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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 3  |  Page : 521-525
Transient IgA nephropathy with acute kidney injury in a patient with dengue fever


1 Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

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Date of Web Publication26-Apr-2010
 

   Abstract 

Dengue virus infection can clinically manifest as dengue fever, dengue shock syn­drome and dengue hemorrhagic fever. Acute kidney injury as a result of dengue virus infection can occur due to various reasons including hypotension, rhabdomyolysis, sepsis and rarely immune complex mediated glomerular injury. However, glomerulonephritis associated with IgA Nephropathy in dengue virus infection has not been reported previously. We report a case of 15­year-old boy who was admitted with dengue fever and dialysis dependant acute kidney injury. Urine examination showed microscopic glomerular hematuria and proteinuria. Kidney biopsy showed mesangial proliferation with mesangial IgA dominant immune complex deposits and acute tubular necrosis. A repeated kidney biopsy 6 weeks after clinical recovery showed reversal of glomerular changes as well as resolution of mesangial IgA deposits.

How to cite this article:
Upadhaya BK, Sharma A, Khaira A, Dinda AK, Agarwal SK, Tiwari SC. Transient IgA nephropathy with acute kidney injury in a patient with dengue fever. Saudi J Kidney Dis Transpl 2010;21:521-5

How to cite this URL:
Upadhaya BK, Sharma A, Khaira A, Dinda AK, Agarwal SK, Tiwari SC. Transient IgA nephropathy with acute kidney injury in a patient with dengue fever. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2019 Nov 15];21:521-5. Available from: http://www.sjkdt.org/text.asp?2010/21/3/521/62702

   Introduction Top


Dengue virus infection clinically manifests as uncomplicated Dengue Fever (DF), Dengue He­morrhagic fever (DHF) or Dengue Shock syn­drome (DSS). DF is a common arthropod­borne viral disease endemic in more than 100 countries of the world and is caused by one of the four serotypes (types 1-4) of Dengue virus, an RNA flavivirus within family flaviviridae. Worldwide, more than 2.5 billion people are at risk, and about 50-100 million cases of Den­gue virus infection occur annually. [1]

Renal involvement and acute kidney injury has been reported in patients with dengue virus infection as a result of shock, hemolysis, rhab­domyolysis, sepsis, and rarely immune com­plex mediated glomerular injury. [2],[3],[4],[5],[6] Although immunoglobulin A (IgA) containing immune complex deposits in glomeruli may be seen in several viral infections, [7],[8] these have not been reported in association with dengue virus in­fection.

We present a case of acute kidney injury (RIFLE-F) (P0/C0) that needed hemodialysis support for four weeks. A kidney biopsy eva­luation for prolonged renal shutdown showed mesangioproliferative glomerulonephritis with mesangial IgA deposition and features of acute tubular necrosis (ATN). A repeat kidney bio­psy after six weeks; once the patient had cli­nically recovered showed resolution of mesan­gial proliferation as well as the IgA immune complex deposits.


   Case Report Top


A previously healthy 15-year-old boy was ad­mitted with complaints of fever with chills of one week duration. He also complained of oli­guria for two days. There was no history of rash or bleeding from any muco-cutaneous site. Exa­mination showed blood pressure of 150/90 mm Hg and mild icterus sclerae. The rest of the systemic examination including fundi was un­remarkable. Investigations revealed anemia (he­moglobin 9.2 mg/dL), mild neutrophilic leuko­cytosis (total count-16500/mm 3 ) with and mild thrombocytopenia (platelets-100000/mm 3 ). The total serum bilirubin was 2.1 mg% with direct fraction of 1.2 mg/dL. Liver enzymes aspar­tate transaminase (AST) and alanine transami­nase (ALT) were elevated (AST 120 IU/L and ALT 140 IU/L). Serum total protein and albu­min were 6.0 gm/dL and 3.2 gm/dL respec­tively. Blood urea was 167 mg/dL and serum creatinine was 8.4 mg/dL at presentation. Urine dipstick examination showed 2 + proteinuria, while microscopy revealed glomerular hema­turia (8-10 RBC's/hpf with 30% dysmorphic forms). The peripheral smear examination re­vealed normocytic and mildly hypochromic RBC's and was negative for malarial parasite and fragmented red blood cells. Immunological spot test for malarial antigen was negative. Se­rological tests for leptospira, Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) and Human immunodeficiency virus (HIV) were negative. Dengue serology showed elevated titres of dengue specific IgM and was negative for IgG. The patient had normal anti neutro­philic antibody (ANA) titres and was negative for c and p anti neutrophilic cytoplasmic anti­body (ANCA). Serum C3 (complement) levels were normal (112 mg%)

The patient was hemodialyzed along with in­travenous piperacillin + tazobactum and levo­floxacin in renal modified doses. After two weeks, the hematological profile and liver func­tion parameters returned to normal values.

However, as the patient's renal functions did not improve, and he remained oliguric (urine output 100-150 mL/day) a repeated kidney biopsy was performed. The light microscopic examination of the renal biopsy revealed eight glomeruli with increased mesangial cellularity and mild mesangial matrix expansion, [Figure 1]. The tubules showed features of acute tubular necrosis, and the interstitium showed wide­spread edema mild endothelial swelling of the blood vessels. The direct immunofluoroscence examination of the biopsy showed mesangial deposits of IgA (++), IgM (+) and C3 (+), [Figure 2]; no IgG deposits were detected. Based on the above features, a diagnosis of mesangioproliferative glomerulonephritis asso­ciated with IgA nephropathy was made. Sub­sequently, the patient's serum IgA levels were found to be mildly elevated (247 mg%) with preponderence of IgA 1 (219 mg%).

By the end of four weeks, the patient had received 6 sessions of hemodialysis along with two units of blood transfusion. Around this time, his renal functions showed improvement and urine output increased to 2.5-3.0 liters/day by the end of 5 th week. Serum creatinine de­creased to 1.3 mg%. A routine urine examina­tion at the time of discharge showed no he­maturia.

As the finding of glomerular IgA deposits and mesangioproliferative glomerulonephritis coinciding with dengue virus infection was un­usual, we decided to perform a repeat renal biopsy after 6 weeks of clinical remission to further evaluate this association. A urine exa­mination prior to the repeat biopsy did not show any RBC's. Serum IgA levels were nor­mal (180 mg%). The light microscopic exami­nation of the renal biopsy showed resolution of the mesangioproliferative changes. The tubu­lointerstitial changes had recovered with no residual inflammation or fibrosis [Figure 3]. The direct immunofluoroscence examination showed mesangial deposits of IgM (+) and C3 (+) and was negative for IgA and IgG.


   Discussion Top


The pathogenic links between viral infections and concomitant renal dysfunction are often difficult to establish. The causal association could be suggested by factors such as the sero­logical identification of specific viral anti­genemia and detection of viral antigens and host antibodies in renal structures. While it may not be possible to demonstrate complete cure after eradication of the virus in all the cases, improvement of the renal disease con­comitant with clearance of the suspected anti­gen or recurrence of the glomerulonephritis after reinfection may be additional criteria to prove the cause-effect link. The present case provokes several such issues, which relate to the immunopathologic mechanisms operating in the course of DF and its implications in the development of acute kidney injury.

Various mechanisms are implicated in the pathogenesis of renal injury associated with viral infections. These include the direct cyto­pathic effects of viral proteins on glomerular and tubular cells, in-situ immune mediated mechanisms involving viral antigens bound to glomerular structures, injury due to circulating immune complexes composed of viral antigens and host anti-viral antibodies and injury due to various inflammatory mediators released in response to glomerular or tubular cytopathic effects. [9],[10]

While transient renal abnormalities are seen in several viral infections, acute kidney injury is associated mostly with arboviral hemorrha­gic fevers, parvo virus B 19, measles, yellow fever and rarely dengue virus infections. [11],[12],[13],[14],[15] Renal involvement in dengue virus infection may occur with any of the clinical syndromes including DF, DHF, and DSS. Acute kidney injury in association with DF is rare and only eight cases have been adequately described in the literature. [3],[4],[5],[16] Most of these patients pre­sented with hypotension, shock, hemolysis, rhabdomyolysis and required HD support for varying durations. An eventual recovery was seen in most of the cases where follow-up was available. Our patient did not show any fea­tures of shock, hemolysis, or rhabdomyolysis, and he required hemodialysis support for three weeks and showed complete clinical recovery in five weeks. The acute renal failure could be in part mediated by the tubular damage media­ted by direct cytopathic effects of the virus and cytokine induced injury.

Furthermore, the finding of glomerular hema­turia at presentation and the presence of me­sangial IgA deposits followed by eventual re­solution of IgA deposits and hematuria conco­mitant with clinical recovery point towards an association between the IgA deposits and viral infection. Studies on the kinetics of dengue virus specific serum immunoglobulin classes in pa­tients with DF have shown that virus specific IgA antibodies are detectable between days 8­11 after the onset of fever and levels of dengue specific IgA correlate with the severity of di­sease outcome, thus emphasizing their role in the pathogenesis of the disease. [17] Indeed, the measurement of dengue specific IgA antibo­dies in serum is considered an important tool for diagnosis of a primary dengue virus infec­tion. [18] In the present case, total serum IgA le­vels were elevated when performed three weeks after the onset of fever and touched nor­mal values after 12 weeks. This coincided with the resolution of the mesangial IgA deposits in the repeat renal biopsy performed at the same time.

We hypothesize that Dengue virus infection was able to elicit an altered IgA immune res­ponse to viral antigens and resulted in the for­mation of nephritogenic circulating immune complexes, which subsequently deposited in the glomerular mesangium, and the ensuing cytokine and chemokines response resulted in the mesangial proliferation. This phenomenon may be transient and could be similar to that observed in other infections where immune complexes are cleared from the glomerulus in about three to four weeks time. [19],[20] Immune complex mediated glomerulonephritis associa­ted with DHF has been reported earlier, how­ever, the immune complex deposits in these cases consisted predominantly of IgG, IgM and C3 and deposited in the mesangium in a coarse granular pattern. [2] The renal biopsy fin­dings have been described in only one case of acute renal injury associated with DF, which revealed features of a thrombotic microan­giopathy. [5]

In conclusion we have presented a case of acute kidney injury related to dengue fever without any evidence of third space loss, hypo­volemia, hypotension, sepsis, or rhabdomyo­lysis. We attribute the renal failure to acute tubular necrosis with transient IgA nephro­pathy due to an immune related phenomenon. This phenomenon may be under-recognized and contribute to the severity of renal injury in the setting of dengue viral infection particu­larly DF.

 
   References Top

1.Gubler DJ. Epidemic dengue and dengue he­morrhagic fever: A global public health pro­blem in the 21st century. In: Scheld, WM, Armstrong, D, Hughes, JM (Eds). Emerging Infections. ASM Press, Washington DC; 1998:1.  Back to cited text no. 1      
2.Boonpucknavig V, Bhamarapravati N, Boon­pucknavig S, Futrakul P, Tanpaichitr P. Glo­merular changes in dengue hemorrhagic fever. Arch Pathol Lab Med 1976;100:206-12.  Back to cited text no. 2      
3.Hommel D, Talarmin A, Reynes JM, Hulin A. Acute renal failure associated with dengue fever in French Guiana. Nephron 1999;83:183.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Nair VR, Unnikrishnan D, Sathish B, Sahadulla MI. Acute renal failure in dengue fever in absence of bleeding manifestations or shock. Infec Dis Clin Pract 2005;13:142-43.  Back to cited text no. 4      
5.Weirsinga WJ, Scheepstra CG, Kasanaedjo JS, de Vries PJ, Zaaijer H, Geerlings SE. Dengue fever induced hemolytic uremic syndrome. Clin Infec Dis 2006;43:800-1.  Back to cited text no. 5      
6.Karakus A, Banga N, Voorn GP, Meinders AJ. Dengue shock syndrome and rhabdomyolysis. Neth J Med 2007;65:78-81.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]  
7.Cheema SR, Arif F, Charney D, Meisels IS. IgA dominant glomerulonephritis associated with hepatitis A. Clin Nephrol 2004;62:1238­-143.  Back to cited text no. 7      
8.Lai KN, Lai FM, Tam JS, Vallance-Owen J. Strong association between IgA nephropathy and hepatitis B surface antigenemia in endemic areas. Clin Nephrol 1988;29:229-34.  Back to cited text no. 8  [PUBMED]    
9.Glassock RJ. Immune complex-induced glo­merular injury in viral diseases: an overview. Kidney Int 1991;40(supp 35):S5-7.  Back to cited text no. 9      
10.Couser WG. Mechanisms of glomerular injury in immune complex disease. Kidney Int 1985; 28:569-83.  Back to cited text no. 10  [PUBMED]    
11.Globus SM, Wilson C. Experimental glome­rulonephritis induced by in-situ formation of immune complexes in glomerular capillary wall. Kidney Int 1979;16:148-57.  Back to cited text no. 11      
12.Nakazawa T, Tomosugi N , Sakamoto K, et al. Acute glomerulonephritis after human parvovirus B19 infection. Am J Kidney Dis 2000;35:E31.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]  
13.Monath TP. Yellow fever: a medically neglec­ted disease: Report on a seminar. Rev Infect Dis 1987;9:165-75.  Back to cited text no. 13  [PUBMED]    
14.Lin CY, Hsu HC. Measles and acute glome­ rulonephritis. Pediatrics 1983;71:398-401.  Back to cited text no. 14  [PUBMED]    
15.Lima EQ, Gorayeb FS, Zanon JR, Nogueira ML, Ramalho HJ, Burdmann EA. Dengue hemorrhagic fever induced acute kidney injury without hypotension, hemolysis or rhabdo­myolysis. Nephrol Dial Transplant 2007;22: 3322-6.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]  
16.George R, Liam CK, Chua CT, Lam SK, Pang T, Geethan R, Foo LS. Unusual clinical mani­festations of dengue virus infection. Southeast Asian J Trop Med Public Health 1988;19:585­-90.  Back to cited text no. 16  [PUBMED]    
17.Koraka P, Suharti C, Setiati TE, et al. Kinetics of Dengue virus specific serum immunoglo­bulin classes correlate with clinical outcome of infection. J Clin Microbiol 2001;39:4332-8.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]  
18.Nawa M, Takasaki T, Ito M, Inoue S, Morita K, Kurane I. Immunoglobulin A antibody res­ponses in dengue patients: A useful marker for serodiagnosis of dengue virus infection. Clin Diag Lab Immunol 2005;12:1235-7.  Back to cited text no. 18      
19.Bhamarapravati, N, Boonpucknavig S, Boon­pucknavig V, Yaemboonruang C. Glomerular changes in acute falciparum infection. Arch Pathol 1973;96:289-93.  Back to cited text no. 19      
20.Sitprija V, Pipatanagul V, Boonpucknavig V, Boonpucknavig S. Glomerulitis in typhoid fever. Ann Intern Med 1974;81:210-3.  Back to cited text no. 20      

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Correspondence Address:
Amit K Dinda
Department of Pathology, All India Institute of Medical Sciences, New Delhi
India
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