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We introduce a novel method to represent time independent, scalar data sets as complex networks. We apply our method to investigate gene expression in the response to osmotic stress of Arabidopsis thaliana. In the proposed network representation, the most important genes for the plant response turn out to be the nodes with highest centrality in appropriately reconstructed networks. We also performed a target experiment, in which the predicted genes were artificially induced one by one, and the growth of the corresponding phenotypes compared to that of the wild-type. The joint application of the network reconstruction method and of the in vivo experiments allowed identifying 15 previously unknown key genes, and provided models of their mutual relationships. This novel representation extends the use of graph theory to data sets hitherto considered outside of the realm of its application, vastly simplifying the characterization of their underlying structure.

Background: Approximately 25% of haemodialysis (HD) patients use catheters as vascular access. Catheter-related bloodstream infections (CRBSI) are a major risk in this population. The objective of our study was to determine whether endoluminal catheter colonization (ECC) predicts CRBSI., Methods: We followed up a cohort of HD patients in our institution who underwent HD with tunnelled cuffed central venous catheters (TCC) between December 2006 and June 2008. Colonization of the inner catheter lumen was assessed every 15 days immediately before HD by culture of blood-heparin mixture and the time to positivity (TTP) was recorded by the BacT/Alert automated system. CRBSI was confirmed by differential TTP (> 2 h) between TCC and peripheral blood cultures., Results: We studied 51 patients who required 64 TCC. The incidence of CRBSI was 1.65 episodes per 1000 catheter-days, with Staphylococcus epidermidis being the most common cause of infection (76.2%). ECC was more frequent in the CRSBI group than in the non-CRBSI group (100 vs 5.4%, P < 0.001). For S. epidermidis CRBSIs, the median time from ECC to CRBSI was 31.5 days (interquartile range, 27.0-79.0). The sensitivity, specificity and negative and positive predictive values of arterial lumen cultures for S. epidermidis CRBSIs were 100, 96.3, 92.3 and 100%, respectively, while for venous culture, these values were 92.3, 96.3, 92.3 and 96.3%, respectively. For predicting S. epidermidis CRBSI, endoluminal cultures with a TTP of ≤ 14 h had sensitivity and specificity of 52.1 and 97.7%, respectively., Conclusions: This study shows that ECC may predict the risk of developing CRSBI. Surveillance cultures could, therefore, be used to triage individual HD patients who might benefit from specific intervention measures.

Occult hepatitis C virus (HCV) infection (i.e., detectable HCV-RNA in the liver or peripheral blood mononuclear cells) in the absence of both serum HCV-RNA and anti-HCV antibodies has not been investigated in hemodialysis patients. In this study, real-time PCR and in situ hybridization was used to test for the presence of genomic and antigenomic HCV-RNA in peripheral blood mononuclear cells of 109 hemodialysis patients with abnormal levels of liver enzymes. Occult HCV infection, determined by the presence of genomic HCV-RNA, was found in 45% of the patients; 53% of these patients had ongoing HCV replication, indicated by the presence of antigenomic HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on hemodialysis and had significantly higher mean alanine aminotransferase levels during the 6 mo before study entry. Logistic regression analysis revealed that mortality was associated with age >60 yr (odds ratio 3.30; 95% confidence interval 1.05 to 10.33) and the presence of occult HCV infection (odds ratio 3.84; 95% confidence interval 1.29 to 11.43). In conclusion, the prevalence of occult HCV infection is high among hemodialysis patients with persistently abnormal values of liver enzymes of unknown cause. The clinical significance of occult HCV infection in these patients requires further study.

Ischemic nephropathy is a long-term cause of hypertension and renal failure. Although its real incidence is unknown, ischemic nephropathy is growing because of the increased mean age of the population and the greater prevalence of hypertensive and diabetic populations. This review describes the clinical profile of afflicted patients. Atherosclerosis in different vascular beds is common in these patients. The evolution of ischemic nephropathy is generally progressive, although some patients present with acute renal failure, either secondary to the administration of angiotensin-converting enzyme inhibitors or caused by thrombosis of the renal arteries. Revascularizing surgery may stabilize or improve renal function, even in patients with nonfunctioning kidneys. The results obtained with intraluminal angioplasty are worse, with a high percentage of restenosis. Placement of an endoprothesis is recommended when the lesions affect the ostium or proximal third of the artery. This complex disease typically affects multiple organs, thus making individual assessment essential.

Background: The appearance of hyperkalemia has been described in human immunodeficiency virus (HIV)-positive patients treated with drugs with amiloride-like properties. Recent in vitro data suggest that individuals infected with HIV have alterations in transcellular K+ transport., Methods: With the objective of examining the presence of alterations in transmembrane K+ equilibrium in HIV-positive patients, we designed a prospective, interventional study involving 10 HIV-positive individuals and 10 healthy controls, all with normal renal function. An infusion of L-arginine (6%, intravenously, in four 30-min periods at 50, 100, 200, and 300 ml/hr) was administered, and plasma and urine electrolytes, creatinine, pH and osmolality, total and fractional sodium and potassium excretion, transtubular potassium gradient, plasma insulin, renin, aldosterone, and cortisol were measured., Results: A primary disturbance consisting of a significant rise in plasma [K+] induced by L-arginine was detected in only the HIV patients but not in the controls (P < 0.001 between groups). A K+ redistribution origin of the hyperkalemia was supported by its rapid development (within 60 min) and the lack of significant differences between HIV-positive individuals and controls in the amount of K+ excreted in the urine. The fact that the HIV-positive individuals had an inhibited aldosterone response to the increase in plasma K+ suggested a putative mechanism for the deranged K+ response., Conclusions: These results reveal that HIV-infected individuals have a significant abnormality in systemic K+ equilibrium. This abnormality, which leads to the development of hyperkalemia after the L-arginine challenge, may be related, in part, to a failure in the aldosterone response to hyperkalemia. These results provide a new basis for understanding the pathogenesis of hyperkalemia in HIV individuals, and demonstrate that the risk of HIV-associated hyperkalemia exists even in the absence of amiloride-mimicking drugs or overt hyporeninemic hypoaldosteronism.

Despite evidence from individuals with diabetes mellitus or reduced renal mass, the actual relationship between protein- or amino acid-induced changes in renal function and urinary albumin excretion (UAE) is largely unknown in subjects without renal disease. In humans, infusions of l-arginine have been used recently in vascular and renal pathophysiological studies. The present study was undertaken to analyze the mechanisms involved in a particular effect; namely, the behavior of UAE during amino acid loading. A prospective interventional protocol was performed on 10 healthy adults by means of an intravenous infusion of l-arginine. The main results show that l-arginine induced a significant increase in UAE from 13.1 +/- 3.8 before to 53.3 +/- 11.1 microgram/min after the infusion (P < 0.005). This increment was simultaneous to an increase in glomerular filtration rate (GFR) and renal plasma flow (RPF). Furthermore, l-arginine markedly increased the urinary excretion of beta2-microglobulin. UAE correlated significantly with GFR (r = 0. 738; P = 0.014) and RPF (r = 0.942; P < 0.0001), but not with urinary beta2-microglobulin (r = 0.05; P = not significant). Furthermore, marked differences (P = 0.001) were found between the percentage of increase in UAE (306.8% +/- 163.2%) with respect to either albumin filtered load (FLAlb; 57.9% +/- 16.3%) and beta2-microglobulin excretion (1,088.5% +/- 424.6%). No changes were found in vehicle-infused individuals. In conclusion, the present study shows, in controlled conditions, that l-arginine infusion induces a relevant increase in UAE in healthy individuals that significantly exceeds that expected from the increase in GFR alone. The intense and simultaneous increment in beta2-microglobulin excretion strongly suggests that the effect of l-arginine on UAE is, in a relevant part, mediated through a blockade in the tubular protein reabsorption pathways. However, the profound differences observed in the changes induced by l-arginine on UAE and beta2-microglobulin excretion and the differences in the correlation of UAE and beta2-microglobulin with respect to GFR suggest that substantial diversity exists in the mechanisms by which l-arginine affects the renal management of albumin and beta2-microglobulin. These findings are relevant for understanding the renal response to l-arginine and protein/amino acid loads.

A defect in the endothelium-dependent vasorelaxation could contribute to the development of arterial hypertension through the facilitation of renal vasoconstriction and sodium retention. In this study, we tested the hypothesis that aging impairs kidney function in essential hypertension through a derangement of nitric oxide-dependent renal mechanisms. To this end, we compared the renal response to an intravenous infusion of the precursor of nitric oxide synthesis, L-arginine, in young and aged essential hypertensives. In young hypertensives, L-arginine induced a significant increase in renal plasma flow, glomerular filtration rate, natriuresis and kaliuresis, without changes in filtration fraction. These effects were not observed in aged hypertensives. Neither PRA nor PA were affected by L-arginine infusion in any group. These results indicate that aging produces a derangement of endothelial function in essential hypertension.

Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic and cardiovascular complications in the general population and in hemodialysis patients. Increased Lp(a) levels have been also described as a possible predictor of vascular access occlusion in patients on chronic hemodialysis. We have studied prospectively the relationship between vascular access survival and Lp(a) levels in 40 hemodialysis patients. The Lp(a) plasma concentrations were measured by enzyme-linked immunosorbent assay in all patients in April 1993. Throughout the following year, evolution and survival of their vascular accesses were analyzed. Failure of vascular access was established when there were complications requiring surgical repair or transluminal angioplasty. Fourteen patients showed failure of vascular access, and the cumulative survival of vascular accesses after 1 year of follow-up was 63.8%. The Lp(a) levels were higher in patients with failure of vascular access than in the others (35.2 +/- 31 vs. 22.4 +/- 25 md/dl), but this difference did not reach statistical significance (p = 0.064). The vascular access survival in patients with Lp(a) levels > 75th percentile (52.5 mg/dl) was significantly lower than in the remaining patients (40 vs. 72%; p = 0.045). This difference increased when we analyzed the patients with Lp(a) levels > 90th percentile (76 md/dl; 25 vs. 68%; p = 0.002). Our results suggest that patients with the highest levels of Lp(a) are at risk of developing complications in their vascular accesses, and they also have lower vascular access survival.

Accidental hypothermia is defined as a spontaneous decrease in core temperature to 35 degrees C or below. Several techniques of active core rewarming have been described. We present the case of a 34-year-old man with severe hypothermia (27 degrees C) caused by cold environment exposure and barbiturate intoxication treated with general supportive measures and active core rewarming with hemodialysis. Core temperature increased by 2.15 degrees C/h with hemodialysis and became normal in 4 h. The clinical situation clearly improved during the hemodialysis session and the patient recovered without any defect. Hemodialysis is a rapid and effective treatment for accidental hypothermia.

The calcium antagonist verapamil has been demonstrated to be effective in reducing hypertension in patients in whom sodium intake was not restricted. The present study evaluated the effect of verapamil in reducing hypertension in patients with chronic renal failure on low or high sodium diets. Also, the present study evaluated the effect of verapamil on proteinuria in chronic renal failure patients who were administered a normal and low protein diet. The results reveal that verapamil-SR 240 mg daily is effective in reducing hypertension in patients with chronic renal failure and the effect of verapamil is equal in patients on a high or low sodium intake. In addition, verapamil-SR 240 mg daily is effective in maintaining reduced proteinuria in chronic renal failure patients on low protein diet and may prevent proteinuria in such patients on a normal protein diet. Therefore, verapamil-SR 240 mg daily appears to be an excellent choice for the treatment of hypertensive chronic renal failure patients.

The hypothesis that converting enzyme inhibition and a protein-restricted diet could have additive antiproteinuric effects has been tested. A group of 17 patients with proteinuria in excess of 3 g/24 h per 1.73 m2 of body surface area were submitted to a 3-wk period of study, after a 4-wk wash-out period during which protein intake was 1.0 g/kg per day and in the absence of any medication. During the first and second weeks of the study, protein intake was lowered to 0.3 g/kg per day, and in the third week, it returned to 1.0 g/kg per day. Enalapril (20 mg daily) was administered during the second and third weeks of the study. Initially and at the end of each week thereafter, we determined blood pressure, GFR (inulin clearance), RPF (para-aminohippurate clearance), plasma sodium and potassium, PRA and aldosterone, and the 24-h urine excretion of sodium potassium, protein, and urea. The low protein intake during the first week induced a significant fall of proteinuria (P < 0.01), GFR (P < 0.01), and RPF (P < 0.01) in the absence of changes in filtration fraction. The addition of enalapril induced a further decrease of proteinuria (P < 0.01) and a fall in filtration fraction (P < 0.05), whereas plasma potassium, PRA, GFR, and RPF values increased (P < 0.01). The rise in protein intake during the last week of the study induced a significant rise in proteinuria, GFR, and RPF (P < 0.01), although the first of these parameters attained values significantly lower (P < 0.05) than those observed initially.(ABSTRACT TRUNCATED AT 250 WORDS)

To test the tolerance to nitrendipine in arterial hypertension secondary to chronic renal parenchymatous disease, a group of 10 patients so diagnosed and adequately controlled with a diuretic alone or with a beta-blocker were switched to nitrendipine at a dose to insure similarly adequate control of blood pressure. Patients were followed for 1 year at monthly intervals during which blood pressure measurement and the determination of a biochemical profile were performed. During the follow-up, nitrendipine adequately controlled blood pressure and a significant fall was observed in hematocrit (p less than 0.05) and serum uric acid (p less than 0.01) values. Meanwhile, the glomerular filtration rate, determined by the creatinine clearance, did not exhibit significant changes nor did the 24-h urinary excretion of proteins. The tolerance of the drug was adequate, with two patients presenting minimal ankle edema. These results seem to indicate that nitrendipine can be safely used in patients with arterial hypertension secondary to chronic renal parenchymatous disease.

Calcium entry blockers exert several characteristic effects on renal function that contribute to their blood-pressure lowering capacity. They are able to dilate renal vasculature and, in certain circumstances, can increase the glomerular filtration rate, both effects being dependent on the preexisting vascular tone. Calcium blockers are also able to increase renal sodium excretion, mainly through a direct tubular effect that remains during the chronic administration of these drugs. These effects clearly differentiate calcium entry blockers from nonspecific vasodilators and contribute to their effectiveness when they are used as first-step drugs in the therapy of arterial hypertension.

We analyzed the clinical course of 120 patients who were diagnosed as having primary hypertension and subsequently given standard stepped-care therapy (diuretic, beta-blocker and vasodilator) for 9 years. At the end of the follow-up period, 21 patients (17.5%) had developed overt proteinuria. The initial study showed no difference in systolic blood pressure, age, sex, serum creatinine and its clearance, glucose, cholesterol and triglycerides between these patients and those who had not become proteinuric, but uric acid levels and diastolic blood pressure were higher (both P less than 0.01). An adequate control of blood pressure was obtained and maintained in all patients, who had similar therapeutic needs. During the follow-up period, uric acid levels remained significantly elevated (P less than 0.01) in the proteinuric patients, while changes in serum glucose, cholesterol and triglycerides were similar in all patients. These results indicate that long-term treatment of primary hypertensives does not fully protect kidney function and that initially elevated uric acid levels could be a predictor of a poor prognosis.

One of the main objectives of antihypertensive therapy is to preserve renal function from the deleterious effects of elevated blood pressure. Diuretics alone or in combination are effective for the treatment of arterial hypertension. Nevertheless, their use is accompanied by unwanted biochemical side effects, which have been attributed to their renal effects. During the last 10 years a group of 211 patients, diagnosed as having essential hypertension, were followed up. During the follow-up, they received a stepped-care therapeutic regimen consisting of nonpharmacologic measures (group 1), hydrochlorothiazide and amiloride (group 2), propranolol (group 3) and, if necessary, hydralazine (group 4). During the study, blood pressure remained within comparable, well-controlled levels in the 4 groups of patients. A progressive elevation of the levels of total serum cholesterol and glucose was observed in every group. The elevation attained statistical significance (p less than 0.01) after 4 years of therapy in those groups receiving the diuretic alone or in combination. Nevertheless, after 8 years of follow-up, the increment observed in these 2 parameters did not differ when patients in group 1 were compared with those in the remaining groups, indicating that thiazide diuretics could contribute to the earlier appearance of forthcoming events. Serum potassium levels were significantly lower (p less than 0.01) in groups 2 and 3 than in group 1. At the same time, we have observed the progressive appearance of clinically relevant proteinuria in 15.2% of patients, and the range of protein excretion ranged from 350 to 3,700 mg/24 hours. The appearance of proteinuria did not depend on the lack of control of blood pressure, nor on the different therapeutic requirements but was accompanied by a progressive decrease in creatinine clearance. The consequences of the renal effects of diuretics are of great importance during long-term therapy. The present results indicate that diuretics preempt the appearance of a forthcoming increase in serum glucose and cholesterol, and lessen the clinical relevance of these events.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis B is a frequent complication in haemodialysis patients because of their repeated exposure to blood products, and their impaired cellular and humoral response; trials with plasma-derived hepatitis B vaccine (PDV) show lower immune responses than those in healthy adults. Using a yeast-derived hepatitis B vaccine (YDV), the immunogenicity of two different dose levels (20 and 40 micrograms) and three vaccination schedules were compared in over 270 seronegative dialysis patients. Vaccination with 40 micrograms gave slightly better results than with the 20 micrograms dose. Seroconversion rates were higher with four dose, 40 micrograms vaccination schedules than a three dose schedule, and ranged from 80 to 86%. As the 40 micrograms, 0, 1, 2, 6 month schedule leads to a more rapid rise in antibody levels than the 40 micrograms, 0, 1, 2, 12 month schedule, it appears to be the most appropriate schedule in this patient group.

In order to control the progression of chronic renal failure through the maintenance of low-normal levels of serum phosphate, 10 patients (group I) were followed over a period of 10 months. They were maintained on a low phosphate diet and 12 g/day of aluminum hydroxide. Under this treatment, the serum phosphate decreased significantly compared to the phosphate levels determined prior to initiation of treatment, and compared to the serum phosphate levels of 10 controls with the same degree of renal failure (group II) but receiving conventional treatment. Despite the maintenance of normal levels of serum phosphate in group I, serum creatinine increased in the same proportion as in group II. A paired t test did not show any difference between the progression of the renal failure before or after the control of serum phosphate.

The participation of renal prostaglandins in the nephrotic syndrome has been investigated by the measurement of the urinary excretion of prostaglandin E2 (PGE2), renal function and the renin-angiotensin-aldosterone system before, during and after the administration of indomethacin in a group of patients diagnosed as having chronic idiopathic glomerulonephritis with and without nephrotic syndrome. Our results indicate increased renal production of PGE2 in nephrotic patients. This contributes to the maintenance of renal function, probably by counteracting an activated renin-angiotensin system and could be accompanied by a simultaneous and deleterious enhancement of the degree of proteinuria. Nevertheless, the participation of angiotensin II in this last even cannot be excluded.

The combination of hydrochlorothiazide and amiloride has been used in a group of patients diagnosed as having essential hypertension. Sixty-five percent of the patients for whom dietary restrictions did not achieve a reduction in blood pressure were initially controlled with this combination; the addition of a second or third drug was required by the remaining patients. During the six-month follow-up, the control of blood pressure was satisfactory with increased drug requirements, but the diuretic had to be discontinued in 12 patients because of side effects.

We report a case of cystinuria with staghorn renal lithiasis in a solitary right kidney and chronic renal failure. Right nephropyelolithotomy was performed and although 29 renal calculi were extracted many stones remained in situ. A permanent nephrostomy was left in the kidney. Several months later the urine was infected chronically with a ureolytic Citrobacter freundii bacteria and urinary pH oscillated between 8.0 and 9.2. Spontaneous dissolution of the cystine calculi was observed and many tiny fragments of cystine were expulsed through the nephrostomy, following which renal function improved. Despite the conditions favoring struvite calculi, formation did not occur.

The prolonged effects (42 days) of indomethacin treatment on the renin-angiotensin-aldosterone axis, renal hemodynamics, and renal excretory function in humans were studied. Indomethacin produced a 41% sustained depression in the 24-hour excretion of prostaglandin E2 and a mild (7%) decrease in inulin clearance but did not affect the clearance of p-aminohippurate, the 24-hour excretion of sodium and potassium, or the basal values of plasma aldosterone; however, it decreased the basal values of renin and prevented the stimulated (3 hours of walking) responses of plasma renin activity and plasma aldosterone. Indomethacin also produced a decrease in both the diuretic and saluretic response to furosemide and in the renal ability to concentrate urine. The indomethacin-induced hyporeninism and hypoaldosteronism were more pronounced when the subjects were receiving a sodium-restricted diet. This finding indicates that prolonged administration of anti-inflammatory drugs induces chronic hyporeninism and hypoaldosteronism. Prolonged treatment with indomethacin also produced some of the symptoms of a syndrome of hypoprostaglandinism, such as decreased plasma renin activity, plasma aldosterone, and urinary prostaglandin E2 in association with increases in plasma potassium levels and diastolic pressure.

In a multicenter study of hemodialysis patients in Spain, the immunogenicity of a yeast-derived recombinant deoxyribonucleic acid hepatitis B vaccine was evaluated. Two different vaccination schedules were examined: zero, one, two, six months and zero, one, two, 12 months. Two different dose levels (20 micrograms and 40 micrograms) were also compared. No serious adverse effects were reported by any of the vaccinees; the most frequently reported reaction was soreness at the injection site. This study also indicated that higher concentrations of antibodies are attained when more frequent doses of vaccine are administered. The yeast-derived vaccine produced an immune response similar to that of the plasma-derived vaccines.

In a retrospective study we have examined 20 liver specimens from haemodialysis patients with a mean time on treatment of 27 months. Thirteen specimens were biopsies, the remaining came from autopsies. The presence of refractile particles was found in 55 per cent of biopsies and 100 per cent of autopsies. Its presence was not constantly associated with morphological lesions of the liver. We believe that the deposition of this material could be a fortuitous finding with uncertain clinical implications.

The appearance of renal failure during episodes of macroscopic hematuria (EMH) in IgA nephropathy (IgAN) has been described as very unusual. The results of a prospective investigation on the effect of EMH on renal function in IgAN are presented. During a 3-year period, 29 episodes of EMH occurring in 21 patients with IgAN have been studied. A derangement of renal function (increase of serum creatinine by more than 0.5 mg/dl) was observed in 11 episodes (37.9%) with peak creatinine values ranging from 1.2 to 6.7 mg/dl. The worsening of renal function was accompanied by a longer duration of EMH (4.8 +/- 1.3 vs. 3.5 +/- 1.5 days; P less than 0.05) but not by arterial hypertension or edema. A complete recovery of renal function was observed in every patient 1 to 2 months after the start of EMH. The histological survey disclosed that the decrease of renal function correlated closely with the presence of red blood cell casts in as much as 50% of the tubular lumen and with findings of tubular necrosis. We conclude that a worsening of renal function can be observed frequently during the EMH. Tubular damage and obstruction by red blood cell casts may play a significant role in the pathogenesis of this complication.

Fenoldopam, a dopamine-1 (D1) agonist, was administered by a 6-h intravenous infusion to patients with refractory hypertension [diastolic blood pressure (DBP) greater than 115 mmHg while on triple therapy] in order to achieve a fall in DBP of 30 mmHg. The evolution of blood pressure, heart rate, glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, renal excretion of sodium, potassium, chloride, calcium, uric acid, phosphate, plasma renin activity (PRA), aldosterone and prolactin were evaluated. A significant fall in blood pressure (P less than 0.01) accompanied by an increase in heart rate (P less than 0.01) was attained after 30 min. GFR and RPF increased significantly (P less than 0.01) but the filtration fraction fell. Urine volume and urinary output of sodium, potassium, chloride, calcium, uric acid and phosphate increased markedly (P less than 0.01). Meanwhile, plasma potassium fell (P less than 0.01) and the hormonal parameters showed no significant change. We concluded that in refractory hypertension fenoldopam has potent renal and systemic vasodilatory properties through which blood pressure falls. The hypotensive effect of fenoldopam is also facilitated by its marked diuretic and natriuretic properties. The absence of variations of plasma prolactin confirm the D1 selectivity of fenoldopam and the lack of increase in PRA indicates that fenoldopam blocks the renin-angiotensin-aldosterone system.

16 chronic haemodialysis patients (group I), with non-microcytic anaemia (mean haemoglobin 7.2 g/dl, SD 1.0, range 5.8-9.8), moderate aluminium overload (serum aluminium 44 micrograms/l, SD 16, range 21-74), and normal or high iron stores (ferritin 800 micrograms/l SD 464, range 34-2013) were treated with intravenous desferrioxamine 1 g at the end of each dialysis for six months. 8 patients with similar characteristics served as controls (group II). After six months group I showed a rise in haemoglobin to 9.1 (SD 2.5) g/dl and a decrease in blood transfusion requirements, both significant, whereas group II showed no changes. Other significant changes observed in group I, but not group II, were a rise in reticulocytes and in red cell creatine and a fall in red cell protoporphyrin and serum ferritin. Ferritin decreased more in the patients whose anaemia improved. Minor increases in serum aluminium in group I did not differ from those in the control group. Desferrioxamine may benefit the anaemia of chronic haemodialysis patients through improvement of erythropoiesis. The effect seems not to be related to chelation of a heavy aluminium overload.

The hypothesis that pregnancy induced hypertension (PIH) is associated with abnormal physiological control of plasma renin activity (PRA) was tested by studying the effects of graded infusion of angiotensin II (ANG II) on PRA, plasma aldosterone (PA), and blood pressure in normal pregnancy, PIH, non-pregnant women in luteal and follicular phase of the menstrual cycle, and males. PIH occurring in the second trimester was associated with elevated PRA, PA and blood pressure compared with all other groups, and reduced urinary thromboxane excretion compared with normal pregnancy. Exogenous ANG II infusion failed to suppress existing PRA in patients with PIH, in contrast to all other groups, but increased PA in all groups. It is concluded that PIH occurring in the second trimester is associated with elevated PRA, PA and blood pressure. The inability of circulating ANG II to reduce PRA in PIH may constitute a major alteration underlying the pathophysiology of PIH.

To evaluate the renal effects of nisoldipine (N), a dihydropyridine derivative, we have evaluated the variations of blood pressure (BP), heart rate, glomerular filtration rate (GFR), renal plasma flow (RPF), 24-h natriuresis, and renal capacity to excrete an i.v. sodium load (2,000 ml isotonic saline in 4-h) in response to a 4-day course of therapy with placebo (P) and N in six normotensive volunteers and six mild-to-moderate essential hypertensive patients. Both volunteers and patients were studied on two constant diets (20 and 150 mEq of sodium daily). No parameters changed after P. On the contrary, N induced a significant fall of BP (p less than 0.01) in the group of patients but not in volunteers. In both groups RPF and GFR increased significantly (p less than 0.05-0.01) while on a low sodium intake but remained constant when sodium intake was high. In the two groups studied, nisoldipine exhibited natriuretic properties manifested by an increase in the 24-h output of sodium as well as by an increased renal capacity to excrete the i.v. sodium load. These natriuretic properties were present in both situations of sodium load and could be facilitated by the change in renal hemodynamics observed when the intake of sodium was low.

We reviewed the evolution of FENa in the EPP (first 4 weeks) in a group of CyA-treated patients as well as Aza-treated patients who did not present with acute rejection during this period of time. The CyA-treated patients showed lower values of FENa than did Aza-treated patients. Values of FENa below 1% were found in 51% of CyA- and 0% Aza-treated patients (P less than .01) before RFR. The finding of low FENa values was accompanied by more prolonged oliguric and RFR phases. Furthermore, the lower the level of FENa, the higher the prolongation of renal failure. We concluded that FENa values could probably be an index of CyA nephrotoxicity in the EPP.

In order to elucidate whether or not the natriuretic properties of calcium entry blockers persist during the long-term administration of the drug, we have investigated the renal capacity to excrete an intravenous sodium load (2,000 ml of isotonic saline in 4 h) in a group of eight mild to moderate essential hypertensive patients, before and after 1, 8, and 24 weeks of treatment with nitrendipine. The following parameters were measured before and hourly during saline infusion: blood pressure, and plasma and urine sodium and potassium. For 5 days prior to the performance of the test, the patients received a diet containing 120 mEq of sodium daily. Nitrendipine induced a significant fall of both systolic and diastolic blood pressure (p less than 0.05-0.01) that was maintained throughout the study. A significant increase of the cumulative renal sodium output (microEq/min/h) was observed after 1, 8, and 24 weeks (p less than 0.05-0.001) of therapy with the calcium entry blocker. Meanwhile, plasma sodium and potassium and the kaliuresis did not change significantly. These results indicate that the natriuretic effect of calcium entry blockers is still present after long-term treatment.