppressive therapy and those with cancer, hepatitis B, or HIV, and those having a peritonitis episode within the previous 30 days, or three or more episodes during the previous 12 months, were excluded. MAIN MEASURES: Peritoneal transport type as classified by creatinine and urea dialysis-to-plasma (D/P) ratios by PET and DATT. RESULTS: Correlation coefficients between D/P ratios for creatinine and urea, obtained for the PET and the DATT, were 0.73 for D/P creatinine and 0.96 for D/P urea. Patients were classified into high, high-average, low-average, and low transport categories according to the mean and standard deviation of D/P creatinine values obtained from the PET at 4 hours. These values showed excellent concordance with those generated from the DATT data (alpha = 0.82, 95% confidence interval 0.67 - 0.93). Nineteen percent of patients showed discordance in their category when classified according to the PET versus the DATT. Patients' acceptance was better for the DATT than for the PET, as evaluated with a questionnaire. CONCLUSION: The DATT is an easy, inexpensive, and reliable test to assess peritoneal transport type, and it also provides information about peritoneal clearance of solutes and ultrafiltration. The DATT has better patient acceptance than the PET. Since the DATT has only been validated for patients on a fixed CAPD daily schedule of 4 x 2 L, the results should be confined only to patients receiving such a prescription.
Adolescent↗
Dialysis in acute renal failure--muddying the waters.
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Acute Kidney Injury↗