Top

Pediatric Nephrology

Published in:

01-09-2017 | Original Article

Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia

Authors: Jeffrey D. Lebensburger, Gary R. Cutter, Thomas H. Howard, Paul Muntner, Daniel I. Feig

Published in: Pediatric Nephrology | Issue 9/2017

Abstract

Background

Patients with sickle cell anemia (SCA) have an increased prevalence of nephropathy and mortality from chronic kidney disease (CKD).

Methods

We evaluated the association of hyperuricemia and nocturnal hypertension with lower estimated glomerular filtration rate (eGFR) using cystatin-C in patients aged 10–21 years with the HbSS or HbSB0 form of the disease during a non-acute clinic visit. eGFR and uric acid measurements were obtained in 83 and 81 participants, respectively, and 24-h ambulatory blood pressure monitoring (ABPM) was performed in 44 participants. Annual testing included vital signs, complete blood count, comprehensive metabolic panel, medications, urine microalbumin/creatinine, and lactate dehydrogenase measurements. Hyperuricemia was defined as a uric acid level of ≥5.5 mg/dL. Nocturnal hypertension was defined as >25% of nocturnal readings at >95th percentile according to norms established by the American Heart Association Statement on ABPM in children and adolescents.

Results

The mean eGFR was statistically significantly lower in patients with hyperuricemia than in those with normal uric acid levels (143 vs. 161 mL/min/1.73 m², respectively). Of the 44 participants for whom ABPM data were available, 14 (32%) had systolic nocturnal hypertension and 12 (27%) had diastolic nocturnal hypertension. The mean eGFR was statistically significantly lower in participants with nocturnal systolic and diastolic hypertension than in those with normal nocturnal blood pressure. In a regression model, nocturnal hypertension and hyperuricemia were associated with a lower eGFR.

Conclusions

Two risk factors for CKD, i.e., nocturnal hypertension and hyperuricemia, were associated with lower eGFR in older children and adolescent patients with SCA. Long-term studies on their association with progression to CKD in this population are warranted.

Key point

Nocturnal hypertension and hyperuricemia are established risk factors for nephropathy in other diseases and may play a role in SCA nephropathy.

Available only for authorised users

McClellan AC, Luthi JC, Lynch JR, Soucie JM, Kulkarni R, Guasch A, Huff ED, Gilbertson D, McClellan WM, DeBaun MR (2012) High one year mortality in adults with sickle cell disease and end-stage renal disease. Br J Haematol 159:360–367CrossRefPubMedPubMedCentral

Nielsen L, Canoui-Poitrine F, Jais JP, Dahmane D, Bartolucci P, Bentaarit B, Gellen-Dautremer J, Remy P, Kofman T, Matignon M, Suberbielle C, Jacquelinet C, Wagner-Ballon O, Sahali D, Lang P, Damy T, Galacteros F, Grimbert P, Habibi A, Audard V (2016) Morbidity and mortality of sickle cell disease patients starting intermittent haemodialysis: a comparative cohort study with non- sickle dialysis patients. Br J Haematol 174:148–152CrossRefPubMed

Powars DR, Elliott-Mills DD, Chan L, Niland J, Hiti AL, Opas LM, Johnson C (1991) Chronic renal failure in sickle cell disease: risk factors, clinical course, and mortality. Ann Intern Med 115:614–620CrossRefPubMed

Alvarez O, Miller ST, Wang WC, Luo Z, McCarville MB, Schwartz GJ, Thompson B, Howard T, Iyer RV, Rana SR, Rogers ZR, Sarnaik SA, Thornburg CD, Ware RE, BABY HUG Investigators (2012) Effect of hydroxyurea treatment on renal function parameters: results from the multi-center placebo-controlled BABY HUG clinical trial for infants with sickle cell anemia. Pediatr Blood Cancer 59:668–674CrossRefPubMedPubMedCentral

Aygun B, Mortier NA, Smeltzer MP, Hankins JS, Ware RE (2011) Glomerular hyperfiltration and albuminuria in children with sickle cell anemia. Pediatr Nephrol 26:1285–1290CrossRefPubMedPubMedCentral

Lebensburger JD, Miller ST, Howard TH, Casella JF, Brown RC, Lu M, Iyer RV, Sarnaik S, Rogers ZR, Wang WC, BABY HUG Investigators (2012) Influence of severity of anemia on clinical findings in infants with sickle cell anemia: analyses from the BABY HUG study. Pediatr Blood Cancer 59:675–678CrossRefPubMed

Bodas P, Huang A, O’Riordan MA, Sedor JR, Dell KM (2013) The prevalence of hypertension and abnormal kidney function in children with sickle cell disease—a cross sectional review. BMC Nephrol 14:237CrossRefPubMedPubMedCentral

McPherson Yee M, Jabbar SF, Osunkwo I, Clement L, Lane PA, Eckman JR, Guasch A (2011) Chronic kidney disease and albuminuria in children with sickle cell disease. Clin J Am Soc Nephrol 6:2628–2633CrossRefPubMedPubMedCentral

Hamideh D, Alvarez O (2013) Sickle cell disease related mortality in the United States (1999-2009). Pediatr Blood Cancer 60:1482–1486CrossRefPubMed

10.

Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP (1994) Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med 330:1639–1644CrossRefPubMed

11.

Powars DR, Chan LS, Hiti A, Ramicone E, Johnson C (2005) Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore) 84:363–376CrossRef

12.

Ojo AO, Govaerts TC, Schmouder RL, Leichtman AB, Leavey SF, Wolfe RA, Held PJ, Port FK, Agodoa LY (1999) Renal transplantation in end-stage sickle cell nephropathy. Transplantation 67:291–295CrossRefPubMed

13.

Gosmanova EO, Zaidi S, Wan JY, Adams-Graves PE (2014) Prevalence and progression of chronic kidney disease in adult patients with sickle cell disease. J Investig Med 62:804–807CrossRefPubMed

14.

Saraf SL, Zhang X, Kanias T, Lash JP, Molokie RE, Oza B, Lai C, Rowe JH, Gowhari M, Hassan J, Desimone J, Machado RF, Gladwin MT, Little JA, Gordeuk VR (2014) Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia. Br J Haematol 164:729–739CrossRefPubMed

15.

Mitsnefes M, Ho PL, McEnery PT (2003) Hypertension and progression of chronic renal insufficiency in children: a report of the north American pediatric renal transplant cooperative study (NAPRTCS). J Am Soc Nephrol 14:2618–2622CrossRefPubMed

16.

Mitsnefes MM, Kimball TR, Daniels SR (2003) Office and ambulatory blood pressure elevation in children with chronic renal failure. Pediatr Nephrol 18:145–149PubMed

17.

Rodenbach KE, Schneider MF, Furth SL, Moxey-Mims MM, Mitsnefes MM, Weaver DJ, Warady BA, Schwartz GJ (2015) Hyperuricemia and progression of CKD in children and adolescents: the chronic kidney disease in children (CKiD) cohort study. Am J Kidney Dis 66:984–992CrossRefPubMedPubMedCentral

18.

Feig DI, Kang DH, Johnson RJ (2008) Uric acid and cardiovascular risk. N Engl J Med 359:1811–1821CrossRefPubMedPubMedCentral

19.

Feig DI (2014) Serum uric acid and the risk of hypertension and chronic kidney disease. Curr Opin Rheumatol 26:176–185CrossRefPubMed

20.

Flynn JT, Daniels SR, Hayman LL, Maahs DM, McCrindle BW, Mitsnefes M, Zachariah JP, Urbina EM, American Heart Association Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young (2014) Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American Heart Association. Hypertension 63:1116–1135CrossRefPubMedPubMedCentral

21.

Becker AM, Goldberg JH, Henson M, Ahn C, Tong L, Baum M, Buchanan GR (2014) Blood pressure abnormalities in children with sickle cell anemia. Pediatr Blood Cancer 61:518–522CrossRefPubMed

22.

Shatat IF, Jakson SM, Blue AE, Johnson MA, Orak JK, Kalpatthi R (2013) Masked hypertension is prevalent in children with sickle cell disease: a Midwest pediatric nephrology consortium study. Pediatr Nephrol 28:115–120CrossRefPubMed

23.

Aloni MN, Ngiyulu RM, Gini-Ehungu JL, Nsibu CN, Ekila MB, Lepira FB, Nseka NM (2014) Renal function in children suffering from sickle cell disease: challenge of early detection in highly resource-scarce settings. PLoS One 9:e96561CrossRefPubMedPubMedCentral

24.

Minniti CP, Taylor JG, Hildesheim M, O’Neal P, Wilson J, Castro O, Gordeuk VR, Kato GJ (2011) Laboratory and echocardiography markers in sickle cell patients with leg ulcers. Am J Hematol 86:705–708CrossRefPubMedPubMedCentral

25.

Joshi K, Anjum F, Gowda S, Damania D, Graham-Hill S, Gillette P, Zein J, Jamaleddine G, Demetis S, Wadgaonkar R (2011) Uric acid as a potential biomarker of pulmonary arterial hypertension in patients with sickle cell disease. Indian J Hematol Blood Transfus 27:96–100CrossRefPubMedPubMedCentral

26.

King L, MooSang M, Miller M, Reid M (2011) Prevalence and predictors of microalbuminuria in Jamaican children with sickle cell disease. Arch Dis Child 96:1135–1139CrossRefPubMed

27.

Aban I, Baddam S, Hilliard LM, Howard TH, Feig D, Lebensburger JD (2017) Severe anemia early in life as a risk factor for sickle cell kidney disease. Blood 129:385–387CrossRefPubMed

28.

Lebensburger J, Johnson SM, Askenazi DJ, Rozario NL, Howard TH, Hilliard LM (2011) Protective role of hemoglobin and fetal hemoglobin in early kidney disease for children with sickle cell anemia. Am J Hematol 86:430–432CrossRefPubMed

29.

Pegelow CH, Colangelo L, Steinberg M, Wright EC, Smith J, Phillips G, Vichinsky E (1997) Natural history of blood pressure in sickle cell disease: risks for stroke and death associated with relative hypertension in sickle cell anemia. Am J Med 102:171–177CrossRefPubMed

30.

Feig DI, Johnson RJ (2003) Hyperuricemia in childhood primary hypertension. Hypertension 42:247–252CrossRefPubMedPubMedCentral

31.

Gordeuk VR, Sachdev V, Taylor JG, Gladwin MT, Kato G, Castro OL (2008) Relative systemic hypertension in patients with sickle cell disease is associated with risk of pulmonary hypertension and renal insufficiency. Am J Hematol 83:15–18CrossRefPubMedPubMedCentral

32.

DeBaun MR, Sarnaik SA, Rodeghier MJ, Minniti CP, Howard TH, Iyer RV, Inusa B, Telfer PT, Kirby-Allen M, Quinn CT, Bernaudin F, Airewele G, Woods GM, Panepinto JA, Fuh B, Kwiatkowski JK, King AA, Rhodes MM, Thompson AA, Heiny ME, Redding-Lallinger RC, Kirkham FJ, Sabio H, Gonzalez CE, Saccente SL, Kalinyak KA, Strouse JJ, Fixler JM, Gordon MO, Miller JP, Noetzel MJ, Ichord RN, Casella JF (2012) Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure. Blood 119:3684–3690CrossRefPubMedPubMedCentral

33.

Ohene-Frempong K, Weiner SJ, Sleeper LA, Miller ST, Embury S, Moohr JW, Wethers DL, Pegelow CH, Gill FM (1998) Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 91:288–294PubMed

34.

Lebensburger JD, Hilliard LM, McGrath TM, Fineberg NS, Howard TH (2011) Laboratory and clinical correlates for magnetic resonance imaging (MRI) abnormalities in pediatric sickle cell anemia. J Child Neurol 26:1260–1264CrossRefPubMed

35.

Dionne JM, Turik MM, Hurley RM (2008) Blood pressure abnormalities in children with chronic kidney disease. Blood Press Monit 13:205–209CrossRefPubMed

36.

Westerstahl M, Hedvall Kallerman P, Hagman E, Ek AE, Rossner SM, Marcus C (2014) Nocturnal blood pressure non-dipping is prevalent in severely obese, prepubertal and early pubertal children. Acta Paediatr 103:225–230CrossRefPubMed

37.

Lee SH, Kim JH, Kang MJ, Lee YA, Won Yang S, Shin CH (2011) Implications of nocturnal hypertension in children and adolescents with type 1 diabetes. Diabetes Care 34:2180–2185CrossRefPubMedPubMedCentral

38.

Atabek ME, Akyurek N, Eklioglu BS, Alp H (2014) Impaired systolic blood dipping and nocturnal hypertension: an independent predictor of carotid intima-media thickness in type 1 diabetic patients. J Diabetes Complicat 28:51–55CrossRefPubMed

39.

Goicoechea M, Garcia de Vinuesa S, Verdalles U, Verde E, Macias N, Santos A, Perez de Jose A, Cedeno S, Linares T, Luno J (2015) Allopurinol and progression of CKD and cardiovascular events: long-term follow-up of a randomized clinical trial. Am J Kidney Dis 65:543–549CrossRefPubMed

40.

Zhu P, Liu Y, Han L, Xu G, Ran JM (2014) Serum uric acid is associated with incident chronic kidney disease in middle-aged populations: a meta-analysis of 15 cohort studies. PLoS One 9:e100801CrossRefPubMedPubMedCentral

41.

Feig DI, Soletsky B, Johnson RJ (2008) Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA 300:924–932CrossRefPubMedPubMedCentral

42.

Hulbert ML, McKinstry RC, Lacey JL, Moran CJ, Panepinto JA, Thompson AA, Sarnaik SA, Woods GM, Casella JF, Inusa B, Howard J, Kirkham FJ, Anie KA, Mullin JE, Ichord R, Noetzel M, Yan Y, Rodeghier M, Debaun MR (2011) Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with sickle cell disease. Blood 117:772–779CrossRefPubMedPubMedCentral

43.

Griessenauer CJ, Lebensburger JD, Chua MH, Fisher WS 3rd, Hilliard L, Bemrich-Stolz CJ, Howard TH, Johnston JM (2015) Encephaloduroarteriosynangiosis and encephalomyoarteriosynangiosis for treatment of moyamoya syndrome in pediatric patients with sickle cell disease. J Neurosurg Pediatr 16:64–73CrossRefPubMed

44.

de la Sierra A, Gorostidi M, Banegas JR, Segura J, de la Cruz JJ, Ruilope LM (2014) Nocturnal hypertension or nondipping: which is better associated with the cardiovascular risk profile? Am J Hypertens 27:680–687CrossRefPubMed

45.

Guasch A, Navarrete J, Nass K, Zayas CF (2006) Glomerular involvement in adults with sickle cell hemoglobinopathies: prevalence and clinical correlates of progressive renal failure. J Am Soc Nephrol 17:2228–2235CrossRefPubMed

46.

Odden MC, Amadu AR, Smit E, Lo L, Peralta CA (2014) Uric acid levels, kidney function, and cardiovascular mortality in US adults: National Health and nutrition examination survey (NHANES) 1988-1994 and 1999-2002. Am J Kidney Dis 64:550–557CrossRefPubMedPubMedCentral

47.

Acosta AA, McNiece KL (2008) Ambulatory blood pressure monitoring: a versatile tool for evaluating and managing hypertension in children. Pediatr Nephrol 23:1399–1408CrossRefPubMed

Title: Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia
Authors: Jeffrey D. Lebensburger
Gary R. Cutter
Thomas H. Howard
Paul Muntner
Daniel I. Feig
Publication date: 01-09-2017
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 9/2017
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-017-3658-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia

Abstract

Background

Methods

Results

Conclusions

Key point

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Key point

Please log in to get access to this content

Other articles of this Issue 9/2017

Uncommon cause of fever in a pediatric kidney transplant recipient: Answers

Race, obesity, and the renin-angiotensin-aldosterone system: treatment response in children with primary hypertension

Renal findings in patients with Mulibrey nanism

C3 glomerulonephritis with a severe crescentic phenotype

Abstracts of the 50th Anniversary ESPN Meeting, Glasgow, September 2017

How best to quantify and express the levels of substances in the urine?