Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 2328 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 

Table of Contents   
ORIGINAL ARTICLE  
Year : 2015  |  Volume : 26  |  Issue : 3  |  Page : 497-506
Serum cystatin C, urinary neutrophil gelatinase-associated lipocalin and N-acetyl-beta-D-glucosaminidase in juvenile and adult patients with systemic lupus erythematosus: Correlation with clinical manifestations, disease activity and damage


1 Rheumatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
2 Department of Pediatrics, National Research Center, Cairo, Egypt
3 Department of Internal Medicine, National Research Center, Cairo, Egypt
4 Department of Clinical and Chemical Medicine, National Research Center, Cairo, Egypt

Click here for correspondence address and email

Date of Web Publication20-May-2015
 

   Abstract 

Lupus nephritis (LN) is a potentially devastating outcome of systemic lupus erythematosus (SLE). It is important to identify reliable, non-invasive methods to assess the kidneys in patients with SLE. The aim of the study was to measure the level of novel markers of renal involvement in these patients and assess their correlation with disease activity and damage. Sixtyone patients with SLE (33 adults and 28 juvenile) were included in the study. Fifty-two ageand sex-matched healthy individuals served as controls. Full history taking, thorough clinical examination and laboratory investigations were performed and disease activity and damage were assessed for all patients. Renal bio-markers including serum cystatin C, urinary neutrophil gelatinase-associated lipocalin (UNGAL) and N-acetyl-beta-D-glucosaminidase (UNAG) were assessed in patients and controls. There was a significant increase in serum cystatin C, UNGAL and UNAG levels in the adult SLE patients compared with controls (P = 0.000, P = 0.013 and P = 0.018, respectively); serum cystatin C and UNGAL levels were higher in the juvenile patients compared with controls (P = 0.038 and P = 0.000, respectively). Serum cystatin C significantly correlated with the damage index, renal biopsy class and negatively with the serum albumin; UNGAL correlated with albuminuria and the level of nephritis and UNAG negatively correlated with serum albumin level. Our study suggests that serum cystatin C, UNGAL and UNAG are important markers of LN and both cystatin C and UNAG would help in predicting the renal biopsy class.

How to cite this article:
Gheita TA, Abd El Baky AM, Assal HS, Farid TM, Rasheed IA, Thabet EH. Serum cystatin C, urinary neutrophil gelatinase-associated lipocalin and N-acetyl-beta-D-glucosaminidase in juvenile and adult patients with systemic lupus erythematosus: Correlation with clinical manifestations, disease activity and damage. Saudi J Kidney Dis Transpl 2015;26:497-506

How to cite this URL:
Gheita TA, Abd El Baky AM, Assal HS, Farid TM, Rasheed IA, Thabet EH. Serum cystatin C, urinary neutrophil gelatinase-associated lipocalin and N-acetyl-beta-D-glucosaminidase in juvenile and adult patients with systemic lupus erythematosus: Correlation with clinical manifestations, disease activity and damage. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2021 Jan 20];26:497-506. Available from: https://www.sjkdt.org/text.asp?2015/26/3/497/157336

   Introduction Top


Systemic lupus erythematosus (SLE) is a multisystem autoimmune rheumatic disease. Lupus nephritis (LN) is known to be the most serious complication of SLE and the strongest predictor of poor outcome. LN poses a real challenge in the management of SLE patients because of difficulty in diagnosing at onset and identifying relapses before serious renal damage has occurred. [1],[2] It is a major cause of morbidity and mortality in SLE and, because the course of LN is often unpredictable, it is important to identify reliable, non-invasive methods to repeatedly assess the condition of the kidneys in these patients. [3] LN is very common in childhood-onset SLE, [4] and it has been reported that more than 60% of children with SLE develop LN [5] that begins early in the disease course. LN carries a poor outcome, with end-stage renal disease occurring in about 10% of patients within 10 years. [4]

Accurate measurement of glomerular filtration rate (GFR) is complicated and costly and is therefore estimated by assessing serum creatinine or cystatin C levels. [6] Cystatin C, which is a cationic low-molecular weight protein seems to be a promising marker of GFR in both adults and children. [7] Novel kidney markers such as serum cystatin C and urinary neutrophil gelatinase-associated lipocalin (UNGAL) serve as more accurate markers for acute kidney injury compared with the more traditional markers, creatinine and blood urea nitrogen (BUN), and showed a better diagnostic capability for detecting glomerular injury. [8],[9] Although low-grade albuminuria has traditionally been considered to be an indicator of early renal pathology, there is an emerging view that albuminuria is also a marker of generalized vascular pathology such as endothelial dysfunction. [10]

Serum cystatin C concentration is a novel measure of kidney function that seems to have overcome many of the limitations of using creatinine-based estimates and GFR. This is because the relationship between kidney function and cystatin C concentration does not appear to vary with age, sex, race and body mass and is therefore considered to be a more reliable indicator in both adults and children. [10],[11],[12],[13],[14] Thus, measurement of cystatin C rather than creatinine appears more practical for monitoring GFR in the pediatric population. [15],[16]

Currently available renal biomarkers are relatively insensitive and non-specific for diagnosing LN. [17] Neutrophil gelatinase-associated lipocalin (NGAL) is a protein secreted by leukocytes during inflammation and is overexpressed in the kidneys following ischemic or nephrotoxic damage. [5] It has been demonstrated to be a novel biomarker in acute and chronic kidney disease in SLE [18] and has been implicated in the pathogenesis of several disease states in different organ systems, especially in kidney diseases. The UNGAL levels have been shown to increase in both acute and chronic kidney damage and found to be elevated in the urine of patients with active LN. [18],[19] Clinically, UNGAL significantly correlates with LN disease activity and may be an important and convenient marker for relapses. [2]

It has been suggested that urinary N-acetyl-beta-D-glucosaminidase (UNAG) activity may be a useful supplement to the routine biochemical analysis performed on urine in cases with SLE and can be used as an early indicator of damage to the tubular epithelium [1] as an increase in activity of UNAG has also been shown in SLE patients without clinical or laboratory signs of LN. [20]

The aim of the present study was to measure the level of these three novel markers of renal involvement in SLE patients and assess their correlation with the clinical manifestations, disease activity and damage.


   Patients and Methods Top


Sixty-one patients with SLE (33 adults and 28 juvenile) fulfilled the updated revised criteria for the classification of SLE [21] and were consecutively recruited from the rheumatology outpatient clinics of Cairo University Hospitals and National Research Center. Fifty-two age-and sex-matched healthy volunteers served as controls (30 adults and 22 children). The study was approved by the local university ethics committee and performed in accordance with the ethical standards of the 1964 Helsinki declaration. All patients gave their informed consent prior to inclusion in the study.

Full history taking and thorough clinical examination were performed on all the patients and their current drug therapy was also recorded. The laboratory investigations performed included complete blood count (CBC), erythrocyte sedimentation rate (ESR), serum creatinine (Se Cr), blood urea nitrogen (BUN), transaminases, serum albumin, serum uric acid (SUA), cholesterol, triglycerides, complement (C3 and C4), anti-cardiolipin (IgG and IgM), anti-nuclear antibody (ANA), anti-double-stranded DNA (anti-ds-DNA) and anti-Ro and anti-La antibodies. Assessment of albuminuria, urinary creatinine and 24-h urinary protein was performed on the patients. Renal biopsy classification was considered for adults and 16 of the juvenile cases according to the World Health Organization (WHO) criteria. [22] Disease activity and damage were assessed using the SLE disease activity index (SLEDAI) [23] and the Systemic Lupus International Collaborating Clinics/Damage Index (SLICC/ACR DI), [24] respectively.

Renal bio-markers including serum cystatin C, UNGAL and UNAG were assessed for all the patients and control subjects. The GFR was calculated according to the Schwartz formula in juvenile SLE patients [25] and on the MDRD4 equation, which uses age, sex, ethnicity and serum creatinine in adult SLE patients as follows. [26]

GFR = 186 (Cr 1.154 × age 0.203) × (1.212 if black) × (0.742 if female)

Blood samples were centrifuged and the plasma was stored at -80°C. Serum cystatin C was measured using the immune-nephelometric method (BN ProSpec-II, Siemens Healthcare Diagnostics). Fresh random urine samples were obtained and tested for NAG [enzyme-linked immunosorbent assay (ELISA) colorimetric, Diazyme Laboratories, La Jolla, CA, USA], NGAL (using a comercially available ELISA kit; Bioporto Diagnostics, Gentofte, Denmark) and creatinine levels (Jaffe reaction, auto-analyzer, RA 1000).


   Statistical Analysis Top


Statistical Package for Social Science (SPSS) program version 15 was used for the analysis of data. Data were presented as mean ± SD. The Mann-Whitney test was used for analysis of two quantitative data, Spearman's correlation was used for detection of the correlation between two variables and multiple regression analysis was performed for dependent variables to detect the risk among many independent variables. P-value <0.05 was considered significant.


   Results Top


The study included 28 juvenile and 33 adult SLE patients (13 had juvenile onset of the disease). There was no significant difference in the studied parameters according to the type of onset in the adult cases. [Table 1] shows a comparison of the clinical features and laboratory investigations, including renal function tests and markers, between patients with SLE and controls.
Table 1: Comparison of the clinical features and laboratory investigations including renal function tests and markers between patients with systemic lupus erythematosus and controls.

Click here to view


On comparing the juvenile SLE cases with the corresponding age-matched controls, there were significantly higher levels of cystatin C and UNGAL in the patients with SLE (P = 0.000 and P = 0.001, respectively), but the difference in UNAG was not significant (P = 0.13) [Figure 1]. The ESR, platelet count and 24-h urinary protein levels were significantly higher in SLE patients while the Hb was significantly lower (P = 0.000). The systolic blood pressure was higher (P = 0.005), as also the BUN and cholesterol levels (P = 0.002 and 0.007, respectively).
Figure 1: Box plot of the studied parameters: (A) serum cystatin C, (B) urine neutrophil gelatinaseassociated lipocalin and (C) urine N-acetyl-beta-D-glucosaminidase in juvenile and adult patients with systemic lupus erythematosus and controls.

Click here to view


Comparing the adult patients with control subjects revealed significantly higher cystatin C, UNGAL and UNAG levels (P = 0.001, P = 0.019 and P = 0.027, respectively). Also, the diastolic blood pressure was significantly higher (P = 0.002). Furthermore, the ESR, 24-h urine protein and SUA were significantly higher (P = 0.000, P = 0.000 and P = 0.009, respectively) and the Hb was significantly lower (P = 0.000).

The demographic and clinical manifestations of the studied SLE patients are shown in [Table 2] and laboratory characteristics are shown in [Table 3].
Table 2: Demographic features and clinical manifestations of the study patients.

Click here to view
Table 3: Laboratory characteristics of the studied patients.

Click here to view


All the patients were on oral prednisolone. The adult patients were receiving a mean dose of 25.15 ± 11.91 mg/day and the juvenile patients were receiving a mean dose of 18.13 ± 9.25 mg/day. Twenty-seven adult SLE patients (81.82%) and 19 juvenile cases (67.86%) were receiving other drugs in addition.

Renal biopsy was performed on all adult patients and in 16/28 juvenile cases. Renal biopsy class I was present in four adult and four juvenile SLE patients, class II in seven adult and four juvenile, class III in seven adult and four juvenile, class IV in nine adults and one juvenile and class V in six adult and two juvenile patients.

There was a significant increase in the serum cystatin C and UNGAL levels (1.88 ± 1.72 mg/L and 53.2 6± 110.39 ng/mL, respectively) in patients with renal involvement (42 patients; 68.85%) compared with those without (19 patients) (1.24 ± 0.52 mg/L and 11.25 ± 9.66 ng/mL, respectively; P = 0.035 and P = 0.019), while the UNAG levels showed a tendency to be higher (13.07 ± 21.42 U/L versus 6.51 ± 2.49 U/L; P = 0.057). Patients with renal involvement also had a significantly higher SLEDAI (4.38 ± 1.17) and SLICC/DI (1.09 ± 1.12) compared with those without (3.74 ± 1.05 and 0.42 ± 1.17; P = 0.04 and P = 0.01, respectively). Patients with mucocutaneous manifestations had higher serum cystatin C levels (1.79 ± 1.64 mg/L) compared with those without (1.27 ± 0.28 mg/L; P = 0.047). There was no significant difference in the level of the studied parameters between those with and without other clinical manifestations.

There was a significant correlation between the studied renal markers and some clinical manifestations and laboratory investigations of the SLE patients: GFR correlated with the cholesterol level (r = 0.28, P = 0.04), cystatin C significantly correlated with the SLICC damage index, triglycerides and renal biopsy class (r = 0.38, P = 0.003; r = 0.27, P = 0.03; r = 0.54, P = 0.00, respectively). There was a negative correlation with serum albumin and alkaline phosphatase (r = -0.26, P = 0.045 and r = -0.33, P = 0.01). The UNGAL levels significantly correlated with the presence of nephritis and albuminuria (r = 0.3, P = 0.02 and r = 0.32, P = 0.014, respectively) and SUA levels (r = 0.39 and P = 0.003). However, there was a negative correlation with serum albumin levels (r = -0.35, P = 0.007). The dose of steroids and cyclophosphamide used by the patients significantly correlated only with the cystatin C level (r = 0.26, P = 0.04 and r = 0.33, P = 0.01). There was a significant negative correlation between the GFR and both the cystatin C (r = -0.64, P = 0.00) and UNAG levels (r = 0.3, P = 0.02). Furthermore, the cystatin C level correlated with the UNAG level (r = 0.33, P = 0.012) and both the UNAG and UNAGL significantly correlated with one another (r = 0.28, P = 0.03). In this study, only cystatin C levels correlated significantly with the duration of the disease (r = 0.45, P <0.001).

On considering a regression analysis having the renal biopsy class as the dependent factor, both cystatin and UNAG significantly predicted the severity of renal involvement (P = 0.03 and P = 0.02, respectively) among other independent factors including GFR and UNGAL.


   Discussion Top


Renal involvement in SLE is associated with poor prognosis. [17] In the present study, renal involvement was present in 68.85% of the patients, being much higher in adults. Serum creatinine, BUN and albuminuria could not properly reflect the magnitude of renal involvement. The levels of serum cystain C, UNGAL and UNAG were significantly higher in the adult SLE patients compared with the control subjects, while only the cystatin C and UNGAL levels were remarkably higher in children with SLE compared with the controls.

Serum cystatin C levels can identify reduced GFR more accurately than sCr-eGFRs [27] and is thus considered a reliable endogenous marker for the assessment of renal function and impairment. [28],[29] Serum cystatin C levels were higher in patients with SLE than in control subjects even after adjustment for conventional measures of renal function. [30]

Because creatinine is an unreliable marker of kidney function, the search for a new and more sensitive marker of kidney function is under-way. UNGAL has been recently shown to be useful in the quantitation of chronic kidney disease. Serum NGAL could be a sensitive marker of kidney function, particularly in elderly patients. [31]

It has been found that patients with LN had elevated UNAG. [32] In another study, UNAG excretion was significantly higher in the SLE group than in the healthy controls, especially in those with nephritic-range proteinuria. [1]

In the present study, the serum cystatin C and UNGAL levels were significantly higher in juvenile SLE patients compared with the controls, while the creatinine level was comparable. In accordance, it has been found that there is diagnostic superiority of serum cystatin-C levels versus creatinine levels in children. [33] Measurement of serum cystatin C is a feasible, non-invasive and sensitive diagnostic tool to detect renal dysfunction at an early stage, particularly in children. [34] Children with SLE had higher levels of UNGAL than their controls, and the levels were higher in patients with LN. [5] It has been suggested that serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhoodonset SLE disease activity. [4]

In the present study, there was a significant increase in the serum cystatin C and UNGAL levels in patients with renal involvement, while there was a mild tendency to increase in the UNAG level. In a recent study, SLE patients had significantly higher serum cystatin C compared with the controls, and the level was higher in those with a history of LN. [35] UNGAL is a sensitive and specific forecaster of renal disease activity in all SLE patients as determined by SLEDAI and a significant predictor for flare-up in patients with a history of biopsy-proven nephritis, which outperformed anti-dsDNA antibody titers. [36] UNGAL excretion in the SLE-renal group was higher than that in the SLE-non-renal, non-SLE auto-immune diseases and normal control groups. [18] In patients with LN, an increase of activity of UNAG was observed. [20] It has been reported by others that in SLE, serum cystatin C may be influenced by low-grade inflammation as well as by renal dysfunction, [35] and considered by others as a marker of inflammation as well as renal function. [37]

In the present study, only serum cystatin C significantly correlated with the disease duration. Urinary biomarkers such as UNGAL and serum cystatin C may improve the ability to detect early acute kidney injury (AKI) and determine the clinical prognosis of AKI at the time of diagnosis. [38]

Among the studied parameters, only UNGAL significantly correlated with the presence of nephritis, while cystain C significantly correlated with the increased severity class on renal biopsy of the studied patients. Accordingly, it has been reported that in juvenile-onset SLE patients, UNGAL levels correlated strongly to moderately with renal disease activity and damage, but not with extra-renal activity or damage. [17] UNGAL excretion may be a predictor of renal damage in SLE patients. [18] UNGAL correlated with the renal score of the SLEDAI and was significantly predictive of class III and IV LN. It is considered a sensitive marker of proliferative nephritis in juvenile SLE. [5] In contrast, a new study has mentioned that NGAL failed to show any association with LN. [19]

It is thus suggested that both markers are important in giving a better overview on the real sum of renal involvement. There seems to be a correlation between the concentrations of each marker (cystatin C and UNGAL) and the level of deterioration of kidneys. In the present study, cystatin C and UNAG negatively correlated with the serum albumin level but showed a non-significant relation with albuminuria, while only the UNGAL correlated with the level of albuminuria. In disagreement, it has been reported that cystatin C [39] and UNAG [1] show a positive relationship with severity of microalbuminuria.

In the present study, only cystatin C correlated with the steroid dose (P = 0.04). Serum cystatin C concentration remains unaffected by a standardized high-dose corticosteroid therapy in children with corticosteroid-sensitive nephrotic syndrome, supporting its potential as an endogenous marker of GFR. In patients with impaired renal function receiving corticosteroids, cystatin C may be increased out of proportion to GFR impairment. [7] In agreement, it has been found that glucocorticoid medication in adult renal transplant patients is associated with increased cystatin C in a dosedependent manner, leading to systematic underestimation of GFR. This does not preclude the use of cystatin C in detecting impaired renal function in renal transplant patients receiving glucocorticoids as it is significantly more accurate. [40] Glucocorticoids have low impact on the diagnostic accuracy of cystatin C. [41]

In conclusion, serum cystatin C, UNGAL and UNAG are important markers of LN and both cystatin C and UNAG would help in predicting the renal biopsy class. In childhood SLE, serum cystatin C and UNGAL were remarkably increased compared with the controls. Although serum cystatin C was the only marker to best correlate with the SLE disease damage index, it is recommended that all three markers should be taken into consideration when evaluating renal involvement in patients with SLE.

Conflict of interest: None declared.

 
   References Top

1.
Erdener D, Aksu K, Biçer I, Doğanavşargil E, Kutay FZ. Urinary N-acetyl-beta-D-glucosaminidase (NAG) in lupus nephritis and rheumatoid arthritis. J Clin Lab Anal 2005;19:172-6.  Back to cited text no. 1
    
2.
Rubinstein T, Pitashny M, Putterman C. The novel role of neutrophil gelatinase-B associated lipocalin (NGAL)/Lipocalin-2 as a biomarker for lupus nephritis. Autoimmun Rev 2008;7:229-34.  Back to cited text no. 2
    
3.
Schwartz N, Michaelson JS, Putterman C. Lipocalin-2, TWEAK, and other cytokines as urinary biomarkers for lupus nephritis. Ann N Y Acad Sci 2007;1109:265-74.  Back to cited text no. 3
    
4.
Hinze CH, Suzuki M, Klein-Gitelman M, et al. Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity. Arthritis Rheum 2009;60: 2772-81.  Back to cited text no. 4
    
5.
Hammad A, Mosaad Y, Elhanbly S, et al. Urinary neutrophil gelatinase-associated lipocalin as a marker of severe lupus nephritis in children. Lupus 2013;22:486-91.  Back to cited text no. 5
    
6.
Eriksen BO, Mathisen UD, Melsom T, et al. Cystatin C is not a better estimator of GFR than plasma creatinine in the general population. Kidney Int 2010;78:1305-11.  Back to cited text no. 6
    
7.
Bökenkamp A, van Wijk JA, Lentze MJ, Stoffel-Wagner B. Effect of Corticosteroid Therapy on Serum Cystatin C and ß2-Microglobulin Concentrations. Clin Chem 2002;48: 1123-6.  Back to cited text no. 7
    
8.
Dieterle F, Perentes E, Cordier A, et al. Urinary clusterin, cystatin C, beta 2-microglobulin and total protein as markers to detect drug-induced kidney injury. Nat Biotechnol 2010;28:463-9.  Back to cited text no. 8
    
9.
Ho E, Fard A, Maisel A. Evolving use of biomarkers for kidney injury in acute care settings. Curr Opin Crit Care 2010;16:399-407.  Back to cited text no. 9
    
10.
Arnlöv J. Diminished renal function and the incidence of heart failure. Curr Cardiol Rev 2009;5:223-7.  Back to cited text no. 10
    
11.
Sambasivan AS, Lepage N, Filler G. Cystatin C Intrapatient Variability in Children with Chronic Kidney Disease Is Less than Serum Creatinine. Clin Chem 2005;51:2215-6.  Back to cited text no. 11
    
12.
Sharma AP, Kathiravelu A, Nadarajah R, Yasin A, Filler G. Body mass does not have a clinically relevant affect on cystatin C eGFR in children. Nephrol Dial Transplant 2009;24: 470-4.  Back to cited text no. 12
    
13.
Hoke M, Amighi J, Mlekusch W, et al. Cystatin C and the risk for cardiovascular events in patients with asymptomatic carotid atherosclerosis. Stroke 2010;41:674-9.  Back to cited text no. 13
    
14.
Weinert LS, Prates AB, do Amaral FB, Vaccaro MZ, Camargo JL, Silveiro SP. Gender does not influence cystatin C concentrations in healthy volunteers. Clin Chem Lab Med 2010; 48:405-8.  Back to cited text no. 14
    
15.
Finney H, Newman DJ, Thakkar H, Fell JM, Price CP. Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children. Arch Dis Child 2000;82:71-5.  Back to cited text no. 15
    
16.
Hari P, Bagga A, Mahajan P, Lakshmy R. Effect of malnutrition on serum creatinine and cystatin C levels. Pediatr Nephrol 2007;22: 1757-61.  Back to cited text no. 16
    
17.
Brunner HI, Mueller M, Rutherford C, et al. Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhoodonset systemic lupus erythematosus. Arthritis Rheum 2006;54:2577-84.  Back to cited text no. 17
    
18.
Yang CC, Hsieh SC, Li KJ, et al. Urinary neutrophil gelatinase-associated lipocalin is a potential biomarker for renal damage in patients with systemic lupus erythematosus. J Biomed Biotechnol 2012;2012:759313.  Back to cited text no. 18
    
19.
Kiani AN, Wu T, Fang H, et al. Urinary vascular cell adhesion molecule, but not neutrophil gelatinase-associated lipocalin, is associated with lupus nephritis. J Rheumatol 2012; 39:1231-7.  Back to cited text no. 19
    
20.
Delektorskaya L, Janushkevich T, Okunev D. The significance of the assays of urinary enzymes activity in patients with systemic lupus erythematosus. Z Med Lab Diagn 1990; 31:375-9.  Back to cited text no. 20
    
21.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725.  Back to cited text no. 21
    
22.
Churg J, Sobin DH. Renal disease: Classification and atlas of glomerular diseases. IgakuShoin, Tokyo, 1982;127-49.  Back to cited text no. 22
    
23.
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992;35:630-40.  Back to cited text no. 23
    
24.
Gladman D, Ginzler E, Goldsmith C, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 1996;39:363-9.  Back to cited text no. 24
    
25.
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; 34:571-90.  Back to cited text no. 25
    
26.
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2 suppl 1):S1-266.  Back to cited text no. 26
    
27.
Sato H, Kuroda T, Tanabe N, et al. Cystatin C is a sensitive marker for detecting a reduced glomerular filtration rate when assessing chronic kidney disease in patients with rheumatoid arthritis and secondary amyloidosis. Scand J Rheumatol 2010;39:33-7.  Back to cited text no. 27
    
28.
Choe JY, Park SH, Kim SK. Serum cystatin C is a potential endogenous marker for the estimation of renal function in male gout patients with renal impairment. J Korean Med Sci 2010;25:42-8.  Back to cited text no. 28
    
29.
Coll E, Botey A, Alvarez L, et al. Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment. Am J Kidney Dis 2000;36:29-34.  Back to cited text no. 29
    
30.
Lertnawapan R, Bian A, Rho YH, et al. Cystatin C is associated with inflammation but not atherosclerosis in systemic lupus erythematosus. Lupus 2012;21:279-87.  Back to cited text no. 30
    
31.
Przybylowski P, Malyszko J, Malyszko J. Kidney function assessed by eGFR, cystatin C and NGAL (neutrophil gelatinase-associated lipocalin) in relation to age in heart allograft recipients. Med Sci Monit 2010;16:CR440-4.  Back to cited text no. 31
    
32.
Marks SD, Shah V, Pilkington C, Woo P, Dillon MJ. Renal tubular dysfunction in children with systemic lupus erythematosus. Pediatr Nephrol 2005;20:141-8.  Back to cited text no. 32
    
33.
Zaffanello M, Franchini M, Fanos V. Is serum Cystatin-C a suitable marker of renal function in children? Ann Clin Lab Sci 2007;37:233-40.  Back to cited text no. 33
    
34.
Brinkert F, Kemper MJ, Briem-Richter A, van Husen M, Treszl A, Ganschow R. High prevalence of renal dysfunction in children after liver transplantation: Non-invasive diagnosis using a cystatin C-based equation. Nephrol Dial Transplant 2011;26:1407-12.  Back to cited text no. 34
    
35.
Chew C, Pemberton PW, Husain AA, Haque S, Bruce IN. Serum cystatin C is independently associated with renal impairment and high sensitivity C-reactive protein in systemic lupus erythematosus. Clin Exp Rheumatol 2013;31: 251-5.  Back to cited text no. 35
    
36.
Rubinstein T, Pitashny M, Levine B, et al. Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis. Rheumatology (Oxford) 2010;49:960-71.  Back to cited text no. 36
    
37.
Okura T, Jotoku M, Irita J, et al. Association between cystatin C and inflammation in patients with essential hypertension. Clin Exp Nephrol 2010;14:584-8.  Back to cited text no. 37
    
38.
Koyner JL, Vaidya VS, Bennett MR, et al. Urinary Biomarkers in the Clinical Prognosis and Early Detection of Acute Kidney Injury. Clin J Am Soc Nephrol 2010;5:2154-65.  Back to cited text no. 38
    
39.
Mena C, Robles NR, de Prado JM, Gallego FG, Cidoncha A. Cystatin C and blood pressure: Results of 24 h ambulatory blood pressure monitoring. Eur J Intern Med 2010;21: 185-90.  Back to cited text no. 39
    
40.
Risch L, Herklotz R, Blumberg A, Huber AR. Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin Chem 2001;47:2055-9.  Back to cited text no. 40
    
41.
Abbink FC, Laarman CA, Braam KI, et al. Beta-trace protein is not superior to cystatin C for the estimation of GFR in patients receiving corticosteroids. Clin Biochem 2008;41:299-305.  Back to cited text no. 41
    

Top
Correspondence Address:
Dr. Abeer M. Nour El Din Abd El Baky
Department of Pediatrics, National Research Center, Cairo
Egypt
Login to access the Email id


DOI: 10.4103/1319-2442.157336

PMID: 26022020

Rights and Permissions


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
   
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
   Introduction
   Patients and Methods
   Statistical Analysis
   Results
   Discussion
    References
    Article Figures
    Article Tables
 

 Article Access Statistics
    Viewed2413    
    Printed24    
    Emailed0    
    PDF Downloaded401    
    Comments [Add]    

Recommend this journal