Polymorphic acetylation and aminopyrine demethylation in Gilbert's syndrome.

Polymorphic acetylation was investigated in twenty-seven patients with Gilbert's syndrome using the sulphadimidine test. Whereas the finding of 51% slow acetylators in seventy-eight control persons agreed well with the expected frequency in a continental European population, the prevalence of slow acetylators in Gilbert's syndrome was increased to 78% (P less than 0.03, Woolf's G-test). After oral administration of 14C-aminopyrine there was no significant difference between seventeen patients with Gilbert's syndrome and twenty-seven normal controls in total plasma clearance of aminopyrine (280 +/- SD 100 and 270 +/- 60 ml/min) and in the disappearance curve of 14CO2 in breath (0.23 +/- 0.04 and 0.22 +/- 0.03 h-1, respectively). Thus, whereas aminopyrine metabolism appears unaffected in the examined patients, the data documents a new association between slow acetylator status and Gilbert's syndrome.     

Propafenone in the conversion of atrial fibrillation in patients suffering from chronic renal failure.

Propafenone is a class Ic agent for the treatment of atrial arrhythmias with a main hepatic metabolism. This approach might play an important role in the management of atrial arrhythmias in patients with chronic renal failure. The goal of this study was to investigate the effects of propafenone in patients with atrial fibrillation and chronic renal failure. We studied 24 patients with atrial fibrillation that was associated with chronic renal failure. The conversion time was 8.4 +/- 3.2 minutes (range, 5-19 minutes) with intravenous propafenone at 1 mg/kg bolus over 5 minutes. In 21 patients (87%) sinus rhythm was restored and no serious adverse and proarrhythmic effects were noted. Corrected QT interval was not prolonged after conversion (from 0.33+/-0.06 mm to 0.32+/-0.04 mm, p = not significant). Two and 6 months later the cardioversion left atrial size significantly decreased in 19 patients who had been converted to sinus rhythm. The parameters of renal function were unchanged after propafenone therapy. We concluded that: 1) propafenone is active and acts significantly faster in converting atrial fibrillation in patients with chronic renal insufficiency; 2) propafenone administration appears to be safe in patients with chronic renal failure; and 3) left atrial size decreases upon conversion to sinus rhythm as seen at 6-month follow-up.     

Increased salivary concentration of human epidermal growth factor in patients undergoing CAPD

Epidermal growth factor (EGF) was measured in the saliva of 36 patients with chronic renal failure (CRF) and 29 matched control subjects. Salivary EGF in controls was 0.65 +/- 0.009 nmol/L compared with 0.99 +/- 0.24 nmol/L in nondialyzed CRF patients, 1.15 +/- 0.23 in hemodialyzed patients and 1.96 +/- 0.25 (p less than 0.01, Wilcoxon Rank Sum Test) in CAPD-treated patients. On Sephadex chromatography, the major peak of immunoreactive EGF from patient and control saliva samples coeluted with purified human EGF. We conclude that salivary concentrations of human EGF are significantly elevated in end-stage renal failure, particularly in patients treated by CAPD.     

Immunoreactive N-terminal pro-atrial natriuretic peptide in human plasma: plasma levels and comparisons with alpha-human atrial natriuretic peptide in normal subjects, patients with essential hypertension, cardiac transplant and chronic renal failure

1. Plasma levels of immunoreactive N-terminal pro-atrial natriuretic peptide (N-terminal ANP) have been measured in 25 normal subjects, 29 patients with essential hypertension, six cardiac transplant recipients, seven patients with dialysis-independent chronic renal failure and 11 patients with haemodialysis-dependent chronic renal failure. Plasma was extracted on Sep-Pak cartridges and N-terminal ANP immunoreactivity was measured using an antibody directed against pro-ANP (1-30). 2. Plasma levels of N-terminal ANP (means +/- SEM) were 235.3 +/- 19.2 pg/ml in normal subjects and were significantly raised in patients with essential hypertension (363.6 +/- 36.3 pg/ml), in cardiac transplant recipients (1240.0 +/- 196.2 pg/ml), in patients with chronic renal failure not requiring dialysis (1636.6 +/- 488.4 pg/ml) and patients with chronic renal failure on maintenance haemodialysis (10336.1 +/- 2043.7 pg/ml). 3. There were positive and significant correlations between the plasma levels of N-terminal ANP and alpha-human ANP (alpha-hANP) with individual correlation coefficients of 0.68 within the normal subjects, 0.47 in patients with essential hypertension, 0.78 in patients with dialysis-independent chronic renal failure and 0.68 in patients with haemodialysis-dependent chronic renal failure (P less than 0.05 in every case).(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased plasma endothelin in NIDDM patients with retinopathy.

OBJECTIVE--To elucidate the significance of ET in diabetic microvascular disease. RESEARCH DESIGN AND METHODS--We determined plasma levels of ir-ET-1 in 25 NIDDM patients without hypertension and/or renal dysfunction. RESULTS--The plasma levels of ir-ET-1 in NIDDM patients with simple (n = 8) and proliferative (n = 8) retinopathy were 0.58 +/- 0.04 pM and 0.60 +/- 0.04 pM, respectively, which were significantly higher than those in normal, nondiabetic subjects (0.24 +/- 0.02 pM [n = 31]) and NIDDM patients without retinopathy (0.30 +/- 0.05 pM [n = 9]). CONCLUSIONS--These results suggest that plasma ET-1 is related to diabetic microvascular disease.     

Inhibition of drug metabolism by cimetidine in man: dependence on pretreatment microsomal liver function

The effect of cimetidine on hepatic microsomal drug metabolism was studied in six patients with normal liver and eleven patients with chronic liver disease using the aminopyrine breath test. Before administration of cimetidine, the elimination rate constant of 14CO2 from breath (Kb) was 28.3 +/- SD 1.3%/h in patients with normal liver and 13.5 +/- 7.7%/h in patients with liver disease (P less than 0.001). After 7 days of cimetidine therapy (1 g/day) Kb decreased to 23.3 +/- 5.2%/h (19.0 +/- 13.8% decrease; P less than 0.05) and 7.4 +/- 5.8%/h (50.5 +/- 14.4% decrease; P less than 0.001), respectively. Plasma levels of cimetidine were not significantly different (1.05 +/- 0.14% micrograms/ml v. 0.88 +/- 0.41; P greater than 0.05). The findings indicate that therapeutic doses of cimetidine lead to an inhibition of drug metabolism which is more pronounced in patients with impaired liver function than in liver normals. Therefore, patients with chronic liver disease may be at increased risk with respect to interactions between cimetidine and other drugs which are demethylated by the liver.     

Single-dose pharmacokinetics of 14C-lovastatin in chronic renal failure

An open study on the pharmacokinetics of lovastatin was conducted in six patients with chronic renal failure (mean creatinine clearance, 0.40 ml/sec; range, 0.20 to 0.65 ml/sec) and seven healthy subjects. Plasma levels of 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitory activity (total and active) and total radioactivity were determined over 168 hours after a single dose of 80 mg 14C-lovastatin. The mean area under the plasma concentration-time curve for active inhibitors were 606 +/- 346 and 282 +/- 138 ngEq.hr/ml (p = 0.04) in patients and control subjects, respectively. Total inhibitors in plasma and total radioactivity were similarly elevated in patients with chronic renal failure. Results indicate that patients with severe renal dysfunction have altered elimination kinetics of lovastatin. Current ongoing clinical studies in patients with renal dysfunction will allow better assessment of the pharmacodynamic meaning of our observations.     

Abnormal erythrocyte choline transport in patients with chronic renal failure.

1. Erythrocyte choline transport has been studied in nine patients on maintenance haemodialysis for chronic renal failure, six patients on continuous ambulatory peritoneal dialysis, 31 patients with renal transplants and in nine normal control subjects. 2. The mean maximum rate of choline influx (Vmax., measured at an extracellular choline concentration of 250 mumol/l) was 66.7 (SD 14.1) mumol h-1 l-1 cells in patients on haemodialysis, 87.8 (SD 18.5) mumol h-1 l-1 cells in patients on continuous ambulatory peritoneal dialysis and 30.5 (SD 4.9) mumol h-1 l-1 cells in control subjects. The increase in choline flux in patients on haemodialysis and patients on continuous ambulatory peritoneal dialysis compared with control subjects was highly significant (P less than 0.001). 3. Renal transplant patients showed variable values for the Vmax. of choline influx (range 17.7-71.7 mumol h-1 l-1 cells). The values showed a significant negative correlation with creatinine clearance and this correlation correctly extrapolated to the maximum choline flux in normal subjects and in patients on dialysis. 4. The kinetics of choline transport have been studied in erythrocytes of patients on haemodialysis and control subjects in 'zero-trans' conditions after depletion of intracellular choline. The mean Vmax. in these conditions was 38.4 (SD 4.6) mumol h-1 l-1 cells in patients on haemodialysis compared with 14.2 (SD 3.7) mumol h-1 l-1 cells in control subjects. The mean Km under 'zero-trans' conditions was 19.4 (SD 2.4) mumol/l in patients on haemodialysis and 7.4 (SD 1.4) mumol/l in control subjects. These differences were significant (P less than 0.001).     

Substrate utilization during exercise in chronic cardiac failure

1. Skeletal muscle metabolism in chronic cardiac failure may be influenced by the many circulatory and neurohumoral adaptations in the condition. We investigated aerobic metabolism during exercise using indirect calorimetry in 15 patients with chronic cardiac failure and in 14 control subjects. Subjects exercised on a treadmill for 20 min at a steady-state submaximal workload. 2. Venous lactate levels were relatively constant throughout the exercise, although they were slightly greater in the patients with chronic cardiac failure than in the control subjects. The respiratory exchange ratio was lower in patients with chronic cardiac failure (0.777 +/- 0.021 vs 0.833 +/- 0.037, means +/- SD; P less than 0.0002, Mann-Whitney U-test). Relative fat utilization, expressed as a percentage of total energy expenditure, was therefore greater in patients with chronic cardiac failure (71.8 +/- 7.0 vs 54.1 +/- 12.3%, P less than 0.0005) and this was mirrored in a lower carbohydrate utilization (24.7 +/- 6.5 vs 43.3 +/- 12.1%, P less than 0.0002). Levels of free fatty acids, glycerol and noradrenaline were greater in patients with chronic cardiac failure. 3. We conclude that there is an increased reliance on fat, as opposed to carbohydrate, metabolism during exercise in chronic cardiac failure, and that this may relate to the elevated catecholamine and free fatty acid levels present. This may be a compensatory mechanism to preserve muscle glycogen stores, but as fat utilization is less efficient in terms of oxygen consumed, this shift may further impair exercise capacity.     

Mobilizable lead in patients with chronic renal failure

Blood lead (Pb) and urinary Pb before and after i.v. infusion of 1 g of Na2Ca EDTA were determined (atomic absorption) in 46 control subjects and 91 patients with various stages of renal failure (median serum creatinine 2.5 mg dl-1). Under baseline conditions, patients with renal failure had higher blood Pb levels (112 ng ml-1, range 44-272 vs. 76; 36-187 in controls; P less than 0.001) and lower urinary Pb (16.2 nmol 24 h-1 1.73 m-2, 4.86-66.8 vs. 33; 11-91 in controls; P = 0.001). The increment in urinary Pb after EDTA infusion (mobilizable Pb) was higher (795 nmol 4 days-1 1.73 m-2, range 155-5611 vs. 307; 131-1587 in controls; P = 0.001). In 12 patients with renal failure (13%) mobilizable Pb was above the highest value in controls. Mobilizable urinary Pb correlated (r = 0.68) significantly (P = 0.001) with blood Pb, but only marginally with serum creatinine (r = 0.32; P less than 0.007). Mobilizable Pb was higher in patients with renal failure and a history of smoking or occupational Pb exposure and tended to be higher in patients with alcoholism. Ten of 91 patients had gout; increased mobilizable Pb was present in three of the 10. The data confirm relatively high prevalence of elevated body Pb burden in European patients with chronic renal failure. The question is unresolved whether Pb plays a role in the progression of renal failure.     

Decreased hepatic microsomal reserve in patients with cirrhosis. Studies using aminopyrine as model drug.

It is unclear whether hepatic drug metabolism which is decreased in patients with liver disease, can be stimulated by enzyme-inducing drugs. Hepatic microsomal reserve, defined as the difference between the basal and phenobarbital-stimulated ABT, was therefore studied in eight healthy control subjects and 12 patients with stable alcoholic cirrhosis. The ABT increased significantly (p less than 0.01) from a basal value of 6.1% +/- 0.8 (mean +/- S.D.) to 8.9% +/- 0.8 in the eight control subjects after phenobarbital ingestion. In the 12 patients with alcoholic cirrhosis the basal ABT was 2.9% +/- 1.5 and did not change significantly after phenobarbital ingestion, when the value was 3.0% +/- 1.6. A small increase in the ABT occurred after phenobarbital ingestion in five of the patients with alcoholic cirrhosis, but in no patient did this increase bring the ABT within normal limits. We conclude that in many patients with stable alcoholic cirrhosis aminopyrine metabolism is decreased and cannot be corrected by treatment with phenobarbital.     

Renal excretion of antidiuretic hormone in healthy subjects and patients with renal failure

Urinary clearance of antidiuretic hormone (ADH) has been measured under basal conditions and during intravenous administration of arginine vasopressin in ten healthy subjects, and only under basal conditions in 18 patients with chronic renal failure and seven patients with acute renal failure at the polyuric phase of the disease. In healthy subjects studied under conditions of mild water diuresis plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 3.3 +/- 0.36 pg/ml, 25.2 +/- 5.5 pg/min, 7.5 +/- 1.2 ml/min and 6.4 +/- 1.0% (means +/- SEM) respectively. When plasma ADH was raised to levels between 7 and 26 pg/ml during intravenous administration of the hormone, urinary excretion rate and urinary clearance of ADH increased. Tubular reabsorption of ADH did not reach a plateau but progressively increased in the range of plasma ADH studied. In patients with chronic renal failure, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 2.8 +/- 0.19 pg/ml, 9.4 +/- 2.0 pg/min, 3.4 +/- 0.6 ml/min and 10.0 +/- 2.9% (means +/- SEM) respectively. Urinary excretion rate and urinary clearance were significantly lower than in healthy subjects. In patients with acute renal failure, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 4.6 +/- 0.47 pg/ml, 52.8 +/- 15.8 pg/min, 9.5 +/- 2.7 ml/min and 24.9 +/- 4.4% (means +/- SEM) respectively. Urinary excretion rate and fractional clearance were higher than in healthy subjects and patients with chronic renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired hepatic glycogen synthesis in glucokinase-deficient (MODY-2) subjects.

All glucokinase gene mutations identified to date have been localized to exons that are common to the pancreatic and hepatic isoforms of the enzyme. While impaired insulin secretion has been observed in glucokinase-deficient subjects the consequences of this mutation on hepatic glucose metabolism remain unknown. To examine this question hepatic glycogen concentration was measured in seven glucokinase-deficient subjects with normal glycosylated hemoglobin and 12 control subjects using 13C nuclear magnetic spectroscopy during a day in which three isocaloric mixed meals were ingested. The relative fluxes of the direct and indirect pathways of hepatic glycogen synthesis were also assessed using [1-13C]glucose in combination with acetaminophen to noninvasively sample the hepatic UDP-glucose pool. Average fasting hepatic glycogen content was similar in glucokinase-deficient and control subjects (279+/-20 vs 284+/-14 mM; mean+/-SEM), and increased in both groups after the meals with a continuous pattern throughout the day. However, the net increment in hepatic glycogen content after each meal was 30-60% lower in glucokinase-deficient than in the control subjects (breakfast, 46% lower, P < 0.02; lunch, 62% lower, P = 0.002; dinner; 30% lower, P = 0.04). The net increment over basal values 4 h after dinner was 105 +/-18 mM in glucokinase-deficient and 148+/-11 mM in control subjects (P = 0.04). In the 4 h after breakfast, flux through the gluconeogenic pathway relative to the direct pathway of hepatic glycogen synthesis was higher in glucokinase-deficient than in control subjects (50+/-2% vs 34+/-5%; P = 0.038). In conclusion glucokinase-deficient subjects have decreased net accumulation of hepatic glycogen and relatively augmented hepatic gluconeogenesis after meals. These results suggest that in addition to the altered beta cell function, abnormalities in liver glycogen metabolism play an important role in the pathogenesis of hyperglycemia in patients with glucokinase-deficient maturity onset diabetes of young.     

Plasma levels of endothelin in chronic renal failure and after renal transplantation: impact on hypertension and cyclosporin A-associated nephrotoxicity.

1. Plasma levels of endothelin were measured in 30 patients with chronic renal failure, 32 patients on chronic haemodialysis treatment and 25 renal graft recipients with stable renal graft function. 2. In patients with chronic renal failure as well as in patients on regular haemodialysis treatment, mean plasma levels of endothelin were significantly increased (4.59 +/- 2.09 pg/ml, 10.08 +/- 3.12 pg/ml, respectively) when compared with normal subjects (1.88 +/- 0.6 pg/ml, P less than 0.01, P less than 0.001, respectively). 3. In the group with chronic renal failure a positive correlation between the plasma level of endothelin and the plasma concentration of creatinine was observed (P less than 0.003). 4. Renal graft recipients on cyclosporin A with stable renal graft function had a normal plasma level of endothelin suggesting that cyclosporin A nephrotoxicity is not mediated by endothelin. 5. Hypertensive patients with chronic renal failure or on regular haemodialysis and hypertensive renal graft recipients did not differ from the corresponding normotensive population with regard to the plasma level of endothelin, demonstrating that an increased plasma level of endothelin does not play a major role in the pathogenesis of renal hypertension.     

Lomefloxacin pharmacokinetics in subjects with normal and impaired renal function.

Lomefloxacin pharmacokinetics were investigated in 6 normal subjects and 24 uremic patients after a single oral dose of 400 mg. In subjects with normal renal function, the peak level in plasma averaged 3.5 +/- 0.9 micrograms/ml (mean +/- standard deviation) and was obtained at 1.3 +/- 0.9 h. The absorption rate constant was 3.8 +/- 1.6 h-1. The terminal half-life was 7.77 +/- 0.95 h. The apparent volume of distribution was 2.54 +/- 0.66 liters/kg. Total body and renal clearances were 259 +/- 83 and 200 +/- 55 ml/min per 1.73 m2, respectively. The percentage of the dose recovered unchanged in 48-h urine was 80.6 +/- 2.8. In uremic patients, the terminal half-life increased in relation to the degree of renal failure: from 8 h in normal subjects to 38 h in severely uremic patients (glomerular filtration rate, less than 10 ml/min). Renal insufficiency did not significantly modify the peak level in plasma, the time to peak, the apparent volume of distribution, or the nonrenal clearance of lomefloxacin. The dialysis clearance of lomefloxacin was 54 +/- 13 ml/min. Linear relationships were found between lomefloxacin pharmacokinetic parameters and glomerular filtration rate data. Dosage adjustments are necessary in uremic patients.     

Resting energy expenditure in chronic cardiac failure.

1. Resting energy expenditure has previously been shown to be elevated in the acute phase of heart failure, but the situation in the compensated state of chronic cardiac failure is unclear. Resting energy expenditure was assessed in 14 patients with stable chronic cardiac failure and 14 matched control subjects by using indirect calorimetry. 2. Resting energy expenditure was significantly elevated in the patients with chronic cardiac failure (112.6 +/- 18.1 versus 87.1 +/- 12.2 kJ day-1 kg-1 total body weight, P less than 0.0002; mean +/- SD) as were resting O2 consumption (3.88 +/- 0.64 versus 3.00 +/- 0.43 ml min-1 kg-1, P less than 0.0002), ventilation (164 +/- 40.3 versus 104 +/- 16.2 ml min-1 kg-1, P less than 0.0001) and heart rate (85.8 +/- 16.9 versus 66.6 +/- 6.9 beats/min, P less than 0.001). Both the resting plasma concentration of noradrenaline (4.48 +/- 1.52 versus 2.28 +/- 0.96 nmol/l, P less than 0.0001) and the serum concentration of free fatty acids (0.78 +/- 0.21 versus 0.57 +/- 0.27 mmol/l, P less than 0.03) were greater in the patients with chronic cardiac failure. Analysis of covariance indicated that most of the difference in resting energy expenditure could be accounted for by the elevated ventilation in the patients with chronic cardiac failure. Arm muscle area, an index of wasting, was lower in the patients with chronic cardiac failure (39.1 +/- 13.1 versus 50.5 +/- 9.4 cm2, P less than 0.02) and resting energy expenditure was found to account for some of this difference. 3. We conclude that an elevated basal metabolism occurs in chronic cardiac failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of ciprofloxacin on antipyrine metabolism

The effect of multiple-dose ciprofloxacin on antipyrine metabolism was studied in patients suffering from bacterial infections. The patients were given antipyrine 15 mg/kg intravenously before and after ciprofloxacin treatment. The dosage of ciprofloxacin was 500 mg bd by mouth for 8-10 days. Blood samples were taken at 0, 2, 4, 6, 10 h. Antipyrine total clearance was significantly decreased after ciprofloxacin treatment (0.85 +/- 0.45 vs. 0.52 +/- 0.24 ml/min/kg): elimination rate constants for antipyrine were decreased in all patients after ciprofloxacin, whereas no change in volume of distribution was observed. The average half-life of antipyrine was increased from 9.45 +/- 3.74 h to 14.92 +/- 3.32 h. In two males with advanced chronic hepatic failure the antipyrine half-lives were extremely prolonged. Our results support the hypothesis that ciprofloxacin inhibits intrinsic hepatic drug-metabolizing capacity and may be a source of clinically important drug interactions, particularly in patients with liver disease.     

The aminopyrine breath test, an inadequate early indicator of methotrexate-induced liver disease in patients with psoriasis

The aminopyrine breath test has been shown to be a sensitive noninvasive indicator of liver cell dysfunction. In a search for a noninvasive method of monitoring the effects of methotrexate therapy, we have investigated the use of the aminopyrine breath test in patients receiving methotrexate for the treatment of severe psoriasis. The [14C]-aminopyrine breath test was performed in 20 normal control subjects, 32 patients with psoriasis receiving methotrexate therapy, and 8 patients with histologically confirmed cirrhosis of differing etiology. Eighteen patients on methotrexate had liver biopsies classified as grade I changes, 6 patients as grade II, and 8 patients as grade III. The normal value for the breath test was 11.0 +/- 1.6% (mean +/- 1 SD). The mean [14C]-CO2 excretion (8.3 +/- 4.4%) of the 8 patients with grade III liver disease was significantly different from the control subjects (p less than 0.02), and those with grade I liver changes (p less than 0.04). The aminopyrine breath test was only able to detect the later severe stages of methotrexate hepatotoxicity, grade III, when fibrosis occurs, before established cirrhosis was present. Our data suggests that the aminopyrine breath test is not a sensitive indicator for the detection of early methotrexate-induced hepatotoxicity, (stages I and II), but will detect the precirrhotic stage III change. Consequently, we recommend that a liver biopsy should be performed annually in all psoriatic patients receiving methotrexate, to detect histological damage, especially when the aminopyrine breath test score falls below the 95% confidence limits of normal.     

Kidney and plasma renin in human renovascular hypertension.

Renin activities were determined in plasma and in single, microdissected juxtaglomerular apparatus in 19 patients with unilateral renal artery stenosis. The mean juxtaglomerular apparatus renin concentration in the stenosed kidneys was 5.5 +/- 1.2 (SEM) mug.l-1.h-1 which is about ten times that of the suppressed renin concentration in the contralateral kidneys (0.6 +/- 0.05 mug.l-1.h-1). On the affected side a positive correlation was found between intrarenal and renal venous renin concentration (r = 0.93; p less than 0.001). Both intrarenal and renal venous renin concentrations of the stenosed kindeys were positively correlated to renin secretion rates, as calculated from renin analysis in plasma from the vena cava and renal veins. No relationship could be demonstrated between intrarenal or renal venous renin concentration and the degree of blood pressure elevation or transstenotic pressure gradient. However, a positive correlation was evident between peripheral plasma renin activity and diastolic blood pressure (r = 0.88; p less than 0.001). Comparative enzyme kinetic analyses of renin from the juxtaglomerular apparatus and renal venous plasma were performed using sheep substrate. The lowest apparent Km-values of renin were found in renal venous plasma from the stenosed kidneys (198 +/- 13 mug/l) compared with the contralateral side (301 +/- 20 mug/l; p less than 0.001). Mean apparent Km-values of juxtaglomerular apparatus renin in the stenosed (270 +/- 36 mug/l) and contralateral (292 +/- 37 mug/l) kidneys did not differ. No significant differences were found between mean apparent Km-values for renin in peripheral plasma of renovascular hypertensive patients and control subjects using either homologous human or heterologous sheep renin substrate. The results suggest that, in addition to the renin concentration other factors are relevant to chronic high blood pressure in renovascular hypertension.     

Unmasking artifactual increases in creatine kinase isoenzymes in patients with renal failure

Previous reports have suggested that creatine kinase isoenzymes are elevated in patients with chronic renal failure and thus are less useful in the evaluation of chest pain in such patients. Our data in 88 patients with chronic renal failure receiving maintenance dialysis confirm this observation for total plasma creatine kinase. However, elevations in MB and BB creatine kinase, although statistically significant, were biologically unimpressive (5.9 +/- 0.05 [SEM] IU/L compared with 4.8 +/- 0.04 IU/L for MB creatine kinase [p less than 0.02], and 5.5 +/- 0.08 ng/ml compared with 3.2 +/- 0.05 ng/ml for BB creatine kinase [p less than 0.0002] ), and were unlikely to cause diagnostic confusion. In 92% of patients with chronic renal failure, plasma MB creatine kinase activity was within the normal range (less than 13 IU/L). Eight percent of patients manifested abnormal MB creatine kinase values; the highest was 20 IU/L. The glass bead method for measuring MB creatine kinase was used to avoid the potential confusion induced by non-creatine kinase-mediated fluorescence, which occurs in the region of MB and BB creatine kinase on electrophoresis. The infrequent and modest increases in plasma MB creatine kinase observed in patients with chronic renal failure should be appreciated, but it should not cause diagnostic confusion, because acute myocardial infarction usually results in more substantial elevations of MB creatine kinase.