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Glomerülonefritli hastalarda karotis intima media kalınlığının prediktörü hangisidir; nötrofil-lenfosit oranı mı proteinüri mi?

Yıl 2019, Cilt: 12 Sayı: 2, 269 - 279, 28.05.2019
https://doi.org/10.31362/patd.500277

Öz

Amaç:Glomerülonefrit glomerüllerin inflamasyondur ve proteinüri kendisi
glomerüler inflamasyonun klinik bir yansımasıdır. Bu çalışmada, aterosklerozun
en erken bulgularından biri olan karotis intima media kalınlığı (KIMK) ile
glomerüler inflamasyon belirteçleri arasındaki ilişkiyi araştırmayı amaçladık.



Gereç ve yöntem: Biyopsi ile kanıtlanmış 40 glomerülonefrit
hastası ve 46 sağlıklı kontrol çalışmaya dahil edildi. Serum örneklerinde Growth
arrest spesific protein 6 (Gas6) düzeyleri ELISA ile çalışıldı. KIMK ölçümü
aynı radyolog tarafından yapıldı.
Nötrofil-lenfosit oranı (NLO) tam kan test sonucundan elde edilen
nötrofil sayısının lenfosit sayısına bölünmesiyle hesaplandı.



Bulgular: Hasta grubunda ortalama yaş 42,88±15,41, kontrol grubunda
38,26±9,04 idi. Ortalama hastalık süresi 29.07±52.90 ay, proteinüri
4027.05±4030.22 mg/gün, MDRD-GFR 53.80±48.32 mL/dk/1.73m2 idi. KIMK
hasta grubunda 0.62±0.17 mm, kontrol grubunda 0.46±0.10 mm idi. NLO hasta
grubunda 3.69±4.46, kontrol grubundan anlamlı derecede yüksekti (1.74±0.63).
Kontrol grubunda Gas6 düzeyleri istatistiksel olarak daha yüksekti. KIMK yaş,
fibrinojen, ferritin, proteinüri ve NLO ile pozitif korelasyon gösterdi ve
glomerülonefrit grubunda HDL kolesterol ve Gas6 ile negatif korelasyon
gösterdi. Lojistik regresyon modelinde yaş KIMK için belirleyiciydi. Tüm grupta
KIMK yaş, kreatinin, ürik asit, fibrinojen, ferritin, CaxP çarpımı, proteinüri
ve NLO ile pozitif ve hemoglobin düzeyi, Gas6 ile negatif korelasyon gösterdi.
Lineer lojistik regresyon analizinde karotis IMK, yaş ve ferritin ve proteinüri
ile anlamlı şekilde ilişkiliydi.



Sonuç: Çalışmamızda proteinürinin böbrek fonksiyonu göreceli olarak korunmuş glomerülonefritte
GFR düzeylerinden bağımsız olarak artmış KIMK'nın temel belirleyicilerinden
biri olduğunu gösterdik.

Kaynakça

  • REFERENCES1. Ahbap E, Sakaci T, Kara E et al. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in evaluation of inflammation in end-stage renal disease. Clinical Nephrology 2016;85:199–208.
  • 2. Benites-ZapataVA, Hernandez AV, Nagarajan V, Cauthen CA, Starling RC, Tang WH. Usefulness of neutrophil-to-lymphocyte ratio in risk stratification of patients with advanced heart failure. Am J Cardiol 2015;115:57-61.
  • 3. Li H, Lu X, Xiong R, Wang S. High neutrophil-to-lymphocyte ratio predicts cardiovascular mortality in chronic hemodialysis patients. Mediators Inflamm 2017;doi: 10.1155/2017/9327136. Epub 2017 Feb 21.
  • 4.Erkan E, Devarajan P, Schwartz GJ. Mitochondria are the major targets in albumin-induced apoptosis in proximal tubule cells. J Am Soc Nephrol 2007;18:1199–1208.
  • 5. Erkan E, Garcia CD, Patterson LT et al. Induction of renal tubular cell apoptosis in focal segmental glomerulosclerosis: roles of proteinuria and Fas-dependent pathways. J Am Soc Nephrol 2005;16:398–407.
  • 6. Son BK, Kozaki K, Iijima K, Eto M, Kojima T, Ota H. Statins protect human aortic smooth muscle cells from inorganic phosphate-induced calcification by restoring Gas6-Axl survival pathway. CircRes 2 006;98:1024-31.
  • 7.Li W, WangJ, Ge L, Shan J, Zhang C, Liu J. Growth arrest-specific protein 6 (Gas6) as a noninvasive biomarker for early detection of diabetic nephropathy. Clin Exp Hypertens 2017;39:382-387.
  • 8. Erek-Toprak A, Bingol-Ozakpinar O, Karaca Z. Association of plasma growth arrest specific protein 6 (Gas6) concentrations with albuminuria in patients with type 2 diabetes. Renal Fail 2014;36:737–42.
  • 9. Hyde GD, Taylor RF, Ashton N et al. Axl tyrosinekinase protects against tubulo-interstitial apoptosis and progression of renal failure in a murine model of chronic kidney disease and hyperphosphataemia. PLoS One 2014;9:e102096. doi:10.1371/journal.pone.0102096. eCollection 2014.
  • 10. Abe T, Kato S, Tsuruta Y et al. Neutrophil/lymphocyte ratio as a predictor of cardiovascular events in incident dialysis patients: A Japanese prospective cohort study. Clin Exp Nephrol 2015;19:718–724.
  • 11. Erdem E. Neutrophil lymphocyte ratio in acute renal failure. Indian J Nephrol 2015;25:126–127.
  • 12. Küçük H, Göker B, Varan Ö et al. Predictive value of neutrophil/lymphocyte ratio in renal prognosis of patients with granulomatosis with polyangiitis. Ren Fail 2017;39:273-276.
  • 13. Nunez J, Nunez E, Bodi V et al. Usefulness of the neutrophil to lymphocyte ratio in predicting long-term mortality in ST segment elevation myocardial infarction. Am J Cardiol 2008;101:747–752.
  • 14. Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol 2008;102:653–657.
  • 15. Corriere T, DiMarca S, Cataudella E et al. Neutrophil-to-Lymphocyte Ratio is a strong predictor of atherosclerotic carotid plaques in older adults. Nutr Metab Cardiovasc Dis 2018;28:23-27.
  • 16. Yilmaz G, Sevinc C, Ustundag S et al. The relationship between mean platelet volume and neutrophil/lymphocyte ratio with inflammation and proteinuria in chronic kidney disease. Saudi J Kidney Dis Transpl 2017;28:90-94.
  • 17. Emokpae MA, Aruomaren A, Osime E. Relationship between Neutrophil-to-Lymphocyte Ratio and Inflammatory Markers in Sickle Cell Anaemia Patients with Proteinuria. Med Sci (Basel) 2016;4.pii: E11. doi: 10.3390/medsci4030011.
  • 18. Lai S, Dimko M, Galani A et al. Early markers of cardiovascular risk in chronic kidney disease. Ren Fail 2015;37:254-61.
  • 19.Van den Munckhof ICL, Jones H, Hopman MTE et al. Relation between age and carotid artery intima-medial thickness: a systematic review. Clin Cardiol 2018;41:698-704.
  • 20. Gustafsson JT, Herlitz Lindberg M, Gunnarsson I et al. Excess atherosclerosis in systemic lupus erythematosus, A matter of renal involvement: Case control study of 281 SLE patients and 281 individually matched population controls. PLoS One 2017;12:e0174572. doi:10.1371/journal.pone.0174572.
  • 21. Falaschi F, Ravelli A, Martignoni A et al. Nephrotic-range proteinuria, the major risk factor for early atherosclerosis in juvenile-onset systemic lupus erythematosus. Arthritis Rheum 2000;43:1405-1409.
  • 22. Hafizi S, Dahlback B. Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosinekinase subfamily. FEBS J2006;273:5231–5244.
  • 23. Melaragno MG, Fridell YW, Berk BC. The Gas6/Axl system: a novel regulator of vascular cell function. Trends Cardiovasc Med 1999;9:250–253.
  • 24. Morony S, Tintut Y, Zhang Z et al. Osteoprotegerin inhibits vascular calcification without affecting atherosclerosis in ldl r(-/-) mice. Circulation 2008;117:411–420.
  • 25. Son BK, Kozaki K, Iijima K et al. Gas6/ Axl-PI3K/Aktpathwayplays a central role in theeffect of statins on inorganicphosphate-inducedcalcification of vascularsmoothmusclecells. Eur. J. Pharmacol2007;556:1–8.
  • 26. Craneburg ECM, Schurgers LJ, Uiterwijk HH, Beulens JWJ, Dalmeijer GW, Westerhuis R. Vitamin K intake and status are low in hemodialysis patients. Kidney Int 2012;82:605-610.
  • 27. Holden RM, Morton AR, Garland JS, Pavlov A, Day AG, Booth SL. Vitamins K and D status in stages 3-5 chronic kidney disease. Clin J Am Soc Nephrol 2010;22:387-395.
  • 28. Boxma PY, van den Berg E, Geleijnse JM, Laverman GD, Schurgers LJ, Vermeer C. Vitamin K intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients. PLoS One 2012;7:e47991.
  • 29. Jiang X, Tao H, Qiu C et al. Vitamin K2 regression aortic calcification induced by warfarin via Gas6/Axl survival pathway in rats. Eur J Pharmacol 2016;786:10-18.
  • 30. Wu CS, Hu CY, Tsai HF et al. Elevated serum level of growth arrest-specific protein 6 (Gas6) in systemic lupus erythematosus patients is associated with nephritis and cutaneous vasculitis. Rheumatol Int 2014;34:625-629.
  • 31. Nagai K, Miyoshi M, Kake T et al. Dual involvement of growth arrest-specific gene 6 in the early phase of human IgA nephropathy. Plos One 2013;doi: 10.1371/journal.pone.0066759.
  • 32. Guo JK, Marlier A, Shi H et al. Increased tubular proliferation as an adaptive response to glomerular albuminuria. J Am Soc Nephrol 2012;23:429–437.
  • 33. Tselios K, Gladman DD, Su J, Urowitz MB. Does Renin-Angiotensin System Blockade Protect Lupus Nephritis Patients From Atherosclerotic Cardiovascular Events? A Case-Control Study. Arthritis Care Res (Hoboken) 2016;68:1497-1504.
  • 34. Melaragno MG, Wuthrich DA, Poppa V et al. Increased expression of Axl tyrosinekinase after vascular injury and regulation by G protein-coupled receptor agonists in rats. Circ Res 1998;83:697-704.

Which one is the predictor of carotid intima media thickness in patients with aglomerulonephritis; neutrophil-to-lymphocyte ratio or proteinuria?

Yıl 2019, Cilt: 12 Sayı: 2, 269 - 279, 28.05.2019
https://doi.org/10.31362/patd.500277

Öz

Purpose:Glomerulonephritis is inflammation of the glomeruli and proteinuria
itself is a reflection of the glomerular inflammation. In this study we aimed
to investigate the relationship between carotid intima media thickness (CIMT)
one of the earliest findings of atherosclerosis and markers of glomerular
inflammation.

Materials and methods:40 patients with biopsy proven
glomerulonephritis and 46 healthy controls were enrolled in the study.Human
Growth arrest spesific protein 6 (Gas6) levels in serum samples were studied by
ELISA.CIMT measurement was performed by the same radiologist.

Results: The mean age was 42,88±15,41in patient group and 38,26±9,04 in
controls. The mean duration of illness was 29.07±52.90 mounts, proteinuria  was4027.05±4030.22 mg/day, MDRD-GFR  was 53.80±48.32 mL/min/1.73m2.
CIMT was 0.62±0.17 mm in patient group,0.46±0.10 mm in  controls.
Neutrophil-to-Lymphocyte
Ratio (NLR) was 3.69±4.46 in
patient group and significantly higher than control group (1.74±0.63). Gas6
levels were statistically higher in control group. CIMT was positively
correlated with age, fibrinogen, ferritin, proteinuria and NLR and negatively
correlated with HDL cholesterol and Gas6 
in glomerulonephritis group.  Age  was the predictor  for CIMT in the logistic regression model. In
all group CIMT was positively correlated with age, creatinine, uric acid,
fibrinogen, ferritin, CaxP product, proteinuria and NLR and negatively
correlated with hemoglobin level, Gas6. In lineer logistic regression analysis
carotid IMT was significantly associated with age and ferritin and proteinuria.







Conclusion: We have shown that proteinuria is one of the main
determinants of increased CIMT independent from the GFR levels in
glomerulonephritis with relatively preserved renal function. 

Kaynakça

  • REFERENCES1. Ahbap E, Sakaci T, Kara E et al. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in evaluation of inflammation in end-stage renal disease. Clinical Nephrology 2016;85:199–208.
  • 2. Benites-ZapataVA, Hernandez AV, Nagarajan V, Cauthen CA, Starling RC, Tang WH. Usefulness of neutrophil-to-lymphocyte ratio in risk stratification of patients with advanced heart failure. Am J Cardiol 2015;115:57-61.
  • 3. Li H, Lu X, Xiong R, Wang S. High neutrophil-to-lymphocyte ratio predicts cardiovascular mortality in chronic hemodialysis patients. Mediators Inflamm 2017;doi: 10.1155/2017/9327136. Epub 2017 Feb 21.
  • 4.Erkan E, Devarajan P, Schwartz GJ. Mitochondria are the major targets in albumin-induced apoptosis in proximal tubule cells. J Am Soc Nephrol 2007;18:1199–1208.
  • 5. Erkan E, Garcia CD, Patterson LT et al. Induction of renal tubular cell apoptosis in focal segmental glomerulosclerosis: roles of proteinuria and Fas-dependent pathways. J Am Soc Nephrol 2005;16:398–407.
  • 6. Son BK, Kozaki K, Iijima K, Eto M, Kojima T, Ota H. Statins protect human aortic smooth muscle cells from inorganic phosphate-induced calcification by restoring Gas6-Axl survival pathway. CircRes 2 006;98:1024-31.
  • 7.Li W, WangJ, Ge L, Shan J, Zhang C, Liu J. Growth arrest-specific protein 6 (Gas6) as a noninvasive biomarker for early detection of diabetic nephropathy. Clin Exp Hypertens 2017;39:382-387.
  • 8. Erek-Toprak A, Bingol-Ozakpinar O, Karaca Z. Association of plasma growth arrest specific protein 6 (Gas6) concentrations with albuminuria in patients with type 2 diabetes. Renal Fail 2014;36:737–42.
  • 9. Hyde GD, Taylor RF, Ashton N et al. Axl tyrosinekinase protects against tubulo-interstitial apoptosis and progression of renal failure in a murine model of chronic kidney disease and hyperphosphataemia. PLoS One 2014;9:e102096. doi:10.1371/journal.pone.0102096. eCollection 2014.
  • 10. Abe T, Kato S, Tsuruta Y et al. Neutrophil/lymphocyte ratio as a predictor of cardiovascular events in incident dialysis patients: A Japanese prospective cohort study. Clin Exp Nephrol 2015;19:718–724.
  • 11. Erdem E. Neutrophil lymphocyte ratio in acute renal failure. Indian J Nephrol 2015;25:126–127.
  • 12. Küçük H, Göker B, Varan Ö et al. Predictive value of neutrophil/lymphocyte ratio in renal prognosis of patients with granulomatosis with polyangiitis. Ren Fail 2017;39:273-276.
  • 13. Nunez J, Nunez E, Bodi V et al. Usefulness of the neutrophil to lymphocyte ratio in predicting long-term mortality in ST segment elevation myocardial infarction. Am J Cardiol 2008;101:747–752.
  • 14. Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol 2008;102:653–657.
  • 15. Corriere T, DiMarca S, Cataudella E et al. Neutrophil-to-Lymphocyte Ratio is a strong predictor of atherosclerotic carotid plaques in older adults. Nutr Metab Cardiovasc Dis 2018;28:23-27.
  • 16. Yilmaz G, Sevinc C, Ustundag S et al. The relationship between mean platelet volume and neutrophil/lymphocyte ratio with inflammation and proteinuria in chronic kidney disease. Saudi J Kidney Dis Transpl 2017;28:90-94.
  • 17. Emokpae MA, Aruomaren A, Osime E. Relationship between Neutrophil-to-Lymphocyte Ratio and Inflammatory Markers in Sickle Cell Anaemia Patients with Proteinuria. Med Sci (Basel) 2016;4.pii: E11. doi: 10.3390/medsci4030011.
  • 18. Lai S, Dimko M, Galani A et al. Early markers of cardiovascular risk in chronic kidney disease. Ren Fail 2015;37:254-61.
  • 19.Van den Munckhof ICL, Jones H, Hopman MTE et al. Relation between age and carotid artery intima-medial thickness: a systematic review. Clin Cardiol 2018;41:698-704.
  • 20. Gustafsson JT, Herlitz Lindberg M, Gunnarsson I et al. Excess atherosclerosis in systemic lupus erythematosus, A matter of renal involvement: Case control study of 281 SLE patients and 281 individually matched population controls. PLoS One 2017;12:e0174572. doi:10.1371/journal.pone.0174572.
  • 21. Falaschi F, Ravelli A, Martignoni A et al. Nephrotic-range proteinuria, the major risk factor for early atherosclerosis in juvenile-onset systemic lupus erythematosus. Arthritis Rheum 2000;43:1405-1409.
  • 22. Hafizi S, Dahlback B. Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosinekinase subfamily. FEBS J2006;273:5231–5244.
  • 23. Melaragno MG, Fridell YW, Berk BC. The Gas6/Axl system: a novel regulator of vascular cell function. Trends Cardiovasc Med 1999;9:250–253.
  • 24. Morony S, Tintut Y, Zhang Z et al. Osteoprotegerin inhibits vascular calcification without affecting atherosclerosis in ldl r(-/-) mice. Circulation 2008;117:411–420.
  • 25. Son BK, Kozaki K, Iijima K et al. Gas6/ Axl-PI3K/Aktpathwayplays a central role in theeffect of statins on inorganicphosphate-inducedcalcification of vascularsmoothmusclecells. Eur. J. Pharmacol2007;556:1–8.
  • 26. Craneburg ECM, Schurgers LJ, Uiterwijk HH, Beulens JWJ, Dalmeijer GW, Westerhuis R. Vitamin K intake and status are low in hemodialysis patients. Kidney Int 2012;82:605-610.
  • 27. Holden RM, Morton AR, Garland JS, Pavlov A, Day AG, Booth SL. Vitamins K and D status in stages 3-5 chronic kidney disease. Clin J Am Soc Nephrol 2010;22:387-395.
  • 28. Boxma PY, van den Berg E, Geleijnse JM, Laverman GD, Schurgers LJ, Vermeer C. Vitamin K intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients. PLoS One 2012;7:e47991.
  • 29. Jiang X, Tao H, Qiu C et al. Vitamin K2 regression aortic calcification induced by warfarin via Gas6/Axl survival pathway in rats. Eur J Pharmacol 2016;786:10-18.
  • 30. Wu CS, Hu CY, Tsai HF et al. Elevated serum level of growth arrest-specific protein 6 (Gas6) in systemic lupus erythematosus patients is associated with nephritis and cutaneous vasculitis. Rheumatol Int 2014;34:625-629.
  • 31. Nagai K, Miyoshi M, Kake T et al. Dual involvement of growth arrest-specific gene 6 in the early phase of human IgA nephropathy. Plos One 2013;doi: 10.1371/journal.pone.0066759.
  • 32. Guo JK, Marlier A, Shi H et al. Increased tubular proliferation as an adaptive response to glomerular albuminuria. J Am Soc Nephrol 2012;23:429–437.
  • 33. Tselios K, Gladman DD, Su J, Urowitz MB. Does Renin-Angiotensin System Blockade Protect Lupus Nephritis Patients From Atherosclerotic Cardiovascular Events? A Case-Control Study. Arthritis Care Res (Hoboken) 2016;68:1497-1504.
  • 34. Melaragno MG, Wuthrich DA, Poppa V et al. Increased expression of Axl tyrosinekinase after vascular injury and regulation by G protein-coupled receptor agonists in rats. Circ Res 1998;83:697-704.
Toplam 34 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri
Bölüm Araştırma Makalesi
Yazarlar

Aysun Toraman 0000-0003-2290-3342

Berna Eren Bu kişi benim 0000-0003-1459-3663

Fatih Duzgun Bu kişi benim 0000-0003-2199-0640

Fatma Taneli 0000-0002-5194-0460

Seyhun Kursat 0000-0001-9437-8474

Yayımlanma Tarihi 28 Mayıs 2019
Gönderilme Tarihi 20 Aralık 2018
Kabul Tarihi 18 Nisan 2019
Yayımlandığı Sayı Yıl 2019 Cilt: 12 Sayı: 2

Kaynak Göster

APA Toraman, A., Eren, B., Duzgun, F., Taneli, F., vd. (2019). Which one is the predictor of carotid intima media thickness in patients with aglomerulonephritis; neutrophil-to-lymphocyte ratio or proteinuria?. Pamukkale Medical Journal, 12(2), 269-279. https://doi.org/10.31362/patd.500277
AMA Toraman A, Eren B, Duzgun F, Taneli F, Kursat S. Which one is the predictor of carotid intima media thickness in patients with aglomerulonephritis; neutrophil-to-lymphocyte ratio or proteinuria?. Pam Tıp Derg. Mayıs 2019;12(2):269-279. doi:10.31362/patd.500277
Chicago Toraman, Aysun, Berna Eren, Fatih Duzgun, Fatma Taneli, ve Seyhun Kursat. “Which One Is the Predictor of Carotid Intima Media Thickness in Patients With Aglomerulonephritis; Neutrophil-to-Lymphocyte Ratio or Proteinuria?”. Pamukkale Medical Journal 12, sy. 2 (Mayıs 2019): 269-79. https://doi.org/10.31362/patd.500277.
EndNote Toraman A, Eren B, Duzgun F, Taneli F, Kursat S (01 Mayıs 2019) Which one is the predictor of carotid intima media thickness in patients with aglomerulonephritis; neutrophil-to-lymphocyte ratio or proteinuria?. Pamukkale Medical Journal 12 2 269–279.
IEEE A. Toraman, B. Eren, F. Duzgun, F. Taneli, ve S. Kursat, “Which one is the predictor of carotid intima media thickness in patients with aglomerulonephritis; neutrophil-to-lymphocyte ratio or proteinuria?”, Pam Tıp Derg, c. 12, sy. 2, ss. 269–279, 2019, doi: 10.31362/patd.500277.
ISNAD Toraman, Aysun vd. “Which One Is the Predictor of Carotid Intima Media Thickness in Patients With Aglomerulonephritis; Neutrophil-to-Lymphocyte Ratio or Proteinuria?”. Pamukkale Medical Journal 12/2 (Mayıs 2019), 269-279. https://doi.org/10.31362/patd.500277.
JAMA Toraman A, Eren B, Duzgun F, Taneli F, Kursat S. Which one is the predictor of carotid intima media thickness in patients with aglomerulonephritis; neutrophil-to-lymphocyte ratio or proteinuria?. Pam Tıp Derg. 2019;12:269–279.
MLA Toraman, Aysun vd. “Which One Is the Predictor of Carotid Intima Media Thickness in Patients With Aglomerulonephritis; Neutrophil-to-Lymphocyte Ratio or Proteinuria?”. Pamukkale Medical Journal, c. 12, sy. 2, 2019, ss. 269-7, doi:10.31362/patd.500277.
Vancouver Toraman A, Eren B, Duzgun F, Taneli F, Kursat S. Which one is the predictor of carotid intima media thickness in patients with aglomerulonephritis; neutrophil-to-lymphocyte ratio or proteinuria?. Pam Tıp Derg. 2019;12(2):269-7.
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