Renal abnormalities in sickle-cell beta-thalassemia.
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Biomedical subjects
Publications and source records attributed to K C Siamopoulos.
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PURPOSE: This study was undertaken to determine individual renal function in patients with autosomal dominant polycystic kidney disease (ADPKD). MATERIALS AND METHODS: The authors initially examined (study t1) 25 patients with ADPKD (12 female, 13 male; ages 18 to 68 years). The serum creatinine concentration and glomerular filtration rate, measured by Tc-99m DTPA, were 1.5 +/- 0.56 mg/dl and 65.7 +/- 31 ml.minute-1.1.73 m2, respectively. Thirteen patients had a follow-up study (t2) 2 years after their initial evaluations. Individual renal function was assessed on Tc-99m DMSA renal scans. RESULTS: The mean (+/- SD) difference between left kidney DMSA (DMSA-L) and right kidney DMSA (DMSA-R) was 7.04 % +/- 16.48%. In 20 patients (80%), the left kidney had a lower percentage contribution to the total renal function compared with the right kidney. When the results of the two studies were compared, deterioration in renal function was noted. In the t1 study, the mean serum creatinine concentration and glomerular filtration rate were 1.7 mg/dl and 67.02 ml.minute-1.1.73 m2 respectively, and in the t2 study these values were 2.01 mg/dl and 57.15 ml.minute-1.1.73 m2, respectively. No difference, however, was found in individual renal function in the two studies. CONCLUSIONS: In patients with ADPKD, the percentage contribution of each kidney to total renal function is not equal and remains stable during the progression of renal failure.
In order to define the effects of chronic renal failure (CRF) in the progress of gingival inflammation, we studied 6 patients (4 male, 2 female) with CRF who were on chronic hemodialysis for 4.25 (range 1-15) years. Six healthy individuals, age and sex matched were used as controls. The protocol which we used comprised of two periods (a) a 40-day duration period of preparation and (b) a 28-day duration experimental period. During the (a) period, all subjects went through: (1) therapy of the chronic gingivitis and (2) complete control of dental plaque by oral hygiene. During the experimental period, all subjects were advised to avoid, for at least 21 days, any mechanical or chemical media of oral hygiene and went through photographing, recording of gingival index (GI), recording of plaque index (PII), and the collection and quantification of gingival crevicular fluid (GCF). On the 21st day, root planning and polishing were performed and subjects were advised to carry out oral hygiene. On the 28th day, all previous examinations (GI, PII, GCF) were repeated. In both patients and controls, GI, PII and GCF were increased on 7th, 14th and 21st day, without significant differences between the groups and returned to normal (close to zero point) on the 28th day. There are no significant differences between patients with CRF and normal controls in the evolution of experimental gingivitis. Therefore, chronic uremia has no effect on the defense of periodontal tissue against microbial plaque.
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Disturbances of acid-base balance and electrolyte abnormalities are commonly seen in patients with acute leukemia. Our study aimed at illuminating the probable pathogenetic mechanisms responsible for these disturbances in patients with acute leukemia admitted to our hospital. We studied 66 patients (24 men and 44 women) aged between 17 and 87 years old on their admission and prior to any therapeutic intervention. Patients with diabetes mellitus, acute or chronic renal failure, hepatic failure, patients receiving drugs that influence acid-base status and electrolyte parameters during the last month, such as corticosteroids, cisplatin, diuretics, antacids, aminoglycosides, amphotericin, penicillin, and K(+), PO(4)(3-), or Mg(2+) supplements were excluded. Forty-one patients had at least one acid-base or electrolyte disturbance. There were no significant differences in the incidence of acid-base balance and electrolyte abnormalities between patients with acute myeloid leukemia (AML) and patients with acute lymphoblastic leukemia (ALL). The most frequent electrolyte abnormality was hypokalemia, observed in 41 patients (63%), namely in 34 patients with AML, and 7 with ALL; the main underlying pathophysiologic mechanism was inappropriate kaliuresis. Furthermore, hypokalemic patients more frequently experienced concurrent electrolyte disturbances (i.e., hyponatremia, hypocalcemia, hypophosphatemia, and hypomagnesemia), as well as various acid-base abnormalities compared to normokalemic patients. Hypokalemia in patients with acute leukemia may serve as an indicator of multiple concurrent, interrelated electrolyte disturbances, especially in patients with AML.
OBJECTIVES: To evaluate the analytical performance of a new homogeneous HDL-cholesterol assay (Olympus Diagnostica). To investigate possibly discrepant results in chronic hemodialysis patients who commonly exhibit quantitative and qualitative lipoprotein abnormalities, responsible for atherogenic complications in these patients. DESIGN AND METHODS: Serum samples were collected from 50 healthy subjects and 65 chronic hemodialysis patients. HDL-C levels measured by the homogeneous assay were compared with the routine dextran sulfate-Mg2+ precipitation method and the ultracentrifugation/dextran sulfate-Mg2+ precipitation as reference method. RESULTS: The homogeneous assay was linear up to at least 220 mg/dL. The analytical precision was estimated with three different sets of commercial controls and one set of human pooled serum control. The within-day CV ranged between 1.7% and 3.8% and the between-day CV ranged between 1.0% and 2.3%. HDL-C values in both populations correlated highly with the dextran sulfate-Mg2+ precipitation method and the ultracentrifugation/dextran sulfate-Mg2+ precipitation method (r > or = 0.96, bias between -0.9 and 2.3 mg/dL). Lipemia up to triglyceride concentration of 600 mg/dL did not alter the HDL-C value. CONCLUSIONS: The homogeneous assay for HDL-C (Olympus) uses much less sample, is accurate and convenient to handle, and allows full automation. The test should considerably facilitate the screening of individuals at an increased risk of cardiovascular disease, including hemodialysis patients.
Patients with renal failure have an increased incidence of atherosclerotic disease. Numerous studies have shown that these patients show increased serum lipoprotein(a) [Lp(a)] concentrations compared with the control population. However, variable alleles at the apolipoprotein(a) [apo(a)] gene locus determine to a large extent the Lp(a) concentration in the general population. We therefore undertook the present study to evaluate apo(a) phenotypes and Lp(a) serum concentrations in a large number of patients with renal disease. Seventy-nine patients treated by hemodialysis (HD), 47 patients treated by continuous ambulatory peritoneal dialysis (CAPD), 68 patients with mild/moderate chronic renal failure (CRF) and serum creatinine levels of 1.8 to 8 mg/dL, and 73 healthy controls were studied. All patients showed significantly elevated median serum Lp(a) concentrations in comparison with controls: HD patients, 15.7 mg/dL (P < 0.01); CAPD patients, 20 mg/dL (P < 0. 005); CRF patients, 15.1 mg/dL (P < 0.01) versus controls, 7 mg/dL. The greater Lp(a) values in all groups were not explained by differences in isoform frequencies, whereas their increase was apo(a)-type specific. Thus, patients in all groups with high-molecular-weight (HMW) apo(a) isoforms showed a significant elevation of Lp(a) levels, whereas serum Lp(a) concentrations in patients with low-molecular-weight (LMW) isoforms were not significantly different from controls, except for CAPD patients, who presented increased serum Lp(a) concentrations. We conclude that in patients with renal failure, even of mild/moderate degree, as well as in patients with end-stage renal disease undergoing HD or CAPD, elevated Lp(a) concentrations are mainly observed in those with HMW apo(a) phenotypes.
The effectiveness as well as the metabolic effects of the combination of diuretics [hydrochlorothiazide (HCT) vs indapamide (IND)] and perindopril (P) in 14 patients (7 male, 7 female) aged 37-62 years with mild idiopathic hypertension were studied. Following a 4-week wash-out period and a 4-week period of monotherapy with P (4 mg/daily), IND (2.5 mg/daily) or HCT (25 mg/daily) was added for 4 weeks. Selection of the diuretic agent was random. Following a 4-week wash-out period from the diuretic, in which only P was given, the alternative diuretic was administered for another period of 4 weeks. P decreased blood pressure levels significantly. However, the drug was more efficacious in patients with higher plasma renin activity (PRA). Combination treatment induced an additional decrease in the blood pressure levels, mainly in patients with lower PRA. The combination of P + HCT was more effective than the combination P + IND. The addition of either HCT or IND evoked a small but statistically significant increase in serum glucose levels while fasting as well as during the 75 g oral glucose challenge. However, insulin levels did not change significantly during the study. Small but not statistically significant changes in serum electrolytes and lipid parameters were observed during the various phases of the study, while a statistically significant increase in the serum uric acid was noticed when the combination P + HCT was given. We conclude: (1) P in small doses is an effective and safe antihypertensive agent, (2) PRA has a predictive value in determining the effectiveness of P treatment, (3) the combination of P with small doses of HCT or IND is more efficacious than P alone, (4) the combination treatment has adverse effects in the carbohydrate tolerance, while there are not significant changes in serum electrolyte and lipid parameters.
Moxonidine is a new antihypertensive agent whose mechanism of action appears to involve specific stimulation of imidazoline receptors resulting in an inhibition of the activity of the central and peripheral sympathetic nervous system. The drug seems to behave neutrally with respect to plasma lipid parameters. However, there are no data on the effects of moxonidine on the low-density lipoprotein (LDL) subclass pattern or on the LDL oxidation susceptibility, both of which are known to play a prominent role in the pathogenesis of atherosclerosis. Thus, we undertook the present study to examine the influence of moxonidine on the LDL subspecies profile and their susceptibility to copper-induced oxidative modification in 20 hypertensive patients (11 men, 9 women) aged 38-61 years. Moxonidine administered at a dose of 0.4 mg daily for 8 weeks produced a significant decrease in both systolic and diastolic blood pressure (from 147 +/- 10 to 131 +/- 11 mm Hg, P < 0.001, and from 98 +/- 4.5 to 86 +/- 5 mm Hg, P < 0.001, respectively). No significant change in plasma lipid profile was observed after moxonidine administration. Additionally, no change in the susceptibility of LDL subclasses to copper-induced oxidative modification was noticed. Finally, drug therapy was not followed by any change in either LDL phenotype or in mass and composition of the three LDL subfractions. We conclude, that unlike other antihypertensive drugs, such as beta-blockers which may predispose to expression of a relatively atherogenic lipoprotein subclass pattern, moxonidine does not affect either plasma lipid parameters or lipoprotein composition.
UNLABELLED: Plasma and Lp(a)-associated PAF-acetylhydrolase activity in uremic patients undergoing different dialysis procedures. BACKGROUND: Platelet-activating factor (PAF) is a potent inflammatory mediator associated with several physiopathological conditions, including renal diseases. PAF is degraded to the inactive metabolite lyso-PAF by PAF-acetylhydrolase (PAF-AH), which is considered as a potent anti-inflammatory and anti-atherogenic enzyme associated with lipoproteins. In this study, we evaluated the plasma- and lipoprotein(a) [Lp(a)]-associated PAF-AH activity in relationship to plasma lipid parameters and Lp(a) isoform size in patients with mild/moderate chronic renal failure (CRF), as well as in hemodialysis (HD) and chronic ambulatory peritoneal dialysis (CAPD) patients. METHODS: We studied 74 patients undergoing maintenance HD, 44 patients undergoing CAPD, 56 patients with mild/moderate CRF, and 98 healthy subjects whose lipid profile, as well as plasma and high-density lipoprotein (HDL)-associated PAF-AH activity, was determined. Moreover, the effect of Lp(a) plasma levels on the distribution of PAF-AH among plasma lipoproteins, as well as the specific activity and kinetic properties of PAF-AH on two different Lp(a) isoforms, was measured in each studied group. RESULTS: The plasma PAF-AH activity in all studied groups was significantly higher than in controls, and the increase was more profound in CAPD patients. The HDL-associated PAF-AH activity, expressed per milliliter of plasma, was similar among all studied groups; however, when it was expressed as either per milligrams of HDL cholesterol or per milligrams of plasma apolipoprotein (apo) AI, the PAF-AH activity was significantly higher in all patient groups compared with controls. All patient groups had significantly elevated plasma Lp(a) levels, which altered the distribution of PAF-AH among the plasma lipoproteins compared with that observed in subjects with very low plasma Lp(a) levels (<8 mg/dl). Additionally, in each studied group, the specific activity as well as the apparent Km and Vmax values of the 19K4 apo(a) isoform were significantly higher (P < 0.01) compared with the values of the 23K4 isoform. However, the specific activity, as well as the Km and Vmax values on either the 19K4 apo(a) isoform or the 23K4 isoform, was significantly higher in CAPD patients compared with the other three groups. CONCLUSIONS: Plasma PAF-AH activity is increased in uremic patients. This elevation is more profound in CAPD patients, who also exhibit a more atherogenic lipid profile and more pronounced alterations in the specific activity and the kinetic constants of Lp(a)-associated PAF-AH.
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It has been reported that micronized fenofibrate and losartan can significantly decrease serum uric acid levels by augmenting uric acid excretion. We undertook this study to evaluate the effects of the combination treatment with micronized fenofibrate and losartan in nondiabetic hypertensive dyslipidemic patients with hyperuricemia (serum uric acid, >7 mg/ dl). A total of 25 patients (15 men, 10 women) aged 21-66 years was studied. In all patients, serum lipid parameters, including Lp(a), fibrinogen, and uric acid levels, as well as fractional excretion of uric acid (FEUA) were obtained before treatment, 8 weeks after micronized fenofibrate treatment (200 mg daily), and 8 weeks after combination therapy with micronized fenofibrate (200 mg daily) and losartan (50 mg daily). Fenofibrate alone significantly decreased total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, Apo B, Lp(a), fibrinogen, and uric acid levels (from 7.6+/-0.55 to 5.6 +/-0.5 mg/dl; p < 0.0001) and increased high-density lipoprotein (HDL) cholesterol, Apo A1, and FEUA (from 6.5+/-1.8% to 12.2+/-4%; p < 0.0001). The addition of losartan beyond the decrease in blood pressure values did not significantly alter serum metabolic parameters. However, a small additional decrease in serum uric acid levels (from 5.6+/-0.5 to 4.9+/-1 mg/dl; p < 0.05) was found because of a further increase in FEUA (from 12.2+/-4% to 14+/-5.5%; p < 0.05). It is concluded that the combination of micronized fenofibrate and losartan is useful for the management of patients with multiple metabolic abnormalities, including hyperuricemia.
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Normotensive patients with microvascular angina exhibit increased diastolic blood pressure and blood pressure loads during daily activities and decreased diurnal variation of systolic blood pressure, compared with age- and sex-matched normotensive controls. The abnormal blood pressure profile could play a role in the pathogenesis of microvascular angina.
Patients with hyporeninemic hypoaldosteronism show mild to moderate renal insufficiency, with a creatinine clearance of 20-75 ml/min, and asymptomatic hyperkalemia. A low degree of sodium wasting and mild hyperchloremic metabolic acidosis are also usually present. However, severe sodium wasting and volume depletion are not typically seen unless the patient is placed on severe sodium restriction or has some other cause of extrarenal sodium loss. In fact, acute renal failure has not been reported in such patients. We describe a diabetic patient with hyporeninemic hypoaldosteronism and autonomic neuropathy who developed recurrent episodes of acute renal failure due to prerenal azotemia during acute exacerbations of diarrhoea. In our case, despite significant hypovolemia, the renin-aldosterone axis was markedly suppressed, implying that sympathetic tone played a decisive role in renin regulation.
BACKGROUND: Hepatitis E virus (HEV) has been found to be the causative agent of enterically transmitted non-A, non-B hepatitis in tropical and subtropical countries. Several investigators, however, have indicated that HEV could be endemic in Europe, albeit at a low prevalence. STUDY DESIGN AND METHODS: The purpose of this study was to estimate the prevalence of anti-HEV in various populations in northwestern Greece (Epirus region). Healthy blood donors (2636), refugees from southern Albania (350), children (165), injecting drug users (IDUs) (65), multiply transfused patients (62), patients with chronic viral hepatitis (75), and chronic hemodialysis patients (149) were investigated for anti-HEV by enzyme immunoassay and confirmatory Western blot assay. In addition, 380 consecutive healthy blood donors and 62 hemodialysis patients from a neighboring area (Agrinion, Greece) were investigated. RESULTS: A very low presence of anti-HEV antibody was found among healthy blood donors from Epirus (0.23%) and Agrinion (0.53%). Anti-HEV was not detected in children, IDUs, or multiply transfused patients. In contrast, a low but significant prevalence of anti-HEV was found among refugees (4.85%), patients with chronic viral hepatitis (5.3%), and hemodialysis patients from Epirus (1.34%), as compared with healthy blood donors from Epirus: p < 0.0001, p < 0.00001, and p < 0.10, respectively. A high prevalence (9.7%) of anti-HEV was revealed in patients at the hemodialysis unit of the General Hospital of Agrinion (p < 0.00005, compared to healthy blood donors from Agrinion). No significant association was found between anti-HEV positivity and the age or sex of donors, the duration of hemodialysis, positivity for hepatitis B or C virus infection markers, history of hepatitis, increased alanine aminotransferase, renal transplantation, a history of transfusion, or the number of units transfused. CONCLUSION: This study demonstrated a high prevalence of anti-HEV in a separate hemodialysis unit, without an association with the known routes of transmission of blood-borne viruses. This observation suggests that a still-undefined intra-unit factor or other factors are associated with HEV transmission.
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BACKGROUND: Immunologic alterations have been reported in chronic haemodialysis (HD) patients. Some HD patients may have, therefore, an inability to produce detectable amounts of serum antibodies to hepatitis C virus (anti-HCV). Previous studies have shown the presence of HCV viraemia in anti-HCV-negative HD patients (ranging from 1 to 15%). However, the universal epidemiologic impact of these cases remains uncertain since there are conflicting results. In this context, we conducted a study in an attempt to investigate the presence of HCV viraemia among anti-HCV-negative HD patients in a well-defined geographic area of the northwestern part of Greece. METHODS: During a 6 month period, 81 anti-HCV-negative HD patients were tested twice for the presence of HCV RNA, using the reverse transcriptase polymerase chain reaction (RT-PCR) combined with a DNA enzyme immunoassay (DEIA). At the same time, periodic testing for anti-HCV by two commercially available third generation assays was done. In addition, 15 anti-HCV-positive HD patients and 20 non-HD patients with well established chronic HCV infection used as internal controls were tested for the presence of HCV RNA and anti-HCV. RESULTS: None of the anti-HCV-negative HD patients were shown to be viraemic by the combined RT-PCR and DEIA method. During the same time period, all remained anti-HCV negative by the third generation assays. By contrast, all the patients with known HCV-infection were positive by the two enzyme immunoassays, whereas 13 anti-HCV-positive HD patients (86.7%) and 18 non-HD patients (90%) were viraemic by RT-PCR. CONCLUSIONS: This study demonstrated that routine HCV RNA testing in anti-HCV-negative HD patients appears not to be necessary particularly when third generation assays are used for the detection of anti-HCV.