Effect of interleukin-1beta on transforming growth factor-beta and bone morphogenetic protein-2 expression in human periodontal ligament and alveolar bone cells in culture: modulation by avocado and soybean unsaponifiables.

BACKGROUND: In periodontal disease, interleukin-1beta (IL-1beta) is responsible for the matrix breakdown through excessive production of degrading enzymes by periodontal ligament fibroblasts and osteoblasts. Transforming growth factor-beta (TGF-beta) plays an important role in tissue regeneration as one of the factors capable of counteracting IL-1beta effects. In this study, we investigated the in vitro effect of avocado and soya unsaponifiables (ASU) on the expression of TGF-beta1, TGF-beta2, and bone morphogenetic protein-2 (BMP-2) by human periodontal ligament (HPL) and human alveolar bone (HAB) cells in the presence of IL-1beta. METHODS: HPL and HAB cells were incubated for 48 hours with ASU (10 microg/ml) in the presence or absence of IL-1beta (10 ng/ml). The steady-state levels of TGF-beta1, TGF-beta2, and BMP-2 mRNAs were determined by Northern blot or reverse transcription-polymerase chain reaction (RT-PCR). The amounts of TGF-beta1 and TGF-beta2 proteins were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The data indicated that IL-1beta strongly decreases the expression of TGF-beta1 and TGF-beta2 by HPL cells. ASU were capable of opposing the cytokine effect. In HAB cells, TGF-beta1 and BMP-2 mRNA levels were downregulated by the cytokine. ASU were found to reverse the IL-1beta-inhibiting effect. In contrast, the cytokine stimulated the production of TGF-beta2 in alveolar bone cells, with no significant effect of ASU. CONCLUSIONS: The results indicate that the IL-1beta-driven erosive effect in periodontitis could be enhanced by a decreased expression of members of the TGF-beta family. The ASU stimulation of TGF-beta1, TGF-beta2, and BMP-2 expression may explain their promoting effects in the treatment of periodontal disorders, at least partly. These findings support the hypothesis that ASU could exert a preventive action on the deleterious effects exerted by IL-1beta in periodontal diseases.

Long-term knowledge retention following predialysis psychoeducational intervention.

BACKGROUND/AIMS: Early identification and predialysis psychoeducation are gaining acceptance. Although research supports the immediate value of predialysis interventions, long-term benefits remain unknown. We examined long-term knowledge retention following a psychoeducational intervention. METHODS: 47 progressive renal failure patients completed the Kidney Disease Questionnaire at baseline and 18, 30, 42, and 54 months after initiating renal replacement therapy (RRT; the 'longitudinal' sample). A larger cohort provided data at one or more of these points (n = 132, 117, 101, and 70 at 18, 30, 42, and 54 months, respectively; the 'cross-sectional' sample). RESULTS: Initial knowledge gains among psychoeducation recipients were followed by a significant knowledge advantage for three groups throughout follow-up. Patients who received predialysis psychoeducation either before or after starting dialysis demonstrated superior Kidney Disease Questionnaire scores as compared with those identified before the initiation of RRT who received the usual standard of practice. Patients identified after the initiation of RRT and who received standard education, however, demonstrated the same level of knowledge retention as produced by psychoeducation. The results were identical across the longitudinal and cross-sectional samples. CONCLUSIONS: Patient education produces important benefits in end-stage renal disease, but the incremental value of early intervention remains to be demonstrated.

Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy.

BACKGROUND: Hemoglobin levels below 10 g/dL lead to left ventricular (LV) hypertrophy, LV dilation, a lower quality of life, higher cardiac morbidity, and a higher mortality rate in end-stage renal disease. The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown. METHODS: One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were randomly assigned to receive doses of epoetin alpha designed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks. The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation. RESULTS: In patients with concentric LV hypertrophy, the changes in LV mass index were similar in the normal and low target hemoglobin groups. The changes in cavity volume index were similar in both targets in the LV dilation group. Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved (8 mL/m2 per 1 g/dL hemoglobin decrement, P = 0.009). Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation. Normalization of hemoglobin led to improvements in fatigue (P = 0.009), depression (P = 0.02), and relationships (P = 0.004). CONCLUSIONS: Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation. It may, however, prevent the development of LV dilation, and it leads to improved quality of life.

A tale of two homocysteines--and two hemodialysis units.

Pharmacologic doses of folic acid are commonly used to reduce the hyperhomocysteinemia of end-stage renal disease (ESRD). Vitamin B12 acts at the same metabolic locus as folic acid, but information is lacking about the specific effects of high doses of this vitamin on homocysteine levels in renal failure. We therefore compared the plasma homocysteine concentrations of maintenance hemodialysis patients in two McGill University-affiliated urban tertiary-care medical centers that differed in the use of vitamin B12 and folic acid therapy. Patients in the first hemodialysis unit are routinely prescribed high-dose folic acid (HI-F, 6 mg/d), whereas those in the second unit receive high-dose vitamin B12 in the form of a monthly 1-mg intravenous injection, along with conventional oral folic acid (HI-B12, 1 mg/d). Predialysis homocysteine was 23.4 +/- 6.8 micromol/L (mean +/- SD) in the HI-F unit and 18.2 +/- 6.1 micromol/L in the HI-B12 unit (P < .002). Postdialysis homocysteine was 14.5 +/- 4.1 in the HI-F unit and 10.6 +/- 3.4 micromol/L in the HI-B12 unit (P = .0001). Multiple regression analysis indicated that high-dose parenteral vitamin B12 was associated with a lower homocysteine concentration even after controlling for the potential confounders of sex, serum urea, serum creatinine, urea reduction ratio, and plasma cysteine. Because this was a cross-sectional observational study, we cannot exclude the possibility that unidentified factors, rather than the different vitamin therapies, account for the different homocysteine levels in the two units. Careful prospective studies of the homocysteine-lowering effect of high-dose parenteral vitamin B12 in ESRD should be undertaken.

Semiquantitative reverse transcription-polymerase chain reaction analysis of syndecan-1 and -4 messages in cartilage and cultured chondrocytes from osteoarthritic joints.

OBJECTIVE: To determine the steady-state of messenger RNA (mRNA) levels of syndecan-1 and syndecan-4 in cartilage samples and chondrocytes derived from human osteoarthritic knee joints. METHODS: Steady-state levels of gene-specific mRNA (relative to beta-actin) were measured by semiquantitative polymerase chain reaction (PCR). RESULTS: RT-PCR allowed detection of syndecan-1 (for the first time) and syndecan-4 in both cartilage samples and articular chondrocytes cultured as primary monolayers. The mRNA levels of syndecan-1 were reduced in cartilage tissue from heavily damaged compared to normal-looking areas whereas those of syndecan-4 were significantly increased. In contrast, the expression of syndecan-1 was higher in cultured chondrocytes derived from the fibrillated osteoarthritic cartilage than in cells obtained from intact cartilage, while the syndecan-4 message levels did not differ between the two sites. CONCLUSION: The expression of the cell-surface syndecans 1 and 4 is altered during the osteoarthritic degradative process of the knee joint. The discoordinate syndecan gene expression, which is probably related to the chondrocyte proliferation and clustering, may contribute to the disorganization of the cartilage and the development of OA processes. Isolation and culturing the chondrocytes as monolayers dramatically change the expression of these genes and cannot reflect the in situ condition.

Long-term evolution of cardiomyopathy in dialysis patients.

BACKGROUND: Left ventricular enlargement is very common at the inception of dialysis therapy, and highly predictive of future cardiac morbidity and mortality. It is not known whether cardiac size increases further while on dialysis therapy and whether potentially reversible risk factors for later progression can be identified. METHODS; Baseline and yearly echocardiograms were performed in a prospective inception cohort of 433 dialysis patients. The mean patient follow-up was 41 months; 29 patients had four consecutive echocardiograms at yearly intervals. RESULTS: The patient subset with four echocardiograms was older (58 vs. 51 years, P = 0.02) and had a lower mass ventricular mass index (128 vs. 149 g/m2, P = 0.02) than the parent group. Using repeated measures analysis of variance, applied to those with four echocardiograms, there were progressive increases over time in posterior wall thickness (P = 0.015), left ventricular end-diastolic diameter, left ventricular mass index (P = 0.001), and cavity volume index (P = 0. 001). Mass-to-volume ratios did not change. The biggest changes in mass (18 g/m2 - 14%)and volume index (13 ml/m2 - 18%) occurred between baseline and year 1, although increases in both were seen after year 1. Hemodialysis versus peritoneal dialysis (41 g/m2, P = 0.008) and anemia (10 g/m2 per 1 g/dl drop in hemoglobin, P = 0.02) were associated with progressive left ventricular enlargement, but only within the first year of dialysis therapy. The left ventricular enlargement seen after year 1 was independent of anemia, blood pressure, serum albumin and mode of dialysis. CONCLUSIONS: Progressive cardiac enlargement, particularly left ventricular dilation with compensatory hypertrophy, continues after starting dialysis therapy. Most of the additional cardiac enlargement seems to occur in the first year of dialysis therapy, suggesting that intervention beyond one year may be relatively ineffective.

Mode of dialysis therapy and mortality in end-stage renal disease.

Despite considerable differences in technique and blood purification characteristics, hemodialysis and peritoneal dialysis have been thought to have similar patient outcomes. An inception cohort of 433 end-stage renal disease patients was followed prospectively for a mean of 41 mo. The outcomes of hemodialysis (HD) and peritoneal dialysis (PD) patients were compared using intention to treat analysis based on the mode of therapy at 3 mo. After adjustment for PD patients less likely to have chronic hypertension and more likely to have diabetes, ischemic heart disease, and cardiac failure at baseline (P < 0.05), a biphasic mortality pattern was observed. For the first 2 yr, there was no statistically significant difference in mortality. After 2 yr, mortality was greater among PD patients with an adjusted PD/HD hazard ratio of 1.57 (95% confidence interval [CI], 0.97 to 2.53). Both the occurrence (adjusted hazards ratio 6.87 [95% CI, 2.01 to 23.5]) and the direction (toward PD, adjusted hazards ratio 6.25 [95% CI, 1.54 to 25]) of a therapy switch were subsequently associated with mortality after 2 yr. Progressive clinical and echocardiographic cardiac disease were not responsible for this late mortality. Lower mean serum albumin levels in PD patients in the first 2 yr of therapy (3.5 +/- 0.5 versus 3.9 +/- 0.5 g/dl, P < 0.0001) accounted for a large proportion of the increase in subsequent mortality. Hemodialysis has a late survival advantage over peritoneal dialysis; antecedent hypoalbuminemia is a major marker of the increased late mortality in PD patients.

Cardiac disease in diabetic end-stage renal disease.

Little is known about the epidemiology of cardiac disease in diabetic end-stage renal disease. We therefore prospectively followed a cohort of 433 patients who survived 6 months after the inception of dialysis therapy for an average of 41 months. Clinical and echocardiographic data were collected yearly. At baseline, diabetic patients (n = 116) had more echocardiographic concentric left ventricular hypertrophy (50 vs 38%, p = 0.04), clinically diagnosed ischaemic heart disease (32 vs 18%, p = 0.003) and cardiac failure (48 vs 24%, p < 0.00001) than non-diabetic patients (n = 317). After adjusting for age and sex, diabetic patients had similar rates of progression of echocardiographic disorders, and de novo cardiac failure, but higher rates of de novo clinically diagnosed ischaemic heart disease (RR 3.2, p = 0.0002), overall mortality (RR 2.3, p < 0.0001) and cardiovascular mortality (RR 2.6, p < 0.0001) than non-diabetic patients. Mortality was higher in diabetic patients following admission for clinically diagnosed ischaemic heart disease (RR 1.7, p = 0.05) and cardiac failure (RR 2.2, p = 0.0003). Among diabetic patients older age, left ventricular hypertrophy, smoking, clinically diagnosed ischaemic heart disease, cardiac failure and hypoalbuminaemia were independently associated with mortality. The excessive cardiac morbidity and mortality of diabetic patients seem to be mediated via ischaemic disease, rather than progression of cardiomyopathy while on dialysis therapy. Potentially remediable risk factors include smoking, left ventricular hypertrophy, and hypoalbuminaemia.

Outcome and risk factors for left ventricular disorders in chronic uraemia.

BACKGROUND: Left ventricular disease occurs frequently in dialysis patients. It may be manifest as concentric LV hypertrophy, LV dilatation with or without LV hypertrophy, or systolic dysfunction. Little is known concerning the clinical outcome and risk factors for these disorders. METHODS: A cohort of 432 end-stage renal disease patients who survived at least 6 months had an echocardiogram on initiation of dialysis therapy. Clinical, laboratory and echocardiographic data was obtained annually during follow-up. RESULTS: On initiation of ESRD therapy 16% of patients had systolic dysfunction, 41% concentric LV hypertrophy, 28% LV dilatation, and only 16% had normal echocardiograms. Median time to development of heart failure was 19 months in patients with systolic dysfunction, 38 months in concentric LV hypertrophy and 38 months in LV dilatation. The relative risks of heart failure in the three groups were significantly worse than in the normal group, after adjusting for age, diabetes and ischaemic heart disease. Median survival was 38 months in systolic dysfunction, 48 months in concentric hypertrophy, 56 months in LV dilatation, and >66 months in the normal group. Two hundred and seventy-five patients had a follow-up echocardiogram 17 months after starting dialysis therapy together with serial measurement of potential risk factors prior to the echocardiogram. On follow-up echocardiogram the degree of concentric LV hypertrophy was independently related to hypertension while on dialysis, older age, and anaemia while on dialysis; the degree of LV dilatation was related to ischaemic heart disease, anaemia, hypertension and hypoalbuminemia while on dialysis; the degree of systolic dysfunction was associated with ischaemic heart disease and anaemia during follow-up. CONCLUSIONS: Manifestations of left ventricular disease are frequent and persistent in chronic uraemia, and are associated with high risks of heart failure and death. Potentially reversible risk factors include anaemia, hypertension, hypoalbuminaemia and ischaemic heart disease.

The impact of anemia on cardiomyopathy, morbidity, and and mortality in end-stage renal disease.

To determine the possible association between anemia and clinical and echocardiographic cardiac disease, a cohort of 432 end-stage renal disease patients (261 on hemodialysis and 171 on peritoneal dialysis) who started dialysis therapy between 1982 and 1991 were followed prospectively for an average of 41 months. Baseline demographic, clinical, and echocardiographic assessments were performed, as well as monthly serial clinical and laboratory tests while the patients were on dialysis therapy. The mean (+/-SD) hemoglobin level during dialysis therapy was 8.8 +/- 1.5 g/dL. After adjusting for age, diabetes, and ischemic heart disease, as well as for blood pressure and serum albumin levels measured serially, each 1 g/dL decrease in mean hemoglobin was independently associated with the presence of left ventricular dilatation on repeat echocardiogram (odds ratio, 1.46; P = 0.018) and the development of de novo (relative risk [RR] = 1.28; P = 0.018) and recurrent (RR = 1.20; P = 0.046) cardiac failure. In addition, each 1 g/dL decrease in the mean hemoglobin level was independently associated with mortality while the patients were on dialysis therapy (RR = 1.14; P = 0.024). Anemia had no independent association with the development of ischemic heart disease while the patients were on dialysis therapy. Anemia, an easily reversible feature of end-stage renal disease, is an independent risk factor for clinical and echocardiographic cardiac disease, as well as mortality in end-stage renal disease patients.

Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease.

A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was followed up prospectively for an average of 41 months. Baseline and annual demographic, clinical, and echocardiographic assessments were performed, as well as serial clinical and laboratory tests measured monthly while patients were on dialysis therapy. Among hemodialysis patients, after adjustment was made for age, diabetes, and ischemic heart disease, as well as hemoglobin and blood pressure levels measured serially, a 10-g/L fall in mean serum albumin level was independently associated with the the development of de novo (relative risk [RR], 2.22; P = 0.001) and recurrent cardiac failure (RR, 3.84; P = 0.003), de novo (RR, 5.29; P = 0.001) and recurrent ischemic heart disease (RR, 4.24; P = 0.005), cardiac mortality (RR, 5.60; P = 0.001), and overall mortality (RR, 4.33; P < 0.001). Among peritoneal dialysis patients, a 10-g/L fall in mean serum albumin level was independently associated with the progression of left ventricular dilation as seen on follow-up echocardiography (beta, 13.4 mL/m2; P = 0.014), the development of de novo cardiac failure (RR, 4.16; P = 0.003), and overall mortality (RR, 2.06; P < 0.001). Hypoalbuminemia, a major adverse prognostic factor in dialysis patients, is strongly associated with cardiac disease.

Impact of hypertension on cardiomyopathy, morbidity and mortality in end-stage renal disease.

A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was followed prospectively for an average of 41 months. Baseline and annual demographic, clinical and echocardiographic assessments were performed, as well as serial clinical and laboratory tests measured monthly while on dialysis therapy. The average mean arterial blood pressure level during dialysis therapy was 101 +/- 11 mm Hg. After adjusting for age, diabetes and ischemic heart disease, as well as hemoglobin and serum albumin levels measured serially, each 10 mm Hg rise in mean arterial blood pressure was independently associated with: the presence of concentric LV hypertrophy (OR 1.48, P = 0.02), the change in LV mass index (beta = 5.4 g/m2, P = 0.027) and cavity volume (beta = 4.3 ml/m2, P = 0.048) on follow-up echocardiography, the development of de novo cardiac failure (RR 1.44, P = 0.007), and the development of de novo ischemic heart disease (RR 1.39, P = 0.05). The association with LV dilation was of borderline statistical significance (OR 1.48, P = 0.06). Mean arterial blood pressures greater than 106 mm Hg were associated with both echocardiographic and clinical endpoints. Paradoxically, low mean arterial blood pressure (RR 1.36 per 10 mm Hg fall, P = 0.009) was independently associated with mortality. The association of low blood pressure with mortality was a marker for having had cardiac failure prior to death. We conclude that even moderate hypertension worsens the echocardiographic and clinical outcome in ESRD patients, especially in those without previous clinical cardiac disease.

Outcome and risk factors of ischemic heart disease in chronic uremia.

To determine the prognosis and risk factors for ischemic heart disease in chronic uremia, a cohort of 432 dialysis patients were followed prospectively from start of dialysis therapy until death or renal transplantation. Baseline demographic, clinical and echocardiographic data were obtained. After the initiation of dialysis laboratory data were collected at monthly intervals, and clinical and echocardiographic data at yearly intervals. Twenty-two percent of patients (N = 95) had either a history of angina pectoris or myocardial infarction on starting dialysis therapy. Median time to onset of heart failure was 24 months in those with ischemic heart disease on initiation of dialysis, compared to 55 months in those without (P < 0.0001). This effect was independent of age, diabetes and underlying cardiomyopathy. Median survival was 44 months in those with ischemic disease compared to 56 months in those without (P = 0.0001). This adverse impact was independent of age and diabetes mellitus but, when cardiac failure was added to the Cox's model, ischemic heart disease was no longer an independent predictor of survival. De novo ischemic heart disease, not evident on starting dialysis therapy, occurred in 41 (9%) patients. When compared to patients who never developed ischemic disease (N = 296; 69%), significant and independent predictors of de novo disease were older age (P = 0.0007), diabetes mellitus (P = 0.0001), high blood pressure during follow up on dialysis (P = 0.02) and hypoalbuminemia (P = 0.03), whereas anemia was not an independent predictor. LV mass index was 174 +/- 7 g/m2 in those who developed de novo ischemic disease compared to 155 +/- 3 g/m2 (P < 0.001) in those who did not. Concentric LV hypertrophy, LV dilation and systolic dysfunction were independent risk factors for de novo ischemic heart disease. We conclude that ischemic heart disease occurs frequently in dialysis patients, that its adverse impact is mediated through the development of heart failure, and that the most important, potentially reversible risk factors are hypertension, hypoalbuminemia, and underlying cardiomyopathy.

Hypocalcemia, morbidity, and mortality in end-stage renal disease.

BACKGROUND: Hypocalcemia and hyperphosphatemia with secondary hyper-parathyroidism are characteristic of end-stage renal disease (ESRD). Although calcium levels critically affect almost all cellular processes, the impact of chronic hypocalcemia and other abnormalities of calcium-phosphate homeostasis on the prognosis of ESRD patients is unknown. METHODS: An inception cohort of 433 patients starting ESRD therapy was followed prospectively for an average of 41 months. Serum calcium and other parameters were measured monthly. The mean calcium levels were 9.4 +/- 0.7 mg/dl. 23% of the patients had mean calcium levels < 8.8 mg/dl. After adjusting for baseline age, diabetes mellitus, ischemic heart disease, smoking and cholesterol levels, as well as serial albumin, hemoglobin, mean arterial blood pressure, phosphate and alkaline phosphatase levels, chronic hypocalcemia was strongly associated with mortality (RR 2.10, p = 0.006 for a mean calcium level < 8.8 mg/dl). The association with mortality was similar in hemodialysis (RR 2.10, p = 0.006) and peritoneal dialysis patients (2.67, p = 0.034). Using similar covariate adjustment, chronic hypocalcemia was associated with de novo ischemic heart disease (RR 5.23, p < 0.001), recurrent ischemic heart disease (RR 2.46, p = 0.006), de novo cardiac failure (RR 2.64, p < 0.001), and recurrent cardiac failure (RR 3.30, p < 0.001). Hypocalcemia retained its independent impact on morbidity and mortality when analyzed as a time-dependent covariate. CONCLUSIONS: Chronic hypocalcemia, a very common, reversible feature of chronic uremia, is independently associated with morbidity and mortality in ESRD patients.

Impact of renal transplantation on uremic cardiomyopathy.

In chronic uremia, cardiomyopathy manifests itself as systolic dysfunction, concentric left ventricular (LV) hypertrophy, or LV dilatation. To determine the impact of renal transplantation on uremic cardiomyopathy, all dialysis patients participating in a long-term cohort study who received a successful renal transplant were followed with echocardiography. The transplanted group comprised 102 of 433 (24%) endstage renal disease (ESRD) patients. They were significantly younger and, on starting ESRD therapy, had significantly less ischemic heart disease and cardiac failure than the overall ESRD cohort. During followup, ischemic heart disease developed in only 1 patient and none experienced cardiac failure. In the 12% (n = 12) of patients with systolic dysfunction before renal transplant, fractional shortening normalized in all patients, increasing from 21.5 +/- 4.6% to 33.5 +/- 5.6% after transplantation. In the 41% (n = 41) with concentric LV hypertrophy before transplantation, the LV mass index improved from 158 +/- 39 g/m2 to 132 +/- 39 g/m2. LV dilatation was present in 32% (n = 32) of patients before transplantation. After transplantation, LV volume fell from 116 +/- 3.1 ml/m2 to 89 +/- 21 ml/m2, and LV mass index in this group fell from 166 +/- 55 g/m2 to 135 +/- 37 g/m2. It was not possible to associate risk factors characteristic of the uremic state with the improvement in cardiac structure and function, although the fall in LV mass was significantly associated with fall in blood pressure. We conclude that correction of the uremic state by renal transplantation leads to normalization of LV contractility in systolic dysfunction, regression of hypertrophy in concentric LV hypertrophy, and improvement of cavity volume in LV dilatation. The degree of improvement suggests that dialysis patients with uremic cardiomyopathy would benefit from renal transplantation.

The prognostic importance of left ventricular geometry in uremic cardiomyopathy.

The objective of this study was to determine the effect of left ventricular (LV) mass, volume, and mass-to-volume ratio on mortality in chronic dialysis patients. The Design was a multicenter, prospective inception cohort study with a median follow-up of 41 months. The Setting was three university-affiliated nephrology units. A total of 433 patients who (1) survived > 6 months from the start of ESRD therapy and (2) had a technically satisfactory baseline echocardiogram were studied. Measurements included a baseline clinical, laboratory and echocardiographic assessment. LV hypertrophy was present in 74% and LV dilation was present in 36% of patients. In patients with normal cavity volume (< or = 90 mL/m2) and normal systolic function, high LV mass index (> 120 g/m2) and mass-to-volume ratios (> 2.2 g/mL) were independently associated with late mortality (> 2 yr after starting dialysis therapy). After adjusting for baseline age, diabetes, and ischemic heart disease, the relative risk for the former was 3.29 and for the latter was 2.24. Cavity volume was of no prognostic significance in this group. In patients with LV dilation and normal systolic function, high cavity volume (> 120 mL/m2) and low mass-to-volume ratio (< 1.8 mL/m2) were independently associated with late mortality, the relative risk in the former being 17.14 and the latter being 4.27. LV mass index was of no prognostic significance in this group. The baseline echocardiographic classification, based on LV mass and cavity volume, was the strongest predictor of late mortality, after adjusting for age, gender, diabetes mellitus, coronary artery disease, angina pectoris, chronic hypertension, and hemoglobin and serum albumin levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Congestive heart failure in dialysis patients: prevalence, incidence, prognosis and risk factors.

Cardiovascular disease is the most common cause of death in dialysis subjects. Congestive heart failure (CHF) is a common presenting symptom of cardiovascular disease in the dialysis population. Information regarding prevalence, incidence, risk factors and prognosis is crucial for planning rational interventional studies. A prospective multicenter cohort study of 432 dialysis patients followed for a mean of 41 months was carried out. Prospective information on a variety of risk factors was collected. Annual echocardiography and clinical assessment was performed. Major endpoints included death and the development of morbid cardiovascular events. One hundred and thirty-three (31%) subjects had CHF at the time of initiation of dialysis therapy. Multivariate analysis showed that the following risk factors were significantly and independently associated with CHF at baseline: systolic dysfunction, older age, diabetes mellitus and ischemic heart disease. Seventy-six of 299 subjects (25%) who did not have baseline CHF subsequently developed CHF during their course on dialysis. Compared to those subjects who never developed CHF (N = 218) multivariate analysis identified the following risk factors for the development of CHF: older age, anemia during dialysis therapy, hypoalbuminemia, hypertension during dialysis therapy, and systolic dysfunction. Seventy-five of the 133 (56%) subjects with CHF at baseline had recurrent CHF during follow-up. Independent and significant risk factors for CHF recurrence were ischemic heart disease and systolic dysfunction, anemia during dialysis therapy and hypoalbuminemia. The median survival of subjects with CHF at baseline was 36 months compared to 62 months in subjects without CHF. In this study the prevalence of CHF on starting ESRD therapy and the subsequent annual incidence was high.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and echocardiographic disease in patients starting end-stage renal disease therapy.

End-stage renal disease (ESRD) patients have a high cardiovascular mortality rate. Precise estimates of the prevalence, risk factors and prognosis of different manifestations of cardiac disease are unavailable. In this study a prospective cohort of 433 ESRD patients was followed from the start of ESRD therapy for a mean of 41 months. Baseline clinical assessment and echocardiography were performed on all patients. The major outcome measure was death while on dialysis therapy. Clinical manifestations of cardiovascular disease were highly prevalent at the start of ESRD therapy: 14% had coronary artery disease, 19% angina pectoris, 31% cardiac failure, 7% dysrhythmia and 8% peripheral vascular disease. On echocardiography 15% had systolic dysfunction, 32% left ventricular dilatation and 74% left ventricular hypertrophy. The overall median survival time was 50 months. Age, diabetes mellitus, cardiac failure, peripheral vascular disease and systolic dysfunction independently predicted death in all time frames. Coronary artery disease was associated with a worse prognosis in patients with cardiac failure at baseline. High left ventricular cavity volume and mass index were independently associated with death after two years. The independent associations of the different echocardiographic abnormalities were: systolic dysfunction-older age and coronary artery disease; left ventricular dilatation-male gender, anemia, hypocalcemia and hyperphosphatemia; left ventricular hypertrophy-older age, female gender, wide arterial pulse pressure, low blood urea and hypoalbuminemia. We conclude that clinical and echocardiographic cardiovascular disease are already present in a very high proportion of patients starting ESRD therapy and are independent mortality factors.

Risk factors for the development of left ventricular hypertrophy in a prospectively followed cohort of dialysis patients.

The objective of this study was to determine the role of hypertension, age, anemia, and hyperparathyroidism in the pathogenesis of left ventricular hypertrophy (LVH) developing after the initiation of dialysis for ESRD. A cohort of dialysis patients who were being treated for ESRD and whose initial echocardiograms after the start of dialysis therapy do not show LVH were studied. Three hundred and thirty-nine patients have been monitored at three centers since 1985. Serial echocardiograms have been performed with M-mode and two-dimensional echocardiography. Data on blood pressure, height, weight, hemoglobin, number and type of antihypertensive medications, and the presence of functioning vascular access have been collected prospectively. Prospective data on serum calcium, serum phosphorus, alkaline phosphatase, and parathyroid hormone levels and skeletal x-rays have also been collected. By the use of set criteria and blinding to echocardiographic outcome, the presence and severity of hyperparathyroidism were graded by consensus. Fifty-one patients met eligibility criteria for inclusion; of these, 14 developed LVH (cases) and 37 did not (controls). Cases had significantly higher systolic blood pressure (P = 0.009) and were older (P = 0.01) than controls. Systolic blood pressure correlated significantly with final posterior left ventricular wall thickness (r = 0.39; P < 0.01). By the use of multivariate analysis, age and systolic blood pressure were significantly and independently associated with increased left ventricular mass index. The frequency of hyperparathyroidism was low and equal in both groups. There was a trend toward more severe anemia in cases that did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)