|Year : 2017 | Volume
| Issue : 1 | Page : 21-25
Assessment of kidney function in sickle cell anemia patients in Zaria, Nigeria
Rasheed Yusuf1, Abdulaziz Hassan2, IN Ibrahim2, AA Babadoko2, PO Ibinaiye3
1 Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
2 Department of Haematology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
3 Department of Radiology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
|Date of Web Publication||11-Apr-2017|
Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, Zaria
Introduction: Sickle cell anemia (SCA) patients are prone to kidney injury by various mechanisms including reduced blood flow, ischemia, and papillary necrosis. Sickle cell nephropathy may progress to end-stage renal disease with increased morbidity and mortality. Objective: To assess renal function tests and their relationship with kidney length in steady state SCA patients. Subjects and Methods: Seventy-four adult SCA patients in steady state and 20 hemoglobin AA controls were enrolled into the study. Serum urea, electrolytes, creatinine, and uric acid were assayed while estimated glomerular filtration rate (eGFR) was calculated. Renal scan was also performed to assess the kidney length. Results: Serum potassium, phosphate, and uric acid were statistically significantly higher while sodium, chloride, bicarbonate, calcium, and eGFR were significantly lower in SCA patient than in controls (P < 0.05). eGFR of <90 ml/min was found in 50 (67.6%) of SCA patients out of which 7 (9.5%) had Stage 3 chronic kidney disease (CKD) (<60 ml/min) and one patient with Stage 4 CKD who also had shrunken kidneys with elevated serum creatinine (203 μmol/L) and urea (11.7 mmol/L) concentration. Renal ultrasonography revealed reduced renal size in 20 (27.1%) of the patients while 2 (2.7%) had a renal enlargement. There was no correlation between renal length and serum electrolytes, urea, creatinine, and eGFR. Conclusion: The majority of steady state SCA patients in Zaria have reduced eGFR and dyselectrolytemia. However, there was no association between the kidney length and the biochemical parameters. We, thus, recommend renal function tests to be routinely requested for proper management of these patients.
Keywords: Chronic kidney disease, renal length, sickle cell anemia
|How to cite this article:|
Yusuf R, Hassan A, Ibrahim I N, Babadoko A A, Ibinaiye P O. Assessment of kidney function in sickle cell anemia patients in Zaria, Nigeria. Sahel Med J 2017;20:21-5
|How to cite this URL:|
Yusuf R, Hassan A, Ibrahim I N, Babadoko A A, Ibinaiye P O. Assessment of kidney function in sickle cell anemia patients in Zaria, Nigeria. Sahel Med J [serial online] 2017 [cited 2019 Sep 23];20:21-5. Available from: http://www.smjonline.org/text.asp?2017/20/1/21/204326
| Introduction|| |
Kidney involvement in sickle cell disease (SCD) includes a variety of glomerular and tubular disorders, which are associated with increased mortality. The pathophysiology of sickle cell nephropathy (SCN) is related to the normal medullary environment which is characterized by low oxygen tension, low pH, and high osmolality, these conditions in SCD patients predispose to red blood cell sickling. SCD affects the kidney by acute mechanisms, as a form of the sickle crisis and insidiously with renal medullary/papillary necrosis, with resulting tubular defects.
The disruption of distal nephron and medullary function leads to a reduction of renal concentrating capacity, urinary acidification, and to impaired potassium metabolism which are often observed in these patients. At lower hydrogen ion concentration (pH), urea was able to stimulate potassium-chloride (K-Cl) loss from sickle cells, leading to cellular dehydration.
The main renal functional abnormalities in patients with SCD are alterations in the glomerular filtration rate (GFR) and proteinuria. However, measurement of GFR in SCD is problematic due to hyperfiltration, which makes identification and monitoring of chronic kidney disease (CKD) difficult in patients with SCD.
In the early stage of SCN, the kidneys are normal in size or enlarged, however as the disease progress they become shrunken.
SCD is associated with many functional and structural abnormalities of the kidney which may progress to end-stage renal disease. This study, therefore, attempt to determine the pattern of biochemical renal function tests and their relationship with kidney size obtained on ultrasound scan in steady state adult sickle cell anemia (SCA) patients in Zaria, North-West, Nigeria.
| Subjects and Methods|| |
This was a cross-sectional descriptive study of adult SCA patients in the steady state conducted at a tertiary hospital. The study was approved by the Ethical and Scientific Committee of the Hospital. The research subjects were adult Nigerians of both genders who volunteered and provided informed written consent. Patients attending the hematology clinic were enrolled consecutively as they present. The exclusion criteria included subjects with established renal diseases and those on drugs such as cephalosporin or cotrimoxazole which reduces creatinine tubular secretion. Seventy-four SCA subjects (35 males and 39 females) and 20 controls (10 males and 10 females) were recruited into the study.
Subjects underwent a complete history, physical examination, renal function tests, hemoglobin electrophoresis, and abdominal ultrasound scan. On electrophoresis, all patients with SCD showed no HbA (but showed elevated levels of HbS), consistent with HbSS phenotype; while the control subjects showed no HbS, consistent with HbAA. There was no history of previous blood transfusion in the control subjects. Biochemical parameters were determined by SELECTRA XL chemistry autoanalyzer. Estimated GFR (eGFR) was calculated using the Cockcroft and Gault equation  and CKD was classified into stages (Stages 1–5) based on National Kidney Foundation New York Guideline.
All subjects were scanned by B-mode ultrasonography with Aloka product (mode SSD-3500) ultrasound diagnostic equipment with a variable frequency probe at 2–5 MHz or 5–10 MHz depending on the physical built of the subject for better resolution. The examination was performed with the patient in supine, right, and left oblique positions to obtain an optimal view of the kidneys. Measurements of the kidneys were performed in all subjects by obtaining the length in centimeters.
Data obtained were analyzed using Statistical Package for Social Sciences (SPSS) software version 15.0 (Chicago, USA) for windows. Student's t-test was used to compare means of variables and Pearson's linear correlation analysis to test the significance of association. A P ≤ 0.05 was considered statistically significant.
| Results|| |
The mean age of the SCA patients was 23.22 ± 5.35 years while that of the control group was 22.70 ± 1.22 years (P > 0.05). Of the 74 SCA patients, 35 (47.3%), and 39 (52.7%) were males and females, respectively; while of the 20 controls, 10 (50.0%) each were males and females. The packed cell volume of SCA patients (25.37 ± 4.34%) was significantly lower (P < 0.001) than that of the controls (40.90 ± 4.57%).
The biochemical results are presented in [Table 1]. The serum potassium, phosphorus, and uric acid were statistically significantly higher while serum sodium, chloride, bicarbonate, total calcium, and eGFR were significantly lower in SCA patient than in controls (P < 0.05). There was no significant difference in the mean values of serum urea and creatinine.
|Table 1: Serum analytes and estimated glomerular filtration rate (mean±standard deviation) in sickle cell anemia patients and controls|
Click here to view
eGFR of <90 ml/min was found in 66.3% (50) of SCA patients out of which 56.8% (42) in Stage 2 (60–89 ml/min), 9.5% (7) in Stage 3 (30–59 ml/min), and 1.4% (1) in Stage 4 (15–29 ml/min); none in Stage 5 CKD (<15 ml/min). Only 32.4% (24) of the patients and all the controls had eGFR of ≥90 ml/min [Table 2]. The patient with Stage 4 CKD also had shrunken kidneys with elevated serum creatinine (203 μmol/L) and urea (11.7 mmol/L) concentrations.
Of the SCA patients studied, 5.4% had hyponatremia, 13.5% had hyperkalemia, 31.1% had metabolic acidosis, 41.9% had hypocalcemia, and 12.2% had hyperuricemia. Low serum urea levels were recorded in 14.9% of the patient while 1.4% had elevated urea and creatinine, respectively.
The mean values of the kidney length on ultrasound scan showed significantly higher (P < 0.05) values of both right and left kidneys in SCA patients than in the controls [Table 3]. Reduced renal size was observed in 20 (27.1%) patients while 2 (2.7%) of them had a renal enlargement. All the controls had normal kidney size.
There was a negative and statistically significant correlation between eGFR and serum urea (r = −0.434; P< 0.0001), and also between eGFR and serum creatinine (r = −0.696; P< 0.0001) in the patients [Figure 1] and [Figure 2]. There was no correlation between renal length and serum electrolytes, urea, creatinine, and eGFR.
|Figure 1: Relationship between serum urea and estimated glomerular filtration rate in sickle cell anemia patients|
Click here to view
|Figure 2: Relationship between serum creatinine and estimated glomerular filtration rate in sickle cell anemia patients|
Click here to view
| Discussion|| |
In this study, the pattern of biochemical renal function tests and relationship with kidney size was evaluated in SCA patients in the steady state, and the results clarify important aspects of tubular and glomerular dysfunction in these patients.
There was a significantly lower concentration of serum sodium and chloride in SCA patients in this study. This is consistent with finding of other studies ,,,,, and it is attributable to increased and continued obligatory losses of body fluids and electrolytes which rapidly result in dehydration and subsequently salt (sodium, chloride) and other electrolyte imbalance.,,
It was suggested that dehydration and deoxygenation, and also in-vitro hemolysis caused excessive potassium losses from the cell into the extracellular fluid which caused a rise in plasma potassium concentration., The above-stated suggestion could be a reason for the significantly higher serum potassium in SCA patients compared with controls in this study which is in agreement with findings of other studies.,,,,
There is inability of kidneys in SCA patients to acidify the urine to a normal extent leading to a disturbed exchange of H + for Na + with subsequent accumulation of H + in the extracellular fluid. This could account for the significantly lower level of bicarbonate concentration among our SCA patients with a sizable number (31.1%) of them having metabolic acidosis. The finding in our study is comparable with that of Silva Junior et al.
The significantly lower serum calcium level among SCA subjects in this study is similar to the findings of Pandey et al., Nduka et al. and Oladipo et al. who attributed the lower calcium level to increased Ca 2+-Mg 2+ ATPase activity, reduced calcium absorption from the intestinal tract and impaired Vitamin D synthesis.
In agreement with findings of other studies,, the serum phosphate level was higher in SCA patients in our study. This finding is thought to be due to increase tubular reabsorption of phosphate  and release of phosphate from the cells in the chronic hemolytic states occurring in these patients.
The finding of significantly higher concentration of serum uric acid among SCD patients in our study agrees with the reports of al-Naama et al. and Khalid et al. but is in contrast to the finding of Pandey et al. and Nduka et al. The elevated level of uric acid in the patients could be due to a sustained high state of erythropoiesis in SCA patient which causes an increased turnover of purines and hence the generation of a greater than normal uric acid level. Hyperuricemia could also be attributed to the failure of the kidney to keep pace with increased production, this often occurred as a result of impaired tubular function due to infarction and hypoxia resulting from sickling.
In our study, there was no significant difference in both serum concentration of urea and creatinine between patients and controls. This is similar to the findings of Silva Junior et al. and Pandey et al. but in contrast to that of al-Naama et al. who found a significant difference in the level of both analytes.
The present study showed a significantly lower eGFR in patients than controls, also, there was a significant number of SCA patients with decreased eGFR (<60 ml/min), which was found in 10.8% of cases. This is comparable to the finding of 11.5% in a study by Silva Junior et al. in Brazil, though higher than that of Silva Junior  who found 5.1% also in Brazil but lower than that of Arogundade et al. and Aneke et al. who found 37.2% and 47% respectively, both in Ile-Ife, Nigeria. The lower prevalence in our study compared to that of Aneke et al. may be due to the use of eGFR instead of 24 h creatinine clearance with its attendant shortcomings such as incomplete collection of urine. The relatively high prevalence of renal failure in SCA patients in our study may be as a result of decrease GFR due to glomerulosclerosis which is a long-term effect of glomerular hyperfiltration. The kidney length was significantly higher in SCA patients studied, though the etiology of renal enlargement in SCD is unknown, however, glomerular hypertrophy and increased renal blood volume have been suggested as likely contributors.
| Conclusion|| |
This study observed that abnormalities of electrolytes and renal insufficiency present significantly in SCA patients in our environment. The relatively high prevalence of renal insufficiency and electrolytes imbalances in adult SCA patients suggests that renal function should be monitored regularly for early detection and prevention of chronic renal complication and adverse effects on disease outcome.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Silva Junior GB, Vieira AP, Couto Bem AX, Alves MP, Meneses GC, Martins AM, et al.
Renal tubular dysfunction in sickle cell disease. Kidney Blood Press Res 2013;38:1-10.
Okafor UH, Aneke E. Outcome and challenges of kidney transplant in patients with sickle cell disease. J Transplant 2013;2013:614610.
Scheinman JI. Sickle cell disease and the kidney. Semin Nephrol 2003;23:66-76.
Sesso R, Almeida MA, Figueiredo MS, Bordin JO. Renal dysfunction in patients with sickle cell anemia or sickle cell trait. Braz J Med Biol Res 1998;31:1257-62.
Agoreyo FO, Nwanze N. Plasma sodium and potassium changes in sickle cell patients. Int J Genet Mol Biol 2010;2:14-9.
Marouf 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.
Alleyne GA, Statius van Eps LW, Addac SK, Nicholson GD, Schouten H. The kidney in sickle cell anaemia. Kidney Int 1975;7:371-9.
Balci A, Karazincir S, Sangün O, Gali E, Daplan T, Cingiz C, et al.
Prevalence of abdominal ultrasonographic abnormalities in patients with sickle cell disease. Diagn Interv Radiol 2008;14:133-7.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41.
Kara LL, Wu AH. Renal function. In: Micheal LB, Edward PF, Larry ES, editors. Clinical Chemistry Techniques, Principle, Correlations. 6th
ed. Lippincott, USA: Williams and Wikins; 2010. p. 574.
Ibe EO, Ezeoke AC, Emeodi I, Akubugwo EI, Elekwa E, Ugonabo MC et al
. Electrolyte profile and prevalent causes of sickle cell crisis in Enugu, Nigeria. Afr J Biochem Res 2009;3:370-4.
Pandey S, Sharma A, Dahia S, Shah V, Sharma V, Mishra RM, et al.
Biochemical indicator of sickle cell disease: Preliminary report from India. Indian J Clin Biochem 2012;27:191-5.
Vikas G, Ajay KS, Jayant S, Prasant N, Patil KS, Neelima S. Variation in serum electrolyte in sickle cell patients in Chhattisgarh population. Int J Sci Innov Discov 2012;2:239-43.
Akah RT, Charles FN, Fernand-Nestor TF, Armel HN. Three serum electrolytes profile (Na +
, K +
and Cl -
) of anaemic patients at the Biyem-Assi district hospital in Yaounde (Cameroon). J Dis Med Plants 2015;1:42-7.
Nduka N, Kazem Y, Saleh B. Variation in serum electrolytes and enzyme concentrations in patients with sickle cell disease. J Clin Pathol 1995;48:648-51.
Oladipo OO, Temiye EO, Ezeaka VC, Obomanu P. Serum magnesium, phosphate and calcium in Nigerian children with sickle cell disease. West Afr J Med 2005;24:120-3.
al-Naama LM, al-Sadoon EA, al-Sadoon TA. Levels of uric acid, urea and creatinine in Iraqi children with sickle cell disease. J Pak Med Assoc 2000;50:98-102.
Khalid EK, Hala IM, Omer HD, Ahmed AA, Gad AO, Khalid EA. Evaluation of biochemical changes in homozygous sickle cell disease patients in Western Sudan. NMJ 2012;2:24-36.
Silva Junior GB, Libório AB, Vieira AP, Bem AX, Lopes Filho AS, Figueiredo Filho AC, et al.
Evaluation of renal function in sickle cell disease patients in Brazil. Braz J Med Biol Res 2012;45:652-5.
Arogundade FA, Sanusi AA, Hassan MO, Salawu L, Durosinmi MA, Akinsola A. An appraisal of kidney dysfunction and its risk factors in patients with sickle cell disease. Nephron Clin Pract 2011;118:c225-31.
Aneke JC, Adegoke AO, Oyekunle AA, Osho PO, Sanusi AA, Okocha EC, et al.
Degrees of kidney disease in Nigerian adults with sickle-cell disease. Med Princ Pract 2014;23:271-4.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]