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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2015  |  Volume : 26  |  Issue : 3  |  Page : 584-588
Coexistence of sickle cell nephropathy and lupus nephritis in a Sudanese child


1 Jaffer Ibn Auf Pediatric Specialized Hospital, Khartoum, Sudan
2 Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan
3 Faculty of Medical Lab Science, Alzaeim Alazhari University, Khartoum, Sudan
4 School of Medicine, Ahfad University for Women, Khartoum, Sudan

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Date of Web Publication20-May-2015
 

   Abstract 

In spite of the wide distribution of sickle cell disease (SCD) in Africa, an association with systemic lupus erythromatosis (SLE) is seldom reported. This may be due to the poor association between the two diseases or the high prevalence of missed cases. Progressive renal injury is prominent in both SCD and SLE. In this communication, we are presenting a case of an 11-year-old male who presented with sickle cell nephropathy that manifested as nephrotic syndrome with no response to conservative therapy, alongside unexplained massive hemolysis. His renal biopsy proved SLE superimposed on sickle cell nephropathy. We are stressing the importance of considering alternate disease processes in patients with SCD when symptoms change or when there is an atypical clinical course.

How to cite this article:
Idris AB, Abdulgayoom A, Mudawi E, El Hassan A M, Elamin EM, El Hassan LA. Coexistence of sickle cell nephropathy and lupus nephritis in a Sudanese child. Saudi J Kidney Dis Transpl 2015;26:584-8

How to cite this URL:
Idris AB, Abdulgayoom A, Mudawi E, El Hassan A M, Elamin EM, El Hassan LA. Coexistence of sickle cell nephropathy and lupus nephritis in a Sudanese child. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2021 Jun 14];26:584-8. Available from: https://www.sjkdt.org/text.asp?2015/26/3/584/157397

   Introduction Top


Sickle cell disease (SCD) is the most common hematologic hereditary disorder in humans. The worldwide estimated prevalence is 7%, [1] and many patients with SCD present with a wide spectrum of renal dysfunction. In patients with SCD, relative hypoxia in the renal medulla and slow blood flow through the vasa rectae predisposes red blood cells to sickle, resulting in a significant veno-occlusion and subsequent local infarction. The early manifestations of sickle cell nephropathy include impaired urinary concentrating ability, supranormal proximal tubular function manifested by a mild degree of hypophosphatemia and increased creatinine clearance and defects in both urinary acidification and potassium excretion. With increasing age and additive tubulointerstitial nephritis secondary to analgesic overuse, renal abnormalities may progress to manifestations such as hematuria, proteinuria, papillary necrosis, glomerulonephritis and acute and chronic renal failure. [2],[3],[4]

Systemic lupus erythematosis (SLE) is a classic prototype of a multi-system disease of immunological origin with autoantibodies, polyclonal B-cell activation and T-cell dysfunction. The ensuing immune complexes are deposited or formed in situ in many organs and commonly affect the kidneys as lupus nephritis. Histological evidence of lupus nephritis is present in most patients with SLE, even if they do not have clinical manifestations of renal disease. The symptoms are generally related to hypertension, proteinuria and/or renal failure. [5]

The diagnosis of SLE in patients with an underlying chronic hemoglobinopathy can be challenging to establish because the musculoskeletal, central nervous system and renal manifestations are similar in both diseases.


   Case Report Top


We are presenting an 11-year-old male who presented with penile trauma to the surgical department of the Khartoum Teaching Hospital, Sudan. The patient was very pale and referred to the hospital to investigate his anemia. He is not known to have any chronic illness, chronic anemia or G6PD deficiency. He denied any past medical history of dactilitis, joint pain, jaundice, fatigability or blood transfusion. His family did not have any history of sickle cell anemia or blood transfusion. On admission, he was unwell, pale and jaundiced but not cyanosed and had no skin rash; his blood pressure was 110/70 mm Hg. His apex beat was on the 5th intercostals space in the mid-clavicular line with no signs of heart failure. No abnormality was detected on chest examination. He had a non-tender hepatomegaly with liver span of 16 cm and abdominal distention with no ascites detected. The spleen was not palpable. No scrotal abnormality was noted and the patient was catheterized due to his penile injury. There was no joint pain or swelling. His initial investigation revealed Hb of 3.5 g/dL for which he received blood transfusion in the surgical department and then they referred him to the Pediatric Unit. On the day of admission, his Hb was 4.8 g/dL, TWBCs were 44.1 × 10 9 /L, 41% neutrophils, platelet 114 × 10 9 /L, ESR 70/hr and reticulocyte count was 12%. His renal function tests were normal. His serum albumin was 2.4 g/dL and globulin was 3 g/dL. He had indirect hyper-bilirubinemia of 3.4 mg/dL and the direct bilirubin was 0.1 mg/dL with normal liver enzymes and coagulation profile. Urine analysis showed uncountable pus cells, no red blood cells (RBCs) and proteinuria (++) with granular casts. HIV, hepatitis B, hepatitis C and cytomegalovirus (CMV) screening were all negative. His sickling test was positive. Hemoglobin electrophoresis for the patient was delayed due to multiple blood transfusions, but his parents' electrophoresis showed AS profile. Throughout his stay in the hospital, the proteinuria was persistent and his albumin/ creatinine ratio was 300 mg/mmol, which is significant for nephrotic syndrome. He also had a high triglyceride level (392.7 mg/dL, normal <200 mg/dL). Abdominal ultrasound proved hepatomegaly with normal liver texture and revealed a thick gallbladder indicative of a calcular cholecystitis and enlarged bulky kidneys (right kidney 9.5 cm × 4 cm, left kidney 9.7 cm × 4.7 cm) with increased echogenicity and reduced cortico-medullary differentiation, indicating acute renal parenchymal disease. Up to this stage, the diagnosis was that of sickle cell nephropathy with features of nephrotic syndrome based on positive sickling test, proteinuria, hypoalbuminemia and hyperlipidemia.

The patient received antibiotics to treat his urinary tract infection, angiotensin-converting enzyme (ACE) inhibitor (Captopril) for proteinuria, albumin infusions and multiple blood transfusions. Few days later, urinary tract infection got resolved but the proteinuria and hemolysis persisted in spite of the conservative therapy. Because of his massive hemolysis and rapid decline of Hb, he received ten more blood transfusions of -10 mL/kg, but his Hb never reached 8 g/dL. Autoimmune hemolytic anemia was suggested; therefore, Coomb's test was ordered that revealed consecutive negative results. He received three doses of methyl prednisolone without improvement. SLE screening with ANA profile was positive, but negative for anti-double-stranded DNA.

Renal biopsy was taken. Histopathology showed 15 glomeruli in the biopsy. A variety of changes were seen in the glomeruli. Some showed hyperor normal cellularity with dilated capillaries and microthrombi of sickled red cells [Figure 1] and others revealed wire loop lesions [Figure 2]. The proximal tubules contain hyaline droplets indicating heavy reabsorption of protein. The tubules and veins at the cortico-medullary junction were markedly dilated, indicating scarring in this area [Figure 3]. There were deposits of iron around the tubules. Immunostaining highlighted IgG, IgM and C3c deposits [Figure 4] and [Figure 5] in the glomeruli. Diagnosis was SLE superimposed on sickle cell nephropathy. The patient was then started on prednisolone along with cyclophosphamide to which the response unfortunately could not be assessed because he left against medical advice.
Figure 1: Hypercellularity and micro-thrombi in the lower part of the glomerulus (hematoxylin and eosin, ×40).

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Figure 2: Shows wire loop lesions (Silver stain).

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Figure 3: Shows a markedly dilated tubule on the lower right and a dilated and thrombosed vein in the left upper corner (hematoxylin and eosin, ×40).

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Figure 4: IGM deposits in a glomerulus (immunoperoxidase stain, ×40).

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Figure 5: C3c deposits in a glomerulus (immunoperoxidase stain, ×40).

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   Discussion Top


In spite of the wide distribution of SCD in Africa, an association with SLE is seldom reported. That may be due to the poor association between the two diseases or high prevalence of missed cases.

A few cases with coexistence of SCD and SLE have been previously reported. [6],[7],[8],[9],[10],[1],[12],[13],[14],[15] The incidence of SLE in SCD is not known because most of the published studies are case reports. The diagnosis of SLE in the presence of SCD is usually difficult due to their similar clinical features. Furthermore, approximately 20% of SCD patients have positive ANA antibodies with titers greater than 1/160. [16] Because of that, differentiating SCD and SLE renal disease can be difficult without a renal biopsy and a knowledge in the wide array of overlapping pathologies. In our patient, SLE is indicated by the immune deposits and wire loop changes in the glomeruli, which was diagnosed to be class IV lupus nephritis. The microthrombi, the dilated tubules and veins in the cortico-medullary junction are features of scarring in the area, a feature of SCD. The hemosiderin is due to the hemolysis.

As a rule, progressive renal injury is prominent in both SCD and SLE. It is postulated that a defect in the alternate pathway of complement activity seen in patients with SCD may predispose to immune complex disorders. [17] Identifying the etiology of a renal abnormality in the setting of coexisting SLE and SCD is important because there are different implications for morbidity, mortality and therapeutic options.


   Conclusion Top


We are stressing the importance of considering alternate disease processes in patients with SCD when symptoms change or when there is an atypical clinical course. A concurrent illness should be considered in the differrential diagnosis as early recognition of a coexisting disease such as SLE is important to institute appropriate therapy and prevent potential complications. Coexistence of sickle cell nephropathy with lupus nephritis is a rare clinico-pathologic entity that requires timely diagnosis and aggressive management.

Conflict of interest: None declared .

 
   References Top

1.
Wang WC. Sickle cell anemia and other sickling syndromes. In: Greer JP, Foerster J, Rodgers GM, Paraskevas F, Glader B, Arber DA, eds. Wintrobe's clinical hematology, 12th ed. Philadelphia: Lippincott Williams & Wilkins; 2009. p. 1038-82.  Back to cited text no. 1
    
2.
Ataga KI, Orringer EP. Renal abnormalities in sickle cell disease. Am J Hematol 2000;63: 205-11.  Back to cited text no. 2
    
3.
Becker AM. Sickle cell nephropathy: Challenging the conventional wisdom. Pediatr Nephrol 2011;26:2099-109.  Back to cited text no. 3
    
4.
Aygun 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.  Back to cited text no. 4
    
5.
Nandi M, Mondal R. Renal involvement in childhood lupus: A study from Kolkata, India. Saudi J kidney Dis Transpl 2012;23:871-5.  Back to cited text no. 5
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6.
Saxena VR, Mina R, Moallem HJ, Rao SP, Miller ST. Systemic lupus erythematosus in children with sickle cell disease. J Pediatr Hematol Oncol 2003;25:668-71.  Back to cited text no. 6
    
7.
Khalidi NA, Ajmani H, Varga J. Coexisting systemic lupus erythematosus and sickle cell disease: a diagnostic and therapeutic challenge. J Clin Rheumatol 2005;11:86-92.  Back to cited text no. 7
    
8.
Shetty AK, Kumar SR, Gedalia A, Warrier RP. Sickle cell anemiawith systemic lupus erythematosus: Response to hydroxyurea therapy. J Pediatr Hematol Oncol 1998;20:335-7.  Back to cited text no. 8
    
9.
Eissa MM, Lawrence JM 3rd, McKenzie L, Little FM, Mankad VN, Yang YM. Systemic lupus erythematosus in a child with sickle cell disease. South Med J 1995;88:1176-8.  Back to cited text no. 9
    
10.
Katsanis E, Hsu E, Luke KH, McKee JA. Systemic lupus erythematosus and sickle hemoglobinopathies: A report of two cases and review of the literature. Am J Hematol 1987;25:211-4.  Back to cited text no. 10
    
11.
Kanodia KV, Vanikar AV, Goplani KR, pta SB, Trivedi HL. Sickle cell nephropathy with diffuse proliferative lupus nephritis: A case report. Diagn Pathol 2008;3:9.  Back to cited text no. 11
    
12.
Appenzeller S, Fattori A, Saad ST, Costallat LT. Systemic lupus erythematosus in patients with sickle cell disease. Clin Rheumatol 2008; 27:359-64.  Back to cited text no. 12
    
13.
Saxena VR, Mina R, Moallem HJ, Rao SP, Miller ST. Systemic Lupus Erythematosus in Children With Sickle Cell Disease. J Pediatr Hematol Oncol 2003;25:668-71.  Back to cited text no. 13
    
14.
Cherner M, Isenberg D. The overlap of systemic lupus erythematosus and sickle cell disease: Report of two cases and a review of the literature. Lupus 2010;19:875-83.  Back to cited text no. 14
    
15.
Khalidi NA, Ajmani H, Varga J. Coexisting Systemic Lupus Erythematosus and Sickle Cell Disease. J Clin Rheumatol 2005;11:86-92.  Back to cited text no. 15
    
16.
Baethge BA, Bordelon TR, Mills GM, Bowen LM, Wolf RE, Bairnsfather L. Antinuclear antibodies in sickle cell disease. Acta Haematol 1990;84:186-9.  Back to cited text no. 16
    
17.
Shariff S, Al-Hemi B, Al Yousif R, Jabreel N, Al Gharreb S, Balaji D. Spectrum of renal disease in sickle cell anemia. Indian J Nephrol 2006;16:157-63.  Back to cited text no. 17
    

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Correspondence Address:
Dr. Ahmed B Idris
Jaffer Ibn Auf Pediatric Specialized Hospital, Khartoum
Sudan
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DOI: 10.4103/1319-2442.157397

PMID: 26022033

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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