Year : 2008 | Volume
: 51 | Issue : 4 | Page : 509--511
A case of collapsing glomerulopathy associated with febrile illness
Vinita Agrawal1, PB Vinod2, N Krishnani1, RK Sharma2,
1 Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India
2 Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India
Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226 014, Uttar Pradesh
Collapsing glomerulopathy (CG) is a distinct clinicopathological entity characterized by high levels of nephrotic range proteinuria, rapidly progressive renal failure, marked parenchymal injury, and poor response to present therapeutic regimens. Growing awareness has led to the identification of associated conditions other than human immunodeficiency virus (HIV) and idiopathic. We report a case of CG from India in a HIV-negative young female, presenting with heavy proteinuria and rapidly progressing renal failure preceded by a febrile illness.
|How to cite this article:|
Agrawal V, Vinod P B, Krishnani N, Sharma R K. A case of collapsing glomerulopathy associated with febrile illness.Indian J Pathol Microbiol 2008;51:509-511
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Agrawal V, Vinod P B, Krishnani N, Sharma R K. A case of collapsing glomerulopathy associated with febrile illness. Indian J Pathol Microbiol [serial online] 2008 [cited 2022 Jan 23 ];51:509-511
Available from: https://www.ijpmonline.org/text.asp?2008/51/4/509/43743
Collapsing glomerulopathy (CG), also referred to as collapsing focal and segmental glomerulosclerosis (FSGS), was first recognized and is most often reported in HIV patients. The growing identification of this entity has led to reports discussing its association with disorders other than HIV and idiopathic. ,, CG is uncommonly reported from the tropics with only one case report from India.  We report a case of CG in a young female resident of North India, preceded by a febrile illness, rapidly progressing to unremitting renal failure resistant to prednisolone and mycophenolate (MMF) treatment.
A non obese 20-year-old female presented with pedal edema for 2 months and vomiting of 1.5 months duration with a history of high-grade fever associated with chills at the onset of the disease lasting for 1 week. She also complained of decreased urine output for 1 month and breathlessness, generalized weakness, and anorexia for 15 days. She had no history of prior medication, blood transfusions, or intravenous drug use.
On examination, she was afebrile (97.6°F) with pulse rate 80 beats/min, respiratory rate 22/min and blood pressure 130/90 mm Hg. She had pallor, marked pedal edema, and mild ascitis. Laboratory investigations showed hemoglobin levels of 6.8 gm%, a total leucocyte count of 7300/µL, a erythrocyte sedimentation rate (ESR) of 66 mm (1 hr), unremarkable peripheral blood smear, serum creatinine of 5.3 mg/dl, blood urea nitrogen (BUN) of 144 mg/dl, serum cholesterol was 233 mg/dl, serum triglycerides were 412 mg/dl, total serum protein was 3.6 g/dl, and serum albumin was 1 g/dl. A 24-hour urine protein test done at presentation was initially 12.9 gm/day and a subsequent report after a month at our institute showed it to be 3.2 gm/day, perhaps due to the marked fall in serum albumin. A 24-hour urine creatinine test was 0.120 gm (urine volume 800 ml). A microscopic urinalysis showed 40-60 pus cells/hpf, occasional RBCs, and hyaline casts. Serum complement levels of C3 and C4 were within normal limits. Anti-nuclear antibodies (ANA) and anti-neutrophilic cytoplasmic antibodies (ANCA) were negative. She was HbsAg (Hepatitis B surface antigen) and Hepatitis C virus negative. An ultrasound of the abdomen showed the right kidney to be 10.9x6.4 cm and the left kidney to be 11x5.8 cm. A renal Doppler study showed no evidence of renal vein thrombosis. An HIV test done after the report of the renal biopsy was negative by two enzyme linked immunosorbent assay (ELISA) kits.
A light microscopic examination of the renal biopsy showed 7 glomeruli displaying relative expansion of the bowman space, diffuse global collapse, and retraction of capillaries and hypertrophy of the overlying visceral epithelial cells with prominent vacuolated cytoplasm and Periodic Acid Schiff (PAS) positive resorption droplets [Figure 1A]. There was significant tubulo-interstitial injury represented by micro-cystic tubular dilatation, large dense PAS positive tubular casts, focal features of acute tubular necrosis, regenerative atypia in tubular epithelial cells, focal tubular atrophy, interstitial mononuclear cell infiltrates, and mild fibrosis [Figure 1B]. Immunofluorescence showed only weak nonspecific glomerular IgM deposits and IgA-positive tubular casts. Glomeruli showed no IgG, IgA, C3, C1q, or fibrin deposits. An electron microscopy revealed marked wrinkling and retraction of the glomerular basement membrane (GBM) with sub-occlusion of the capillary lumens, visceral epithelial cell hypertrophy, extensive foot process fusion, and effacement along with detachment of podocytes from the GBM with accumulation of sub-epithelial lamellated neo-membrane material [Figure 2]. No immune deposits or endothelial tubuloreticular inclusions were found.
The patient was started on three doses of methyl prednisolone followed by oral prednisolone (40 mg OD) and MMF (500 mg 1.5 twice daily). However, she required multiple episodes of hemodialysis due to uremic symptoms. On request due to financial constraints, the patient was discharged when the urine output was 1 lit/day and the serum creatinine was 4 mg%. Subsequent outpatient visits showed a rising trend of serum creatinine and at 6 months she had serum creatinine of 9.54 mg%, BUN of 112 mg%, serum ferritin of 170.20 ng/mL (Normal range in females 15-200 ng/mL), and serum chloride of 88.66 meq/L (Normal range 96- 106 meq/L) requiring renal replacement therapy.
CG is an aggressive form of glomerular disease defined by the presence of at least one glomerulus with a typical collapsing lesion on biopsy. It is presently classified as a variant of FSGS and is characterized by glomerular tuft collapse, variable degree of visceral epithelial cell hyperplasia, and prominent tubulointerstitial injury with frequent microcystic changes and a black racial predominance. Apart from HIV, various etiological factors have been reported namely infections, autoimmune disorders, malignancies, genetic disorders, drug exposures, and post transplant. The various infections reported are cytomegalovirus, human T cells lymphotropic virus (HTLV-1), Hepatitis C virus, parvovirus B19, pulmonary tuberculosis, leishmaniasis, and poorly defined febrile illness.  There is only one case of CG previously reported in literature from India, which was associated with malignancy. 
Our case was a 20-year-old female with acute nephrotic syndrome developing marked renal function deterioration within a month of the illness. At the onset, she had fever associated with chills and loose motions and developed pedal edema. No cause for the high fever could be ascertained and a possibility of some viral infection was considered. The fever subsided after a week of taking antipyretics. However, the renal function continuously deteriorated and the patient became dependent on dialysis. Only 8 cases of CG presenting with idiopathic febrile illness have been reported in literature.  Hamad reported a case of a black male patient with acute nephrotic syndrome associated with non specific febrile illness diagnosed as collapsing glomerulosclerosis who was lost to follow-up.  Our patient received corticosteroids and MMF therapy, but showed no persistent response. Different studies on collapsing glomerulopathy have stated the role of steroids, cyclosporine, and cytotoxic therapy in HIV-negative patients of collapsing glomerulopathy, but none appears promising.  Our case was one of the few cases of CG in literature treated by MMF.
We recommend that CG should be categorized as a separate disease entity because as compared with other variants of FSGS, collapsing FSGS often has global lesions involving >50% of the glomeruli with the highest level of injury to the glomeruli, tubules, and interstitium; clinically, patients usually have heavy proteinuria and a renal survival rate of 1 year against 3 years for FSGS. , The therapeutic strategies to be followed are yet unclear, with only occasional reports of remission. 
We hope that future patients with CG will benefit from the growing awareness and extensive research into the pathogenesis and treatment of CG seen in the last two decades.
|1||Albaqumi M, Soos TJ, Barisoni L, Nelson PJ. Collapsing glomerulopathy. J Am Soc Nephrol 2006;17:2854-63. Epub 2006 Aug 16.|
|2||Laurinavicius A, Rennke HG. Collapsing Glomerulopathy- a new pattern of renal injury. Semin Diagn Pathol 2002;19:106-15.|
|3||Joshua A. Schwimmer, Glen S. Markowitz, Anthony Valeri, Gerald B. Appel. Collapsing Glomerulopathy. Seminars in Nephrology;23:209-18.|
|4||Bhowmik D, Dinda AK, Gupta S, Agarwal SK, Tiwari SC, Dash SC. Multiple myeloma presenting as collapsing glomerulopathy. Indian J Pathol Microbiol 2003;46:233-4.|
|5||Hamad A, Balsam L. Fulminant acute nephrotic syndrome in a patient with idiopathic collapsing focal segmental glomerulosclerosis after a febrile illness. Am J Nephrol 2001;21:84-5.|
|6||Thomas DB, Franceschini N, Hogan SL, Ten Holder S, Jennette CE, Falk RJ, Jennette JC. Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int 2006;69:920-6.|