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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 2  |  Page : 194-199
Renal Abnormalities in Patients with Sickle Cell Disease: A Single Center Report from Saudi Arabia


Department of Medicine, Division of Hematology/Oncology, College of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia

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   Abstract 

Patients with sickle cell disease (SCD) are at increased risk of serious morbidity and mortality. Renal abnormalities in SCD are well known but renal involvement in Saudi patients with SCD has not been studied. We sought to identify renal abnormalities in adolescent and adult Saudi patients with SCD. We prospectively studied 73 patients with SCD followed up at King Khalid University Hospital, Riyadh, Saudi Arabia from July 2005 to November 2006,. All patients underwent evaluation of kidney function and urine examination to detect proteinuria and other urinary abnormalities. In addition, 53 patients from the cohort had 24-hour urine collection to measure creatinine clearance and to quantitate proteinuria. The patient population consisted of 34 males (46.5%) and 39 females (53.5%) with a median age of 23 years (range 14-40). Proteinuria was present in 30 patients (41%). Creatinine clearance was low in 12 patients (22.5%) and seven of these patients had low or low-normal serum creatinine despite reduced creatinine clearance. Low serum creatinine was common and present in 28 patients (38%). Two patients had chronic renal failure and one of them is on regular dialysis. Other abnormalities detected include hematuria in seven patients (8.5%) and hemoglobinuria in 12 patients (14.5%). In conclusion, renal abnormalities are present in a significant number of Saudi patients with SCD and proteinuria is the most common abnormality. Serum creatinine may remain low or within low-normal range in SCD patients despite reduced creatinine clearance. As proteinuria is a risk factor for developing renal failure in future, routine screening of SCD patients is recommended for timely intervention in order to prevent or delay renal damage.

Keywords: Sickle cell disease, Renal abnormalities, Proteinuria, Saudi patients

How to cite this article:
Aleem 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

How to cite this URL:
Aleem A. Renal Abnormalities in Patients with Sickle Cell Disease: A Single Center Report from Saudi Arabia. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Dec 7];19:194-9. Available from: http://www.sjkdt.org/text.asp?2008/19/2/194/39029

   Introduction Top


Sickle cell disease (SCD) is an autosomal recessive, chronic hemolytic disorder with many acute and chronic complications. Sickling of red cells in various parts of the body causes acute and chronic ischemia leading to progressive tissue damage. The rate of deve­lopment of various complications is variable but many patients develop organ damage. [1],[2] This, in turn, is associated with increased morbidity and mortality. Survival for patients with SCD has improved because of signi­ficant advances in medical care. This has resulted in more frequent observation of various chronic complications of SCD, parti­cularly organ failure. [1],[2],[3] By the fifth decade of life, nearly one-half of the surviving patients develop some form of irreversible organ damage.Virtually any organ of the body may be affected including the kidneys. [4] The prevalence of renal involvement in Saudi patients with SCD is not known. This study was conducted to evaluate the presence of renal abnormalities in adolescent and adult Saudi patients with SCD.


   Patients and Methods Top


Patients with SCD followed up at the hematology outpatient clinic, the King Khalid University Hospital, Riyadh, were prospectively studied. Eligibility criteria included age of 14 years or older and docu mented homozygous or heterozygous SCD. Patients were evaluated in steady state with no acute illness during the two weeks prior to the assessment. All patients gave informed consent. Patients with sickle cell trait were excluded. A total of 77 patients with SCD were studied. Four patients were excluded because three of them had incomplete data and one patient proved to have sickle cell trait later. All 73 patients had blood extraction for blood urea nitrogen (BUN) and serum creatinine determination as well as urine dipstick examination. In addition, 53 patients had 24-hour urine collection to measure creatinine clearance and to quantify proteinuria. Urine samples were collected in the morning (not necessarily the first sample in the morning). Urine samples were tested by dipstick for the presence of blood, protein, hemoglobin and other abnormalities. Significant proteinuria was defined as at least 1+ protein in the urine on dipstick examination. Twenty-four hour urine samples were collected from 8 AM to 8 AM next day according to the standard protocol. Twenty-four hour urine samples were analyzed for creatinine clearance and quantitative proteinuria. Protein excretion of more than 0.150 grams per 24 hours was considered abnormal.


   Results Top


The studied population consisted of 39 females (53.5%) and 34 males (46.5%) with a median age of 23 years (range 14-40). Majority of the patients (67) had HbSS disease and six patients had HbSβ0 disease. The median BUN was 2.8 mmol/L (range 0.8-38) and median serum creatinine was 48 µmol/L (range 26 to 1026). Two patients had persistently raised serum creatinine (chronic renal failure) and one of them is on regular dialysis at the time of reporting. Kidney biopsy in this patient showed focal glomerulosclerosis. Low serum creatinine was common and present in 28 patients (38%). Median creatinine clearance in the patients tested was 92.1 ml/minute (range 6-162). Creatinine clearance was low in 12 patients (22.5%) and in seven of these patients, the serum creatinine was low or low-normal despite reduced creatinine clearance. Median protein excretion in 24-hours for the patient cohort was abnormal (0.1601 g/day, range 0.037-14.47). The most common abnormality was proteinuria found in 30 patients (41%). Majority of the patients with protein in the urine had mild proteinuria while three patients (4%) had nephrotic range proteinuria. Both the patients with renal failure had nephrotic range proteinuria. Characteristics and values of various parameters measured in the patients are presented in [Table - 1]. Other abnormalities detected include hematuria in seven patients (9.5%) and hemoglobinuria in 12 patients (16.5%). Renal and urinary abnormalities found in patients with SCD are summarized in [Table - 2].


   Discussion Top


Sickle cell nephropathy is a large group of renal abnormalities, which encompasses many structural and functional disorders. Various forms of renal abnormalities have been observed in SCD patients. These include impaired urinary concentrating ability, defects of urinary acidification, defects of potassium excretion and glomerular hyperfiltration in children with progressive decrease in glome­rular filtration rate with advancing age. Recurrent hematuria, proteinuria, renal papillary necrosis and progressive renal impairment with end-stage renal disease (ESRD) are all well recognized.[5],[6],[7],[8],[9],[10]

Pathogenesis of nephropathy in SCD is complex and still not fully understood. Development of transgenic mice has provided useful information in understanding the pathophysiology of renal damage in SCD. In one such study, 50% of the hemizygous SS mice showed mild-to-severe kidney lesions of various types. [11] The rate of oxygen con­sumption by the kidney is very high rendering it particularly susceptible to hypoxia caused by vaso-occlusion. The renal medulla favors red cell sickling due to presence of hypertonic environment and acidosis leading to hypoxic damage. [12] Research evidence suggests that prolonged glomerular hyperfiltration due to any cause, including SCD during childhood, leads to glomerular damage resulting in glo­merular sclerosis, proteinuria and progressive renal failure. [13]

In this study, we focused mainly on the clinically relevant aspects of renal abnorma­lities. Our results show that renal abnorma­lities, particularly proteinuria, are common in our patient population. Forty-one percent of the patients had proteinuria although majority of them had only mild proteinuria. Only three patients had nephrotic range proteinuria and both the patients with renal failure belonged to this group.

Twenty-eight patients had reduced serum creatinine below the normal range for age and sex. This possibly reflects smaller body mass index (BMI) in many of these patients although some patients with normal or near normal BMI also had low serum creatinine. Seven patients had reduced creatinine clea­rance despite low or low normal serum creatinine. These observations suggest that a serum creatinine level in the upper range of normal in SCD patients should be consi­dered suspicious and further work-up should be carried out to rule out deterioration of renal function. [14]

Hematuria has been described as one of the most common abnormalities, not only in homozygous SCD but also in sickle cell trait. [12]

Hematuria is usually a result of red cell sickling in the renal medulla. In some cases, it may result from papillary necrosis. Hematuria was less common in our patients and was present in only 8.5% of the patients. Presence of hemoglobinuria in 14.5% of patients obviously reflects ongoing red cell hemolysis. Hemoglobinuria can cause acute renal failure in patients with massive intra­vascular hemolysis but its role in chronic renal damage is doubtful. Hemosiderosis is one of the earliest lesions observed in sickle cell nephropathy. [12],[14] There is one report of a patient with paroxysmal nocturnal hemoglo­binuria, in whom chronic or recurrent hemoglobinuria was thought to be the main factor contributing to renal iron deposition and chronic renal failure. [15] It is possible that hemoglobinuria and iron deposition in the kidneys may have a role, albeit minor, in the pathogenesis of sickle cell nephropathy.

Proteinuria is usually an early manifes­tation of sickle cell nephropathy. [16] The inci­dence of proteinuria increases with advancing age. In a large prospective follow-up study of pediatric patients with SCD, none of the patients up to the age of six years had proteinuria but it developed in more than 10% of teenage patients. [17] Approximately 18% of patients with SCD and proteinuria will have clinically manifest glomerulopathy and many patients with SCD and the nephrotic syndrome develop renal failure with the passage of time. [18],[19] In a prospective study, 40% of patients with the nephrotic syndrome eventually developed ESRD. [20] The lesion in these patients is usually focal glomerulosclerosis. [21]

As proteinuria in the early stages of nephro­pathy is a hallmark of future deterioration of renal function, it is important to detect this early with routine surveillance. Intervention at this stage may prevent or at least delay the renal damage. [22],[23],[24] This is particularly relevant because patients with SCD do not do well on renal replacement therapy with dialysis or renal transplantation because of frequent vaso­occlusive crises and other complications. In a large study of SCD patients with renal failure, survival was only four years in spite of dialysis. [20] Prognosis of these patients, however, has improved in recent times because of better understanding of patho­physiology of the disease and improvement in general medical care. A recent study by Abbott et al showed that patients with sickle cell nephropathy and ESRD had an increased risk of mortality and they were much less likely to be placed on transplant waiting list as compared to other patients with ESRD. [25] This further highlights the importance of preventive measures in these patients.

We appreciate certain limitations in our study. Being a tertiary care referral center, we are likely to have patient population with more severe disease. This may have resulted in overestimation of renal complications. Our patients originate from different parts of Saudi Arabia and it is well known that patients from south-western province have a more severe form of the disease as compared to patients from eastern province. [26] It was not possible for us to analyze patients on the basis of their area of origin and this may have influenced our results. Nevertheless, this study highlights the presence of renal complications in Saudi patients with SCD. Future studies should be community based and carried out in different regions separately.

In summary, renal abnormalities, particularly proteinuria, are common in adolescent and adult Saudi patients with SCD. As proteinuria is a risk factor for developing renal impairment in future, these patients should be actively monitored and those who develop proteinuria, should be considered for early intervention.

 
   References Top

1.Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease: Life expec­tancy and risk factors for early death. N Engl J Med 1994;330(23):1639-44.  Back to cited text no. 1    
2.Powars D. Sickle cell anemia: βS --genecluster haplotypes as prognostic indicators of vital organ failure. Semin Hematol 1991;28:202-8.  Back to cited text no. 2    
3.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;84: 363-76.  Back to cited text no. 3    
4.Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med 1997;337 (11):762-9.  Back to cited text no. 4    
5.Pham PT, Pham PC, Wilkinson AH, Lew SQ. Renal abnormalities in sickle cell disease. Kidney Int 2000;57(1):1-8.  Back to cited text no. 5    
6.Al-Harbi N, Annobil SH, Abbag F, Dzaku F, Bassuni W. Renal reabsorption of phosphate in children with sickle cell anemia. Am J Nephrol 1999;19(5):552-4.  Back to cited text no. 6    
7.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(10):1257-62.  Back to cited text no. 7    
8.Katopodis KP, Elisaf MS, Pappas HA, et al. Renal abnormalities in patients with sickle cell-beta thalassemia. J Nephrol 1997;10(3): 163-7.  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.Manis T, Friedman EA. Sickle hemoglo­binopathy and the kidney. Contrib Nephrol 1977;7:211-9.  Back to cited text no. 10    
11.Diwan BA, Gladwin MT, Noguchi CT, Ward JM, Fitzhugh AL, Buzard GS. Renal pathology in hemizygous sickle cell mice. Toxicol Pathol 2002;30(2):254-62.  Back to cited text no. 11    
12.Ataga KI, Orringer EP. Renal abnormalities in sickle cell disease. Am J Hematol 2000;63(4):205-11.  Back to cited text no. 12    
13.Brenner BM, Meyer TM, Hostetter TH. Dietary protein and the progressive nature of Kidney disease: The role of hemo­dynamically mediated gromerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation and intrinsic renal disease. N Engl J Med 1982; 307(11):652-9.  Back to cited text no. 13    
14.Sklar AH, Campbell H, Caruana RJ, Lightfoot BO, Gaier JG, Milner A. A population study of renal function in sickle cell anemia. Int J Artif Organs 1990;13(4):231-6.  Back to cited text no. 14    
15.Zachee P, Henckens M, Van Damme B, Booqaerts MA, Riqauts H, Verberckmoes RK. Chronic renal failure due to renal hemosiderosis in a patient with paroxysmal nocturnal hemoglobinuria. Clin Nephrol 1993;39(1):28-31.  Back to cited text no. 15    
16.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. 16    
17.Wigfall DR, Ware RE, Burchinal MR, Kinney TR. Prevalence and clinical correlates of glomerulopathy in children with sickle cell disease. J Pediatr 2000;136(6):749-53.  Back to cited text no. 17    
18.Murthy VD, Haywood J. Survival analysis by sex, age, group and hemotype in sickle cell disease. J Chron Dis 1981;34(7):313-9.  Back to cited text no. 18    
19.Thomas AN, Pattison C, Sergeant GR. Causes of death in sickle cell disease in Jamaica. Br Med J Clin Res 1982;285:633-5.  Back to cited text no. 19    
20.Powars DR, Elliott-Mills DD, Chan L, et al. Chronic renal failure in sickle cell disease: Risk factors, clinical course and mortality. Ann Intern Med 1991;115(8):614-20.  Back to cited text no. 20    
21.Bakir AA, Hathiwala SC, Ainis H, et al. Prognosis of the nephrotic syndrome in sickle cell glomerulopathy: A retrospective study. Am J Nephrol 1987;7(2):110-5.  Back to cited text no. 21    
22.Alvarez O, Montane B, Lopez G, Wilkinson J, Miller T. Early blood transfusions protect against microalbuminuria in children with sickle cell disease. Pediatr Blood Cancer 2006;47(1):71-6.  Back to cited text no. 22    
23.Fitzhugh CD, Wigfall DR, Ware RE. Enalapril and hydroxyurea therapy for children with sickle nephropathy. Pediatr Blood Cancer 2005;45:982-5.  Back to cited text no. 23    
24.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. 24    
25.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. 25    
26.Padmos MA, Roberts GT, Sackey K, et al. Two different forms of homozygous sickle cell disease occur in Saudi Arabia. Br J Haematol 1991;79(1):93-8.  Back to cited text no. 26    

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Correspondence Address:
Aamer Aleem
Department of Medicine, King Khalid University Hospital, P.O. Box 7805, Riyadh 11472
Saudi Arabia
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PMID: 18310866

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    Tables

  [Table - 1], [Table - 2]

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