Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Pediatric Nephrology
Published in: Pediatric Nephrology 10/2014

01-10-2014 | Original Article

Albuminuria correlates with hemolysis and NAG and KIM-1 in patients with sickle cell anemia

Authors: Dima Hamideh, Vimal Raj, Thomas Harrington, Hua Li, Emilio Margolles, Folasade Amole, Monica Garcia-Buitrago, Phillip Ruiz, Gaston Zilleruelo, Ofelia Alvarez

Published in: Pediatric Nephrology | Issue 10/2014

Login to get access

Abstract

Background

Although hyperfiltration and albuminuria are common pathological conditions, kidney injury (KI) biomarkers have been seldom studied in individuals with sickle cell anemia (SCA).

Methods

We undertook a cross-sectional assessment of urine KI biomarkers in children and adults with SCA with and without albuminuria and a normal estimated glomerular filtration rate (eGFR). Albumin, KI molecule 1 (KIM-1), N-acetyl-ß-D-glucosaminidase (NAG), endothelin-1 and transforming growth factor-β1 (TGF-β1) were measured. Assays were normalized by urine creatinine. Urine intracellular hemosiderin and serum lactate dehydrogenase (LDH) were assessed as markers of hemolysis. Albuminuria was associated to the biomarkers by Pearson and Spearman correlation coefficients. Differences between the albuminuria (yes, no) groups were assessed by the t test.

Results

Nineteen patients with albuminuria (mean urine albumin/creatinine 527.14 ± 1070 mg/g, range 38.3-–190 mg/g) and 19 patients without albuminuria (mean urine albumin/creatinine 15.93 ± 5.17 mg/g, range 7.9–28.4 mg/g) were studied. The age range for the whole group was 11–48 years, and 47 % were males. Patients with albuminuria were older, had lower hematocrit, were more likely to test positive for urine hemosiderin and had a higher KIM-1 (P = 0.0035) and NAG/ creatinine ratios (P = 0.0062). Urine hemosiderin strongly correlated to a higher LDH level (P < 0.001).

Conclusions

Despite a normal or increased eGFR, KI biomarkers were detected in the urine of individuals with SCA. NAG, KIM-1 and urine hemosiderin correlated with the presence of albuminuria.
Literature
1.
2.
Kaul DK, Hebbel RP (2000) Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice. J Clin Invest 106:411–420PubMedPubMedCentralCrossRef
3.
Osarogiagbon UR, Choong S, Belcher JD, Vercellotti GM, Paller MS, Hebbel RP (2000) Reperfusion injury pathophysiology in sickle transgenic mice. Blood 96:314–320PubMed
4.
5.
6.
Powars DR, Elliot-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 115:614–620PubMedCrossRef
7.
Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP (1994) Mortality in sickle cell disease. N Engl J Med 330:1639–1644PubMedCrossRef
8.
Becker AM (2011) Sickle cell nephropathy: Challenging the conventional wisdom. Pediatr Nephrol 26:2099–2109PubMedCrossRef
9.
Sharpe CC, Thein SL (2011) Sickle cell nephropathy – a practical approach. Br J Haematol 155:287–297PubMedCrossRef
10.
Alvarez O, Zilleruelo G, Wright D, Montane B, Lopez-Mitnik G (2006) Serum cystatin C levels in children with sickle cell disease. Pediatr Nephrol 21:533–537PubMedCrossRef
11.
Alvarez O, Montane B, Lopez G, Wilkinson J, Miller T (2006) Early blood transfusions protect against microalbuminuria in children with sickle cell disease. Pediatr Blood Cancer 47:71–76PubMedCrossRef
12.
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 17:2228–2235PubMedCrossRef
13.
Koyner JL, Vaidya VS, Bennett MR, Ma Q, Worcester E, Akhter SA, Raman J, Jeevanandam V, O'Connor MF, Devarajan P, Bonventre JV, Murray PT (2010) Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury. Clin J Am Soc Nephrol 5:2154–2165PubMedPubMedCentralCrossRef
14.
Vaidya VS, Ozer JS, Dieterle F, Collings FB, Ramirez V, Troth S, Muniappa N, Thudium D, Gerhold D, Holder DJ, Bobadilla NA, Marrer E, Perentes E, Codier A, Vonderscher J, Maurer G, Goering PL, Sistare FD, Bonventre JV (2010) Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol 28:478–485PubMedPubMedCentralCrossRef
15.
16.
Hoffmann D, Adler M, Vaidya VS, Rached E, Mulrane L, Gallagher WM, Callanan JJ, Gautier JC, Matheis K, Staedtler F, Dieterle F, Brandenburg A, Sposny A, Hewitt P, Ellinger-Ziegelbauer H, Bonventre JV, Dekant W, Mally A (2010) Performance of novel kidney biomarkers in preclinical toxicity studies. Toxicol Sci 116:8–22PubMedPubMedCentralCrossRef
17.
18.
Devarajan P (2010) Review: Neutrophil gelatinase-associated lipocalin: A troponin-like biomarker for human acute kidney injury. Nephrology 15:419–428PubMedCrossRef
19.
Sundaram N, Bennett M, Wilhelm J, Kim MO, Atweh G, Devarajan P, Malik P (2011) Biomarkers for early detection of sickle nephropathy. Am J Hematol 86:559–566PubMedCrossRef
20.
Voskaridou E, Terpos E, Michail S, Hantzi E, Anagnostopoulos A, Margeli A, Simirloglou D, Loukopoulos D, Papassotiriou I (2006) Early markers of renal dysfunction in patients with sickle cell/beta-thalassemia. Kidney Int 69:2037–2042PubMedCrossRef
21.
Mohtat D, Thomas R, Du Z, Boakye Y, Moulton T, Driscoll C, Woroniecki R (2011) Urinary transforming growth factor beta-1 as a marker of renal dysfunction in sickle cell disease. Pediatr Nephrol 26:275–280PubMedCrossRef
22.
Nauta FL, Boertien WE, Bakker SJ, van Goor H, van Oeveren W, de Jong PE, Bilo H, Gansevoort RT (2011) Glomerular and tubular damage markers are elevated in patients with diabetes. Diabetes Care 34:975–981PubMedPubMedCentralCrossRef
23.
24.
Tharaux PL, Hagège I, Placier S, Vayssairat M, Kanfer A, Girot R, Dussaule JC (2005) Urinary endothelin-1 as a marker of renal damage in sickle cell disease. Nephrol Dial Transplant 20:2408–2413PubMedCrossRef
25.
Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637PubMedPubMedCentralCrossRef
26.
Schwartz GJ, Work DF (2009) Measurement and estimation of GFR in children and adolescents. J Am Soc Nephrol 4:1832–1843CrossRef
27.
Chronic Kidney Disease Epidemiology Collaboration, Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F (2006) Using standardized serum creatinine values in the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate. Ann Intern Med 145:247–254PubMedCrossRef
28.
Filler G, Foster J, Acker A, Lepage N, Akbari A, Ehrich JH (2005) The Cockcroft-Gault formula should not be used in children. Kidney Int 67:2321–2324PubMedCrossRef
29.
30.
Palmer LS, Maizels M, Kaplan WE, Firlit CF, Cheng EY (1997) Urine levels of transforming growth factor-beta 1 in children with uretero-pelvic junction obstruction. Urology 50:769–773PubMedCrossRef
31.
Henry JB (2001) Clinical diagnosis and management by laboratory methods, 20th edn. W.B. Saunders, Philadelphia
32.
Zamboni P, Izzo M, Fogato L, Carandina S, Lanzara V (2003) Urine hemosiderin: a novel marker to assess the severity of chronic venous disease. J Vasc Surg 37:132–136PubMedCrossRef
33.
Ashley-Koch AE, Okocha EC, Garrett ME, Soldano K, De Castro LM, Jonassaint JC, Orringer EP, Eckman JR, Telen MJ (2011) MYH9 and APOL1 are both associated with sickle cell disease nephropathy. Br J Haematol 155:386–394PubMedCrossRef
34.
Sklar AH, Campbell H, Caruana RJ, Lightfoot BO, Gaier JG, Milner P (1990) A population study of renal function in sickle cell anemia. Int J Artif Organs 13:231–236PubMed
35.
Montgomery R, Zibari G, Hill G, Ratner LE (1994) Renal transplantation in patients with sickle cell nephropathy. Transplantation 58:618–620PubMedCrossRef
36.
37.
Dharnidharka VR, Kwon C, Stevens G (2002) Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 40:221–226PubMedCrossRef
38.
Roos JF, Doust J, Tett SE, Kirkpatrick CM (2007) Diagnostic accuracy of cystatin C compared to serum creatinine for the estimation of renal dysfunction in adults and children: a meta-analysis. Clin Biochem 40:383–391PubMedCrossRef
39.
Stevens LA, Coresh J, Schmid CH, Feldman HI, Froissart M, Kusek J, Rossert J, Van Lente F, Bruce RD 3rd, Zhang YL, Greene T, Levey AS (2008) Estimated GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3418 individuals with CKD. Am J Kidney Dis 51:395–406PubMedPubMedCentralCrossRef
40.
Alvarez O, Lopez-Mitnik G, Zilleruelo G (2008) Short-term follow-up of patients with sickle cell disease and albuminuria. Pediatr Blood Cancer 50:1236–1239PubMedCrossRef
41.
Abbate M, Benigni A, Bertani T, Remuzzi G (1999) Nephrotoxicity of increased glomerular protein traffic. Nephrol Dial Transplant 14:304–312PubMedCrossRef
42.
Honkanen E, Teppo AM, Tornroth T, Groop PH, Grönhagen-Riska C (1997) Urinary transforming growth factor-βl in membranous glomerulonephritis. Nephrol Dial Transplant 12:2562–2568PubMedCrossRef
43.
44.
Simonson MS, Ismail-Beigi F (2011) Endothelin-1 increases collagen accumulation in renal mesangial cells by stimulating a chemokine and cytokine autocrine signaling loop. J Biol Chem 286:11003–11008PubMedPubMedCentralCrossRef
45.
Kato GJ, Gladwin MT, Steinberg MH (2007) Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev 21:37–47PubMedPubMedCentralCrossRef
46.
Becton LJ, Kalpatthi RV, Rackoff E, Disco D, Orak JK, Jackson SM, Shatat IF (2010) Prevalence and clinical correlates of microalbuminuria in children with sickle cell disease. Pediatr Nephrol 25:1505–1511PubMedCrossRef
47.
Gurkan S, Scarponi KJ, Hotchkiss H, Savage B, Drachtman R (2010) Lactate dehydrogenase as a predictor of kidney involvement in patients with sickle cell anemia. Pediatr Nephrol 25:2123–2127PubMedCrossRef
48.
Schein A, Enriquez C, Coates TD, Wood JC (2008) Magnetic resonance detection of kidney iron deposition in sickle cell disease: a marker of chronic hemolysis. J Magn Reson Imaging 28:698–704PubMedPubMedCentralCrossRef
Metadata
Title
Albuminuria correlates with hemolysis and NAG and KIM-1 in patients with sickle cell anemia
Authors
Dima Hamideh
Vimal Raj
Thomas Harrington
Hua Li
Emilio Margolles
Folasade Amole
Monica Garcia-Buitrago
Phillip Ruiz
Gaston Zilleruelo
Ofelia Alvarez
Publication date
01-10-2014
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 10/2014
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-014-2821-8

Other articles of this Issue 10/2014

Pediatric Nephrology 10/2014 Go to the issue

Rapid Communication

Haemodialysing babies weighing <8 kg with the Newcastle infant dialysis and ultrafiltration system (Nidus): comparison with peritoneal and conventional haemodialysis

Clinical Quiz

An infant with recurrent convulsive seizures of 3 weeks’ duration: Answers

Original Article

An audit analysis of a guideline for the investigation and initial therapy of diarrhea negative (atypical) hemolytic uremic syndrome

Educational Review

Clinical manifestations of autosomal recessive polycystic kidney disease (ARPKD): kidney-related and non-kidney-related phenotypes

Original Article

The duration of hepatitis B vaccine immunity in pediatric dialysis patients

Brief Report

Fludrocortisone as a new tool for managing tubulopathy after pediatric renal transplantation: a series of cases