chronic lymphocytic leukemia ( cll ) is a chronic lymphoproliferative disorder recognized by a mass production of monoclonal incompetent lymphocytes . in most cases it follows an indolent and prolonged clinical course . infiltration with b - cll cells may occur in any organ , mostly lymphoid tissues , such as the spleen , liver , and peripheral lymph nodes . renal infiltration has been described in 6390% of all cll patients who underwent post - mortem autopsy.[24 ] the major complications of cll arise from cytopenias ( anemia , thrombocytopenia ) and immune dysfunction . we present a case of a 83-year - old female with stable cll of 6 years until she presented with rapidly progressive renal impairment due to leukemic infiltration . she was treated with single - agent chemotherapy ( chlorambucil ) and had a gratifying response with significant improvement in her renal function . an 83-year - old caucasian lady referred to the nephrology clinic in january 2011 with rapidly worsening renal impairment . her serum creatinine had risen from the baseline value of 1.40 mg / dl to 2.82 mg / dl over a period of around 7 months [ june 2010 to january 2011 ; figure 1 ] . her past medical history included breast carcinoma treated with right - sided mastectomy and axillary clearance 15 years previously , low - rectal carcinoma treated with chemo- and radiotherapy 6 years previously and cll . the latter had been diagnosed 6 years previously when a full blood count demonstrated a lymphocytosis of 14  10/l , the lymphocytes having the typical morphology and expressing the surface markers cd19 , cd5 , cd23 with weak surface immunoglobulin and no fmc7 ( cll score 5/5 ) . the blood count had been otherwise normal , and she had no lymphadenopathy or hepatosplenomegaly . her regular medications included amlodipine 5 mg od po and ranitidine 150 mg od po . she lived alone but continued to manage with all her activities of daily living despite her fatigue . presentation to the nephrology clinic was in january 2011 clinical examination revealed a comfortable lady at rest with all vital observations within normal limits . cardiovascular , respiratory , and abdominal examinations were unrevealing and in particular there was no evidence of organomegaly or recurrence for the aforementioned solid tumor malignancies . her hemoglobin was measured at 7.7 g / dl , white cell count 107.8  10/l , lymphocytes 101.3  10/l , and platelets 200  10/l [ figure 2 ] . there was no evidence of hemolysis ( no spherocytes , reticulocytes 1.3% , direct coombs test negative , and bilirubin 0.23 mg / dl ) . her renal function was severely compromised ( urea 41.7 mg / dl and creatinine 2.82 mg / dl ) having shown a rapid deterioration over the preceding 8 months [ figure 1 ] . the peak of her creatinine rise coincided with the peak lymphocyte count in january 2011 [ figure 2 ] . treatment of cll with chlorambucil was commenced in february 2011 dipstick urinalysis demonstrated protein+and a protein : creatinine was 44 mg / mmol . serum and urine electrophoresis were normal . a vasculitic screen ( including ana , anca , and dsdna ) was negative . given the lack of an obvious cause for this lady 's renal impairment , a renal biopsy was performed following transfusion two units of packed red cells , local anesthetic and real - time ultrasound imaging guidance . light microscopy of a core revealed dense infiltration of the interstitium with small lymphocytic lymphoma [ figure 3 ] . some of the glomeruli were globally sclerosed consistent with chronic kidney disease ; however the remaining glomerular and tubular architecture remained preserved [ figure 3 ] . renal biopsy demonstrating confluent b - cll infiltration of the interstitum within which there are few glomeruli and tubules with preserved architecture ( h and e ; 40 magnification ) based upon these findings therapy for cll was recommended . she was considered too frail for combination chemotherapy with monoclonal antibodies and was therefore given single alkylating agent therapy with chlorambucil 10 mg daily for 14 days repeated every 4 weeks . this was very well - tolerated apart from the need for two unit red cell transfusions and a short treatment delay for asymptomatic mild thrombocytopenia . her renal function began to improve immediately after starting the first cycle of treatment . by the third , her lymphocytosis had resolved and her serum creatinine had fallen to 1.42 mg / dl [ figures 1 and 2 ] . some degree of renal infiltration in cll is common but the incidence of marked infiltration such as that seen in our patient is probably much less . they found leukemic involvement in 90% of patients , but noted that renal infiltration occurred in only four cases in a more diffuse , although still well - defined , manner . although such infiltration is well recognized in acute leukemia , only 14 cases of renal failure due to cll cell infiltration ( including ours ) have been described in the literature so far . renal failure in the context of cll is usually secondary to complications of disease and/or its treatment ( e.g. , infection or tumor lysis syndrome following chemotherapy ) . in a recent study of 700 patients with non - hodgkin lymphoma and cll , 17 cll patients proposed to have manifestations of renal failure of which only three of them were directly related with cll . several case reports have described patients with only mild cll disease activity ( as in our patient ) although more aggressive forms can also exist along with renal failure.[1117 ] despite thorough initial investigation , a straightforward cause for our patient 's renal impairment was not apparent . in retrospect , renal ultrasound imaging revealed normal sized kidneys on a background of chronic kidney disease possibly suggestive of relative organomegaly due to lymphocyte cell infiltration.[1012 ] however , the kidney size can also be within normal limits.[1315 ] renal histology may demonstrate various lesions known to be associated with cll , including immunotactoid glomerulopathy , membranoproliferative glomerulonephritis type 1 ( with or without mixed cryoglobulinemia ) , urate nephropathy , amyloidosis , and minimal change disease . the biopsy of our patient did not exhibit any features of the latter and clinically there were no signs to support the nephrotic syndrome . interstitial infiltrates are a common occurrence in cll , but more diffuse ones as demonstrated in our case may result in target organ damage . the mechanism by which cll cells cause renal dysfunction is not known , but it has been postulated that tumor infiltration causes compression of the tubular lumen and microvasculature , producing intrarenal obstruction and ischemia respectively . interestingly , our biopsy did not reveal features of tubular compression [ figure 3 ] . given concerns regarding age and potential intolerance of intensive chemotherapy , a decision was made to give chlorambucil only . previous reports in this setting have initiated more aggressive treatment regimes including fludarabine / rituximab / prednisone , methyprednisolone / cyclophosphamide , and adjunctive radiotherapy . response to treatment has varied from complete resolution of the acute renal failure to more often a partial response to no response . to our knowledge , there has only been one previous case in the literature where chlorambucil has been used solely and this did not result in a return to baseline renal function . thus , our case report is the first case to date to demonstrate a marked resolution in renal impairment with chlorambucil alone . in conclusion , we present successful treatment of rapidly progressive renal failure due to leukemic infiltration in an elderly caucasian female with cll . despite leukemic infiltration being common in cll , detailed evaluation is recommended for patients with increased serum creatinine levels and no other apparent cause for deterioration . in particular , our case highlights the value of renal biopsy to confirm diagnosis . when diagnosed , the condition tends to respond well to a variety of chemotherapeutic agents and may avert the need for renal replacement therapy . our case is the first to date to demonstrate a marked resolution in renal impairment with chlorambucil alone . this treatment could be considered as an alternative to more intensive regimes where side effect profiles could be detrimental to the patient given age , frailty , and other comorbidities .
chronic lymphocytic leukemia tends to follow an indolent course and despite infiltration of leukemic cells in numerous organs , resultant target organ damage is uncommon . we present a case of an 83-year - old caucasian lady who presented with rapidly worsening renal impairment over a several month period with a serum creatinine peak of 2.82 mg / dl . despite numerous investigations an immediate cause was not apparent . 
 a renal biopsy was therefore conducted which revealed dense infiltration of the interstitium with small lymphocytic lymphoma . given her age and frailty she was treated with single alkylating agent chemotherapy ( chlorambucil ) . 
 this resulted in a marked decrease in lymphocyte count and resolution of renal impairment close to her previous baseline level . to our knowledge 
 , this is the first case in the literature to demonstrate a marked resolution in renal impairment with chlorambucil alone . 
 we also highlight the value of renal biopsy in identifying a rare cause of renal impairment .