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Saudi Journal of Kidney Diseases and Transplantation
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RENAL DATA FROM ASIA-AFRICA  
Year : 2012  |  Volume : 23  |  Issue : 1  |  Page : 171-175
Renal disease in adult Nigerians with sickle cell anemia: A report of prevalence, clinical features and risk factors


1 Department of Hematology and Blood Transfusion, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria
2 Department of Chemical Pathology, University College Hospital, Ibadan, Nigeria

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Date of Web Publication3-Jan-2012
 

   Abstract 

Renal abnormalities in adult Nigerians with sickle cell anemia (SCA) have not been extensively studied. To determine the prevalence, pattern and the associated risk factors of renal disease, 72 subjects with SCA from two centers in the southwestern Nigeria were investigated. Socio-demographic data, body mass index and clinical findings were documented. The urine analysis, serum bio-chemistry, hemogram and renal factors attributable to SCA were determined. Presence of albuminuria of at least 1+ or microalbuminuria in those negative with dipstick; and the estimated glomerular filtration rate (eGFR) using the Cockcroft-Gault formula categorized subjects to various stages of chronic kidney disease (CKD). Subjects with and without albuminuria were compared to determine the relative risk associated with renal disease. Four (5.6%) subjects had macro-albuminuria, while 32 (44.4%) had micro-albuminuria and 30 (41.7%) had hemoglobinuria. In the subjects with albuminuria, age, hematocrit, systolic blood pressure, serum creatinine, urea and creatinine clearance were numerically higher while the eGFR was numerically lower. There was no significant difference in the clinical parameters studied in the two groups of subjects. The diastolic blood pressure was significantly higher in the albuminuric group. Based on eGFR, 22 (30.6%) subjects had hyperfiltration (GFR > 140 mL/min/1.73 m2), of whom 36.4% had albuminuria, 18 (25.0%) had stage 1 CKD, 30 (41.7%) had stage 2 CKD and two (2.7%) subjects had stage 3 CKD with albuminuria. None had stage 4 and 5 CKD. We conclude that renal abnormalities, importantly albuminuria, is common in adult Nigerians with SCA and the pattern and incidence are similar to those reported from other parts of the world. Regular blood pressure monitoring, early diagnosis and active intervention are advocated to delay progression to end-stage kidney disease in view of poor outcomes of renal replacement therapy in SCA patients with nephropathy.

How to cite this article:
Bolarinwa R A, Akinlade K S, Kuti M, Olawale O O, Akinola N O. 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

How to cite this URL:
Bolarinwa R A, Akinlade K S, Kuti M, Olawale O O, Akinola N O. Renal disease in adult Nigerians with sickle cell anemia: A report of prevalence, clinical features and risk factors. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2019 Jul 22];23:171-5. Available from: http://www.sjkdt.org/text.asp?2012/23/1/171/91416

   Introduction Top


Sickle cell anemia (SCA) has a protean manifestation affecting various organ systems in the body. In those over 20 years of age, organ system failure is common and is a risk factor for early death. [1] As patients age, irreversible organ damage, commonly chronic lung disease, renal insufficiency, or stroke, occurs with increasing risks. [1],[2] The kidney in SCA individuals is affected by both the hemodynamic changes of chronic anemia and the consequences of recurrent vaso-occlusion leading to structural and functional changes and progression to chronic kidney disease (CKD). [3],[4] Sickle cell nephropathy encompasses a spectrum of morphologic, laboratory and clinical changes. It is well characterized by specific manifestations, risk factors, and prognosis ranging from polyuria to hematuria, proteinuria, renal failure syndromes and distinct glomerular or tubular lesions. [5],[6] It is associated with a markedly increased risk of mortality with little way of specific therapy to increase life expectancy. Proteinuria, hypertension, severe anemia, and hematuria were found to be reliable predictors, while the inheritance of the Central African Republic haplotype increased the risk. [1],[7] Previous studies showed proteinuria in 41%, while between 5 and 18% had renal failure in the total population of sickle cell disease (SCD) patients in Saudi Arabia and the United States of America. [8],[9],[10] Progression to endstage renal disease is common in SCA patients with proteinuria. [10],[11] The effective renal plasma flow (ERPF) and the glomerular filtration rate (GFR) are elevated in patients with SCA (though it declines as the patients age), leading to hyperfiltration. The alterations were thought to result from altered glomerular autoregulation and changes in the tone of both the afferent and efferent arterioles, mediated by prostaglandins. [12],[13] In effect, persistent renal hyperfiltration leads to the development of glomerulosclerosis and decline of renal function. [14]

In view of the increasing survival of our cohort of patients coupled with paucity of reports on renal abnormalities seen in them, we sought to evaluate the prevalence, clinical features and risk factors for renal disease in adult Nigerians with SCA.


   Patients and Methods Top


Subjects with SCA attending routine clinic at the hematology units of the Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, and the Ring Road State Hospital, Ibadan, in southwestern Nigeria were prospectively studied from February to July 2009. Included were the subjects aged 15 years and above with documented homozygous sickled gene (HbSS) and in steady clinical condition at least two weeks prior to recruitment. Subjects with acute clinical condition and/or established renal impairment were excluded. Institutional ethical approval was obtained and all the subjects gave informed consent. A total of 72 subjects were studied. A questionnaire was administered to obtain bio-data and some clinical profile of the subjects. All the 72 subjects had serum sample obtained for creatinine, blood urea nitrogen as well as urine dipstick examination. The creatinine clearance and the estimated glomerular filtration rate (eGFR) were obtained by Cockcroft-Gault formula. Urine sample was tested for the presence of blood, hemoglobin, protein and other abnormalities. Proteinuria was defined as at least 1+ protein following dipstick (Medi-Test Combi-9® , Macherey Nagel, GmbH and Co, Duren, Germany) examination. All the subjects had quantitative urinary determination of albumin (Fortress® diagnostic kit) for calculation of urine albumin/creatinine ratio according to the protocol previously described; values >30 μg/mg (range: 30-300 μg/mg) indicate micro-albuminuria. [15] Data were analyzed using inferential statistics; chi-square test was used to compare mean values between non-albuminuric and albuminuric groups and correlations were found using Pearson's correlation. P-value <0.05 was considered significant.


   Results Top


The study group consisted of 20 (27.8%) males and 52 (72.2%) females with a mean (±SD) age of 24.3 ± 9.9 years (range: 15-60 years). Thirty-six (50%) subjects had albuminuria (four had macroalbuminuria and 32 had microalbuminuria) and 30 (41.7%) had hemoglobinuria [Table 1]. The mean urinary albumin/creatinine ratio in patients with microalbuminuria was 97 ± 13.2 μg/mg (range: 31.5-300 μg/mg), while in those without microalbuminuria the mean value was 10.3 ± 6.8 μg/mg (2.3-26.8 μg/mg). All the patients had normal serum creatinine (mean ± SD = 76.9 ± 26.5 mmol/L) and urea (mean ± SD = 2.9 ± 0.9 mmol/L) values. Based on the Cockcroft-Gault formula previously described, 14 (19.4%) subjects had low serum creatinine clearance (<60 mL/min) and 22 (30.6%) had renal hyperfiltration (GFR > 140 mL/min/1.73 m 2 ). All the subjects with low serum creatinine clearance and renal hyperfiltration had normal serum creatinine levels. Stratifying subjects based on eGFR, 18 (25.0%) subjects had stage 1 CKD, 30 (41.7%) had stage 2 and 2 (2.7%) subjects had stage 3 disease. None of the studied subjects had stages 4 and 5 CKD.
Table 1: Urinary and renal abnormalities found in the study subjects with SCA.

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Percentage of subjects with albuminuria increases progressively with the increasing stage of CKD; all subjects in stage 3 of CKD had albuminuria [Table 2]. As shown in [Table 3], the hematological and clinical variables studied in the subjects include the hematocrit, total white cell count (WBC), platelet count and vaso-occlusion/transfusion requirement per year. All the studied variables except the hematocrit and transfusion requirement per year were numerically higher in the albuminuric group. The mean body mass index (BMI) was numerically lower in the albuminuric group, while the blood pressure (BP) was higher with the diastolic BP being significantly higher (P<0.05) when compared with the non-albuminuric group. Interestingly, the mean age of female subjects (mean: 27.6 ± 6.3 years; n=22) in the albuminuric group was found to be significantly higher (P < 0.05) than the mean age of male subjects (mean = 19.6 ± 4.7 years; n=10) in this study.
Table 2: The *stages of kidney disease according to the eGFR (mL/min/1.73 m2) of the study subjects.

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Table 3: The characteristics and laboratory data among non-albuminuric and albuminuric subjects.

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   Discussion Top


The prevalence of albuminuria, hemoglobinuria and renal hyperfiltration in SCA subjects in this series was 50%, 41.7% and 30.6%, respectively, suggesting that renal abnormalities are not uncommon in our patients. Proteinuria is not only a hallmark of renal disease, but also an early manifestation of sickle cell nephropathy, [5],[6] and it increases with the advancing age of the patient. The prevalence of proteinuria in this study was slightly higher than previous reports from other countries, [8],[16] This may be related to the difference in the haplotypes of the patients in these differing populations. The common haplotype found in Nigeria is the Benin haplotype [17] of intermediate disease severity, while the Asian haplotype consistent with mild disease is found among the Saudi Arabian patients. The inclusion of children and the heterogeneous phenotype of the study population in the previous works may also be responsible for the observed differences. As seen in this study, the percentage of subjects with hemoglobinuria was higher than that observed in the Saudi patients, [8] which probably suggests an increased rate of intravascular hemolysis probably attributable to malaria endemicity in the study community.

The eGFR is a vital measure of clinical function, which is used for staging and monitoring progression of CKD, as well as in drug dosing decisions. It is recognized as an independent risk factor for cardiac mortality. We assessed the eGFR of the subjects in this study and found a significant percentage with renal hyperfiltration. The prevalence of renal hyperfiltration in the present study is lower than that observed by Marouf et al [18] among Kuwaiti patients. This might be related to the fact that this study focused only on adult SCA patients. However, percentage of subjects with proteinuria showed increasing trend as the stages of CKD progressed [Table 2], similar to the observations by Marouf et al. [18] The diastolic blood pressure was found to be associated with albuminuria; the mean in non-albuminuric subjects was significantly higher (although within normal limit) than in the albuminuric subjects, consistent with the increased cardiovascular risk of proteinuria. The creatinine clearance was low in 19.4% of the subjects despite normal serum creatinine and urea found in all the study subjects as previously observed. [8],[19] This implies that using serum creatinine and urea as a marker of renal impairment is unreliable in SCA patients. Similarly, the clinical variables, including age, did not correlate with proteinuria probably because the subjects were relatively young in the present study. The vaso-occlusion and blood transfusion requirement per year as well as the hematocrit did not correlate with proteinuria. Although these are markers of disease severity, they do not seem to be contributory to the progression of renal disease in these subjects.

Our findings revealed that renal abnormalities, importantly albuminuria, are common in adult Nigerians with SCA, with a pattern and incidence similar to reports from other parts of the world. The diastolic blood pressure is associated with albuminuria, and a significant portion of our SCA patients had early stage CKDs. Therefore, regular blood pressure monitoring, early diagnosis and active intervention are advocated to delay progression to end-stage renal disease in view of poor outcomes of replacement therapy in SCA patients with nephropathy.[20]

 
   References Top

1.Platt OS, Brambilla DJ, Ross WF, et al. Sickle Cell disease: Life expectancy and risk factors for early death. N Engl J Med 1994;330(33): 1639-64.  Back to cited text no. 1
    
2.Powars DR, Chan LS, Hiti A, Ramicone E, Johnson C. Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine. (Baltimore) 2005;85:363-76.  Back to cited text no. 2
    
3.Serjeant GR, Serjeant BE. Sickle Cell Disease 3 rd ed. Oxford University Press 2001.  Back to cited text no. 3
    
4.Kadiri S. Chronic kidney disease: Sickle cell nephropathy as a likely cause. Annals of Ibadan Postgraduate Med 2006; 4 (7):Editorial .   Back to cited text no. 4
    
5.Phuong-Thu TP, Phuong-Chi TP, Alan HW, Susie QL. Renal abnormalities in sickle cell disease. Kidney Int 2000;57:1-8.  Back to cited text no. 5
    
6.Walker BR, Alexander F, Birdsall TR, Warren RL. Glomerular lesions in sickle cell nephropathy. JAMA 1971;215(3):437-40.  Back to cited text no. 6
    
7.Powars DR, Elliot-Mills DD, Chan L, Hisi AL, Opas LM, Johnson C. Chronic renal failure in sickle cell disease: Risk factors, clinical course and mortality. Ann Intern Med 1991;115:614-20.  Back to cited text no. 7
    
8.Aleem A. Renal abnormalities in patients with sickle cell disease: A single Centre report from Saudi Arabia. Saudi J kidney Dis Transpl 2008;19(2):194-9.  Back to cited text no. 8
    
9.Allon M. Renal abnormalities in sickle cell disease. Arch Intern Med 1990;150(3):501-4.  Back to cited text no. 9
    
10.Abbott KC, Hypolite IO, Ogodoa LY. Sickle cell nephropathy at end stage renal disease in the United States: Patient characteristics and survival. Clin Nephrol 2002;58(1):9-15.  Back to cited text no. 10
    
11.Falk RJ, Scheinman J, Phillips G, Orringer E, Johnson A, Jennette JC. Prevalence and pathologic features of sickle nephropathy and response to inhibition of angiotensin converting enzyme. N Engl J Med 1992;326(14):910-5.  Back to cited text no. 11
    
12.Hatch FE, Azar SH, Ainsworth TE, Nard JM, Culberton JW. Renal circulatory studies in young with sickle cell anaemia. J Lab Clin Med 1970; 76:632-40.  Back to cited text no. 12
    
13.De Jong PE, StatiusVan Eps LW. Sickle cell nephropathy: New insights into its pathophysiology. Kidney Int 1985;27:711-7.  Back to cited text no. 13
    
14.Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM. Hyperfiltration in remnant nephrons: A potentially adverse response to renal ablation. Am J Physiol 1981;241: F85-93.  Back to cited text no. 14
    
15.Sacks DB, Bruns E, Goldstein DE, Maclaren NK, Mcdonald JM, Parrott M. Guidelines and recommendation for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48(3):436-72.  Back to cited text no. 15
    
16.Ackoundou-N'Guessan CK, Tia MW, Lagou DA, Cissoko CM, Guei CM, Gnionsahe DA. Microalbuminuria represents a feature of advanced renal disease in patients with sickle cell haemoglobinopathy. Annals of Ibadan Postgrad Med. 2006; 4(2): 29-34.  Back to cited text no. 16
    
17.Adekile AD, Kitundu MN, Gu LH, Lanclos KD, Adeodu OO, Huisman TH. Haplotypes in SS patients from Nigeria: characterization of one atypical âs haplotype No 19 (Benin) associated with increase HbF. Ann Haematol 1992;65:41-5.  Back to cited text no. 17
    
18.Marouf R, Mojiminiyi O, Abdella N, Kortom M, Al Wazzan H. Comparison of renal functions markers in Kuwaiti patients with sickle cell disease. J Clin Pathol 2006;59(4):345-51.  Back to cited text no. 18
    
19.Ataga KI, Orringer EP. Renal abnormalities in sickle cell disease. Am J Haematol 2000;63:205-11.  Back to cited text no. 19
    
20.Skorecki K, Green J, Brenner BM. Chronic renal failure; In: Harrison's Principles of Internal Medicine 16 th ed. Kasper DL, Fauci AS, Longo DL, Braunwald E, Hauser SL, Jameson JL. McGraw-Hill Inc. 2005;1653-63.  Back to cited text no. 20
    

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Correspondence Address:
R A Bolarinwa
Department of Hematology and Blood Transfusion, Obafemi Awolowo University Teaching Hospital, Complex, Ile-Ife
Nigeria
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PMID: 22237246

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