Abstract

Background: Sickle cell disease (SCD) is one of the most common severe monogenic disorders in the world, characterized by haemoglobin polymerization leading to erythrocyte rigidity and vaso-occlusion. This can potentially lead to ischemia to some organs like the kidneys and subsequent damage which starts early and progresses.

Objective: This study was aimed at assessing renal function in patients with sickle cell disease attending the Yaoundé Central Hospital.

Materials and Methods: A cross-sectional hospital based study was conducted and 80 sickle cell patients were recruited using the consecutive sampling method. A 3ml of venous blood was collected in dry tubes for creatinine measurement and the glomerular filtration rate estimated using the chronic kidney disease epidemiology collaboration (CKD-EPI) and Schwartz equations. Data was analysed using R version 4.2.1 with statistical significance set at p<0.05.

Results: A total of 80 HbSS participants were recruited. Majority (57%) of participants were females. The mean ± standard age was (29.01 ± 12.72) years. The mean ± standard deviation of serum creatinine and estimated glomerular filtration rate (eGFR) were (0.77 ± 0.42) mg/dL and (135.2 ± 41.60176) ml/min per 1.73m2 respectively. Gender was significantly associated with serum creatinine levels (p = 0.004). The prevalence of glomerular hyperfiltration was 63.8% and 7.5% of the participants had renal disease (stage 3 and 4). There was a strong correlation between the age and the eGFR (r = -0.618, p = 0.000). Frequency of crisis and taking of non-steroidal anti-inflammatory drugs (NSAIDs) and age were significant risk factors for the development of renal disease with p = 0.038, p = 0.030 and p = 0.001 respectively.

Conclusion: Sickle cell disease patients are at high risk of developing renal disease hence should be routinely monitored for renal dysfunction. The use of NSAIDs, frequency of crisis and age are risk factors for renal disease.

CHAPTER ONE

INTRODUCTION

1.1 Background

Sickle cell disease (SCD) is one of the most common severe monogenic disorders in the world, characterized by haemoglobin polymerization leading to erythrocyte rigidity and vaso-occlusion [1]. The disease occurs as a result of a point mutation leading to the replacement of the amino acid glutamic acid by valine at position six of the β-globin chain. The mutant haemoglobin (HbS) polymerizes and becomes poorly soluble when the oxygen tension is lowered [2].

SCD has a high prevalence and social impact worldwide, with high mortality within the first three years of life. A high prevalence has been reported in sub-Saharan Africa, the Mediteranean, the Middle East, and India [3]. SCD is the most widespread genetic disease in the world affecting more than 50 million people [4], including 38 million in sub-Saharan Africa [5]. In Cameroon, the statistics are alarming.

SCD causes about 4,000 deaths each year. Currently, the country alone has two of the fifty million SCD in the world. Of the 200,000 sickle cell patients (SCP) surveyed, half die before the age of five making it a serious public health problem [5].

Haemoglobin (Hb) is molecule found in red blood cells responsible for carrying oxygen from the lungs to various organs and tissues, and brings carbon dioxide back to the lungs. After the deoxygenation of haemoglobin from sickle cells, they become insoluble and form polymers that aggregate into tubular fibers, whereas, the normal haemoglobin (HbA) remains soluble after deoxygenation [6].

These structures cause red blood cells (RBCs) to become stiff and assume a crescent shape appearing like the blade of a sickle. Unlike normal RBCs, sickled red cells cannot squeeze through small blood vessels. Instead, they stack up and cause blockages in arterioles thereby depriving organs and tissues of oxygenated blood. This process produces painful episodes which can last from hours to days. These crises can cause pain in the bones and chest.

Chronic kidney disease (CKD) is a well-known and one of the most serious complication of SCD. Hyperfiltration is one of the earliest manifestations of sickle nephropathy, and has been observed in children with SCA as young as 12 months of age with an age-dependent increase until the second decade of life [7].

CKD is the presence of kidney damage or decreased kidney function, which is progressive (from three or more months to years) irrespective of clinical diagnosis. Renal disease is seen in 15-18 % of all SCD patients, and is a cause of early death. CKD from sickle cell involves damage to multiple structures within the kidney.

The haemodynamic changes that occur with chronic anaemia, renal hypoxia that results from recurrent vaso-occlusion and haemolysis-related endothelial dysfunction can lead to functional and structural changes which may progress to CKD [8].

Erythrocyte sickling in the medullary vessels leads to renal ischemia, hematuria and proteinuria with compensatory vasodilation leads to glomerular hyperfiltration [9]. Also, non-steroidal anti-inflammatory drugs (NSAIDs) are used in the management of pain crises in SCD patients which has as one of its side effects renal dysfunction. These factors predispose patients with SCD to an increased risk of developing renal failure [10].

1.2 Rationale

Sickle cell disease is a public health problem and significantly contributes to morbidity and mortality in the society. SCD is more prevalent in Africa and Mediterranean crescent. About 16-18% of mortality in patients with SCD is ascribed to kidney disease. Kidney disease can occur as a result of a reduced blood flow to the kidneys due to vaso-occlusion.

The life expectancy of people with SCD having CKD reduces by 25 to 30 years. Hence markers of kidney function should be monitored for early detection, prognosis and prevention of the complications of having both diseases.

1.3 Research Questions        

1. Are the kidneys of SCD patients functioning properly?
2. What are the risk factors of renal dysfunction in sickle cell disease patients?

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