Lp(a) lipoprotein in patients with arterial insufficiency of the lower extremities.

The serum concentration of Lp(a) lipoprotein was determined in 66 patients with peripheral arterial insufficiency of the lower extremities (PAI) and 164 controls. The mean level was higher among the patients than among the controls (236 +/- 248 vs. 129 +/- 159 mg/l, p = 0.01), and values above 300 mg/l were more common among the patients (22/66 vs. 21/164, p less than 0.001). The difference between the 26 female patients and the 94 female controls was statistically significant (280 +/- 268 vs. 118 +/- 141 mg/l, p less than 0.001), but not the difference between the 40 male patients and the 70 male controls (208 +/- 235 vs. 142 +/- 182 mg/l). A high Lp(a) lipoprotein level was not associated with a high LDL-cholesterol level, and there was no significant correlation between the serum levels of Lp(a) lipoprotein and triglycerides++, total cholesterol or HDL-cholesterol. The results indicate, that high Lp(a) lipoprotein levels may be a risk factor for PAI in women.     

Smoking, but not lipids, lipoprotein(a) and antibodies against oxidised LDL, is correlated to the expansion of abdominal aortic aneurysms.

OBJECTIVES: to study the role of smoking, lipids, lipoprotein (a), and autoantibodies against oxidised low density lipoprotein (Ab-oxLDL) in the expansion of small abdominal aortic aneurysms (AAA). To study the role of Ab-oxLDL and lp(a) in the progression of lower limb atherosclerosis. METHODS AND MATERIALS: one hundred and thirty-eight male patients with AAA were interviewed, examined, and their serum lipids and S-Ab-oxLDL determined. Of these, 117 were followed annually with ultrasound and underwent control scans and blood pressure measurements for a mean of 2.5 (range 1-5) years. RESULTS: initial AAA size, smoking and level of triglycerides were positively correlated to increased aneurysmal expansion, while beta-blocker medication was associated with decreased expansion. Besides initial AAA size, only smoking had persisting significance after adjustment of the other significant variables. Initial ankle brachial pressure index (ABI) and Lp(A) but not ab-oxLDL were significantly correlated to ABI change. CONCLUSION: smoking cessation may inhibit aneurysmal expansion. Lipids seem to play a minor role in the progression of AAA.     

Elevated lipoprotein(a) levels in renal transplantation and hemodialysis patients.

Hyperlipidemia poses a risk for cardiovascular disease in both hemodialysis and renal transplantation patients. Although lipid profiles differ between the 2 populations, we evaluated the possibility that both groups have similar abnormalities of lipoprotein(a) [Lp(a)]. Mean serum Lp(a) and standard error of the mean (SEM) in hemodialysis and transplant recipients was 16.6 +/- 4.7 and 18.3 +/- 3.6 mg/dl, respectively, compared with 10.7 +/- 4.1 mg/dl in healthy controls, p less than 0.05. That serum Lp(a) levels are significantly elevated in dialysis and renal transplantation patients suggests at least 1 common pathogenic mechanism for the high incidence of atherosclerosis in both groups.     

Lp(a) concentrations in NIDDM.

NIDDM patients have a two- to fourfold increased risk of CHD relative to nondiabetic subjects. This excess risk is explained only partially by increased levels of standard risk factors. We compared the plasma concentrations of Lp(a) in NIDDM patients (n = 260) and nondiabetic subjects (n = 336) who participated in a population-based study (San Antonio Heart Study). Lp(a) was measured using a monoclonal anti-Lp(a) antibody. NIDDM patients and nondiabetic subjects had similar Lp(a) concentrations for both men (13.6 +/- 1.5 vs. 16.1 +/- 1.4 mg/dl) and women (12.6 +/- 0.8 vs. 15.9 +/- 1.3 mg/dl) (P = 0.361). Duration of diabetes and level of fasting glycemia were not significantly related to Lp(a) concentrations. Lp(a) levels were significantly higher in patients who had higher total and LDL cholesterol levels. We conclude that in a large population-based study, Lp(a) levels are not increased in NIDDM patients.     

Hyperleptinemia is not correlated with markers of protein malnutrition in chronic renal failure. A cross-sectional study in predialysis, peritoneal dialysis and hemodialysis patients

BACKGROUND: Serum leptin levels are increased in chronic renal failure (CRF) and may potentially contribute to protein malnutrition in this disorder. METHOD: Following a cross-sectional design, we performed a nutritional survey in a wide sample of uremic patients treated conservatively (n = 87), with peritoneal dialysis (n = 71) and with hemodialysis (n = 53). Then, we analyzed the correlation between serum leptin levels and markers of protein malnutrition. We used a multivariate approach, taking into consideration the confounding effect of other factors on the correlation between hyperleptinemia and protein malnutrition. MAIN RESULTS: Both univariate and multivariate analysis disclosed a poor correlation between hyperleptinemia and markers of protein malnutrition. In fact, there were trends to a positive correlation between leptinemia and body protein stores, as estimated from the scrutinized markers. Persistence of the basic correlation between general intake, fat mass and leptin in CRF could partially explain these findings, but neither a negative correlation between leptin levels nor protein nutritional state could be disclosed after controlling for this factor. CONCLUSIONS: Our results do not support a first-line role for hyperleptinemia in the genesis of protein malnutrition of uremia.     

Plasma levels of lipoprotein (a) do not predict progression of human chronic renal failure

Chronic renal failure is frequently accompanied by elevatedplasma levels of lipoprotein (a) [Lp(a)] Elevated Lp(a) levelshave been proposed to contribute not only to increased riskof atherosclerotic and thrombotic complications but also tothe progression of renal insufficiency. To investigate whetherhigher Lp(a) plasma concentrations are associated with an acceleratedrateof progression of renal insufficiency, we have correlated baselineplasma concentrations of Lp(a) with the progressive declineof renal function in an observational study of human chronicrenal disease. Forty-nine non-diabetic patients (40 men, ninewomen) were studied as part of an observational study of patientswith moderately advanced renal insufficiency. The average follow-uptime of the patient population was 3.1 years, and the mean rateof decline in glomer ular filtration rate (⁵¹Cr-EDTA clearance)was –2.8 (SD 4.1) ml/min/1.73 m² The mean plasma concentrationof Lp(a) at the beginning of the study was 19.2 (SD 18.6) mg/100ml with a median value of 12.2 mg/100 ml. There was no associationbetween the initial plasma concentration of Lp(a) and the rateof progression as assessed by linear regression analysis. Furthermore,the progression rate in patients with in the highest quartileof the Lp(a) distribution (30 mg/100 ml) did not differ fromthat in patients with lower levels of Lp(a). In contrast, increasedlevels of apolipoprotein (apo) B, low-density lipoprotein (LDL)-cholesterol,and proteinuria were all significantly associated with a morerapid decline in renal function. Based on these results, itwas concluded that elevated plasma levels of Lp(a) are not associatedwith an increased rate of progression of renal insufficiencyin human chronic renal disease. However, the results of thisstudy suggest that other apoB-containing lipoproteins may playa significant role in this process.     

Association of predialysis serum sodium level with fluid status in patients on maintenance hemodialysis

International Urology and Nephrology - The ability to maintain sodium and water homeostasis is impaired in patients with end-stage renal disease (ESRD), leading to hyponatremia and fluid overload....     

Serum Lp(a) lipoprotein levels in patients with atherosclerotic occlusive disease of the lower extremities.

OBJECTIVE: To evaluate the association between Lp(a) lipoprotein levels, other serum lipids and the presence of lower limb atherosclerotic occlusive disease. MATERIALS AND METHODS: Angiographic findings in 36 patients were related to serum Lp(a). Total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol and Lp(a) levels were compared with those of 73 age- and sex-matched healthy controls. RESULTS: Atheromatous lesions were localised in the femoropopliteal ( approximately 60%) and aortoiliac ( approximately 40%) segments. The number of stenosed arteries was > or =2 and the range of stenosis severity was between 40% and 100%. There was a significant increase in serum Lp(a) (p= 0.000001) and a decrease in serum HDL (p= 0.000009) levels in patients compared to controls. No difference was observed in total cholesterol, LDL-cholesterol or triglyceride. However, the ratio of total cholesterol/HDL-cholesterol was significantly higher (p= 0.005) in patients. CONCLUSION: A dyslipidaemic serum profile, characterised by increased Lp(a) levels and decreased HDL-cholesterol levels, is associated with atherosclerotic occlusive disease of the lower extremities.     

Triglyceride,but not total cholesterol or low-density lipoprotein cholesterol levels,predict development of proteinuria

BACKGROUND: Epidemiological data about the relationship between dyslipidemia and proteinuria are sparse. We conducted a retrospective and longitudinal study in a large screened cohort to evaluate whether triglyceride, high-density lipoprotein (HDL) cholesterol, total cholesterol, and low-density lipoprotein (LDL) cholesterol levels increase the risk of development of proteinuria and loss of renal function. METHODS: Post hoc analysis was performed for 4326 subjects who were free from proteinuria (dipstick 1+ or higher) at baseline (1997) with a follow-up period through 2000. Outcome measures were the development of proteinuria (1+ or higher) and change in glomerular filtration rate (GFR). Multiple logistic analysis and multiple regression analysis were used to analyze baseline characteristics related to the outcome measures. RESULTS: During the observational period, 505 (11.7%) of subjects had one or more episodes of proteinuria (>/=1+). Adjusted relative risk of triglycerides for one or more incidences of proteinuria was 1.007 (95% CI 1.000 to 1.105, P = 0.04) in men and 1.032 (95% CI 1.004 to 1.061, P = 0.02) in women. Total cholesterol, HDL cholesterol, and LDL cholesterol were not significant predictors of proteinuria. The mean change in GFR between 1997 and 2000 was -6.3 (SD = 9.0) mL/min/1.73 m2 in men, and -7.8 (SD = 10.7) mL/min/1.73 m2 in women. HDL cholesterol (beta = 0.04, t = 3.7, P = 0.0002) in men and triglycerides (per 10 mg/dL, beta = -0.09, t = -2.2, P = 0.02) in women were correlated with the change in GFR. CONCLUSIONS: High triglyceride levels predicted a risk of developing proteinuria in both men and women, but not total cholesterol nor LDL cholesterol. High triglyceride in women and low HDL cholesterol in men predicted the decline of renal function. It remains to be determined whether prospective treatment of dyslipidemia will protect against renal injury.     

Lp(a) is increased in hemodialysis patients according to the type of dialysis membrane: a 2-year follow-up study

AIMS: Patients with chronic renal failure treated by hemodialysis develop lipoprotein abnormalities that may contribute to their increased risk ofatherosclerosis. This study shows lipid parameter follow-up procedure according to the type of dialysis membrane in an unselected population of 33 hemodialysis patients. PATIENTS AND METHODS: The study included 33 patients with end-stage renal disease and 110 healthy blood bank donors of Tenon Hospital. Cholesterol and triglycerides were determined by enzymatic methods, apoA-I, apoB by immunoturbidimetry and Lp(a) by immunonephelemetry. Apo(a) phenotyping was performed by agarose gel electrophoresis followed by immunoblotting. Patients and controls subjects were estimated by Student's t- and chi2-tests. RESULTS: Patients dialyzed with low-flux membranes had Lp(a) concentrations higher than patients dialyzed with high-flux membranes. Patients dialyzed with polyacrylonitrile membranes (AN 69) had an apoA-I concentration significantly lower than patients dialyzed with hemophane or polysulfone membranes. We also confirmed some of the lipid abnormalities and high Lp(a) concentrations in ESRD patients. CONCLUSION: These results may contribute to a more rational choice of the dialysis membrane in hemodialysis patients.     

An increased serum level of free Apo(a) in renal patients is more striking than that of Lp(a) and is influenced by homocysteine

Lipoprotein(a) [Lp(a)] excess combined with hyperhomocysteinaemia and hyperfibrinogenaemia may contribute to the high incidence of vascular diseases in dialysis patients. This study is aimed at investigating the role of free apolipoprotein(a) [fapo(a)] in renal patients. We have been able to show that, as compared with controls (0.53 mg/l), the median serum concentrations of fapo(a) in patients with nephrotic syndrome (2.58 mg/l) and with peritoneal dialysis (3. 40 mg/l) were strongly elevated (5- to 7-fold), while the fapo(a) levels in patients undergoing haemodialyis (1.02 mg/l) and after renal transplantation (0.90 mg/l) were about doubled. The observed differences in fapo(a) levels indicate that several mechanisms may increase the level of fapo(a), i.e., reduced renal clearance, enhanced hepatic synthesis, or homocysteine releasing apolipoprotein(a) from Lp(a). In the study collective, the median total homocysteine levels were significantly elevated in all patient groups, stronger in patients on haemodialysis (31.4 micromol/l) and peritoneal dialysis (31.2 micromol/l) than in patients with nephrotic syndrome (19.7 micromol/l) and after renal transplantation (19.5 micromol/l). In transplant patients with adequate renal function and without other apolipoprotein(a)-increasing factors, fapo(a) was significantly increased when total homocysteine exceeded 22 micromol/l. In conclusion, our findings let us presume that an increased fapo(a) level in renal patients possibly could be one of the reasons contributing to the high incidence of vascular diseases in these patients, because fapo(a) not covalently linked with Lp(a) is even more easily able to inhibit the fibrinolytic system than the complete Lp(a). These preliminary results have to be confirmed by further investigations.     

Cytokine release and serum lipoprotein (a) alterations during hemodialysis

It has been reported recently that a number of cytokines, mainly tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6, can alter lipid metabolism and produce hyperlipidemia. Studies in hemodialysis (HD) patients have demonstrated increased production of these cytokines during HD. In order to investigate any possible relationship between changes of cytokines and lipid concentrations during HD in the serum of 25 uremic patients on chronic HD using modified cellulose membranes, TNFalpha, IL-1beta, IL-6, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein a (Lp[a]), and total proteins were measured immediately before (pre-HD) and after HD (post-HD), in one session. The post-HD values were corrected according to the hemoconcentration based on the changes in serum total proteins. Serum TNFalpha and IL-1beta levels were significantly increased from 38.24 +/- 17.85 pg/ml and 2. 60 +/- 3.64 pg/ml pre-HD to 48.86 +/- 25.21 and 3.49 +/- 4.08 pg/ml post-HD, p < 0.001 and p < 0.05 respectively. Also Lp(a) levels presented a statistically significant increase post-HD and were almost doubled (pre-HD: 15.41 mg/dl, to post-HD: 27.39 mg/dl, p < 0. 05). Serum IL-6 as well as serum TC, TG, HDL-C, and LDL-C did not show any statistically significant alterations during HD. A significant positive correlation was detected between TNFalpha and Lp(a) values post-HD (r: 0.413, p: 0.04), but not between pre-HD values. No further relationship between serum cytokines and the other estimated lipid parameters was observed, either between pre- or post-HD values. Our results indicate that release of TNFalpha and IL-1beta during HD have no effect on serum lipids concentration, except on Lp(a). It seems that the acute rise of this lipoprotein during hemodialysis may be related with the TNFalpha overproduction.     

Catheter use is high even among hemodialysis patients with a fistula or graft

At any given time, approximately 27% of patients in the United States (US) receive hemodialysis through a permanent catheter. However, this cross-sectional estimate may significantly underestimate the lifetime exposure of patients to hemodialysis catheters, and hence, to the excess risk of the adverse clinical events associated with catheter use. To further clarify catheter use in hemodialysis patients, we identified a cohort of fistula and graft patients in the US Renal Data System using Current Procedural Terminology (CPT) codes. Patients were included if their first hemodialysis was between 1 January 1996 and 31 December 2001, and Medicare was their primary payer. We identified permanent catheter insertions in these patients using CPT codes starting 6 months before their first hemodialysis session (or fistula or graft placement, if earlier), and ending 40 months afterward. Most patients (82%) were >65 years old, 57% were male, and 72% were white. The overall rate of permanent catheter insertions was 44 per 100 patient years, with 57% of patients having at least one catheter insertion. The percent of patients receiving a catheter was similar before (30%) and after (27%) the first fistula or graft placement. Cross-sectional analysis may significantly underestimate the lifetime risk of exposure to hemodialysis catheters. Because catheter use is common even in fistula and graft patients, measures used to prevent adverse events associated with catheter use are important in all patients regardless of current access type.     

Prostate-specific antigen is not excreted by human kidney or eliminated by routine hemodialysis.

Serum levels of prostate-specific antigen have assumed a prominent clinical role in the management of prostate cancer. Little is known about the production of prostate-specific antigen, its mechanism of entry into the serum in normal and pathologic states, and mechanism(s) of removal from the serum. This study examined nephrostomy urine specimens, finding no significant excretion of prostate-specific antigen into the renal pelvic urine. Similarly, no significant lowering of serum prostate-specific antigen levels occurred during routine hemodialysis in men with chronic renal failure, nor were ambulatory, pre-dialysis serum prostate-specific antigen levels in these same men with chronic renal failure elevated. It appears unlikely that the kidney plays a significant role in the clearance of prostate-specific antigen from human serum.     

Role of lipoprotein (a) and TGF-beta 1 in atherosclerosis of hemodialysis patients

Atherosclerotic vascular disease is a major cause of death for uremic patients who are on hemodialysis (HD). Recent evidence suggests that lipoprotein (a) [Lp(a)] may aggravate atherosclerosis by inhibiting activation of transforming growth factor-beta 1 (TGF-beta 1). Plasma Lp(a) and plasma TGF-beta 1 activation in HD patients (n = 51), chronic renal failure patients not subjected to hemodialysis (non-HD-CRF; n = 12), and healthy volunteers (control; n = 13) were investigated. Plasma Lp(a) was significantly higher in HD (18.75 +/- 1.62 mg/ml) and non-HD-CRF patients (25.0 +/- 8.4 mg/ml) than in control subjects (10.9 +/- 5.8 mg/ml). The degree of atherosclerosis in HD patients was assessed by measuring the intima-media thickness (IMT) and plaque score with the use of an ultrasound scanner. IMT and plaque score were higher in HD and non-HD-CRF patients than in controls. A significant positive correlation was found in HD patients between Lp(a) and IMT (r = 0. 377, P < 0.01) as well as between Lp(a) and plaque score (r = 0.43, P < 0.01). Plasma total TGF-beta 1 significantly increased in HD (119.8 +/- 53.5 ng/ml) and non-HD-CRF patients (93.2 +/- 25.0 ng/ml) compared with control subjects (17.7 +/- 6.4 ng/ml), whereas the plasma level of mature (active) TGF-beta1 did not differ among the groups. When plasma TGF-beta 1 and supernatant TGF-beta 1 from cultured peripheral mononuclear cells were compared before and after an HD session, neither total nor mature TGF-beta 1 showed a significant difference between the values before and after an HD session. There were no significant relationships between plasma total TGF-beta 1 and IMT or plaque score, between mature TGF-beta 1 and IMT or plaque score, or between mature TGF-beta 1 and Lp(a). In conclusion, Lp(a) may be an important atherogenic factor in CRF patients. However, it was not clarified whether Lp(a) exerts its effect by inhibiting TGF-beta 1 activation in CRF patients.     

Serum lipoprotein(a) concentrations and apolipoprotein(a) phenotypes in hemodialysis,chronic ambulatory peritoneal dialysis and post-transplant patients

Serum lipoprotein(a) [Lp(a)] concentrations and apolipoprotein(a) apo(a) phenotypes were determined in 81 hemodialysis (HD) patients, 37 chronic ambulatory peritoneal dialysis (CAPD) patients, 25 post-transplant patients and 99 healthy subjects as the reference group. The CAPD patients had significantly higher serum Lp(a) concentration than HD patients, but both had significantly increased Lp(a) levels as compared with the reference group and post-transplant patients. When all studied groups were divided into two subgroups with at least one low molecular weight (LMW) isoform and with only one high molecular weight (HMW) isoform, they presented a similar distribution. (Pearson's chi-squared = 2,78; df = 3; p = NS). The median serum Lp(a) levels were significantly increased with HMW class versus the reference group and post-transplant patients. In CAPD patients, the LMW phenotypes showed significantly increased median serum Lp(a) concentrations versus the reference group, but they were not statistically elevated in HD patients. In the post-transplant patients, LMW and HMW phenotypes did not differ as compared to the reference group. The elevated Lp(a) levels in HD and CAPD groups were explained by apo(a) type-specific, but not by differences in, isoform frequencies. We conclude that HD and CAPD patients had increased Lp(a) levels compared with the reference group, whereas elevated Lp(a) concentrations were observed mainly in patients with HMW apo(a) phenotypes. Patients after renal transplantation showed a correction of Lp(a) levels mainly in HMW phenotypes. The LMW status corresponding to high Lp(a) levels and apo(a) isoforms could be used together with Lp(a) levels with other risk factors to assess in uremic patients the predisposition to coronary artery disease.     

A study of clinical significance of Lp[a] lipoprotein in patients with chronic renal failure treated by hemodialysis

Lipoprotein [a] (Lp[a]) is known to show high values in patients with ischemic heart disease (IHD). In the present study attempts were made to determine Lp[a] levels and to investigate the association of Lp[a] and other atherosclerotic risk factors in patients with chronic renal failure treated by hemodialysis. Lp[a] concentrations were measured in 30 hemodialysis patients in the age range 34 to 77 years. Mean (+/- SD) levels of serum Lp[a] were not elevated in the hemodialysis patients compared to controls (19.3 +/- 18.0 mg/dl vs. 18.3 +/- 10.4 mg/dl, respectively). We found no statistically significant correlation of Lp[a] with either cholesterol, triglycerides, HDL-C or apoproteins. However, compared with controls, more than fivefold as many of those hemodialysis patients had high risk (greater than 30 mg/dl) concentrations of Lp[a]. Lp[a] tended to increase in hemodialysis patients with diabetes mellitus and/or ischemic heart disease. In patients with high levels of Lp[a] (greater than 30 mg/dl), Lp[a] tended to correlate positively with cholesterol, LDL-, HDL-C, apo B or apo B/AI. Incidence of IHD was also elevated in these patients. Along with other known risk factors such as hyperlipidemia and hypertension, an increased concentration of Lp[a] may play an important role in accelerating development of atherosclerosis in this condition.