Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Subject Collections
    • JASN Podcasts
    • Archives
    • Saved Searches
    • ASN Meeting Abstracts
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Subscriptions
  • More
    • About JASN
    • Alerts
    • Advertising
    • Editorial Fellowship Program
    • Feedback
    • Reprints
    • Impact Factor
  • ASN Kidney News
  • Other
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Subject Collections
    • JASN Podcasts
    • Archives
    • Saved Searches
    • ASN Meeting Abstracts
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Subscriptions
  • More
    • About JASN
    • Alerts
    • Advertising
    • Editorial Fellowship Program
    • Feedback
    • Reprints
    • Impact Factor
  • ASN Kidney News
  • Follow JASN on Twitter
  • Visit ASN on Facebook
  • Follow JASN on RSS
  • Community Forum
Epidemiology and Outcomes
You have accessRestricted Access

Prospective Study of Neuropeptide Y as an Adverse Cardiovascular Risk Factor in End-Stage Renal Disease

Carmine Zoccali, Francesca Mallamaci, Giovanni Tripepi, Francesco A. Benedetto, Saverio Parlongo, Sebastiano Cutrupi, Domenico Iellamo, Graziella Bonanno, Francesco Rapisarda, Pasquale Fatuzzo, Giuseppe Seminara, Alessandro Cataliotti and Lorenzo Salvatore Malatino
JASN October 2003, 14 (10) 2611-2617; DOI: https://doi.org/10.1097/01.ASN.0000089026.28617.33
Carmine Zoccali
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Francesca Mallamaci
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giovanni Tripepi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Francesco A. Benedetto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Saverio Parlongo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sebastiano Cutrupi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Domenico Iellamo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Graziella Bonanno
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Francesco Rapisarda
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pasquale Fatuzzo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giuseppe Seminara
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alessandro Cataliotti
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lorenzo Salvatore Malatino
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading

Abstract

ABSTRACT. Chronic renal insufficiency is a situation characterized by high plasma concentration of neuropeptide Y (NPY). Because this neuropeptide interferes with cardiovascular (CV) function, it is possible that it is involved in the high CV-related morbidity and mortality of these patients. To test this hypothesis, a follow-up study was performed (average duration, 34 mo; range 0.2 to 52.0 mo) in a cohort of 277 patients with end-stage renal disease receiving chronic dialysis. Univariate analysis revealed that plasma NPY was directly related to plasma norepinephrine (r = 0.37, P < 0.001) and epinephrine (r = 0.17, P = 0.005), exceeding the upper limit of the normal range in the majority of patients with end-stage renal disease (170 of 277, 61%). One hundred thirteen patients had one or more fatal and nonfatal CV events; 112 patients died, 66 of them (59%) of CV causes. Plasma NPY failed to predict all-cause mortality but was an independent predictor of adverse CV outcomes (hazard ratio [10 pmol/L increase in plasma NPY], 1.32; 95% confidence interval, 1.09 to 1.60; P = 0.004) in a Cox proportional-hazard model that included a series of traditional and nontraditional CV risk factors. Plasma NPY maintained its predictive power for CV events in statistical model including plasma norepinephrine. Plasma NPY predicts incident CV complications in end-stage renal disease. Controlled trials are needed to establish whether interference with the sympathetic system, NPY, or both may reduce the high CV morbidity and mortality of dialysis patients. E-mail: carmine.zoccali@tin.it

Neuropeptide Y (NPY) is a vasoactive neuropeptide widely distributed in the central and peripheral nervous system. The gut and associated organs are likely to be the source of most circulating NPY, and the release of this substance is stimulated after feeding in a way that does not correlate with norepinephrine (NE) (1). This neuropeptide is also coreleased with NE during sympathetic nerve stimulation, and it is extensively involved in cardiovascular (CV) regulation because it modulates heart rate, cardiac excitability, and ventricular function as well as coronary blood flow (2). NPY behaves as a stress hormone because its plasma concentration is markedly increased in septic shock (3) and in myocardial infarction (4), and because it predicts survival in patients admitted to coronary care units with or without myocardial infarction (5).

Chronic renal insufficiency is a situation characterized by high plasma concentration of NPY (6–13⇓⇓⇓⇓⇓⇓⇓). Because CV risk in patients with chronic renal diseases is much increased (14), it is possible that this neuromediator is involved in the high CV morbidity and mortality of these patients. In keeping with this hypothesis, we have found that NPY is strongly associated to left ventricular concentric hypertrophy and systolic dysfunction in these patients (15).

Given the physiologic role of NPY in CV control, a thorough examination of the relationship of this neuropeptide with plasma catecholamines may provide valuable information on these important functional correlates of NPY in uremic patients. Furthermore, we thought that for establishing the biological and clinical relevance of high circulating NPY in uremic patients, we must assess whether this peptide is related to well defined outcome measures, such as incident CV events.

Materials and Methods

Study Protocol

The study protocol confirmed to the ethical guidelines of our institutions, and informed consent was obtained from each participant. All studies were performed during a nondialysis day, between 8 a.m. and 1 p.m.

Study Cohort

Two hundred seventy-seven patients (154 male and 123 female patients, 226 receiving hemodialysis and 51 receiving chronic ambulatory peritoneal dialysis [CAPD]) who had been receiving regular dialysis treatment for at least 6 mo (average duration of regular dialysis treatment, 67 mo; range, 6 to 98 mo) without history of congestive heart failure and without concomitant illnesses were eligible for the study. The main demographic and clinical characteristics of the patients included in the study are listed in Table 1. The prevalence of diabetes mellitus in this cohort was 16% (44 of 277 patients).

View this table:
  • View inline
  • View popup

Table 1. Clinical and biochemical characteristics of patients divided on the basis of three tertiles of plasma NPYa

Hemodialysis patients were virtually anuric (24 h urine volume <200 ml/d) and were being treated three times a week with standard bicarbonate dialysis (Na 138 mmol/L, HCO3 35 mmol/L, K 1.5 mmol/L, Ca 1.25 mmol/L, Mg 0.75 mmol/L) and cellulose or semisynthetic membranes (dialysis filters surface area, 1.1 to 1.7 m2). The average urea Kt/V in these patients was 1.21 ± 0.27. Patients receiving CAPD were all on a four-exchange-a-day schedule and used standard dialysis bags. The average weekly Kt/V in these patients was 1.67 ± 0.32. Thirty-four patients had a history of myocardial infarction, and 79 had clinical and electroencephalogram evidence of cardiac ischemia. Twenty-five patients had had a stroke, and 29 had experienced transient ischemic attacks. One hundred thirteen patients were habitual smokers (22 ± 17 cigarettes a day). One hundred forty-four patients received erythropoietin therapy. One hundred sixteen patients were being treated with antihypertensive drugs (82 receiving monotherapy with angiotensin-converting enzyme inhibitors, AT-1 antagonists, calcium channel blockers, and α- and β-blockers, and 34 on double- or triple-drug therapy with various combinations of these drugs).

Follow-up

After the initial assessment, patients were followed up for an average of 34 mo (range, 0.2 to 52.0 mo). During the follow-up, CV events (electrocardiogram-documented anginal episodes and myocardial infarction, heart failure, electrocardiogram-documented arrhythmia, transient ischemic attacks, stroke, and other thrombotic events) and death were accurately recorded. Each death was reviewed and assigned an underlying cause by a panel of five physicians. As a part of the review process, all available medical information about each death was collected. This information always included study and hospitalization records. In instances where the patient died when he or she was not hospitalized, family members were interviewed by telephone to better ascertain the circumstances surrounding death.

Laboratory Measurements

Blood sampling was performed between 8.00 a.m. and 10.00 a.m. in steady-state conditions, during a nondialysis day for hemodialysis patients and at empty abdomen for CAPD patients. Samples for the measurement of plasma NPY were taken after 20 to 30 min of quiet resting in semirecumbent position. Plasma NPY was measured after extraction by Sep-Pac C18 cartridges (Waters Associates, Milford, MA) by means of a commercially available RIA kit (Peninsula Laboratories, Merseyside, England). The intra- and interassay variations were 10% and 13%, respectively. The upper limit of the normal range of plasma NPY in a group of 53 healthy control subjects was 8 pmol/L (average: 2.5 ± 2.0 pmol/L). The plasma concentrations of NE and epinephrine (E) were measured by a RIA kit (Amicyl-test; Immunological Laboratories, Hamburg, Germany). Serum lipids, albumin, calcium, phosphate, and hemoglobin measurements were made by standard methods in the routine clinical laboratory. C-reactive protein (CRP) and plasma homocysteine were measured by previously described methods (16).

Statistical Analyses

Data are expressed as mean ± SD (normally distributed data), geometric mean ± SD (nonnormally distributed data), or as percentage of frequency, and comparisons between groups were made by one-way ANOVA or χ2 test, as appropriate.

Probability of survival was analyzed by the Kaplan-Meier survival analysis and by the multivariate Cox proportional-hazard model. For patients who experienced multiple events, survival analysis was restricted to the first event. There was no missing value for plasma NPY. There were only 30 missing values (hemoglobin, cholesterol, albumin, calcium, phosphate, and CRP, five per each variable). Missing values for these covariates were set to the mean value. To identify the independent prognostic power of plasma NPY for all-cause mortality and fatal and nonfatal CV events, we started with saturated Cox proportional-hazard models and included all covariates that were associated (P < 0.10) with plasma NPY (Table 1) as well as covariates that were related (P < 0.10) to all-cause death or CV outcomes at univariate analysis. To obtain parsimonious models, variables in the final models were selected by a stepwise approach. By means of this strategy, we constructed models of adequate statistical power (at least 19 events for each variable in the final model).

The assumption of linearity for the Cox proportional-hazard models was examined through visual inspection, and no violation of proportional hazard was found. Hazard ratios (HR) and their 95% confidence intervals (95% CIs) were calculated by the estimated regression coefficients and their standard errors in the Cox regression analysis. All calculations were made by a standard statistical software package (SPSS for Windows, version 9.0.1).

Results

Plasma NPY (average, 15.0 ± 9.7 pmol/L) exceeded the upper limit of the normal range (cutoff, 8 pmol/L) in the majority of patients with end-stage renal disease (ESRD; 170 of 277, 61%). The clinical characteristics of patients grouped into three tertiles according to plasma NPY are listed in Table 1. Patients in the third tertile of plasma NPY were younger, had higher heart rates, and were more often men or smokers when compared with patients in the second and first NPY tertiles. Patients in the third NPY tertile showed also lower serum albumin and hemoglobin than those in the others two tertiles. Systolic and diastolic BP did not differ significantly among the three NPY tertiles, but the prevalence of patients receiving antihypertensive treatment was higher in patients in the third NPY tertile compared with those in the others two tertiles. Plasma urea was similar in three groups.

NPY, NE and E, and Plasma Urea

Plasma NPY was directly related to plasma NE (Figure 1). A similar but weaker relationship was also found between plasma NPY and plasma E (r = 0.17, P = 0.005). NPY was largely unrelated to plasma urea (r = −0.06, P = 0.32).

Figure1
  • Download figure
  • Open in new tab
  • Download powerpoint

Figure 1. Relationship between plasma norepinephrine (NE) and plasma neuropeptide Y (NPY). Because NE and NPY showed positively skewed distributions, these data were log transformed (log10). Data are Pearson product moment correlation coefficient and P value.

Survival Analysis

No patient was lost to follow-up. One hundred sixty-one fatal and nonfatal CV events occurred in 113 patients; 112 patients died, 66 of them (59%) of CV causes (Table 2). Plasma NPY failed to predict survival either in the Kaplan-Meier analysis (log-rank test, 1.75; P = 0.19) or in a multivariate Cox regression model (P = 0.29). Multivariate analysis found that age (P < 0.001), previous CV events (P = 0.001), male gender (P = 0.002), CRP (P = 0.003), diabetes (P = 0.01), and serum albumin (P = 0.02) were significantly associated with all-cause mortality.

View this table:
  • View inline
  • View popup

Table 2. Cardiovascular events (fatal and nonfatal) and causes of death in the study cohort

In the Kaplan-Meyer analysis, the CV event-free survival was progressively and significantly lower from the first tertile of plasma NPY onward (log-rank test, 9.64; P = 0.002) (Figure 2). In a Cox regression model that tested all covariates associated to incident CV events as well as factors associated to plasma NPY (Table 1) by univariate analysis, plasma NPY was found to be an independent predictor of CV events (HR [10 pmol/L increase in plasma NPY], 1.32; 95% CI, 1.09 to 1.60; P = 0.004) (Table 3, model 1). This relationship was unaffected by treatment modality (hemodialysis versus CAPD) (Table 3). Plasma NPY maintained its predictive power for CV events (HR [10 pmol/L increase in plasma NPY], 1.25; 95% CI, 1.02 to 1.54; P = 0.03) in a statistical model including plasma NE (Table 3, model 2). In this model, plasma NE failed to predict CV outcomes (P = 0.11), and it became a significant predictor of fatal and nonfatal CV events (HR [1 nmol/L increase in plasma NE], 1.07; 95% CI, 1.01 to 1.13; P = 0.01) when plasma NPY was excluded from the model.

Figure2
  • Download figure
  • Open in new tab
  • Download powerpoint

Figure 2. Kaplan-Meier cardiovascular event-free survival curves in patients divided into three tertiles of plasma neuropeptide Y (NPY). First tertile of plasma NPY, <7.41 pmol/L; second tertile, 7.41 to 18.26 pmol/L; third tertile, >18.26 pmol/L.

View this table:
  • View inline
  • View popup

Table 3. COX’s models for fatal and nonfatal cardiovascular eventsa

Discussion

In a large cohort of patients with ESRD, NPY emerged as an independent predictor of incident CV events. This relationship indicates that raised NPY in these patients is either a marker of risk or is directly involved in the high rate of CV complications in these patients. Several lines of evidence suggest that NPY participates in the physiologic response to various stressors, particularly if these are severe or prolonged (17). Increased plasma NPY levels have been observed in situations characterized by high sympathetic activity, such as physical exercise, heart failure (18), and cardiac ischemia (19). In addition, NPY exerts chronic effects because it stimulates vascular smooth muscle and myocardial cell proliferation (20) and may induce left ventricular hypertrophy in experimental models (21). Furthermore, this peptide may enhance platelet aggregation, macrophage activation, and leukocyte adhesion (22).

NPY in ESRD

It is well demonstrated that nerves in the gut are an important source of NPY in humans (1). NPY has a biphasic disappearance from plasma, and the corresponding half-lives are 4 to 6 min and 20 to 40 min (23). The metabolism of NPY in patients with renal failure has not been studied, but it seems likely that enzyme (peptidase) activities (24) that degrade this neuromediator are altered in renal failure (25). NPY was measured in several studies in patients with ESRD and found to be mildly (6,26⇓) to markedly (12,13,27,28⇓⇓⇓) elevated. The pathophysiological implications of increased NPY in these patients are unclear because NPY was reported to be related to arterial pressure (26,29⇓) and to fluid overload (26) in some studies, whereas no such relationships were observed in the other studies (6,12,13,27,28⇓⇓⇓⇓). Furthermore, no consistent evidence has emerged that this peptide participates in CV regulation during dialysis treatment (27,30⇓). Overall, these studies dealt with a fairly small number of patients (8 to 25 patients), which precluded our studying the relationship between this substance and clinically important outcome measures. In this study, we found that NPY was unrelated to arterial pressure, but patients with high NPY (third tertile) had faster heart rates and were more likely to be receiving antihypertensive treatment. The possibility that NPY may be involved in CV complications is suggested by our recent observation that high NPY is strongly associated to left ventricular concentric hypertrophy in patients with ESRD (15).

NPY, Survival, and Incident CV Events

Approximately 39% of patients in our study had had one or more CV events during a 3-yr follow-up, and the mean death rate was 12% a year, which is analogous to that typically observed in European dialysis registries (31). Such a high CV morbidity and mortality in part depends on the fact that traditional (i.e., Framingham) risk factors are highly prevalent in the dialysis population. Interestingly, in this study, NPY was independently related to survival and CV outcomes independently of traditional risk factors (32) as well as of emerging risk factors, such as CRP (33,34⇓) and homocysteine (16,35⇓), and risk factors peculiar to ESRD, such as anemia (36) and hyperphosphatemia (37).

Sympathetic overactivity is an established trigger of CV structural alterations such as left ventricular hypertrophy and arterial remodeling (38), and we have recently reported that high NE in patients with ESRD is associated to left ventricular concentric hypertrophy (39) and that it predicts shorter survival and adverse CV outcomes (40). Because NPY is coreleased with NE, the link between this peptide and survival and incident CV events may well represent an epiphenomenon of sympathetic overactivity. In this study, NPY predicted incident CV events independently of plasma NE (Table 3, model 2). It is therefore possible that this neuropeptide is, at least in part, an event trigger independent of NE. NPY is present in sympathetic innervation of all parts of the conduction system of the heart but also in nerve fibers in the heart that do not represent sympathetic fibers (41). Mechanistic and intervention studies are required to answer this important question.

Plasma NPY predicts CV complications in ESRD. This phenomenon likely depends on the fact that this neuropeptide reflects sympathetic activity, but the notion that high NPY per se might be an event trigger cannot be excluded. Controlled trials with antiadrenergic drugs and with NPY antagonists (42) are needed to establish whether interference with the sympathetic system, with NPY, or both may reduce the high CV morbidity and mortality of dialysis patients. In this regard, it is of interest that high flux dialysis reduces plasma concentration of NPY (43).

Footnotes

  • ↵†Deceased.

  • © 2003 American Society of Nephrology

References

  1. ↵
    Morris MJ, Cox HS, Lambert GW, Kaye DM, Jennings GL, Meredith IT, Esler MD: Region-specific neuropeptide Y overflows at rest and during sympathetic activation in humans. Hypertension 29: 137–143, 1997
    OpenUrlAbstract/FREE Full Text
  2. ↵
    Pedrazzini T, Brunner HR, Waeber B: Neuropeptide Y and cardiovascular regulation. Curr Opin Nephrol Hypertens 2: 106–113, 1993
    OpenUrlCrossRefPubMed
  3. ↵
    Koenig JI: Regulation of the hypothalamo-pituitary axis by neuropeptide Y. Ann N Y Acad Sci 611: 317–328, 1990
    OpenUrlCrossRefPubMed
  4. ↵
    Persson H, Andreasson K, Kahan T, Eriksson SV, Tidgren B, Hjemdahl P, Hall C, Erhardt L: Neurohormonal activation in heart failure after acute myocardial infarction treated with beta-receptor antagonists. Eur J Heart Fail 4: 73–82, 2002
    OpenUrlCrossRefPubMed
  5. ↵
    Ullman B, Hulting J, Lundberg JM: Prognostic value of plasma neuropeptide-Y in coronary care unit patients with and without acute myocardial infarction. Eur Heart J 15: 454–461, 1994
    OpenUrlCrossRefPubMed
  6. ↵
    Klin M, Waluga M, Rudka R, Madej A, Janiszewska M, Grzebieniak E, Wesolowky A: Plasma catecholamines, neuropeptide Y and leucine-enkephalin in uremic patients before and after dialysis during rest and handgrip. Boll Chim Farm 137: 306–313, 1998
    OpenUrlPubMed
  7. ↵
    Bald M, Gerigk M, Rascher W: Elevated plasma concentrations of neuropeptide Y in children and adults with chronic and terminal renal failure. Am J Kidney Dis 30: 23–27, 1997
    OpenUrlPubMed
  8. ↵
    Mouri T, Sone M, Takahashi K, Itoi K, Totsune K, Hayashi Y, Hasegawa S, Ohneda M, Murakami O, Miura Y: Neuropeptide Y as a plasma marker for phaeochromocytoma, ganglioneuroblastoma and neuroblastoma. Clin Sci (Lond) 83: 205–211, 1992
    OpenUrlPubMed
  9. ↵
    Hegbrant J, Martensson L, Thysell H, Ekman R, Boberg U: Changes in plasma levels of vasoactive substances during routine acetate and bicarbonate hemodialysis. Clin Nephrol 41: 106–112, 1994
    OpenUrlPubMed
  10. ↵
    Crum R, Fairchild R, Bronsther O, Dominic W, Ward D, Fernandez R, Brown MR: Neuroendocrinology of chronic renal failure and renal transplantation. Transplantation 52: 818–823, 1991
    OpenUrlPubMed
  11. ↵
    Odar-Cederlof I, Ericsson F, Theodorsson E, Kjellstrand CM: Is neuropeptide Y a contributor to volume-induced hypertension? Am J Kidney Dis 31: 803–808, 1998
    OpenUrlCrossRefPubMed
  12. ↵
    Hegbrant J, Thysell H, Ekman R: Plasma levels of vasoactive regulatory peptides in patients receiving regular hemodialysis treatment. Scand J Urol Nephrol 26: 169–176, 1992
    OpenUrlPubMed
  13. ↵
    Takahashi K, Mouri T, Itoi K, Sone M, Ohneda M, Murakami O, Nozuki M, Tachibana Y, Yoshinaga K: Increased plasma immunoreactive neuropeptide Y concentrations in phaeochromocytoma and chronic renal failure. J Hypertens 5: 749–753, 1987
    OpenUrlCrossRefPubMed
  14. ↵
    Levey AS, Beto JA, Coronado BE, Eknoyan G, Foley RN, Kasiske BL, Klag MJ, Mailloux LU, Manske CL, Meyer KB, Parfrey PS, Pfeffer MA, Wenger NK, Wilson PW, Wright JT Jr: Controlling the epidemic of cardiovascular disease in chronic renal disease: What do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis 32: 853–906, 1998
    OpenUrlPubMed
  15. ↵
    Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Parlongo S, Cutrupi S, Bonanno G, Rapisarda F, Fatuzzo P, Seminara G, Cataliotti A, Malatino LS: Neuropeptide Y and alterations in left ventricular mass and function in patients in patients with end stage renal disease. J Hypertension, in press
  16. ↵
    Mallamaci F, Zoccali C, Tripepi G, Fermo I, Benedetto FA, Cataliotti A, Bellanuova I, Malatino LS, Soldarini A: Hyperhomocysteinemia predicts cardiovascular outcomes in hemodialysis patients. Kidney Int 61: 609–614, 2002
    OpenUrlCrossRefPubMed
  17. ↵
    Zukowska-Grojec Z, Vaz AC: Role of neuropeptide Y (NPY) in cardiovascular responses to stress. Synapse 2: 293–298, 1988
    OpenUrlCrossRefPubMed
  18. ↵
    Maisel AS, Scott NA, Motulsky HJ, Michel MC, Boublik JH, Rivier JE, Ziegler M, Allen RS, Brown MR: Elevation of plasma neuropeptide Y levels in congestive heart failure. Am J Med 86: 43–48, 1989
    OpenUrlCrossRefPubMed
  19. ↵
    Ullman B, Franco-Cereceda A, Hulting J, Lundberg JM, Sollevi A: Elevation of plasma neuropeptide Y–like immunoreactivity and noradrenaline during myocardial ischaemia in man. J Intern Med 228: 583–589, 1990
    OpenUrlCrossRefPubMed
  20. ↵
    Millar BC, Schluter KD, Zhou XJ, McDermott BJ, Piper HM: Neuropeptide Y stimulates hypertrophy of adult ventricular cardiomyocytes. Am J Physiol 266 (5 Pt 1): C1271–C1277, 1994
  21. ↵
    Bohm M, Grabel C, Knorr A, Erdmann E: Treatment in hypertensive cardiac hypertrophy I. Neuropeptide Y and beta-adrenoceptors. Hypertension 25: 954–961, 1995
    OpenUrlAbstract/FREE Full Text
  22. ↵
    Sung CP, Arleth AJ, Feuerstein GZ: Neuropeptide Y upregulates the adhesiveness of human endothelial cells for leukocytes. Circ Res 68: 314–318, 1991
    OpenUrlAbstract/FREE Full Text
  23. ↵
    Pernow J, Lundberg JM, Kaijser L: Vasoconstrictor effects in vivo and plasma disappearance rate of neuropeptide Y in man. Life Sci 40: 47–54, 1987
    OpenUrlCrossRefPubMed
  24. ↵
    Medeiros MS, Turner AJ: Metabolism and functions of neuropeptide Y. Neurochem Res 21: 1125–1132, 1996
    OpenUrlCrossRefPubMed
  25. ↵
    Medeiros MD, Turner AJ: Processing and metabolism of peptide-YY: Pivotal roles of dipeptidylpeptidase-IV, aminopeptidase-P, and endopeptidase-24.11. Endocrinology 134: 2088–2094, 1994
    OpenUrlCrossRefPubMed
  26. ↵
    Odar-Cederlof I, Ericsson F, Theodorsson E, Kjellstrand CM: Is neuropeptide Y a contributor to volume-induced hypertension? Am J Kidney Dis 31: 803–808, 1998
  27. ↵
    Bald M, Gerigk M, Rascher W: Elevated plasma concentrations of neuropeptide Y in children and adults with chronic and terminal renal failure. Am J Kidney Dis 30: 23–27, 1997
  28. ↵
    Mouri T, Sone M, Takahashi K, Itoi K, Totsune K, Hayashi Y, Hasegawa S, Ohneda M, Murakami O, Miura Y: Neuropeptide Y as a plasma marker for phaeochromocytoma, ganglioneuroblastoma and neuroblastoma. Clin Sci (Lond) 83: 205–211, 1992
  29. ↵
    Hegbrant J, Thysell H, Ekman R: Plasma levels of vasoactive regulatory peptides in patients receiving regular hemodialysis treatment. Scand J Urol Nephrol 26: 169–176, 1992
  30. ↵
    Hegbrant J, Martensson L, Thysell H, Ekman R, Boberg U: Changes in plasma levels of vasoactive substances during routine acetate and bicarbonate hemodialysis. Clin Nephrol 41: 106–112, 1994
  31. ↵
    Briggs JD, Berthoux FJE: Predictions of future growth of ESRD prevalence. Kidney Int 57: S46–S48, 2000
    OpenUrlCrossRef
  32. ↵
    Longenecker JC, Coresh J, Powe NR, Levey AS, Fink NE, Martin A, Klag MJ: Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol 13: 1918–1927, 2002
    OpenUrlAbstract/FREE Full Text
  33. ↵
    Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C: Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 55: 648–658, 1999
    OpenUrlCrossRefPubMed
  34. ↵
    Yeun JY, Levine RA, Mantadilok V, Kaysen GA: C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 35: 469–476, 2000
    OpenUrlPubMed
  35. ↵
    Moustapha A, Naso A, Nahlawi M, Gupta A, Arheart KL, Jacobsen DW, Robinson K, Dennis VW: Prospective study of hyperhomocysteinemia as an adverse cardiovascular risk factor in end-stage renal disease. Circulation 97: 138–141, 1998
    OpenUrlAbstract/FREE Full Text
  36. ↵
    Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE: The impact of anemia on cardiomyopathy, morbidity, and mortality in end-stage renal disease. Am J Kidney Dis 28: 53–61, 1996
    OpenUrlPubMed
  37. ↵
    Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK: Association of elevated serum PO(4), Ca × PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 12: 2131–2138, 2001
    OpenUrlAbstract/FREE Full Text
  38. ↵
    Mancia G, Grassi G, Giannattasio C, Seravalle G: Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. Hypertension 34 (4 Pt 2): 724–728, 1999
    OpenUrlAbstract/FREE Full Text
  39. ↵
    Zoccali C, Mallamaci F, Tripepi G, Parlongo S, Cutrupi S, Benedetto FA, Cataliotti A, Malatino LS: Norepinephrine and concentric hypertrophy in patients with end-stage renal disease. Hypertension 40: 41–46, 2002
    OpenUrlAbstract/FREE Full Text
  40. ↵
    Zoccali C, Mallamaci F, Parlongo S, Cutrupi S, Benedetto FA, Tripepi G, Bonanno G, Rapisarda F, Fatuzzo P, Seminara G, Cataliotti A, Stancanelli B, Malatino LS, Cataliotti A: Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation 105: 1354–1359, 2002
    OpenUrlAbstract/FREE Full Text
  41. ↵
    Forsgren S: Neuropeptide Y–like immunoreactivity in relation to the distribution of sympathetic nerve fibers in the heart conduction system. J Mol Cell Cardiol 21: 279–290, 1989
    OpenUrlCrossRefPubMed
  42. ↵
    Balasubramaniam AA: Neuropeptide Y family of hormones: Receptor subtypes and antagonists. Peptides 18: 445–457, 1997
    OpenUrlCrossRefPubMed
  43. ↵
    Akagi S, Nagake Y, Sugimoto T, Nakao K, Yamasaki H, Ichikawa H, Makino H: Plasma neuropeptide Y concentrations in patients on hemodialysis. Nephron 92: 333–338, 2002
    OpenUrlCrossRefPubMed
View Abstract
PreviousNext
Back to top

In this issue

Journal of the American Society of Nephrology: 14 (10)
Journal of the American Society of Nephrology
Vol. 14, Issue 10
1 Oct 2003
  • Table of Contents
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in JASN.
Enter multiple addresses on separate lines or separate them with commas.
Prospective Study of Neuropeptide Y as an Adverse Cardiovascular Risk Factor in End-Stage Renal Disease
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Prospective Study of Neuropeptide Y as an Adverse Cardiovascular Risk Factor in End-Stage Renal Disease
Carmine Zoccali, Francesca Mallamaci, Giovanni Tripepi, Francesco A. Benedetto, Saverio Parlongo, Sebastiano Cutrupi, Domenico Iellamo, Graziella Bonanno, Francesco Rapisarda, Pasquale Fatuzzo, Giuseppe Seminara, Alessandro Cataliotti, Lorenzo Salvatore Malatino
JASN Oct 2003, 14 (10) 2611-2617; DOI: 10.1097/01.ASN.0000089026.28617.33

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Prospective Study of Neuropeptide Y as an Adverse Cardiovascular Risk Factor in End-Stage Renal Disease
Carmine Zoccali, Francesca Mallamaci, Giovanni Tripepi, Francesco A. Benedetto, Saverio Parlongo, Sebastiano Cutrupi, Domenico Iellamo, Graziella Bonanno, Francesco Rapisarda, Pasquale Fatuzzo, Giuseppe Seminara, Alessandro Cataliotti, Lorenzo Salvatore Malatino
JASN Oct 2003, 14 (10) 2611-2617; DOI: 10.1097/01.ASN.0000089026.28617.33
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

  • Survival among Patients with Kidney Failure in Jalisco, Mexico
  • A Population-Based, Prospective Study of Blood Pressure and Risk for End-Stage Renal Disease in China
  • Hepatitis C Virus and Death Risk in Hemodialysis Patients
Show more Epidemiology and Outcomes

Cited By...

  • No citing articles found.
  • Google Scholar

Similar Articles

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Annual Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Author Resources
  • Editorial Fellowship Program
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • JASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About JASN
  • JASN Email Alerts
  • JASN Key Impact Information
  • JASN Podcasts
  • JASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe

© 2021 American Society of Nephrology

Print ISSN - 1046-6673 Online ISSN - 1533-3450

Powered by HighWire