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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2018  |  Volume : 29  |  Issue : 6  |  Page : 1371-1375
G6PD deficiency is not an uncommon cause of pigment nephropathy


1 Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

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Date of Submission28-Dec-2017
Date of Decision05-Feb-2018
Date of Acceptance10-Feb-2018
Date of Web Publication27-Dec-2018
 

   Abstract 

Acute kidney injury (AKI) with evidence of hemolysis is associated with tropical infections. However, pigment-induced AKI can happen with relatively uncommon genetic causes of hemolytic anemia, i.e., glucose 6-phosphate deficiency (G6PD). We share our experience of three such patients whose clinical presentation was similar to jaundice, AKI with hemolysis with suspicion of thrombotic microangiopathy. On evaluation, all had a history of usage of anti-malarial and with G6PD estimation revealing deficient status even during the episode while other tests such as Coomb’s test and bone marrow biopsy was normal in all three patients. The kidney biopsy revealed acute tubular necrosis with red blood cell casts and pigments in all the cases. All patients were managed conservatively and showed complete recovery. Thus in tropical countries G6PD deficiency although is not common, should be considered among patients who have received antimalarial drugs presenting as AKI and a detailed hemolytic work-up needs to be carried out as an important cause of preventable recurrent AKI in tropical countries.

How to cite this article:
Kaul A, Prasad P, Kumari N, Bhaduaria D, Sharma R K, Prasad N, Gupta A, Krishnani N. G6PD deficiency is not an uncommon cause of pigment nephropathy. Saudi J Kidney Dis Transpl 2018;29:1371-5

How to cite this URL:
Kaul A, Prasad P, Kumari N, Bhaduaria D, Sharma R K, Prasad N, Gupta A, Krishnani N. G6PD deficiency is not an uncommon cause of pigment nephropathy. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Jan 17];29:1371-5. Available from: http://www.sjkdt.org/text.asp?2018/29/6/1371/248316

   Introduction Top


Combination of acute kidney injury (AKI), jaundice and hemolysis is a common presentation of thrombotic microangiopathy (TMA), however tropical infections such as malaria, dengue, leptospira, and drugs like antimalarial can have a similar presentation. They can cause AKI by some causes but an important cause of hemolysis leading to pigment nephropathy needs to be worked up while evaluating such patients. Important yet not relatively uncommon genetic causes of hemolytic anemia, i.e., glucose 6-phosphate deficiency (G6PD) can manifest as jaundice, hemolysis, and AKI secondary to pigment nephropathy after receiving anti-malarial.[1],[2] We report three patients of G6PD deficiency presenting as a rare cause for pigment nephropathy.


   Patients and Methods Top


All the three patients in this study were males, aged 20 years, 40 years, and 47 years. The patients initially developed high-grade fever with chills and received anti-malarial (chloro-quine -2.5 g over 3 days) as such fever in tropical countries like India are usually treated with anti-malarial empirically with a provisional diagnosis of malaria despite smears being negative. They then developed hemo-lysis, jaundice, decreased urine output, cola-colored urine and advanced renal failure giving a clinical impression of TMA though there was no definite evidence of low platelets or fragmented red blood cells which can be transient in TMA. All these patients were from the northern part of India and were managed in a tertiary care center in the same region. Hemogram showed low hemoglobin in all three patients with increased reticulocyte count and high-serum lactic dehydrogenase levels suggestive of hemolysis, however, the direct and indirect Coombs test was negative. G6PD estimation was done by the fluorescent spot method test at the time of admission before transfusion. Bone-marrow biopsy was done in all three patients. The clinical features and laboratory parameters are listed in [Table 1].
Table 1: Clinical and laboratory parameters.

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All patients were given artesunate following admission in the hospital given nonresolving fever and advanced renal failure with evidence of hemolysis. They were managed by multiple sessions of hemodialysis and conservative support. After stabilization of hemogram with blood transfusion during dialysis. A tentative diagnosis of TMA was made in view of oliguria and evidence of hemolysis and hence, kidney biopsy was done.

Kidney biopsy

Renal biopsy showed normal glomerular morphology with no evidence of intra-glomerular or extra-capillary hypercellularity. Tubules showed features of acute tubular necrosis [Figure 1]a with red blood cell casts and pigments in all cases [Figure 1]b. Interstitium was edematous with mild mono-nuclear cell infiltrate and the blood vessels were largely unremarkable. A diagnosis of acute tubular injury with pigment nephropathy was suggested.
Figure 1: (a) Microphotograph of kidney biopsy shows dilated tubules (arrows) with flattening of lining epithelium (H and E; ×100), (b) Microphotograph of kidney biopsy shows dilated tubules filled with red blood cell and pigment (arrows) ( H and E; ×200).

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Gradually, urine output improved with settling renal functions. The patients were discharged with a median period of admission of 14 days despite the creatinine being marginally high as tubular functions take time to recover. Follow-up after two weeks showed normal renal functions in all patients [Table 1].


   Discussion Top


The incidence of G6PD deficiency is variable in different parts of the world; however, it varies between 0% and 10% in the Indian population and more so in tribal population.[3] All the three cases described in this report presented with severe hemolysis, along with renal insufficiency. The precipitating cause appeared to be the administration of antimala-rial drugs, i.e., chloroquine. Several groups of drugs have been known to precipitate hemo-lysis in G6PD deficient patients (analgesics, sulfonamides, anti-helminthics and antimala-rial).[4] The proposed mechanism appears to be interaction of these drugs with hemoglobin and oxygen, leading to formation of free oxygen radicals, which in GSH (reduced glutathione) depleted cells, further promotes oxidation of intracellular proteins and resulting in cell death.[5] In our study, all the three patients received chloroquine initially followed by artesunate. Apart from drugs, certain infections may also precipitate hemolysis in G6PD deficient subjects[6],[7] which were however not evident in our cases. Our patients showed signs of intravascular hemolysis in the form of raised LDH, bilirubin levels, and reticulocyte counts. Following this, complete workup for hemolytic anemia was undertaken which showed G6PD deficiency. All the three had deficiency in G6PD at the time of injury. Literature suggests that these values hold no accuracy at the time of injury and may be normal; however in our patients, despite the inciting mechanism existing they all had low values confirming the diagnosis.[1] Coombs tests were negative and the bone-marrow examination was normal. All the cases showed features of acute tubular injury with pigment deposition in tubules on renal biopsies.

The pathogenesis of acute renal failure following intravascular hemolysis is not well understood. Several studies have shown that various factors may contribute to renal injury, like blockage of renal tubules by hemolyzed red cells,[8],[9],[10] intravascular coagulation leading to release of thromboplastin factors,[11] decreased renal blood flow and glomerular filtration rate,[12] or by a combination of the above factors.[11],[12],[13],[14] In a study conducted by Choudhry et al out of 20 G6PD deficient children treated with drugs, 11 developed acute renal insufficiency and intravascular hemolysis, whereas nine developed intravascular hemolysis alone.[15]


   Conclusion Top


Glucose 6-phosphate dehydrogenase deficiency is a relatively uncommon disease presenting as pigment nephropathy and TMA-like picture. In tropical countries, G6PD deficiency although not common, is not a very rare disease and in these patients while prescribing antimalarial drugs, it is important to perform a detailed hemolytic work-up which is an important cause of preventable recurrent AKI in tropical countries.

Conflict of interest: None declared.

 
   References Top

1.
Alving AS, Carson PE, Flanagan CL, Ickes CE. Enzymatic deficiency in primaquine-sensitive erythrocytes. Science 1956;124:484-5.  Back to cited text no. 1
    
2.
Kirkman HN, Hendrickson EM. Sex-linked electrophoretic difference in glucose-6-phosphate dehydrogenase. Am J Hum Genet 1963;15:241-58.  Back to cited text no. 2
    
3.
Kumar P, Yadav U, Rai V. Prevalence of glucose-6-phosphate dehydrogenase deficiency in India: An updated meta-analysis. Egypt J Med Hum Genet 2016;17:295-302.  Back to cited text no. 3
    
4.
Choudhry VP, Madan N, Sood SK. Intra-vascular haemolysis and renal insufficiency in children with glucose-6-phosphate dehydro-genase deficiency, following antimalarial therapy. Indian J Med Res 1980;71:561-6.  Back to cited text no. 4
    
5.
Beutler E. G6PD deficiency. Blood 1994;84: 3613-36.  Back to cited text no. 5
    
6.
Burka ER, Weaver Z 3rd, Marks PA. Clinical spectrum of hemolytic anemia associated with glucose-6-phosphate dehydrogenase deficiency. Ann Intern Med 1966;64:817-25.  Back to cited text no. 6
    
7.
Shannon K, Buchanan GR. Severe hemolytic anemia in black children with glucose-6-phosphate dehydrogenase deficiency. Pediatrics 1982;70:364-9.  Back to cited text no. 7
    
8.
Dobrin RS, Larsen CD, Holliday MA. The critically ill child: Acute renal failure. Pediatrics 1971;48:286-93.  Back to cited text no. 8
    
9.
Srivastava RN, Choudhry VP, Ghai OP. Acute renal failure. In: Ghai OP, editor. Essential Paediatrics. New Delhi: International Publication; 1982. p. 276.  Back to cited text no. 9
    
10.
Goldberg M. Studies of the acute renal effects of hemolyzed red blood cells in dogs including estimations of renal blood flow with krypton. J Clin Invest 1962;41:2112-22.  Back to cited text no. 10
    
11.
Rodríguez-Erdmann F. Bleeding due to increased intravascular blood coagulation. Hemorrhagic syndromes caused by consumption of blood-clotting factors (consumption-coagulopathies). N Engl J Med 1965;273: 1370-8.  Back to cited text no. 11
    
12.
Jaenike JR. The renal lesion associated with hemoglobinemia: A study of the pathogenesis of the excretory defect in the rat. J Clin Invest 1967;46:378-87.  Back to cited text no. 12
    
13.
Salen G, Goldstein F, Haurani F, Wirts CW. Acute hemolytic anemia complicating viral hepatitis in patients with glucose-6-phosphate dehydrogenase deficiency. Ann Intern Med 1966;65:1210-20.  Back to cited text no. 13
    
14.
Owusu SK, Addy JH, Foli AK, Janosi M, Konotey-Ahulu FI, Larbi EB. Acute reversible renal failure associated with glucose-6-phosphate-dehydrogenase deficiency. Lancet 1972;1:1255-7.  Back to cited text no. 14
    
15.
Choudhry VP, Ghafary A, Zaher M, Qureshi MA, Fazel I, Ghani R. Drug-induced haemolysis and renal failure in children with glucose-6-phosphate dehydrogenase deficiency in Afghanistan. Ann Trop Paediatr 1990;10:335-8.  Back to cited text no. 15
    

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Correspondence Address:
Dr. Anupma Kaul
Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
India
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DOI: 10.4103/1319-2442.248316

PMID: 30588969

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