Comparison of the humoral markers of bone turnover and bone mineral density in patients on haemodialysis and continuous ambulatory peritoneal dialysis

Renal osteodystrophy is an important complication in patients with end-stage renal disease on maintenance dialysis. The aim of this study was to compare the biochemical markers of bone formation (serum collagen type I C-terminal propeptide) and resorption (serum deoxypyridinoline - DPD - and pyridinoline - PYR) with the bone mineral density (BMD) at lumbar spine, femoral neck, and forearm in patients with end-stage renal disease on haemodialysis (HD) versus continuous ambulatory peritoneal dialysis (CAPD). Fifty-nine adult patients, 45 on CAPD (18 females, 27 males) and 14 on HD (2 females, 12 males), were studied. The mean age was 44 +/- SEM 1.6 and 54.4 +/- 4.8 years, respectively. No significant differences in serum calcium, phosphorus, creatinine, and parathyroid hormone were found between patients on HD and CAPD in predialysis samples. Serum urea was significantly lower (p = 0.02) in the CAPD group. Serum PYR (nmol/l) and DPD (nmol/l) were significantly higher in patients on HD as compared with those on CAPD: 105 +/- 23.3 versus 43.7 +/- 3.47 (p = 0.007) and 31.0 +/- 2.4 versus 24.4 +/- 1.4 (p = 0.027), respectively. The results were still significantly higher in the HD patients following correction for serum creatinine and body mass index. There was a close correlation between dialysate DPD and creatinine in both dialysis modalities (HD r = 0.9, CAPD r = 0.76). The clearance of DPD did not differ significantly between the CAPD membrane and the HD membrane (p = 0.22). Serum collagen type I C-terminal propeptide was not significantly different between the HD and CAPD patients. The results were unaffected following correction for age and gender. The BMD was measured in 38 (65%) of the patients (HD n = 8, CAPD n = 30) by dual-energy X-ray absorptiometry and expressed as 'Z' scores. This was reduced at all sites in the patients with end-stage renal disease. The BMD was significantly lower at the ultradistal forearm (mostly trabecular bone) in HD patients as compared with CAPD patients (n = 0.02). A similar trend was observed at the lumbar spine, although the results failed to reach significance. In the whole population (n = 38), linear regression analysis revealed a significant negative correlation between BMD at the ultradistal forearm and serum PYR (r = -0.35, p = 0.04) and DPD (r = -0.33, p = 0.049). Combined measurements of BMD and biochemical markers of bone resorption may have potential in the identification of patients at high risk of bone loss who may require further evaluation of bone remodeling by bone histomorphometry.     

Electrocardiography is unreliable in detecting potentially lethal hyperkalaemia in haemodialysis patients.

BACKGROUND: It is speculated, but unconfirmed, that the usual electrocardiographic manifestations of hyperkalaemia are less frequent and less pronounced in persons with end-stage renal disease (ESRD) than in those with normal renal function. We studied 74 consecutively selected stable haemodialysis patients to determine the prevalence of electrocardiographic changes of hyperkalaemia in stable persons with ESRD receiving haemodialysis. METHODS: Pre-dialysis serum potassium concentration and other electrolytes were measured and simultaneous 12-lead electrocardiogram obtained. RESULTS: The 74 study subjects (45 men, 29 women) comprised 63 blacks (85%), four Hispanics (6%), four whites (6%), and three Asians (4%) of mean+/-standard deviation age 55.5+/-14.7 years. Mean pre-dialysis potassium concentration was 4.9+/-0.71 mEq/l (range 3.3-6.7). No study subject evinced arrhythmia or any of the typical electrocardiographic changes associated with hyperkalaemia. There was no significant difference in T wave amplitude (F statistic=2.1; P=0.11) or T wave to R wave ratio (F statistic=2; P=0.12) between quartiles of serum potassium concentration. Also, T wave amplitude was equivalent in patients with serum potassium concentration >5.5 mEq/l (7.1+/-4.1 mm) or < or =5.5 mEq/l (5.2+/-3.5 mm) (P=0.13). Linear regression analysis showed that the total serum calcium concentration had an inverse relation with T wave amplitude (P=0.03) after adjustment for other factors (a high total serum calcium concentration was associated with a low T wave amplitude). CONCLUSION: Haemodialysis patients with hyperkalaemia may not exhibit the usual electrocardiographic sequella of hyperkalaemia, possibly due in part to fluctuations in serum calcium concentration. Thus, the absence of electrocardiographic changes in hyperkalaemic haemodialysis patients should be interpreted with caution.     

Oxalate removal by hemodialysis in end-stage renal disease

Because of mounting evidence of precipitation of calcium oxalate in the soft tissues of patients with end-stage renal disease (ESRD) on maintenance hemodialysis, the plasma oxalate concentrations and calculated dialysis removal of oxalate were studied in seven patients without evidence of either primary or absorption hyperoxaluria prior to ESRD. A reversed-phase high-pressure liquid chromatographic method was developed to quantitate serum oxalate. Mean value +/- SE in four healthy controls was 28 +/- 5 mumol/L, and in the seven patients it was 187 +/- 15 mumol/L predialysis and 89 +/- 11 mumol/L postdialysis. Oxalate deposition in the soft tissues of ESRD patients is the consequence of sustained hyperoxalemia. Oxalate removal by dialysis was calculated from the four-hour oxalate clearance. Since the ionic radii of phosphate and oxalate are similar, total oxalate clearance was calculated midpoint of dialysis. Mean oxalate removal/dialysis was 3.01 +/- 0.283 mmol. On a daily basis this value was 1.645 +/- 0.155 mmol, which is about threefold the normal oxalate excretion rate. It is not significantly different from the excretion rate in absorption oxalurias but is less than that in primary hyperoxaluria. Therefore, it is concluded that hyperoxalemia in ESRD results from loss of renal excretion, failure of hemodialysis to remove enough oxalate to maintain a normal serum concentration, and increased intestinal absorption of oxalate and/or increased endogenous production.     

Free serum leptin but not bound leptin concentrations are elevated in patients with end-stage renal disease.

BACKGROUND: Leptin is a 16-kDa protein that is thought to be a regulator of food intake and body weight. Although total serum leptin levels have been reported to be elevated in obese and normal weight patients with end-stage renal disease (ESRD), it is not known whether serum-free leptin concentrations are also increased in patients with ESRD with no apparent nutritional problems. Furthermore, there are no data on how different dialysis modes (high-flux haemodiafiltration and low-flux dialysis) influence serum leptin subfractions. METHODS: We measured fasting serum free and bound leptin levels in three groups of male subjects: patients on haemodiafiltration with high flux dialysers (n=11), patients on haemodialysis with low-flux dialysers (n=17) and healthy age (61+/-8 years) and BMI (23.8+/-3.1 kg/m(2)) matched control subjects (n=28). Both leptin components were determined before and after a single dialysis session. RESULTS: Body mass indices were correlated with serum free leptin levels in both patients (r=0.69, P<0.001) and controls (r=0.77, P<0.001). Mean (SD) serum free leptin levels were significantly higher in ESRD patients than in control subjects (91+/-33 vs 41+/- 21 pmol/l; P<0.01). Bound leptin levels did not differ in both groups (0.67+/-0.12 vs 0.56+/-0.11 nmol/l, NS). Elevated serum-free leptin levels in ESRD patients could be reduced by haemodiafiltration with high-flux membranes, but not with low-flux haemodialysis membranes.The former led to a reduction of initial serum free leptin values to 76+/-17% (P<0.01), whereas bound leptin remained unaffected. CONCLUSION: Serum-free leptin levels are elevated in ESRD without any apparent effect on body weight. In contrast, serum bound leptin levels remain stable, thus central feedback regulation via the bound form of the hormone may serve as an alternative explanation in the regulation of food intake and energy expenditure in chronic patients on haemodialysis with no apparent nutritional problems.     

Predictive factors of low HCO3- levels in peritoneal dialysis patients

BACKGROUND: Metabolic acidosis is a major metabolic abnormality in end-stage renal disease (ESRD) and alkali is provided with dialysis treatment to patients on chronic peritoneal dialysis (CPD) to keep their acid-base balance within normal serum HCO3- levels. METHODS AND RESULTS: We examined the levels of venous serum HCO3- in 163 patients on CPD and the predictive factors for HCO3- levels low enough to indicate metabolic acidosis. The mean value for HCO3- was 26+/-2.4 mmol/l and for anion gap was 13.1+/-3.1 mEq/l. A serum bicarbonate concentration of less than 24 mmol/l, compatible with metabolic acidosis, was observed in 13.5% of the patients. In a multivariate analysis HCO3- levels were directly correlated with older age and use of CaCO3- as phosphate binders, and inversely associated with serum potassium, the use of sevelamer and low lactate dialysis solutions. Higher serum urea levels, the use of low lactate solutions and sevelamer instead of CaCO3 were significantly predictive factors for HCO3- levels < 24 mmol/l. CONCLUSIONS: Venous HCO3- and anion gap values were within the normal ranges in stable CPD patients. In 13.5% of them, however, chronic metabolic acidosis was observed based on venous HCO3- levels < 24 mmol/l. Dietary protein intake, the use of sevelamer and low (35 mmol/l) concentration of lactate in dialysis solutions are important predictive factors for chronic metabolic acidosis in these patients.     

Brucellosis in cases of end-stage renal disease.

BACKGROUND: Patients with brucellosis frequently present with joint and bone pain. However, brucellosis may be overlooked in patients with end-stage renal disease (ESRD) who undergo dialysis since amyloidosis due to renal osteodystrophy and beta-2 microglobulinaemia may cause bone pain as well. Only four cases of end-stage renal failure accompanied by brucellosis have been reported in the literature. We evaluated clinical and laboratory characteristics and organ involvement of seven brucellosis patients with end-stage renal failure and compared them with brucellosis cases without any renal diseases. METHODS: This is a prospective study and involved 158 patients diagnosed with brucellosis. All the patients were divided into two groups: brucellosis patients with ESRD (Group 1) and brucellosis patients without any renal disease (Group 2). RESULTS: Group 1 included 7 patients (5 males and 2 females with the mean age 52.1 +/- 14 years) and Group 2 included 151 patients (62 males and 89 females with the mean age 45.4 +/- 16 years). Out of seven patients in Group 1, one had neurobrucellosis, one had paravertebral abscess, one had epidural abscess and one had peripheral arthritis. In addition, one patient in Group 1 with accompanying sickle cell anaemia presented with pain crisis and was diagnosed with brucellosis on admission. Serological tests were negative for brucellosis, but Brucella melitensis was isolated in blood cultures in another patient with accompanying continuous ambulatory peritoneal dialysis. Group 1 more frequently had joint pain and malaise. B. melitensis was isolated in blood cultures in blood taken in the absence of fever in half of the cases in Group 1 positive for B. melitensis in blood cultures on admission. CONCLUSION: B. melitensis can be isolated in blood cultures even in the absence of high fever. In fact, in the present study, B. melitensis was isolated in most of the cases without high fever. For this reason, blood cultures should be performed in cases of end-stage renal diseases suspected of having brucellosis although fever is not present. In addition, brucellosis can present various clinical forms in endemic areas, mimics several diseases and can be characterized with severe complications.     

Assessment of vascular calcification in ESRD patients using spiral CT.

BACKGROUND: Dialysis patients have increased vascular calcification of the coronary arteries and aorta by electron beam CT scan. The purpose of the present study was to utilize an alternative machine, spiral CT, to assess calcification in end-stage renal disease (ESRD) patients. METHODS: Two groups of patients with ESRD were evaluated: group 1, those receiving a renal transplant (n=38); and group 2, those remaining on dialysis (n=33). All patients underwent quad-slice spiral CT with retrospective gating to evaluate coronary artery and aorta calcification scores. Both area (Agatston method) and volume calculations were utilized, with retrospective gating in all but 16 subjects. Laboratory tests, medications and clinical characteristics were analysed. RESULTS: Using spiral CT, the intra-reader variability for coronary artery calcification (after correction for very low scores) was 0.9% mean / 0% median using the area (Agatston method) and 2.9% mean / 0% median using volume calculations. Group 1 patients were younger, more likely to be Caucasian and on peritoneal dialysis, had lower serum calcium and higher C-reactive protein levels than group 2. In patients without vs those with coronary artery calcification, only longer duration of dialysis (34+/-64 vs 55+/-50 months, P=0.004; r=0.39, P=0.005) and increasing age (39+/-13 vs 54+/-10 years, P<0.001; r=0.29, P=0.039) were associated, whereas only increasing age was associated with aorta calcification. CONCLUSION: In ESRD patients, the factors correlating with coronary calcification were duration of dialysis and advancing age, whereas only age correlated with aorta calcification. Spiral CT offers an alternative technique for the assessment of these changes.     

Serum erythropoietin levels and hematocrit in end-stage renal disease: influence of the mode of dialysis

Serum erythropoietin (Ep) levels were measured by radioimmunoassay in 70 patients with end-stage renal disease (ESRD) to evaluate the influence of the mode of dialysis on the relationship between serum Ep levels and the severity of anemia. Thirty-five patients were on hemodialysis (HD), seven were on intermittent peritoneal dialysis (IPD), and 28 were on continuous ambulatory peritoneal dialysis (CAPD). Compared to HD, CAPD patients had higher serum Ep (CAPD), 46.1 +/- 13.4 v HD, 16.9 +/- 2.2 mU/mL) and hematocrit (CAPD, 33.9 +/- 2.5 v HD, 24.8 +/- 1.4%; P less than 0.05). The Ep and Hct values for IPD patients were intermediate between the other two groups. Serum Ep levels were higher in CAPD patients in the first 4 weeks of initiation of CAPD (144 +/- 35 mU/mL, n = 6) than later (39 +/- 6.4 mU/mL, n = 24). A significant fluctuation in serum Ep and Hct values was noted in patients on all three modes of dialysis, when multiple samples were obtained at different time intervals. There was a weak correlation between serum Ep and Hct in the three groups of dialysis patients; r = 0.36, P less than 0.005. The data suggest that CAPD provides a better biochemical milieu for Ep production and responsiveness than HD treatment of ESRD.     

Activity of systemic lupus erythematosus in end-stage renal disease patients: study in a Brazilian cohort

BACKGROUND: Dialysis has been associated with lupus remission. We studied the prevalence of systemic lupus erythematosus (SLE) as a cause of end-stage renal disease (ESRD) in the metropolitan area of Rio de Janeiro and assessed disease activity in SLE patients on dialysis. METHODS: Of 3,535 ESRD patients, 63 had SLE (1.8%). Fifty-seven entered the study (54 females, 3 males, 38 +/- 10 years). Hemodialysis consisted of 3 sessions per week of about 4 h duration, blood flow of about 400 ml/min, bicarbonate dialysate ([Ca(2+)] = 2.5-3.5 mEq/l) at 500 ml/min and cellulose acetate or polysulfone dialyzers. Activity was initially defined as: non-renal (nr) SLE disease activity index (SLEDAI) of >0; use of at least 20 mg/day of prednisone; and/or any dose of another activity-controlling drug. Fifty-seven ESRD patients without SLE were used as controls. RESULTS: Eighteen SLE patients were under drug treatment; of the remaining, 30 had an nrSLEDAI of >0 totaling 48 patients (84%) initially labeled as active. An apparent activity was also present in 21 controls (37%). Of those, 19 had an nrSLEDAI of <4. With a cutoff of >or=4, figures in each group would be 49 and 4%. Under this criterion, age was the only significant predictor of flare in our SLE ESRD population in a multivariate logistic regression model. Activity remained high in patients who were on dialysis for >5 years (7/18, 39%). CONCLUSION: SLE accounted for 1.8% of our ESRD patients. Application of SLEDAI to dialysis patients may require consideration of confounding factors related to the ESRD state. Even with a score of >or=4 as a cutoff, SLE activity in dialysis patients was high (49%) and long-lasting. Age was the major determinant of flare.     

Apoprotein A-I and high density lipoprotein subfractions in patients with chronic renal failure receiving hemodialysis

Serum concentration of apoprotein A-I (apo A-I) and cholesterol content in high density lipoprotein (HDL) subfractions have been studied in 19 men and 11 women at the end stage of chronic renal failure undergoing hemodialysis. HDL2 cholesterol concentration was decreased in males [0.33 +/- 0.12 (mean +/- SD) mmol/l, controls 0.45 +/- 0.09 mmol/l; p less than 0.001]; in females HDL2 cholesterol was also decreased although without statistical significance (0.45 +/- 0.15 vs. 0.55 +/- 0.10 mmol/l). HDL3 cholesterol was significantly decreased in men (0.65 +/- 0.11 vs. 0.77 +/- 0.04 mmol/l; p less than 0.001) and also in women (0.61 +/- 0.12 vs. 0.82 +/- 0.07 mmol/l; p less than 0.005). However, serum concentration of apo A-I was within the normal range (1.13 +/- 0.16 milligram in males and 1.25 +/- 0.17 milligram in females; controls 1.24 +/- 0.17 and 1.35 +/- 0.19 milligram, respectively). The raised apo A-I/HDL2 cholesterol ratio in both men and women suggests the existence of qualitative changes in HDL subfractions as has been proposed in previous studies measuring total apo A and total HDL cholesterol in patients with chronic renal failure receiving hemodialysis. These abnormalities in the relative composition of HDL subfractions could play an important role as a vascular risk factor in patients with chronic renal failure undergoing hemodialysis.     

An open-label, crossover study of a new phosphate-binding agent in haemodialysis patients: ferric citrate.

BACKGROUND: Hyperphosphataemia contributes to secondary hyperparathyroidism and renal osteodystrophy in patients with end-stage renal disease (ESRD). Calcium salts are widely employed to bind dietary phosphate (P) but they may promote positive net calcium balance and metastatic calcification. We recently reported that ferric compounds bind intestinal phosphate in studies of normal and azotemic rats. METHODS: To extend this observation, we performed an open-label, random order, crossover comparison study of ferric citrate and calcium carbonate in haemodialysis patients from two teaching hospitals. The study sample consisted of 23 women and 22 men with an average age of 52.5 +/- 11.8 (SD) years and an average weight of 54.5 +/- 10.7 kg. All forms of iron therapy were discontinued. Two weeks before the study, patients were instructed to discontinue all P-binding agents. The patients were randomly assigned to receive either calcium carbonate (3 g/day) or ferric citrate (3 g/day) for 4 weeks followed by a 2 week washout period, and then crossed over to the other P-binding agent for 4 weeks. RESULTS: From a baseline concentration of 5.6 +/- 1.5 mg/dl, the serum P increased during the washout period to 7.2 +/- 1.9 mg/dl prior to calcium carbonate treatment, and to 6.7 +/- 1.9 mg/dl prior to ferric citrate treatment. The serum P concentration fell significantly during treatment with both calcium carbonate (7.2 +/- 1.9 to 5.2 +/- 1.5 mg/dl, P<0.0001) and ferric citrate (6.7 +/- 1.9 to 5.7 +/- 1.6 mg/dl, P<0.0001). The results were not influenced by order of treatment. Under the conditions of the study protocol, ferric citrate was less effective than calcium carbonate at lowering the serum phosphate concentration. The serum Ca concentration increased during treatment with calcium carbonate but not ferric citrate. Ferric citrate treatment did not affect the serum concentration of aluminium. Ferric citrate treatment was associated with mild and generally tolerable gastrointestinal symptoms. CONCLUSION: Ferric citrate shows promise as a means of lowering the serum phosphate concentration in haemodialysis patients. Further studies are needed to find the optimal dose.     

Malnutrition-inflammation-atherosclerosis (MIA) syndrome components in hemodialysis and peritoneal dialysis patients

BACKGROUND: Malnutrition, inflammation, and atherosclerosis (MIA syndrome) are common in end-stage renal disease (ESRD) patients. Each component of MIA syndrome is the predictor of outcomes in ESRD patients. In this cross-sectional study, we aimed to compare both dialysis modalities for MIA syndrome components. MATERIAL AND METHODS: Thirty hemodialysis (HD) (mean age 44 +/- 11 years, 14 male and 16 female, mean time on dialysis: 31.0 +/- 19.0 months) and 30 continuous ambulatory peritoneal dialysis (CAPD) patients (41 +/- 9 years, 12 male and 18 female, mean time on dialysis: 25.5 +/- 21.5 months) were included. In order to determine malnutrition in ESRD patients, serum albumin level and anthropometric measurements were used. For inflammation, serum C-reactive protein level, erythrocyte sedimentation rate, and fibrinogen levels were measured. Mean-carotid artery intima media thickness (m-CIMT), presence of carotid plaque and serum homocysteine level were used to determine atherosclerosis. RESULTS: Five CAPD patients (16%) and one HD patient (3%) was hypoalbuminemic. HD and CAPD groups were similar for inflammation. Mean-CIMT and serum homocysteine level were higher in HD patients than CAPD patients. There was a positive correlation between homocysteine and m-CIMT. CONCLUSION: Before choosing renal replacement therapy, malnutrition, inflammation, and atherosclerosis parameters must be investigated in ESRD patients. Hemodialysis seems to be more advantageous for malnutrition components than CAPD. Both dialysis modalities seem to be similar for inflammation, and CAPD modality has superiority for atherosclerosis. Before choosing the type of renal replacement therapy, assessment of MIA syndrome components could be useful for individualization of the decision on which dialytic modality is appropriate in ESRD patients.     

Thyroid disorders in hemodialysis patients in an iodine-deficient community

There are various changes in the thyroid gland and its function in chronic renal failure (CRF). These changes include lower levels of circulating thyroid hormone, altered peripheral hormone metabolism, decreased binding to carrier proteins, possible reduction in tissue hormone content, and increased iodine storage in the thyroid gland. The decrease of excretion of urinary iodine in CRF increases serum inorganic iodine level and iodine content of the thyroid, which consequently enlarges the gland. This study is designed to investigate the prevalence of goiter and thyroid dysfunction in patients with end-stage renal disease (ESRD) on hemodialysis (HD) in an iodine-deficient community. Eighty-seven (40 females and 47 males) HD patients and 169 (79 females and 90 males) healthy individuals as controls are included. Sex ratios for the patient and control groups are 0.85 and 0.88, respectively. Mean ages for the patient and control groups are 42.94 +/- 11.88 and 40.20 +/- 10.72 years, respectively. Examination of the thyroid gland using ultrasonography along with simultaneous measurement of blood levels of free-T4 (FT4), free-T3 (FT3), and thyrotropin (TSH) are made for every individual. The presence of goiter demonstrable by ultrasonography is found in 32.2% of the uremic patients and in 23.5% of the controls and its prevalence increases with age (P = 0.01). In 32 (36.8%) of the patients and 29 (17.1%) of the controls at least one thyroid nodule is found in ultrasonography. Between patients with or without a nodular goiter the authors could not observe any difference for duration of dialysis and serum levels of TSH, FT4, FT3, calcium, and albumin. In ESRD patients the prevalence of nodular goiter is higher for females (47.5% vs. 27.7%, P = 0.045) and increases with age (P = 0.04). Though incidence of hyperthyroidism is found to be similar for the two groups (1.14% in ESRD patients vs. 1.10% in controls), hypothyroidism is observed in 3.4% of ESRD patients but only 0.6% of controls. This high incidence of hypothyroidism and nodular goiter in ESRD patients shows that screening for thyroid dysfunction and goiter, using appropriate laboratory tests and ultrasonography, should be considered in evaluation of every ESRD patient.     

The influence of the endothelin-converting enzyme-1 gene polymorphism on the progression of autosomal dominant polycystic kidney disease

BACKGROUND; A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD), the most common renal hereditary disease. Endothelin-1 (ET-1) has been suggested to be an important disease-promoting factor of the kidney. Endothelin-converting enzyme-1 (ECE-1) is the main protease responsible for ET-1 generation by cleavage of its functionally inactive precursor. We examined the influence of the ECE-1b C-338A polymorphism on the progression of ADPKD toward end-stage renal disease (ESRD). The A allele was suggested to be associated with higher plasma level of ET-1. METHODS: 200 ADPKD patients (107 males, 93 females) who had reached ESRD were analyzed. Patients were divided into three groups: (1) 47 patients (23 males, 24 females) with ESRD later than in 63 yr (slow progressors); (2) 71 patients (38 males, 33 females) with ESRD before 45 yr (rapid progressors); and (3) 82 patients (46 males, 36 females) with ESRD between 45-63 yr. Moreover, we analyzed 160 genetically unrelated healthy Czech subjects as the control group (82 males, 78 females, mean age 51.4 +/- 8.2 yr). DNA samples from collected blood were genotyped for ECE-1b C-338A polymorphism using described polymerase chain reaction (PCR) followed by restriction enzyme digestion. We compared the frequencies of different genotypes between the groups of slow and rapid progressors and the ages of ESRD with regard to different genotypes. RESULTS: The ECE-1b C-338A genotype distribution showed no differences among the groups of slow progressors, rapid progressors, ADPKD group with ESRD between 45-63 yr and control group. Comparing the ages of ESRD of all patients, we did not find significant differences in the ages with regard to different genotypes: CC (51.5 +/- 10.1 yr), AC (51.6 +/- 11.4 yr), AA (48.2 +/- 5.9 yr). There was a tendency to lower age of ESRD in AA homozygotes in comparison with other genotypes (t-test, p = 0.12). We found no influence of gender. CONCLUSION: We excluded the effect of ECE-1b C-338A polymorphism on the progression of ADPKD. We could observe a mild tendency toward faster decline of renal function in AA homozygous individuals.     

The pathogenesis of pulmonary hypertension in haemodialysis patients via arterio-venous access.

BACKGROUND: We recently have shown a high incidence of unexplained pulmonary hypertension (PHT) in end-stage renal disease (ESRD) patients on chronic haemodialysis (HD) therapy via arterio-venous (A-V) access. This study evaluated the possibility that PHT in these patients is triggered or aggravated by chronic HD via surgical A-V access, and the role of endothelin-1 (ET-1) and nitric oxide (NO) in this syndrome. METHODS: Forty-two HD patients underwent clinical evaluation. Pulmonary artery pressure (PAP) was evaluated using Doppler echocardiography. Levels of ET-1 and NO metabolites in plasma were determined before and after the HD procedure and were compared between subgroups of patients with and without PHT. RESULTS: Out of 42 HD patients studied, 20 patients (48%) had PHT (PAP = 46+/-2; range 36-82 mmHg) while the rest had a normal PAP (29+/-1 mmHg) (P<0.0001). HD patients with PHT had higher cardiac output compared with those with normal PAP (6.0+/-1.2 vs 5.2+/-0.9 l/min, P<0.034). HD patients, with or without PHT, had elevated plasma ET-1 levels compared with controls (1.6+/-0.7 and 2.4+/-0.8 fmol/ml vs 1.0+/-0.2, P<0.05) that remained unchanged after the HD procedure. HD patients without PHT and control subjects showed similar basal plasma levels of NO2 + NO3 (24.2+/-5.2 vs 19.7+/-3.1 microM, P>0.05) that was significantly higher compared with HD patients with PHT (14.3+/-2.3 microM, P<0.05). HD therapy caused a significant increase in plasma NO metabolites that was greater in patients without PHT (from 24.2+/-5.2 to 77.1+/-9.6 microM, P<0.0001, and from 14.3+/-2.3 to 39.9+/-11.4 microM, P<0.0074, respectively). Significant declines in PAP (from 49.8+/-2.8 to 38.6+/-2.2 mmHg, P<0.004) and cardiac output (CO) (from 7.6+/-0.6 to 6.1+/-0.3 l/min, P<0.03) were found in 11 HD patients with PHT that underwent successful transplantation. Similarly, temporary closure of the A-V access by a sphygmomanometer in eight patients with PHT resulted in a transient decrease in CO (from 6.4+/-0.6 to 5.3+/- 0.5 l/min, P = 0.18) and systolic PAP (from 47.2+/-3.8 to 34.6+/-2.8 mmHg, P<0.028). CONCLUSIONS: This study demonstrates a high prevalence of PHT among patients with ESRD on chronic HD via a surgical A-V fistula. In view of the vasodilatory and antimitogenic properties of NO, it is possible that the attenuated basal and HD-induced NO production in patients with PHT contributes to the increased pulmonary vascular tone. Furthermore, the partial restoration of normal PAP and CO in HD patients that underwent either temporal A-V shunt closure or successful transplantation indicates that excessive pulmonary blood flow is involved in the pathogenesis of the disease.     

Survival differences among older dialysis patients in the southeast.

Older end-stage renal disease (ESRD) patients treated by chronic dialysis have higher mortality in the United States than in many other countries. While increasing age, white race, male sex, and/or diabetes are considered risk factors for survival, few studies of older dialysis patients have simultaneously considered multiple predictor variables and their interactions. Using information contained in the 1982 to 1986 ESRD Network 20 database for Georgia and South Carolina, we studied hospitalizations and survival of 1,354 blacks and 965 whites who were age 60 years or older when they began dialysis therapy. Survival time was modeled using the Cox life-table regression method. Older blacks' median age at dialysis initiation was 67.4, compared with 68.7 for older whites (P = 0.001). Blacks were more likely than whites (P < 0.001) to have hypertension-related or diabetes-related ESRD. White patients experienced approximately 25% more hospitalization when adjustment was made for patient-days at risk. Separate multivariate survival models were required for patients with diabetes-related versus non-diabetes-related ESRD. Among diabetics, mortality was higher among whites and among patients who were older when they began dialysis. Among patients with non-diabetes-related ESRD, mortality was higher among patients who were older when they began dialysis, but the age effect was much stronger for white males. Our hospitalization and mortality data support the view that unmeasured severity (or frailty) differences characterize white as compared with black dialysis patients. Among non-diabetes-related ESRD patients, the age effect on survival was more severe in white males than in blacks or in white females. The high mortality we observed among older dialysis patients in Georgia and South Carolina warrants further study; the data may in part reflect patients' lower socioeconomic status compared with age, race, and sex-matched controls.     

Hypoparathyroidism potentiates cardiovascular complications through disturbed calcium metabolism: possible risk of vitamin D(3) analog administration in dialysis patients with end-stage renal disease

BACKGROUND/AIM: Progressive cardiovascular calcification in dialysis patients with end-stage renal disease (ESRD) is a serious complication; however, the precise mechanism remains uncertain. We tested whether metabolic calcium abnormalities and hypoparathyroidism might have a correlation with cardiovascular complications in ESRD patients. METHODS: A series of 48 ESRD patients with cardiovascular diseases and/or congestive heart failure, aged 36-82 (61 +/- 12) years, 23 male and 25 female, were enrolled in this study. Serum total calcium (Ca, mmol/l), inorganic phosphate (mmol/l), and intact parathyroid hormone (iPTH, pg/ml) levels were determined in all cases. RESULTS: Organic heart disease was confirmed in 28 patients (58.3%), including 15 with coronary artery disease: 8 with aortic aneurysm, 8 with stenotic valvular heart disease, 9 with excessive mitral annular calcification, 3 with dialysis cardiomyopathy, and 7 with obstructive arterial disease. Serum iPTH measurement revealed hypoparathyroidism (iPTH <60) in 20 of 48 (41.7%) and hyperthyroidism (iPTH >/=200) in 13 of 48 (27.1%) subjects. The 20 patients with low iPTH had a higher prevalence of valvular heart disease, a higher total Ca level corrected for serum albumin (2.70 +/- 0.30 in low iPTH vs. 2.47 +/- 0.30 in normal iPTH, 2.35 +/- 0.20 in high iPTH, p = 0.003) and a higher tendency of vitamin D(3) analog use (65% in low iPTH vs. 33% in normal iPTH and 46% in high iPTH, p = 0.078). Moreover, corrected serum Ca exhibited a negative logarithmic correlation with serum iPTH: corrected Ca = -0.284x log (iPTH) + 3.021 (r = 0.637, p = 0.0001). Multiple logistic regression analysis revealed diabetes and hypoparathyroidism (iPTH <60) as risk factors for cardiovascular complications in ESRD. CONCLUSION: These results suggest that hypercalcemia and hypoparathyroidism in conjunction with vitamin D(3) use might play an important role in cardiovascular complications of chronic dialysis patients.     

Effect of gender on various parameters of crush syndrome victims of the Marmara earthquake

BACKGROUND: Detailed analyses on crush syndrome resulting from earthquakes is scarce. This study aimed to analyze the effect of gender on clinical course of the renal victims of the catastrophic Marmara earthquake that struck Northwestern Turkey in 1999. METHODS: Questionnaires were prepared within the first week of disaster and sent to 35 reference hospitals that treated the victims. Relationship between gender and various epidemiological, clinical, laboratory parameters, treatment modalities and outcome was then investigated. RESULTS: Of the 639 victims with renal dysfunction, 348 (54%) were males and 291 (46%) females. Mean age was 33 +/- 14 and 31 +/- 15 years in the male and female victims, respectively. At admission, males were characterized by a higher hematocrit and higher serum levels of creatinine, BUN, potassium and phosphorus, while other clinical and laboratory parameters as well as the number of fasciotomized and amputated extremities did not differ between the two genders. Males suffered from longer periods of oliguria, higher rates of sepsis and hypertension. 77.3% of the male patients needed dialysis support as compared to 71.5% in the females. The number of hemodialysis sessions and days for dialysis support were higher in the males. Last serum creatinine before discharge from the nephrology clinics was higher in male victims, while mortality rates were similar in both genders. CONCLUSION: Although males are characterized by more severe laboratory abnormalities of rhabdomyolysis, more frequently suffer from sepsis and need more intensive dialysis support, gender is not a prognostic indicator of final outcome in the renal victims of disasters.     

Associations between plasma ghrelin levels and body composition in end-stage renal disease: a longitudinal study.

BACKGROUND: Ghrelin is a newly detected orexigenic gastric hormone that stimulates food intake. Increased levels of ghrelin are often found in disease states associated with wasting. Wasting is a common phenomenon in end-stage renal disease (ESRD) patients in whom elevated ghrelin levels have been reported. However, no data are available on the relationship between body composition and plasma ghrelin levels in this patient group. METHODS: The study population consisted of 108 (71 males) ESRD patients aged 53+/-12 years. Body composition, nutritional status (subjective global assessment), estimated protein intake (nPNA), plasma ghrelin, plasma insulin and serum leptin were evaluated close to the start of dialysis treatment. Twelve healthy subjects (nine males, 44+/-6 years) served as the control group. A longitudinal evaluation of changes in plasma ghrelin and body composition was performed in 52 of the patients after 12 months of dialysis treatment. RESULTS: Markedly elevated plasma ghrelin levels (843+/-485 vs 443+/-302 pg/ml; P<0.01) were observed in ESRD patients compared with controls. Basal plasma ghrelin levels correlated significantly with plasma insulin (R = -0.32; P<0.05), body mass index (R = -0.24; P<0.05), log serum leptin levels (R = -0.23; P<0.05) and truncal fat mass (R = -0.25; P<0.05). The longitudinal analysis of body composition demonstrated that whereas fat mass increased (23.7+/-8.6 to 25.3+/-9.9 kg; P<0.05) and plasma ghrelin levels decreased (855+/-429 to 693+/-408 pg/ml; P<0.05) significantly in peritoneal dialysis patients, no significant changes in either body composition or plasma ghrelin levels were found in patients treated by haemodialysis. CONCLUSION: Markedly elevated plasma ghrelin levels are found in advanced renal failure and correlate with fat mass, plasma insulin and serum leptin levels. Changes in plasma ghrelin during 12 months of peritoneal dialysis treatment are associated with changes in body composition.