CANARY IN A COALMINE: AN INTERESTING CASE OF RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS (RPGN)

Introduction:

The Case:

A 55 year old non-diabetic male with history of hypertension for 1 year, initially presented to an outside hospital with complaints of progressive bilateral lower limb oedema, facial puffiness abdominal distention and dyspnoea on exertion for the past four months followed by oliguria for 10 days duration. At presentation, the patient had anasarca and uncontrolled hypertension with a blood pressure of  170/110 mmHg, bilateral pleural effusion and ascites. On reviewing his medical records, he had a baseline creatinine of 1.5 mg/dl six months back. Recent lab reports over a period of last three weeks showed gradual drop in hemoglobin (12 to 7g/dl), normal leucocyte count with lymphocytic predominance (63%) and thrombocytopenia (60,000-70,000/mm3). Serum creatinine increased from 4 to 7.7 mg/dl over a period of 2 weeks. Urinalysis showed 3+ albumin, numerous red blood cells per high power field and nephrotic range proteinuria with a urinary protein creatinine ratio (UPCR) of 5.5 g/g. USG showed normal sized kidneys with no organomegaly.  Renal biopsy was deferred in view of bicytopenia and in a high suspicion of  RPGN, intravenous methyl prednisolone pulse(1gm X 3 days) was given followed by oral steroids at 0.5 mg/kg/day along with initiation of hemodialysis and supportive care.

Methods:

The patient’s history was reviewed when he presented to our institute one month later. He was apparently well before with no recent illness or constitutional symptoms. On examination he had a body mass index (BMI) of 29.4kg/m2 along with uncontrolled blood pressure of 210/120 mmHg. There was grade 3 pedal edema with no skin rash or lymphadenopathy. Decreased breath sounds were noted in bilateral basal lung fields along with the presence of ascites on abdominal examination. His serum creatinine settled to 4-4.5 mg/dl with urine output of around 1 liter per day on steroid therapy. Urine analysis showed presence of significant proteinuria and hematuria. Bicytopenia was persistent. Peripheral smear revealed no features of hemolysis with relative lymphocytosis, thrombocytopenia and no abnormal cells. Autoimmune work up, viral serologies and myeloma work up were negative. Serum complement levels were normal (Table 1).  Computed tomography scan of abdomen and thorax showed mild sub centimetric lymphadenopathy. High risk renal biopsy was performed with single donor platelets (SDP)  and packed red blood cell (PRBC) transfusions and pre-biopsy hemodialysis for decongestion.

Results:

The Diagnosis: Chronic Lymphocytic Leukaemia- Modified Rai Stage IV with Cryoglobulinaemic Glomerulonephritis- Type I with renal infiltration

A percutaneous renal biopsy of the kidney showed features of Membranoproliferative glomerulonephritis with pseudo thrombi in favor of type 1 cryoglobulinemic glomerulonephritis and tubulointerstitial nephritis with atypical lymphoid infiltrate (Figure 1a). Immunofluorescence showed immune deposits in pseudo thrombi and capillary membranes with IgG, C3C, C1q, mesangial for IgM and Kappa light chain restriction (Figure 1b and c). Immunohistochemistry (IHC) showed atypical cells positive for CD20, CD5, CD23, focal positive for CD3 in reactive lymphoid cells, favoring a diagnosis of B cell lymphoma, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (Figure 1d).

To look for primary site of lymphoproliferation, bone marrow biopsy was performed. It showed 90% infiltrate with small round to oval cells with scant cytoplasm positive for  CD5 and CD23 on IHC. Bone marrow aspirate flow cytometry was also positive for CD5 and CD23 on IHC. Thus the final diagnosis in our case was of Chronic Lymphocytic Leukemia -Modified Rai Stage IV with Cryoglobulinemic Glomerulonephritis - Type I and renal infiltration.

On follow-up, oral steroid was tapered and stopped. Bendamustine and Rituximab based chemotherapy initiated under the care of Medical Oncology. The patient’s serum creatinine and proteinuria were in improving trend and he no longer required dialysis.

Conclusions:

The unusual features in our case was the finding of concomitant cryoglobulinemia with renal infiltration of CLL/SLL cells. Renal manifestation was the predominant finding in our case with only subtle hints of a haematological malignancy. Thus, the kidney acted as a “Canary in a coal mine” and warned us of a potential danger and finally led us to the diagnosis of CLL. Steroids may not always be the answer in a case of RPGN, and our case underscores the importance of performing a renal biopsy!

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.