Saudi Journal of Kidney Diseases and Transplantation

: 2014  |  Volume : 25  |  Issue : 5  |  Page : 1038--1041

Proteinuria in patients with sickle cell disease

Ahmed M Alkhunaizi1, Adil A Al-Khatti2,  
1 Internal Medicine Services Unit, Nephrology Section, Dhahran Health Center, Dhahran, Saudi Arabia
2 Oncology Unit, Dhahran Health Center, Dhahran, Saudi Arabia

Correspondence Address:
Dr. Ahmed M Alkhunaizi
Nephrology Section, Dhahran Health Center, Saudi Aramco, P. O. Box 10955 Dhahran 31311
Saudi Arabia


Proteinuria is a complication of sickle cell nephropathy that can progress to renal insufficiency and end-stage renal disease. The magnitude of proteinuria among patients with sickle cell disease (SCD) has been reported with variable prevalence. The aim of this study was to determine the prevalence of proteinuria in a large number of patients with SCD in Eastern Saudi Arabia. The urinalyses of 940 non-diabetic patients with SCD were tested for the presence of proteinuria. The glomerular filtration rate (e-GFR) of all patients was estimated using the Cockcroft- Gault equation. Proteinuria was found in 79 of 940 patients with SCD (prevalence 8.4%). The mean age of the affected patients with proteinuria was 33 ± 15.4 years (10-76). The mean GFR was 118 mL/min/1.73 m 2 . This study indicates that patients with SCD in Eastern Saudi Arabia have a low prevalence of proteinuria and preserved GFR.

How to cite this article:
Alkhunaizi AM, Al-Khatti AA. Proteinuria in patients with sickle cell disease.Saudi J Kidney Dis Transpl 2014;25:1038-1041

How to cite this URL:
Alkhunaizi AM, Al-Khatti AA. Proteinuria in patients with sickle cell disease. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2022 Jan 19 ];25:1038-1041
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Full Text


Sickle cell disease (SCD) is associated with a wide spectrum of structural and functional renal abnormalities such as hematuria, proteinuria, papillary necrosis, urinary concentration defect, renal tubular acidosis, renal insufficiency and end-stage renal disease (ESRD). [1],[2],[3],[4],[5] Proteinuria can be an early manifestation of sickle cell nephropathy (SCN) that can progress to nephrotic syndrome, renal insufficiency and ESRD. SCN has been reported with variable prevalence in the different geographical locations. [5],[6],[7],[8],[9],[10],[11],[12] There is a large population of patients with SCD in the Kingdom of Saudi Arabia (KSA); however, the data on proteinuria among these patients are scarce.

The aim of this study was to determine the extent of proteinuria among the patients with SCD in the Eastern region of KSA. Early recognition of proteinuria should prompt initia­tion of therapy to prevent the long-term sequelae of SCN.


The computer database of the Saudi Aramco Medical Services Organization (SAMSO) was used to extract patients' information. Patients who were registered at SAMSO as of March 2012 and had sickle cell screening and hemoglobin electrophoresis in addition to urinalysis performed were identified. Patients with the genotype HbSS, HbSC, HbSD and S-beta zero thalassemia were considered as having SCD. Urinalysis was performed using urine strips from Siemens Healthcare Diagnostics. All strips were read instrumentally using the Clinitek fa­mily of urine chemistry analyzers from Siemens. Positive proteinuria was documented if the test was positive at ≥30 mg/dL. Established protei-nuria was considered if the dipstick was posi­tive on at least two tests at two different time points. Patients with diabetes mellitus were ex­cluded. Glomerular filtration rate (eGFR) was estimated using the Cockcroft-Gault equation.

 Statistical Analysis

The software Microsoft Excel 2010 was used for the statistical analysis. Data were expressed as mean values ± standard deviation. T-test was used to compare the mean values. P-values <0.05 were considered statistically significant.


A total of 940 patients fulfilled the inclusion criteria for SCD. The mean age was 26.7 ± 15.5 years (1.5-85). A positive test for proteinuria was identified in 419 urinary samples from 183 patients. Seventy-nine patients had positive urinalysis for proteinuria in at least two samples and were included in the final analysis. The mean age of the patients with and without pro-teinuria was 33 ± 15.4 and 26 ± 15.8 years, respectively, with no statistically significant difference [Table 1]. All patients with protei-nuria were above the age of 10 years. The over­all prevalence of proteinuria was 8.4%. The eGFR of patients with proteinuria was 118 mL/min/1.73 m 2 , significantly lower than that of the non-proteinuric patients as shown in [Table 1]. Only five patients had ESRD, reflec­ting an overall prevalence of 0.5%.{Table 1}


SCD is found mainly in the Eastern and South Western regions of the KSA. [13],[14] Patients in the Eastern region have less-severe disease, owing to the presence of the Asian beta globin haplo-type, as compared with those in the South Western region, who have the Benin haplo-type. [15] SCN is a severe complication of SCD that has a wide range of manifestations, exten­ding from asymptomatic microalbuminuria to ESRD. Microalbuminuria was thought to be a result of hyperfiltration. [16] When overt protei-nuria is established, glomerular pathology such as focal and segmental glomerulosclerosis is expected. The gold standard to detect micro-albuminuria is to measure albumin in a 24-h urinary collection. This method is cumbersome and impractical to perform for screening pur­poses. A more practical way to determine the presence of microalbuminuria is by performing an albumin to creatinine ratio in spot urine sam­ples. This was not performed in the great majo­rity of patients with SCD at our institution, and therefore, we could not use it to determine the prevalence of albuminuria. Instead, we used urinalysis to detect proteinuria as it was per­formed on the great majority of SAMSO patient population. However, urinalysis is not sensitive enough to detect microalbuminuria, and, if the test is positive, it usually reflects macroalbumi-nuria or overt proteinuria. The possibility of other renal pathologies such as glomerulo-nephritis as a cause of proteinuria could not be ruled out in our study. To minimize the likeli­hood of proteinuria being a result of acute ill­ness such as pain crisis, we only included urinalyses with repetitive presence of proteinuria. Accordingly, the prevalence of proteinuria in our cohort was determined to be 8.4%. The patients with proteinuria in our cohort were somewhat older than those with no proteinuria; however, this age difference did not reach statistical significance.

The eGFRs of the proteinuric patients in our study were lower than those of the patients who did not have proteinuria. However, the eGFRs of both groups were higher than the average eGFR of the healthy population estimated at 100-120 mL/min/1.73 m 2 . This observation goes along with the theory that patients with SCD have supernormal GFR due to hyperfiltration, and this is one of the proposed mechanisms that leads to renal injury in patients with SCD. [16] The difference in GFR between the proteinuric and non-proteinuric subjects indicates that although hyperfiltration may be the underlying mecha­nism for proteinuria, the GFR will drop once proteinuria is established. This may be due to structural glomerular damage related to long­standing hyperfiltration such as glomerular scle­rosis, interstitial fibrosis and papillary necrosis.

The prevalence of ESRD in our patients was only 0.5%, indicating that progression of SCN in this area is very slow. This observation was not a surprise to us as we have previously reported that SCD was not a common cause of renal failure in our area, despite the high prevalence of the disease. [17],[18]

In an earlier report of 73 Saudi patients with SCD, proteinuria was found in 41% of the patients. [12] The number of patients in that report was too small to draw a meaningful conclusion about the true prevalence of proteinuria among SCD patients in KSA. In addition, patients from different areas with different gentotypes may have been included in that study. Reports from Africa, Jamaica and the United States docu­mented a much higher prevalence of proteinuria among SCD patients, most likely due to the difference between the African gene mutation and the less-severe Asian variant, which is present in Eastern Saudi Arabia. [1],[3],[5],[6],[7],[8],[11],[16],[19],[20],[21] In a small report of 59 patients from Kuwait, proteinuria was identified in 13.6%. The prevalence of proteinuria in that report was close to ours, most likely due to close demographics and shared genotype of SCD patients in Kuwait and Eastern Saudi Arabia. [9]

Our study had several limitations associated with a retrospective study. The sample studied, despite the large size, may not be representative of the local SCD patients as a whole. The rea­sons to perform urinalysis were unknown. In addition, it may underestimate the magnitude of microalbuminuria. Requiring at least two urinalyses for inclusion in the proteinuric group may have excluded some patients who had persistent proteinuria but were not tested again. All these factors introduce bias, whose effect on the study findings is unknown. The study also had several strengths, including the large number of patients studied and the certainty of proteinuria using our methodology.

We recommend that all patients with SCD undergo annual testing for microalbuminuria, similar to diabetic patients. Patients with posi­tive tests should have the level of proteinuria quantified, and should be treated with antipro-teinuric agents, such as blockers of the renin angiotensin system. The ultimate goal is to eli­minate the disease by decreasing births of SCD patients, using methods such as routine pre­marital screening and counseling.


The authors acknowledge the use of Saudi Aramco Medical Services Organization (SAMSO) facilities for research data used in this article. Opinions expressed in this article are those of the authors and not necessarily of SAMSO.


1Guasch A, Navarrete J, Nass K, Zayas CF. Glomerular involvement in adults with sickle cell hemoglobinopathies: Prevalence and clin­ical correlates of progressive renal failure. J Am Soc Nephrol 2006;17:2228-35.
2Ataga KI, Orringer EP. Renal abnormalities in sickle cell disease. Am J Hematol 2000;63:205-11.
3Pham PT, Pham PC, Wilkinson AH, Lew SQ. Renal abnormalities in sickle cell disease. Kidney Int 2000;57:1-8.
4Scheinman JI. Sickle cell disease and the kidney. Nat Clin Pract Nephrol 2009;5:78-88.
5Stallworth JR, Tripathi A, Jerrell JM. Preva­lence, treatment, and outcomes of renal condi­tions in pediatric sickle cell disease. South Med J 2011;104:752-6.
6King L, MooSang M, Miller M, Reid M. Preva­lence and predictors of microalbuminuria in Jamaican children with sickle cell disease. Arch Dis Child 2011;96:1135-9.
7Bolarinwa RA, Akinlade KS, Kuti MA, Olawale OO, Akinola NO. Renal disease in adult Nigerians with sickle cell anemia: A report of prevalence, clinical features and risk factors. Saudi J Kidney Dis Transpl 2012;23:171-5.
8McPherson Yee M, Jabbar SF, Osunkwo I, et al. Chronic kidney disease and albuminuria in children with sickle cell disease. Clin J Am Soc Nephrol 2011;6:2628-33.
9Marouf R, Mojiminiyi O, Abdella N, Kortom M, Al Wazzan H. Comparison of renal function markers in Kuwaiti patients with sickle cell disease. J Clin Pathol 2006;59:345-51.
10Derebail VK, Nachman PH, Key NS, Ansede H, Falk RJ, Kshirsagar AV. High prevalence of sickle cell trait in African Americans with ESRD. J Am Soc Nephrol 2010;21:413-7.
11Osei-Yeboah CT, Rodrigues O. Renal status of children with sickle cell disease in Accra, Ghana. Ghana Med J 2011;45:155-60.
12Aleem A. Renal abnormalities in patients with sickle cell disease: A single center report from Saudi Arabia. Saudi J Kidney Dis Transpl 2008;19:194-9.
13Al-Qurashi MM, El-Mouzan MI, Al-Herbish AS, Al-Salloum AA, Al-Omar AA. The prevalence of sickle cell disease in Saudi children and adolescents. A community-based survey. Saudi Med J 2008;29:1480-3.
14Lehmann H, Maranjian G, Mourant AE. Distribution of sickle-cell hemoglobin in Saudi Arabia. Nature 1963;198:492-3.
15Padmos MA, Roberts GT, Sackey K, et al. Two different forms of homozygous sickle cell disease occur in Saudi Arabia. Br J Haematol 1991;79:93-8.
16Aygun B, Mortier NA, Smeltzer MP, Hankins JS, Ware RE. Glomerular hyperfiltration and albuminuria in children with sickle cell anemia. Pediatr Nephrol 2011;26:1285-90.
17Alkhunaizi AM. Pattern of renal pathology among renal biopsy specimens in Eastern Saudi Arabia. Saudi Med J 2007;28:1676-81.
18Alkhunaizi AM, Yousif BM, Amir AA, Brand S. End stage renal disease experience in a general hospital in Eastern Saudi Arabia. Saudi Med J 2003;24:798-800.
19Dharnidharka VR, Dabbagh S, Atiyeh B, Simpson P, Sarnaik S. Prevalence of microalbuminuria in children with sickle cell disease. Pediatr Nephrol 1998;12:475-8.
20Becton LJ, Kalpatthi RV, Rackoff E, et al. Prevalence and clinical correlates of micro-albuminuria in children with sickle cell disease. Pediatr Nephrol 2010;25:1505-11.
21Allon M. Renal abnormalities in sickle cell disease. Arch Intern Med 1990;150:501-4.