Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 114 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 


 
Table of Contents   
CASE REPORT  
Year : 2013  |  Volume : 24  |  Issue : 1  |  Page : 93-96
Acute renal failure in a patient with acute lymphoblastic leukemia: A rare cause


1 Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
2 Department of Nephrology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
3 Department of Hematology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

Click here for correspondence address and email

Date of Web Publication22-Jan-2013
 

   Abstract 

A young adult was diagnosed to have acute lymphoblastic leukemia, T-cell immunophenotype and was initiated on chemotherapy. He presented with acute renal failure two days after the completion of his induction regimen. A renal biopsy showed features of necrotizing crescentic glomerulonephritis (GN). Serology for c-anti-neutrophil cytoplasmic antibody (ANCA) was positive and a final diagnosis of ANCA-associated necrotizing crescentic GN was made. Aggressive immunosuppression could not be used due to the presence of nosocomial pneumonia and the patient expired 26 days after the renal biopsy diagnosis. We report for the first time the association of acute lymphoblastic leukemia with crescentic GN and, hence, expand the list of malignancy-related ANCA-positive GN.

How to cite this article:
Sharma A, Gupta R, Rizvi Y, Rathi S, Mahapatra M, Bhowmik D, Dinda AK. Acute renal failure in a patient with acute lymphoblastic leukemia: A rare cause. Saudi J Kidney Dis Transpl 2013;24:93-6

How to cite this URL:
Sharma A, Gupta R, Rizvi Y, Rathi S, Mahapatra M, Bhowmik D, Dinda AK. Acute renal failure in a patient with acute lymphoblastic leukemia: A rare cause. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2014 Apr 24];24:93-6. Available from: http://www.sjkdt.org/text.asp?2013/24/1/93/106299

   Introduction Top


Glomerular involvement is well known in patients with plasma cell dyscrasias. The same, however, cannot be said about other hematological neoplasms, except chronic lymphocytic leukemia (CLL). [1],[2] Crescentic glomerulonephritis (GN) has been reported very rarely in hematological malignancies, including CLL, Hodgkin's disease and myeloproliferative/myelodysplastic syndromes. [2],[3],[4] The causal relationship between hematological neoplasms and crescentic GN has been linked to immune dysregulation frequently encountered in these patients. [5] To the best of our knowledge, anti-neutrophil cytoplasmic antibody (ANCA)-positive necrotizing crescentic GN has not been reported in a patient with acute lymphoblastic leukemia in the available literature.

We describe the case of a young adult with acute lymphoblastic leukemia who presented with renal failure and was found to have ANCA-associated pauci-immune necrotizing crescentic GN on renal biopsy. This rare association of hematological neoplasms and GN is briefly reviewed.


   Case Report Top


An 18-year-old boy presented with history of chest pain and progressive breathlessness. He was diagnosed as having right hemothorax for which an intercostal chest drain was inserted; he was then referred to our institute for further management. On examination, he was pale, with petechiae and echymoses. Systemic examination revealed hepatosplenomegaly. Hemogram showed marked leukocytosis (total leukocyte count 127,000/mm 3 ) with 90% blasts on peripheral smear. There was severe thrombocytopenia (platelet count 26,000/mm 3 ). Subsequent bone marrow aspiration and trephine biopsy showed near-total replacement of the marrow elements by blasts, morphologically appearing lymphoid in nature. Flow cytometric examination of the peripheral blood showed the blasts to be positive for CD2, CD5, CD7 and CD79a. Hence, a diagnosis of acute lymphoblastic leukemia, T-cell immunophenotype with co-expression of CD79a was made and the patient was started on chemotherapy (induction regimen of prednisolone, vincristine, daunorubicin and L-asparaginase). With this therapy, the patient achieved hematological remission (blast count <1%, absolute neutrophil count >3000/mm 3 , hemoglobin 9.8 g/dL, platelet count 2 × 10 9 /L). At this time, his renal functions were well maintained (serum urea 34 mg/dL, serum creatinine 0.4 mg/dL). Over the next two weeks, steroids were tapered off and stopped.

Two days after the discontinuation of steroids, he was readmitted with complaints of right-sided chest pain, cough, high-grade fever and reduced urine output of 1 day duration. At admission, he was hypertensive and pale and had pedal edema. There was splenomegaly and bilateral coarse crepitations. Laboratory tests revealed anemia and microscopic hematuria with active sediment. Right-sided pleural fluid examination showed exudative effusion with predominantly lymphocytes. He was administered antibiotics for pneumonia and initiated on hemodialysis for advanced azotemia and fluid overload. A kidney biopsy was performed to elucidate the cause of acute renal failure (ARF). On serological investigations, c- and p-ANCA were positive. The salient laboratory parameters at the time of renal biopsy are summarized in [Table 1].
Table 1: Laboratory test values of the study patient at the time of renal biopsy.

Click here to view


Pathologic findings

The kidney biopsy sample showed 23 glomeruli, of which 20 (87%) revealed cellular to fibro-cellular crescents with compression of the glomerular tuft. Two glomeruli with crescents showed necrosis of the glomerular tuft. Focal disruption of the Bowman's capsule was noted in three glomeruli. Patchy tubular atrophy and interstitial fibrosis was seen. Blood vessels appeared relatively unremarkable and no vasculitis was seen [Figure 1].
Figure 1a: A photomicrograph showing variable interstitial edema (H&E ×40). 1b). Higher-power shows cellular crescent in a glomerulus (H&E ×100). 1c). Focal necrosis of the glomerular tuft is noted (H&E ×200). 1d). Silver-methenamine stain highlights the cellular crescent (×200).

Click here to view


Immunofluorescence staining on frozen sections was negative for all immunoglobulins (IgA, IgG, IgM) and complement components (C3c and C1q). A pathologic diagnosis of pauci-immune necrotizing crescentic GN was made.

Follow-up

The patient was managed with regular hemodialysis and other supportive treatment. The pleural fluid was positive for Mycobacterium tuberculosis by polymerase chain reaction. Hence, the patient was started on rifampicin-based anti-tuberculous therapy. He continued to have fever and developed nosocomial pneumonia, which did not allow for high-dose steroids or cyclophosphamide to be used for his renal failure. He further deteriorated with progressive respiratory failure and expired 26 days after the renal biopsy diagnosis was made.


   Discussion Top


Glomerular lesions in the form of amyloidosis, monoclonal immunoglobulin deposition disease and cryoglobulinemia are well characterized in association with plasma cell dyscrasias. [1] However, GN occurs very rarely in other hematological malignancies. A recent review has revealed that CLL was the most common lymphoproliferative disorder associated with GN. The various GNs described in association with CLL include membranous GN, membranoproliferative GN, minimal change disease, IgA nephropathy and, rarely, crescentic GN. [2]

Crescentic GN may be associated with anti-glomerular basement antibody (GBM), immune complex deposition or ANCA positivity. In addition, secondary forms of crescentic GN may be seen with systemic diseases like systemic lupus erythematosus (SLE), malignancies or medications like propylthiouracil, hydralazine, methimazole, enalapril and penicillamine. [5] Among malignancies, solid tumors like prostate cancer, transitional cell carcinoma of bladder, pulmonary adenocarcinoma as well as hematological neoplasms such as myeloproliferative/myelodysplastic syndromes, CLL and Hodgkin's disease have been reported with pauci-immune crescentic GN. [3],[4] Tisler et al described a patient with CLL on treatment with fludarabine who developed ANCA-positive necrotizing crescentic GN. They hypothesized that fludarabine could have played a role in disruption of immune regulation, favoring the formation of anti-neutrophil anti-bodies and subsequent GN. [5]

Acute renal failure in patients with acute leukemia is usually a consequence of chemotherapeutic regimen, leading to the tumor lysis syndrome. The tumor lysis syndrome results in acute uric acid and calcium phosphate nephropathy. [6] A few cases of leukemic infiltration of the kidneys presenting as ARF have also been reported in the literature. [6],[7] Martini et al reported a child presenting with the hemolytic uremic syndrome (HUS), who was later detected to have acute lymphoblastic leukemia (ALL), suggesting that HUS may be a presenting manifestation of ALL. [8] Hence, the elucidation of etiology of ARF in patients with acute leukemia requires consideration of all these factors, in addition to the occurrence of GN.

An extensive review of the available literature did not yield any previous report of ANCA-positive necrotizing crescentic GN in association with ALL. Our patient did not have SLE or serological evidence of anti-GBM disease. Although rifampicin has rarely been reported to cause crescentic GN, [9] the renal biopsy in our patient was performed before rifampicin-based therapy was started and, hence, this etiological agent was ruled out. Of particular interest is the fact that the patient had been tapered off all immunosuppressives few days before he presented with renal impairment. Because this is the first report of this association, the exact causal relationship cannot be elucidated and further cases need to be studied in this regard.

In conclusion, this report adds ALL to the exhaustive list of neoplasms associated with ANCA-positive crescentic GN. Although drug toxicity is the main cause of ARF in patients with acute leukemia, the occurrence of GN should be considered and evaluated by a timely performed renal biopsy.

 
   References Top

1.Herrera GA, Picken MM. Renal diseases associated with plasma cell dyscrasias, amyloidosis, Waldenstrom macroglobulinemia and cryoglobulinemic nephropathies. In: Jennette JC, Olson JL, Schwartz MM, Silva FG, eds. Heptinstall's Pathology of the Kidney. 6 th ed. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 854-910.   Back to cited text no. 1
    
2.Da'as N, Polliack A, Cohen Y, et al. Kidney involvement and renal manifestations in non-Hodgkin's lymphoma and lymphocytic leukemia: A retrospective study. Eur J Haematol 2001;67:158-64.   Back to cited text no. 2
[PUBMED]    
3.von Vietinghoff S, Schneider W, Luft FC, Kettritz R. Crescentic glomerulonephritis and malignancy: guilty or guilt by association? Nephrol Dial Transplant 2006;21:3324-6.   Back to cited text no. 3
[PUBMED]    
4.Wolf G, Krenz I, Hegewisch-Becker S, Hossfeld DK, Helmchen U, Stahl RA. Necrotizing glomerulonephritis associated with Hodgkin's disease. Nephrol Dial Transplant 2001;16:187-8.   Back to cited text no. 4
[PUBMED]    
5.Tisler A, Pierratos A, Lipton JH. Crescentic glomerulonephritis associated with p-ANCA positivity in fludarabine-treated chronic lymphocytic leukaemia. Nephrol Dial Transplant 1996;11:2306-8.   Back to cited text no. 5
[PUBMED]    
6.Suh WM, Wainberg ZA, de Vos S, Cohen AH, Kurtz I, Nguyen MK. Acute lymphoblastic leukemia presenting as acute renal failure. Nature Clin Pract Nephrol 2007;3:106-10.  Back to cited text no. 6
[PUBMED]    
7.Escobar H, Häffner K, Pohl M, et al. Acute renal failure associated with bilateral enlargement of kidneys: A rare manifestation of acute lymphoblastic leukemia (ALL). Klin Padiatr 2009;221:176-8.  Back to cited text no. 7
    
8.Martini G, Dall'Amico R, Murer L, Montini G, D'Avino A, Zacchello G. Haemolytic-uremic syndrome as a presenting form of acute lymphoblastic leukemia. Ann Hematol 2000;79:452-4.  Back to cited text no. 8
[PUBMED]    
9.Muthukumar T, Jayakumar M, Fernando EM, Muthusethupathi MA. Acute renal failure due to rifampicin: A study of 25 patients. Am J Kidney Dis 2002;40:690-6.  Back to cited text no. 9
    

Top
Correspondence Address:
Amit K Dinda
Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi
India
Login to access the Email id


DOI: 10.4103/1319-2442.106299

PMID: 23354200

Get Permissions



    Figures

  [Figure 1]
 
 
    Tables

  [Table 1]



 

Top
   
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
   Introduction
   Case Report
   Discussion
    References
    Article Figures
    Article Tables
 

 Article Access Statistics
    Viewed698    
    Printed20    
    Emailed0    
    PDF Downloaded133    
    Comments [Add]    

Recommend this journal