Lipoprotein(a) and treatment of chronic renal disease

Abstract. Objectives. To compare lipoprotein(a) [Lp(a)] and albumin concentrations in patients with chronic renal disease receiving different forms of treatment and to determine, if any, the relationship between these variables. Design. A prospective cross-sectional, case-controlled study. Setting. A tertiary referral nephrology and dialysis unit. Subjects. Forty-four consecutive non-diabetic patients with chronic renal failure treated by renal transplantation (n = 18), haemodialysis (n = 18), continuous ambulatory peritoneal dialysis (CAPD; n = 8), and 30 healthy controls from subjects drawn from University personnel were studied. Interventions. Fasting morning venous blood was analysed for Lp(a), albumin, total cholesterol and glucose concentrations. Main outcome measures. Comparison of plasma levels of these variables between the sub-groups. Results. Concentrations (median; 95% CI) of Lp(a) were significantly (P < 0.05) higher (38.4 mg dl^?1; range 15.4–72.0) and of albumin lower (31.6 g l^?1; range 28–35.2) in the CAPD group compared with both control subjects and other groups of chronic renal disease patients. Conclusions. The elevated Lp(a) concentrations seen only in association with reduced albumin concentrations in CAPD patients suggest a regulatory role for albumin with albumin losses stimulating production of Lp(a).     

Hyponatraemia as a marker for high renin heart failure.

The factors that might activate the renin-angiotensin system in treated heart failure were explored. Serum Na+ correlated inversely with plasma renin activity. The degree of congestive heart failure measured by right atrial pressure, pulmonary capillary wedge pressure, cardiac index, and systemic vascular resistance did not correlate with plasma renin activity. Similarly, renal function as measured by blood urea nitrogen, creatinine, and urinary Na+ excretion did not correlate with plasma renin activity. In a prospectively screened group, seven patients with congestive heart failure who were found to be hyponatraemic had plasma renin activities greater than 15 ng/ml per h. Serial determinations in one patient showed plasma renin activity to vary inversely with the serum Na+. It is concluded that serum sodium can be used to identify those patients with congestive heart failure who have a high plasma renin activity. The value of identifying these high renin heart failure patients was seen in their response in four cases to specific therapy with a converting enzyme inhibitor.     

Continuous infusion of furosemide in the treatment of patients with congestive heart failure and diuretic resistance

Objectives . To assess the value of treatment with continuous intravenous infusion of furosemide (F) in patients with refractory congestive heart failure. Design . Open uncontrolled dose-response study. Subjects . Patients with congestive heart failure (those with New York Heart Association (NYHA) classes III and IV with an assessed amount of oedema of more than 5 kg and diuretic resistance were included [n = 10]). Diuretic resistance was defined as: failure to lose weight and/or inappropriate urinary sodium excretion (50 mmol 24 h^-1) despite bed rest for a period of 2–3 days, salt and water restriction, orally and intravenously administered furosemide in a dose of 250 mg day^-1, digoxin, and when possible an ACE inhibitor. Included patients were treated with continuous F infusion at a delivery rate of 20 mg^-1 over 24 h. The infusion rate was gradually heightened up to a maximum dose of 160 mg h^-1. Main outcome measures . Daily physical examination, history of side-effects, determination of serum electrolytes and 24-h electrolyte excretion during treatment with furosemide. Results . Weight loss (mean ± sd ; 12.5 ± 5 kg) and relief of symptoms was achieved in all patients. Mean (± sd ) 24-h sodium output rose from 19 ± 16 mmol 24 h^-1 (n = 10) on oral therapy with 250 mg F to 137 ± 85 mmol 24 h^-1 (n = 8) during 80 mg h^-1 and to 268 ± 124 mmol 24 h^-1 (n = 3) on the maximal dose of 160 mg h^-1. Conclusion . Continuous infusion of F under careful monitoring of the patient is a safe, controllable and efficient treatment in patients with severe congestive heart failure and diuretic resistance.     

Sex differences in essential hypertension

Abstract. A group of 41-year-old hypertensive men (n = 35, blood pressure (BP) 149.9 ± 2.1/ 98.9 ± 1.1 mmHg, mean ± SEM) who had never received treatment for their condition were compared with hypertensive women of the same age (n = 18, BP 155.9 ± 4.3/ 98.1 ± 1.6 mmHg) with comparable body mass index (BMI. 25.9 ± 0.5 vs. 24.9 ± 4.5 kg m^?2) who, also, had never received treatment. The lipid profile was more atherogenic in the men, with lower HDL cholesterol (1.21 ± 0.04 vs. 1.38 ± 0.06 mmol l^?1 P = 0.04), higher total cholesterol (6.04 ± 0.14 vs. 5.54 ± 0.18 mmol l^?1. P = 0.04) and triglycerides (1.80 ± 0.16 vs. 0.96 ± 0.10 mmol l^?1, P < 0.001). The hypertensive men had higher haemoglobin (P < 0.001) and haematocrit. Plasma catecholamines were inversely related to BMI in the women only (r = ?0.52, P < 0.05 for both noradrenaline and adrenaline). Women with BMI above 25 kg m^?2 had significantly lower arterial plasma adrenaline and noradrenaline than those with BMI below 25 kg m^?2 (28 ± 5 vs. 78 ± 16 pg ml^?1, P < 0.01 and 101 ± 17 vs. 206 ± 33 pg ml^?1, P < 0.01 respectively). A negative curvelinear relationship appeared between arterial adrenaline and insulin (r = 0.49, P= 0.05). These results suggest a male propensity for athero-thrombogenic risk factors in otherwise comparable hypertensive subjects. A close relationship between metabolic risk factors within the normal range seems to exist even in hypertensive women. The decreased sympathetic activity at rest in the obese hypertensive women indicates different pathophysiological mechanism for hypertension in lean and obese. Decreased sympathetic activity and thus reduced energy expenditure, promotes a risk for weight gain, and could explain the inverse relationship between insulin and adrenaline.     

Serum Erythropoietin in Myelomatosis

Erythropoietin activity in serum was measured using ⁵⁹Fe incorporation into erythrocytes in protein-starved, hypoxic mice. The activity in serum from 20 patients with untreated myelomatosis was not significantly different from that in 31 saline controls. Only three patients had detectable erythropoietin levels in serum: 0.24 IU/ml, 0.27 IU/ml and 0.50 IU/ml (standard B), respectively. The venous haematocrit was correlated positively with the glomerular filtration rate as measured by ⁵¹Cr EDTA-clearance. No correlation could be established between venous haematocrit and serum albumin or serum transferrin. The results are in agreement with the assumption of a defective erythropoietin activity due to renal failure in myelomatosis.     

The captopril test for identification of renovascular hypertension: value and immediate adverse effects

Abstract. To develop a screening test for identification of renovascular hypertension, the blood pressure and plasma renin concentration responses to an oral test dose of captopril (6.25 mg) were studied in 47 hypertensive patients of mean age 61 years (range 34-85 years). Blood pressure was measured at 15-min intervals for 90 min after administration of captopril. Blood samples for plasma renin determination were drawn immediately before and 90 min after drug administration. Eleven patients had renal artery stenosis. The fall in diastolic blood pressure in these patients was greater, on average, than in patients with other forms of hypertension (30 mmHg vs. 14 mmHg, P < 0.01), as was the increase in plasma renin concentration (188 mU l^?1 vs. 2 mU l^?1, P < 0.01). This study demonstrates that the short-term captopril test is useful for distinguishing patients with renovascular disease from those with other forms of hypertension. During the test, 7 patients (15%) exhibited reversible cerebral symptoms. In two of these subjects digital subtraction angiography was performed, which revealed stenosis of the carotid artery. Consequently, it is suggested that captopril should not be used in patients with arteriosclerotic stenoses of the carotids.     

Low-dose warfarin decreases coagulability without affecting prothrombin complex activity

Abstract. Objectives. To asses the efficacy of a fixed, low dose of warfarin in lowering factor VII coagulant activity (FVII: C) and to investigate the effects on the plasma coagulation cascade. Design. An open pilot study with two dose levels of warfarin: 1.25 and 2.5 mg day^?1 during two consecutive 4-week periods. All subjects received aspirin 75 mg day^?1. Prothrombin fragment 1 + 2 (F_{(1 + 2)}), protein C, protein S, FVII:C, factor X and P-prothrombin complex activity (P-PT) were measured at baseline, at 2-week intervals and 4 weeks after end of treatment. Coagulation activation peptide F_{(1 + 2)} was used as a marker of thrombin formation [13]. Subjects. Twelve male patients with a history of myocardial infarction. Inclusion was made through a written questionnaire. Results. Warfarin 1.25 mg day^?1 lowered FVII:C from 113 U dl^?1 to 107 U dl^?1 (P = 0.025) and F_{(1 + 2)} from 1.60 nmol l^?1 to 1.27 nmol l^?1 (P = 0.013) but had no effect on protein C or P-PT. A dose of 2.5 mg day^?1 induced further lowering of FVII:C (91 U dl^?1, P = 0.0042), and also of protein C from 116% to 99% (P = 0.034) and P-PT from 107% to 81% (P = 0.0096) mean values. Conclusion. Warfarin 1.25 mg day^?1 seems to exert an anticoagulant effect without reduction in PT or the natural anticoagulant protein C and is suggested, in combination with aspirin, to be a safe and simple therapy against arterial thrombotic disease, making regular PT controls unnecessary.     

Association between activation of the renin-angiotensin system and secondary erythrocytosis in patients with chronic obstructive pulmonary disease

PURPOSE: An association between activation of the renin-angiotensin system and enhanced erythropoiesis has been observed in patients with several diseases, including congestive heart failure and hypertension. Our goal was to examine whether the renin-angiotensin system is associated with secondary erythrocytosis in patients with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: Plasma renin activity, plasma aldosterone concentration, serum erythropoietin level, and serum angiotensin converting enzyme (ACE) activity were measured in 12 patients with COPD and secondary erythrocytosis [mean (+/-SD) hematocrit of 53% +/- 3%] and in 12 matched controls with COPD who did not have erythrocytosis (hematocrit 45% +/- 5%). All patients had chronic hypoxemia (PaO2 <60 mm Hg). RESULTS: Both plasma renin and aldosterone levels were threefold greater in patients with secondary erythrocytosis compared to controls. No difference in erythropoietin levels was observed between patients with or without secondary erythrocytosis. Renin levels (r = 0.45; P = 0.02) but not erythropoietin levels (r = 0.15; P = 0.47) were correlated with hematocrit in the entire sample. Renin levels and PaO2 were the only variables independently and significantly associated with hematocrit values in a multiple linear regression model. CONCLUSION: Activation of the renin-angiotensin system is associated with the development of secondary erythrocytosis in chronically hypoxemic patients with COPD. The exact mechanism is not yet fully understood, but angiotensin II may be responsible for inappropriately sustained erythropoietin secretion or direct stimulation of erythroid progenitors.     

Hypertension in cyclosporin A-treated patients is independent of circulating endothelin levels

Abstract. Objectives. To measure blood pressure (BP), plasma endothelin-1 (ET-1), atrial natriuretic peptide (ANP), antidiuretic hormone (ADH) and aldosterone (ALDO) concentration, and plasma renin activity (PRA) in patients treated with a low-dose cyclosporin A (CyA). Design. An open study of patients with rheumatoid arthritis (RA) or palmoplantar pustulosis (PPP). Setting. Out-patient clinics at the Central Hospital of Jyväskylä and Helsinki University Central Hospital. Subjects. CyA was given to 25 patients with RA and to 10 patients with PPP. Intervention. RA patients were given CyA at a dose of 2.5±0.13 mg kg^?1 body weight (BW) to 3.47±0.79 mg kg^?1 BW (mean values±SD) at the start of the study and after 6 months, respectively, and the CyA dose was 2.67±0.13 mg kg^?1 BW decreasing to 2.07±0.96 mg kg^?1 (P < 0.001) after 4 months in PPP subjects. Results. Systolic (sBP) and diastolic blood pressure (dBP) increased from 127.8±13.6/79.7±8.4 mmHg to 140.0±19.8/83.8±9.7 mmHg during the study (P < 0.03). Plasma ET-1, ANP, ALDO and ADH concentration and PRA did not change during 4 to 6 months of CyA treatment. The plasma ANP concentration was constantly higher in CyA-treated RA patients (112±87 ng l^?1) to 118±78 ng l^?1) than in PPP patients (37.3±26 ng l^?1 to 47.7±39.9 ng l^?1; P < 0.02). The serum creatinine concentration remained within the normal range, but increased from baseline (76.7±11.9 μmol l^?1), to 90±15.4 μmol l^?1 (P < 0.001). The serum magnesium concentration decreased significantly (P < 0.005) after 6 months of CyA treatment in RA patients. No correlation was found between serum creatinine and plasma ET-1 concentration. Conclusions. Increased blood pressure during CyA treatment was independent of circulating ET-1 levels. A low dose of CyA did not induce increased ET-1 synthesis as judged from plasma samples. The high plasma ANP level observed in RA patients could be due to fluid retention caused by concomitant treatment with non-steroid anti-inflammatory drugs. Fluid retention and decreased magnesium levels could also be involved in the development of hypertension in CyA-treated subjects.     

The activated immune system and the renin–angiotensin–aldosterone system in congestive heart failure

Samsonov M, Lopatin J, Tilz G, Artner-Dworzak E, Nassonov E, Mareev V, Belenkov J, Wachter H, Fuchs D, (Cardiology Research Centre, Moscow, Russia; University of Graz, and the University of Innsbruck, Austria). Activated immune system and the renin–angiotensin–aldosterone system in congestive heart failure. J Intern Med 1998; 243 : 93–98.

Objects

The aim of the study was to investigate a possible relationship between plasma renin activity, angiotensin II, serum levels of angiotensin-converting enzyme, aldosterone and markers of immune activation in congestive heart failure (CHF).

Patients and Methods

Fifty-three patients (50 male, three female, mean age 46 ± 16 years) with congestive heart failure were studied. Twenty-eight patients had I or II NYHA class of CHF and 25 patients had III or IV NYHA class (NYHA class, mean ± SD : 2.3 ± 0.9). Serum neopterin concentration and hormones were measured by commercial radioimmunoassays. Serum soluble receptors of tumour necrosis factor and interleukin-2 were determined by ELISA.

Results

All analytes significantly correlated with NYHA classes (P < 0.05). There existed correlations between neopterin and angiotensin-converting enzyme or aldosterone (rs= 0.35 and rs= 0.36, P < 0.05). The soluble tumour necrosis factor receptor concentrations correlated with plasma renin activity (rs= 0.38, P < 0.05).

Conclusion

The result of our study suggest that there exists some relationship between the renin–angiotensin–aldosterone system and immune activation in severe congestive heart failure, however, the associations found are rather weak.

     

Reduced glutathione concentration in erythrocytes of patients with acute and chronic viral hepatitis

SUMMARY. Reduced glutathione (GSH), the main intracellular mechanism that protects against oxidative stress, is the subject of considerable interest in viral hepatitis. In patients with chronic hepatitis C, results reported from different centres are controversial, demonstrating either a reduction or an elevation of GSH concentration. The aim of this study was to evaluate the glutathione concentration in erythrocytes (normal range 2.45 ± 0.15 mmol l^?1) in patients with acute and chronic viral hepatitis. In 52 patients with acute viral hepatitis (hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infection) there was marked reduction of GSH at the beginning of the disease (0.79 ± 0.43 mmol l^?1. P < 0.001) with high alanine aminotransferase (ALT) activity (1549 ± 772.9 IU l^?1). In 37 patients with chronic HCV infection the mean value of GSH was below the normal range (1.92 ± 0.62 mmol l^?1. P < 0.001). In 60% of patients (n = 22), depletion of GSH was observed and 40% (n = 15) presented with a normal concentration of GSH. In 10 patients with chronic HBV infection the mean value of GSH was also below the normal range (1.93 ± 0.32 mmol l^?1, P < 0.001); in 80% of cases (n = 8) depletion of GSH was observed and 20% of patients (n = 2) had normal GSH concentrations. The ALT activity was not significantly different in patients with depleted and normal GSH concentrations (P > 0.05) in groups with chronic HBV and HCV infection.     

Serum uric acid as an index of impaired renal function in congestive heart failure

Background

Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid (UA) metabolism. This study was to assess their potential relations to UA metabolism in heart failure.

Methods

We retrospectively assessed clinical characteristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure (n = 553). By clustering of indices, those variables were explored using factor analysis.

Results

In factor analysis, serum uric acid (SUA) formed part of a principal cluster of renal functional variables which included serum creatinine (SCr) and blood urea nitrogen (BUN). Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN (r = 0.48, P < 0.001) and SCr (r = 0.47, P < 0.001).

Conclusions

There was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.     

Changes in insulin and lipid metabolism in males with asymptomatic hyperuricaemia

Abstract. Objectives. To define the effect of asymptomatic hyperuricaemia on various facets of glucose, insulin, and lipoprotein metabolism. Design. Case control study in health volunteers. Setting. The volunteers for this study were selected on the basis of their laboratory results from a larger population participating in a general survey in one large factory. Subjects. The study population consisted of 40 healthy males: 20 with asymptomatic hyperuricaemia (serum uric acid concentration equal to or greater than 420 mmol l^?1) and 20 with normal serum uric acid concentrations (180–320 mmol l^?1). The two groups were similar in terms of age, general obesity (estimated by body mass index), smoking and alcohol intake, and estimate of work and leisure time activity. Interventions. All subjects received a 75 g oral glucose challenge, with blood taken before and at frequent intervals thereafter. Main outcome measures. Fasting plasma glucose, insulin, and lipid concentrations and plasma glucose and insulin responses to the oral glucose challenge. Results. By selection, mean (± sem ) serum uric acid concentration was higher in the hyperuricaemic individuals (454 ± 7 vs. 274 ± 12 mmol l^?1). In addition, the plasma insulin response to oral glucose was increased in individuals with asymptomatic hyperuricaemia (P < 0.005) as were both systolic (136 ± 3 vs. 126 ± 3 mmHg, P < 0.05) and diastolic (91 ± 1 vs. 82 ± 1, P < 0.01) blood pressure. Furthermore, subjects with asymptomatic hyperuricaemia were dyslipidaemic (higher plasma TG and cholesterol and lower HDL-cholesterol concentrations) as compared to the normouricaemic control group (P < 0.07–0.005). Conclusions. These results provide a possible explanation for the well-known association of hyperuricaemia with coronary heart disease, as well as suggesting that hyperuricaemia be added to the cluster of metabolic and haemodynamic abnormalities associated with insulin resistance and/or hyperinsulinaemia and designated as Syndrome X.     

Low angiotensinogen levels are related to the severity and liver dysfunction of congestive heart failure: implications for renin measurements.

PURPOSE: To compare the determination of plasma renin activity (PRA) and the direct measurement of active renin by immunoradiometric assay (IRMA) as methods of assessing the renin system in patients with congestive heart failure. PATIENTS AND METHODS: The status of the renin-angiotensin system in congestive heart failure was assessed by measuring the plasma renin substrate concentration, PRA, and plasma concentration of active renin in 37 patients with mild to severe congestive heart failure. Natremia and plasma levels of atrial natriuretic factor (ANF) were determined as biologic indexes of the severity of heart failure, and concentrations of prealbumin and retinol-binding protein were used as indexes of liver dysfunction. RESULTS: The PRA and the concentrations of active renin and ANF were markedly higher in patients with New York Heart Association class IV heart failure than in patients with class II to III heart failure, while natremia and the concentrations of renin substrate, prealbumin, and retinol-binding protein were markedly lower in the class IV patients than in the class II to III patients. Plasma renin substrate concentration was negatively correlated with active renin concentration (n = 37, r = -0.45, p = 0.005), and positively related to natremia (r = 0.56, p less than 0.0005), prealbumin (r = 0.54, p less than 0.001), and retinol-binding protein (r = 0.60, p less than 0.0001). CONCLUSIONS: Low levels of plasma renin substrate can be considered as an indirect index of the severity of heart failure that reflects both the high level of circulating active renin and the decrease in hepatic protein output. In patients with class IV heart failure, low levels of renin substrate led to a marked underestimation of active renin concentration from measurements of PRA. In contrast, direct IRMA of active renin measures the true plasma active renin concentration, independent of plasma renin substrate, and closely reflects renin secretion.     

Pharmacotherapy in congestive heart failure: ACE inhibitors and anemia in congestive heart failure

The use of angiotensin-converting enzyme inhibitors can be accompanied by a number of adverse events, including cough, angioedema, and hyperkalemia, as well as a peculiar form of functional renal insufficiency. Other, less obvious side effects accompany ACE inhibitor use, such as a reduction in red blood cell production. This feature of ACE inhibitor use may be employed to good effect, as in the management of post-transplant erythrocytosis. Alternatively, the suppressive effect of ACE inhibitors on red blood cell production may intensify the anemia of chronic renal failure and/or congestive heart failure. The untreated congestive heart failure patient typically has an increased red blood cell mass as a consequence of increased erythropoietin levels, with the latter governed by congestive heart failure-related renal hypoxia. This is not expressed as an increase in hemoglobin concentration because of the increase in plasma volume that marks advanced congestive heart failure. ACE inhibitor therapy can be expected to both reduce plasma volume and decrease red blood cell production. As a result, the hemoglobin concentration changes very little in the ACE inhibitor-treated congestive heart failure patient and usually falls in the low normal range. Recently, erythropoietin has been employed to good effect in congestive heart failure patients with borderline anemia. (c)2000 by CHF, Inc.     

Rate of decline in renal function in Indo-Asians and Whites with diabetic nephropathy

The incidence of end-stage renal failure (ESRF) is higher in the Indo-Asian ethnic group as compared to the White. To investigate whether this might be associated with faster rates of progression to ESRF in Indo-Asian diabetic patients, we studied a total of 39 Type 2 diabetic patients, using the Department of Nephrology database showing serial serum creatinine measurements from the time of first referral to the clinic until they reached a level of >500 μmol l⁻¹ or ESRF requiring renal replacement therapy (RRT), either dialysis or renal transplantation. They were grouped into Indo-Asian (n = 24) and White (n = 15). The rate of progression of those who developed ESRF, calculated as the slope of log serum creatinine against time, was not significantly different between the Indo-Asian and White patients, p = 0.73. We conclude that the higher incidence of ESRF in the Indo-Asian Type 2 diabetic patient with nephropathy is therefore not due to a faster rate of deterioration in renal function. © 1998 John Wiley & Sons, Ltd.     

Deficiency of erythropoietin is not responsible for the anaemia associated with cyclosporin treatment of insulin-dependent diabetes mellitus

Abstract. Objectives. To explore the possible pathogenetic role of erythropoietin (EPO) in the anaemia associated with cyclosporin (Cs) in newly diagnosed patients with insulin-dependent diabetes mellitus (IDDM). Design. A multicentre randomized placebo controlled prospective trial of Cs immunosuppression for 12 months in IDDM patients. Setting. Patients were recruited from the out-patient clinics of diabetes centres in Europe and Canada. Subjects. Patients 9–35 years old with a clinical diagnosis of ketonuric IDDM entering less than 6 weeks after diagnosis. 188 patients were originally recruited; 105 patients completed the investigation, 52 patients being treated with Cs, and 53 patients receiving placebo. Interventions. Random allocation to receive either Cs or placebo. The initial dose of Cs was 10 mg kg^?1 BW day^?1. Therapy was maintained for 12 months. Main outcome measures. B-Haemoglobin, s-creatinine, and s-EPO concentrations were monitored before, during and after therapy with either Cs or placebo. Results. Blood-haemoglobin (Hgb) fell from 8.5 ± 0.8 to a nadir of 7.8 ± 0.9 mmol l^?1 at 6 months (P < 0.0001) in IDDM patients treated with Cs but not in the placebo patients (8.5 ± 0.8 to 8.8 ± 0.9 mmol l^?1, NS). The mean serum EPO levels remained unaltered throughout the 6-month period of Cs and placebo therapy. No significant differences in serum EPO levels between Cs and placebo-treated diabetic patients were found after 6 months of treatment. Conclusions. The light anaemia associated with Cs therapy in IDDM patients is not related to an insufficient production of EPO, but is caused by other, as yet unknown mechanisms, unrelated to the nephrotoxic action of this drug.     

Activity of the sympathetic nervous system and renin-angiotensin system assessed by plasma hormone levels and their relation to hemodynamic abnormalities in congestive heart failure

Resting hemodynamic measurements and plasma levels of catecholamines and renin activity were studied in 55 hospitalized treated patients with congestive heart failure in clinically stable condition. Plasma norepinephrine (mean ± standard error of the mean 594 ± 51 pg/ml, range 153 to 1,868) and plasma renin activity (mean 12.9 ± 2.4 ng/ml per hr, range 0.6 to 85.2) values were significantly (probability [p] < 0.01) higher than in normal subjects. In 26 of these patients plasma norepinephrine and plasma renin activity measured on 3 successive days including the day of hemodynamic study did not change significantly. In contrast, plasma epinephrine (mean 138 ± 26 pg ml, range 24 to 1,099) increased significantly at the time of invasive studies, probably because of stress-induced adrenal discharge. When baseline plasma norepinephrine was compared with resting hemodynamic values, significant correlations were found with right atrial pressure (correlation coefficient [r] = +0.44), pulmonary arterial pressure (r = +0.45), pulmonary capillary wedge pressure (r = +0.42), pulmonary vascular resistance (r = +0.55), pulmonary arteriolar resistance (r = +0.41), cardiac index (r = ?0.42), systemic vascular resistance (r = +0.30) and heart rate (r = +0.52). Plasma renin activity was only weakly correlated with plasma norepinephrine (r = +0.38) and did not correlate significantly with any hemodynamic measurement.It is concluded that patients with congestive heart failure can be categorized on the basis of neurohumoral activity. The statistically significant correlations between plasma norepinephrine and hemodynamic evidence of cardiac dysfunction suggest that the sympathetic response is either a marker of or a contributor to the hemodynamic derangement. Because hemodynamic abnormalities did not correlate with plasma renin activity despite a statistically significant correlation between plasma norepinephrine and plasma renin activity, it appears that the two systems are independently activated in congestive heart failure but that sympathetic stimulation may be one factor contributing to renin release. Further studies are needed to assess the usefulness of plasma hormone levels in evaluating and treating patients with congestive heart failure.     

Plasma and Skeletal Muscle Electrolytes in Patients on Long-term Diuretic Therapy for Arterial Hypertension and/or Congestive Heart Failure

ABSTRACT Investigations regarding plasma and skeletal muscle electrolytes were carried out in 537 patients on long-term diuretic treatment (>1 year) for arterial hypertension (n=240) and/or congestive heart failure (n=297). In both groups there were significant decreases in both plasma and skeletal muscle K and Mg, while the muscle Na values as well as the total and extracellular water content of skeletal muscle were increased.