Skip to main content
Erschienen in: Journal of Nephrology 5/2019

01.10.2019 | Original Article

The relationship between the concentration of plasma homocysteine and chronic kidney disease: a cross sectional study of a large cohort

verfasst von: Eytan Cohen, Ili Margalit, Tzippy Shochat, Elad Goldberg, Ilan Krause

Erschienen in: Journal of Nephrology | Ausgabe 5/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

High concentrations of homocysteine are considered a risk factor for developing atherosclerosis and coronary artery disease. The aim of this study was to assess the concentrations of homocysteine in subjects with chronic kidney disease (CKD).

Methods

Data were collected from medical records of individuals examined at a screening center in Israel between the years 2000–2014. Cross sectional analysis was carried out on 17,010 subjects; 67% were men.

Results

Significant differences were observed between four quartiles of homocysteine concentrations and estimated glomerular filtration rate (eGFR)—the higher the homocysteine concentration, the lower the eGFR (p < 0.0001). In subjects with CKD, homocysteine plasma levels were correlated with the stage of renal impairment. Mean (SD) homocysteine concentrations in subjects with eGFR < 60 mL/min per 1.73 m2 compared to subjects with eGFR ≥ 60 mL/min per 1.73 m2 were: 16.3 (5.9) vs. 11.5 (5.5) μmol/L respectively. These findings remained significant after adjustment for age, smoking status, body mass index, hypertension and diabetes mellitus (p < 0.0001). Compared to subjects with homocysteine concentrations less than 15 μmol/L, those with homocysteine concentrations equal and above 15 μmol/L, had a significantly higher odds ratio (95% CI) of having an eGFR < 60 mL/min per 1.73 m2; non adjusted model, 8.30 (6.17–11.16); adjusted model for age smoking status, body mass index, hypertension and diabetes mellitus, 7.43 (5.41–10.21).

Conclusion

Plasma homocysteine concentrations are higher in subjects with CKD. This may contribute to an increased risk for developing atherosclerosis and coronary artery disease in these patients.
Literatur
2.
Zurück zum Zitat McCully KS (1969) Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 56:111–128PubMedPubMedCentral McCully KS (1969) Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 56:111–128PubMedPubMedCentral
3.
Zurück zum Zitat Ridker PM, Stampfer MJ, Rifai N (2001) Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA 285:2481–2485CrossRefPubMed Ridker PM, Stampfer MJ, Rifai N (2001) Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA 285:2481–2485CrossRefPubMed
4.
Zurück zum Zitat Stampfer MJ, Malinow MR, Willett WC et al (1992) A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 268:877–881CrossRefPubMed Stampfer MJ, Malinow MR, Willett WC et al (1992) A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 268:877–881CrossRefPubMed
5.
Zurück zum Zitat Giles WH, Croft JB, Greenlund KJ, Ford ES, Kittner SJ (2000) Association between total homocyst(e)ine and the likelihood for a history of acute myocardial infarction by race and ethnicity: results from the Third National Health and Nutrition Examination Survey. Am Heart J 139:446–453CrossRefPubMed Giles WH, Croft JB, Greenlund KJ, Ford ES, Kittner SJ (2000) Association between total homocyst(e)ine and the likelihood for a history of acute myocardial infarction by race and ethnicity: results from the Third National Health and Nutrition Examination Survey. Am Heart J 139:446–453CrossRefPubMed
6.
Zurück zum Zitat Al-Obaidi MK, Stubbs PJ, Collinson P et al (2000) Elevated homocysteine levels are associated with increased ischemic myocardial injury in acute coronary syndromes. J Am Coll Cardiol 36:1217–1222CrossRefPubMed Al-Obaidi MK, Stubbs PJ, Collinson P et al (2000) Elevated homocysteine levels are associated with increased ischemic myocardial injury in acute coronary syndromes. J Am Coll Cardiol 36:1217–1222CrossRefPubMed
7.
Zurück zum Zitat Soinio M, Marniemi J, Laakso M, Lehto S, Ronnemaa T (2004) Elevated plasma homocysteine level is an independent predictor of coronary heart disease events in patients with type 2 diabetes mellitus. Ann Intern Med 140:94–100CrossRefPubMed Soinio M, Marniemi J, Laakso M, Lehto S, Ronnemaa T (2004) Elevated plasma homocysteine level is an independent predictor of coronary heart disease events in patients with type 2 diabetes mellitus. Ann Intern Med 140:94–100CrossRefPubMed
8.
Zurück zum Zitat Bates CJ, Mansoor MA, Pentieva KD, Hamer M, Mishra GD (2010) Biochemical risk indices, including plasma homocysteine, that prospectively predict mortality in older British people: the National Diet and Nutrition Survey of People Aged 65 Years and Over. Br J Nutr 104:893–899CrossRefPubMedPubMedCentral Bates CJ, Mansoor MA, Pentieva KD, Hamer M, Mishra GD (2010) Biochemical risk indices, including plasma homocysteine, that prospectively predict mortality in older British people: the National Diet and Nutrition Survey of People Aged 65 Years and Over. Br J Nutr 104:893–899CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Abraham JM, Cho L (2010) The homocysteine hypothesis: still relevant to the prevention and treatment of cardiovascular disease? Cleve Clin J Med 77:911–918CrossRefPubMed Abraham JM, Cho L (2010) The homocysteine hypothesis: still relevant to the prevention and treatment of cardiovascular disease? Cleve Clin J Med 77:911–918CrossRefPubMed
10.
Zurück zum Zitat Lonn E, Yusuf S, Arnold MJ et al (2006) Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 354:1567–1577CrossRefPubMed Lonn E, Yusuf S, Arnold MJ et al (2006) Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 354:1567–1577CrossRefPubMed
11.
Zurück zum Zitat Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM (2002) Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA 288:973–979CrossRefPubMed Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM (2002) Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA 288:973–979CrossRefPubMed
12.
Zurück zum Zitat Lange H, Suryapranata H, De Luca G et al (2004) Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 350:2673–2681CrossRefPubMed Lange H, Suryapranata H, De Luca G et al (2004) Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 350:2673–2681CrossRefPubMed
13.
Zurück zum Zitat Gilbertson DT, Liu J, Xue JL et al (2005) Projecting the number of patients with end-stage renal disease in the United States to the year 2015. J Am Soc Nephrol 16:3736–3741CrossRefPubMed Gilbertson DT, Liu J, Xue JL et al (2005) Projecting the number of patients with end-stage renal disease in the United States to the year 2015. J Am Soc Nephrol 16:3736–3741CrossRefPubMed
14.
Zurück zum Zitat Frohlich GM, Meier P, White SK, Yellon DM, Hausenloy DJ (2013) Myocardial reperfusion injury: looking beyond primary PCI. Eur Heart J 34:1714–1722CrossRefPubMed Frohlich GM, Meier P, White SK, Yellon DM, Hausenloy DJ (2013) Myocardial reperfusion injury: looking beyond primary PCI. Eur Heart J 34:1714–1722CrossRefPubMed
15.
Zurück zum Zitat Francis ME, Eggers PW, Hostetter TH, Briggs JP (2004) Association between serum homocysteine and markers of impaired kidney function in adults in the United States. Kidney Int 66:303–312CrossRefPubMed Francis ME, Eggers PW, Hostetter TH, Briggs JP (2004) Association between serum homocysteine and markers of impaired kidney function in adults in the United States. Kidney Int 66:303–312CrossRefPubMed
16.
Zurück zum Zitat Chuang CH, Lee YY, Sheu BF et al (2013) Homocysteine and C-reactive protein as useful surrogate markers for evaluating CKD risk in adults. Kidney Blood Press Res 37:402–413CrossRefPubMed Chuang CH, Lee YY, Sheu BF et al (2013) Homocysteine and C-reactive protein as useful surrogate markers for evaluating CKD risk in adults. Kidney Blood Press Res 37:402–413CrossRefPubMed
17.
Zurück zum Zitat Togawa T, Sengupta S, Chen H et al (2000) Mechanisms for the formation of protein-bound homocysteine in human plasma. Biochem Biophys Res Commun 277:668–674CrossRefPubMed Togawa T, Sengupta S, Chen H et al (2000) Mechanisms for the formation of protein-bound homocysteine in human plasma. Biochem Biophys Res Commun 277:668–674CrossRefPubMed
18.
Zurück zum Zitat van Guldener C, Donker AJ, Jakobs C et al (1998) No net renal extraction of homocysteine in fasting humans. Kidney Int 54:166–169CrossRefPubMed van Guldener C, Donker AJ, Jakobs C et al (1998) No net renal extraction of homocysteine in fasting humans. Kidney Int 54:166–169CrossRefPubMed
19.
Zurück zum Zitat van Guldener C, Stehouwer CD (2003) Homocysteine metabolism in renal disease. Clin Chem Lab Med 41:1412–1417CrossRefPubMed van Guldener C, Stehouwer CD (2003) Homocysteine metabolism in renal disease. Clin Chem Lab Med 41:1412–1417CrossRefPubMed
20.
Zurück zum Zitat Ballal RS, Jacobsen DW, Robinson K (1997) Homocysteine: update on a new risk factor. Cleve Clin J Med 64:543–549CrossRefPubMed Ballal RS, Jacobsen DW, Robinson K (1997) Homocysteine: update on a new risk factor. Cleve Clin J Med 64:543–549CrossRefPubMed
22.
Zurück zum Zitat Ingrosso D, Cimmino A, Perna AF et al (2003) Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia. Lancet 361:1693–1699CrossRefPubMed Ingrosso D, Cimmino A, Perna AF et al (2003) Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia. Lancet 361:1693–1699CrossRefPubMed
23.
Zurück zum Zitat Levi A, Cohen E, Levi M et al (2014) Elevated serum homocysteine is a predictor of accelerated decline in renal function and chronic kidney disease: a historical prospective study. Eur J Intern Med 25:951–955CrossRefPubMed Levi A, Cohen E, Levi M et al (2014) Elevated serum homocysteine is a predictor of accelerated decline in renal function and chronic kidney disease: a historical prospective study. Eur J Intern Med 25:951–955CrossRefPubMed
24.
Zurück zum Zitat Ninomiya T, Kiyohara Y, Kubo M et al (2004) Hyperhomocysteinemia and the development of chronic kidney disease in a general population: the Hisayama study. Am J Kidney Dis 44:437–445CrossRefPubMed Ninomiya T, Kiyohara Y, Kubo M et al (2004) Hyperhomocysteinemia and the development of chronic kidney disease in a general population: the Hisayama study. Am J Kidney Dis 44:437–445CrossRefPubMed
25.
Zurück zum Zitat Perna AF, Di Nunzio A, Amoresano A et al (2016) Divergent behavior of hydrogen sulfide pools and of the sulfur metabolite lanthionine, a novel uremic toxin, in dialysis patients. Biochimie 126:97–107CrossRefPubMed Perna AF, Di Nunzio A, Amoresano A et al (2016) Divergent behavior of hydrogen sulfide pools and of the sulfur metabolite lanthionine, a novel uremic toxin, in dialysis patients. Biochimie 126:97–107CrossRefPubMed
26.
Zurück zum Zitat Spence JD, Urquhart BL, Bang H (2016) Effect of renal impairment on atherosclerosis: only partially mediated by homocysteine. Nephrol Dial Transpl 31:937–944CrossRef Spence JD, Urquhart BL, Bang H (2016) Effect of renal impairment on atherosclerosis: only partially mediated by homocysteine. Nephrol Dial Transpl 31:937–944CrossRef
27.
Zurück zum Zitat Perna AF, Ingrosso D, Violetti E et al (2009) Hyperhomocysteinemia in uremia–a red flag in a disrupted circuit. Semin Dial 22:351–356CrossRefPubMed Perna AF, Ingrosso D, Violetti E et al (2009) Hyperhomocysteinemia in uremia–a red flag in a disrupted circuit. Semin Dial 22:351–356CrossRefPubMed
28.
Zurück zum Zitat Haynes WG (2002) Hyperhomocysteinemia, vascular function and atherosclerosis: effects of vitamins. Cardiovasc Drugs Ther 16:391–399CrossRefPubMed Haynes WG (2002) Hyperhomocysteinemia, vascular function and atherosclerosis: effects of vitamins. Cardiovasc Drugs Ther 16:391–399CrossRefPubMed
29.
Zurück zum Zitat Meyrier A, Hill GS, Simon P (1998) Ischemic renal diseases: new insights into old entities. Kidney Int 54:2–13CrossRefPubMed Meyrier A, Hill GS, Simon P (1998) Ischemic renal diseases: new insights into old entities. Kidney Int 54:2–13CrossRefPubMed
31.
Zurück zum Zitat Cianciolo G, De Pascalis A, Di Lullo L et al (2017) Folic acid and homocysteine in chronic kidney disease and cardiovascular disease progression: which comes first? Cardiorenal Med 7:255–266CrossRefPubMedPubMedCentral Cianciolo G, De Pascalis A, Di Lullo L et al (2017) Folic acid and homocysteine in chronic kidney disease and cardiovascular disease progression: which comes first? Cardiorenal Med 7:255–266CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ (1993) Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr 57:47–53CrossRefPubMed Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ (1993) Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr 57:47–53CrossRefPubMed
33.
Zurück zum Zitat Xu X, Qin X, Li Y et al (2016) Efficacy of folic acid therapy on the progression of chronic kidney disease: the renal substudy of the china stroke primary prevention trial. JAMA Intern Med 176:1443–1450CrossRefPubMed Xu X, Qin X, Li Y et al (2016) Efficacy of folic acid therapy on the progression of chronic kidney disease: the renal substudy of the china stroke primary prevention trial. JAMA Intern Med 176:1443–1450CrossRefPubMed
34.
Zurück zum Zitat Jamison RL, Hartigan P, Kaufman JS et al (2007) Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. JAMA 298:1163–1170CrossRefPubMed Jamison RL, Hartigan P, Kaufman JS et al (2007) Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. JAMA 298:1163–1170CrossRefPubMed
35.
Zurück zum Zitat House AA, Eliasziw M, Cattran DC et al (2010) Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial. JAMA 303:1603–1609CrossRefPubMed House AA, Eliasziw M, Cattran DC et al (2010) Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial. JAMA 303:1603–1609CrossRefPubMed
Metadaten
Titel
The relationship between the concentration of plasma homocysteine and chronic kidney disease: a cross sectional study of a large cohort
verfasst von
Eytan Cohen
Ili Margalit
Tzippy Shochat
Elad Goldberg
Ilan Krause
Publikationsdatum
01.10.2019
Verlag
Springer International Publishing
Erschienen in
Journal of Nephrology / Ausgabe 5/2019
Print ISSN: 1121-8428
Elektronische ISSN: 1724-6059
DOI
https://doi.org/10.1007/s40620-019-00618-x

Weitere Artikel der Ausgabe 5/2019

Journal of Nephrology 5/2019 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

So sicher sind Tattoos: Neue Daten zur Risikobewertung

22.05.2024 Melanom Nachrichten

Das größte medizinische Problem bei Tattoos bleiben allergische Reaktionen. Melanome werden dadurch offensichtlich nicht gefördert, die Farbpigmente könnten aber andere Tumoren begünstigen.

CAR-M-Zellen: Warten auf das große Fressen

22.05.2024 Onkologische Immuntherapie Nachrichten

Auch myeloide Immunzellen lassen sich mit chimären Antigenrezeptoren gegen Tumoren ausstatten. Solche CAR-Fresszell-Therapien werden jetzt für solide Tumoren entwickelt. Künftig soll dieser Prozess nicht mehr ex vivo, sondern per mRNA im Körper der Betroffenen erfolgen.

Frühzeitige HbA1c-Kontrolle macht sich lebenslang bemerkbar

22.05.2024 Typ-2-Diabetes Nachrichten

Menschen mit Typ-2-Diabetes von Anfang an intensiv BZ-senkend zu behandeln, wirkt sich positiv auf Komplikationen und Mortalität aus – und das offenbar lebenslang, wie eine weitere Nachfolgeuntersuchung der UKPD-Studie nahelegt.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.