Necla BUYAN, Bülent ÇELİK, Nilgün ÇAKAR, Deniz ERBAŞ, Tayfun GÖKTAŞ, Serdar KULA, Meltem AKÇABOY, Nermin UNCU, Bijen NAZLIEL

Effects of whole blood viscosity and plasma NOx on cardiac function and cerebral blood flow in children with chronic kidney disease

Background/aim: The aim of the study was to investigate the effects of whole blood viscosity and plasma nitric oxide on cerebral and cardiovascular risks associated with chronic kidney disease.Materials and methods: The study group consisted of 40 pediatric patients and 21 healthy control subjects. Hematologic and biochemical variables, viscosity and plasma nitric oxide levels, echocardiographic findings, and middle cerebral artery blood flow velocity were examined. Results: Viscosity values of patients were significantly lower than those of the control group. Lower values of hematocrit, total protein, and albumin and higher values of ferritin in all patient groups resulted in significantly low viscosity levels. Plasma nitric oxide levels were higher in all patient groups than those in the controls. No statistically significant difference was present in middle cerebral artery blood flow velocity between the patient and control groups. Even when systolic functions were normal, the patient group had significant deterioration in diastolic functions, suggesting morbidity and mortality risks. Conclusions: Cerebral blood flow velocities were not affected by viscosity and nitric oxide levels, suggesting that cerebral circulation has the ability to make adaptive modulation. The metabolism of nitric oxide levels needs further investigation and studies in patients with chronic renal disease.

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1. Canaud B, Rodriguez A, Chenine L, Morena M, Jaussent I, Leray-Moragues H, Picard A, Cristol JP. Whole-blood viscosity increases significantly in small arteries and capillaries in hemodiafiltration. Does acute hemorheological change trigger cardiovascular risk events in hemodialysis patient? Hemodial Int 2010; 14: 433-440.
2. London G. Pathophysiology of cardiovascular damage in the early renal population. Nephrol Dial Transplant 2001; 16 Suppl 2: 3-6.
3. Du Y, Yao W, Qian Y, Han M, Wen Z, Ma L. Hemorheologicalchanges in patients with living-donor renal transplantation. Clin Hemorheol Microcirc 2011; 47: 199-209.
4. Malyszko J. Mechanism of endothelial dysfunction in chronic kidney disease. Clin Chim Acta 2011; 411: 1412-1420.
5. Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 1987; 34: 571-590.
6. Lai WW, Geva T, Shirali GS, Frommelt PC, Humes RA, Brook MM, Pignatelli RH, Rychik J; Task Force of the Pediatric Council of the American Society of Echocardiography; Pediatric Council of the American Society of Echocardiography. Guidelines and standards for performance of a pediatric echocardiogram: a report from the Task Force of the Pediatric Council of the American Society of Echocardiography. J Am Soc Echocardiogr 2006; 19: 1413-1430.
7. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986: 57: 450-458.
8. Khoury PR, Mitsnefes M, Daniels SR, Kimball TR. Agespecific reference intervals for indexed left ventricular mass in children. J Am Soc Echocardiogr 2009; 22: 709-714.
9. Mirchandani D, Bhatia J, Leisman D, Kwon EN, Cooper R, Chorny N, Frank R, Infante L, Sethna C. Concordance of measures of left-ventricular hypertrophy in pediatric hypertension. Pediatr Cardiol 2014; 35: 622-626.
10. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelista A. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 2009; 22: 107-133.
11. Aaslid R, Markwalder TM, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 1982; 57: 769-774.
12. Long JA, Undar A, Manning KB, Deutsch S. Viscoelasticity of pediatric blood and its implications for the testing of a pulsatile pediatric blood pump. ASAIO Journal 2005; 51: 563-566.
13. Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001; 5: 62-71.
14. Schaefer B, Wühl E. Educational paper: progression in chronic kidney disease and prevention strategies. Eur J Pediatr 2012; 171: 1579-1588.
15. Hammes MS, Watson S, Coe FL, Ahmed F, Beltran E, Dhar P. Asymmetric dimethylarginine and whole blood viscosity in renal failure. Clin Hemorheol Microcirc 2015; 59: 245-255.
16. Vaisman S, Kensey K, Cho YI. Effect of hemodialysis on whole blood viscosity. Int J Artif Organs 2009; 32: 329-335.
17. Joles JA, Willekes-Koolschijn N, Koomans HA. Hypoalbuminemia causes high blood viscosity by increasing red cell lysophophatidylcholine. Kidney Int 1997: 52: 761-770.
18. McGregor D, Shand B, Lynn K. A controlled trial of the effect of folate supplements on homocysteine, lipids and hemorheology in end-stage renal disease. Nephron 2000; 85: 215-220.
19. von Eckardstein A, Malinow MR, Upson B, Heinrich J, Schulte H, Schönfeld R, Köhler E, Assmann G. Effects of age, lipoproteins, and homeostatic parameters on the role of homocyst(e)inemia as a cardiovascular risk factor in men. Arterioscler Thromb 1994; 14: 460-464.
20. Paulitschke M, Ludat K, Riedel E, Hampl H. Long-term effects of rhEPO therapy on erythrocyte rheology in dialysis patients with different target hematocrits. Clin Nephrol 2000; 53: 36-41.
21. Fathallah-Shaykh SA, Brooks ER, Langman CB, Kensey KR. Sodium modeling attenuates rises in whole-blood viscosity during chronic hemodialysis in children with large interdialytic weight gain. Pediatr Nephrol 2006; 21: 1179-1184.
22. Goren A, Glaser J, Drukker A. Diastolic function in children and adolescents on dialysis and after kidney transplantation: an echocardiographic assessment. Pediatr Nephrol 1993; 7: 725-728.
23. Kovačević P, Dragić S, Rajkovača Z, Veljković S, Kovačević T. Serum levels of nitric oxide and endothelin-1 in patients treated with continuous ambulatory peritoneal dialysis. Ren Fail 2014; 36: 437-440.
24. Vaziri ND, Ni Z, Wang XQ, Oveisi F, Zhou XJ. Down regulation of nitric oxide synthase in chronic renal insufficiency: role of excess PTH. Am J Physiol 1998; 274: F642-649.
25. Kari JA, Donald AE, Vallance PT, Bruckdorfer KR, Leone A, Mullen MJ, Bunce T, Dorado B, Deanfield JE, Rees L. Physiology and biochemistry of endothelial function in children with chronic renal failure. Kidney Int 1997; 52:468- 472.
26. Vallance P, Leone A, Calver A, Collier J, Moncada S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992; 339: 572-575.
27. Kang ES, Miles DE, Tevlin MT, Cates TB, Acchiardo SR. Reversible sequestration of nitric oxide by hemoglobin during hemodialysis in end-stage renal disease. Am J Med Sci 2001; 321: 113-123.
28. Schmidt RJ, Baylis C. Total nitric oxide production is low in patients with chronic renal disease. Kidney Int 2000; 58: 1261- 1266.
29. Schmidt RJ, Yokota S, Tracy TS, Sorkin MI, Baylis C. Nitric oxide production is low in end-stage renal disease patients on peritoneal dialysis. Am J Physiol 1999; 276: F794-797.
30. Schmidt RJ, Domico J, Samsell LS, Yokota S, Tracy TS, Sorkin MI, Engels K, Baylis C. Indices of activity of the nitric oxide system in hemodialysis patients. Am J Kidney Dis 1999; 34: 228-234.
31. Fayed HM, Kame MA, Sultan MM, Mowafy MN, Helmy SM, El-Zoghby MH. Nitric oxide generation by peripheral blood cells in chronic renal failure. Br J Biomed Sci 2002; 59: 24-29.
32. Sarkar SR, Kaitwatcharachai C, Levin NW. Nitric oxide and hemodialysis. Semin Dial 2004; 17: 224-228.
33. Shamszad P, Slesnick TC, Smith EO, Taylor MD, Feig DI. Association between left ventricular mass index and cardiac function in pediatric dialysis patients. Pediatr Nephrol 2012; 27: 835-841.
34. Kasner M, Westermann D, Steendijk P, Gaub R, Wilkenshoff U, Weitmann K, Hoffmann W, Poller W, Schultheiss HP, Pauschinger M et al. Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: a comparative Doppler-conductance catheterization study. Circulation 2007; 116: 637-647.
35. Rivas-Gotz C, Manolios M, Thohan V, Nagueh SF. Impact of left ventricular ejection fraction on estimation of left ventricular filling pressures using tissue Doppler and flow propagation velocity. Am J Cardiol 2003; 91: 780-784.
36. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 2000; 102: 1788-1794.
37. Kim MK, Kim B, Lee JY, Kim JS, Han BG, Choi SO, Yang JW. Tissue Doppler-derived E/e ratio as a parameter for assessing diastolic heart failure and as a predictor of mortality in patients with chronic kidney disease. Korean J Intern Med 2013; 28: 35- 44.
38. Matteucci MC, Wühl E, Picca S, Mastrostefano A, Rinelli G, Romano C, Rizzoni G, Mehls O, de Simone G, Schaefer F; ESCAPE Trial Group. Left ventricular geometry in children with mild to moderate chronic renal insufficiency. J Am Soc Nephrol 2006; 17: 218-226.
39. Mitsnefes MM, Barletta GM, Dresner IG, Chand DH, Geary D, Lin JJ, Patel H. Severe cardiac hypertrophy and long-term dialysis: the Midwest Pediatric Nephrology Consortium study. Pediatr Nephrol 2006; 21; 1167-1170.
40. Tomiyama Y, BrianJr JE, Todd MM. Plasma viscosity and cerebral blood flow. Am J Physiol Heart Circ Physiol 2000; 279: H1949-1954.
41. Macko RF, Ameriso SF, Akmal M, Paganini-Hill A, Mohler JG, Massry SG, Meiselman HJ, Fisher M. Arterial oxygen content and age are determinants of middle cerebral artery blood flow velocity. Stroke 1993; 24: 1025-1028.
42. Schuurman PR, Albrecht KW. Intraoperative changes of transcranial Doppler velocity: relation to arterial oxygen content and whole-blood viscosity. Ultrasound Med Biol 1999; 25: 151-154.
43. Stefanidis I, Bach R, Mertens PR, Liakopoulos V, Liapi G, Mann H, Heintz B. Influence of hemodialysis on the mean blood flow velocity in the middle cerebral artery. Clin Nephrol 2005; 64: 129-137.