Acute cytomegalovirus infection complicated by collapsing glomerulopathy
Laurie Tomlinson1,
Yuri Boriskin2,
Iain McPhee1,
Stephen Holwill3 and
Philip Rice2,
1 Department of Renal Medicine,
2 Department of Medical Microbiology and
3 Department of Histopathology, St George's Hospital Medical School, London, UK
Keywords: collapsing glomerulopathy; end-stage renal disease; focal segmental glomerulosclerosis; primary cytomegalovirus infection; renal injury
 |
Introduction
|
---|
Collapsing glomerulopathy (CG) is a renal injury described initially in association with HIV-induced nephropathy but also seen increasingly in non-HIV-infected individuals. Some authors recognise it as a separate clinicopathological variant of focal segmental glomerulosclerosis (FSGS) associated with nephritic syndrome, rapidly progressive chronic renal failure and the histopathologic features of glomerular capillary collapse [1,2]. It has also been linked with other viral infections including hepatitis C, but to date not with cytomegalovirus (CMV). There may be an association with lymphoproliferative disorders and autoimmune disease, but this is less certain [3]. We report the first case of CG leading to end-stage renal failure in a patient with acute CMV infection. To our knowledge, this is the first well-documented association of acute CMV infection and renal failure in an immunocompetent non-transplant patient.
 |
Subjects and methods
|
---|
A 60-year-old afro-caribbean female was admitted with a 6 week history of increasing dyspnoea, orthopnoea and peripheral oedema. In the week prior to admission she had noticed frothy urine and a reduced urine output. There was no significant past medical history. Six weeks prior to her admission her 28-year-old son, who had also previously been well, had been admitted with high fever, headache and flu-like symptoms. During his admission microscopic haematuria and proteinuria had been noted and 24 h total urinary protein was quantified at 0.8 g although serum creatinine remained in the normal range. A diagnosis of primary CMV infection was made based on the presence of high-level CMV-specific IgM (>400 arbitrary units/ml; Eurogenetics), low avidity CMV-specific IgG (Euroimmune GmbH) and CMV DNA detection in the blood (peak CMV load 6300 copies per ml of plasma). His infection resolved without treatment or subsequent sequelae.
Laboratory diagnosis of primary CMV infection in the woman was based on blood tests for CMV-specific IgM antibody, CMV-specific IgG avidity, infectious CMV detection by rapid antigen test [4], semiquantitative DNA load measurement by PCR [5] and qualitative detection of viral RNA [6]. Plasma HIV-1 antibody and RNA were also assayed by Axsym enzyme immunoassay (Abbot) and HIV-1 RNA 3.0 kit (Bayer), respectively. The patient was also tested for HTLV-1 (Serodia; Fujirebio Inc.), hepatitis B antigen (Axsym; Abbot) and hepatitis C antibodies (Sanofi).
 |
Results
|
---|
The patient was obese at 114 kg and normotensive (blood pressure 120/60 mmHg). Signs of fluid overload were present. ECG was normal and a chest radiograph confirmed pulmonary oedema. Laboratory investigation showed Hb 10.3 g/dl, total WCC 10.5x109/l, lymphocytes 4.5x109/l, urea 19 mmol/l, creatinine 612 µmol/l, albumin 19 g/l and cholesterol 7.4 mmol/l. Twenty-four hour total urine protein was 9.3 g. Blood film examination showed reactive lymphocytes. Abdominal ultrasound showed normal sized kidneys. Antinuclear antibody and antineutrophil cytoplasmic antibody were negative. Immunological parameters were unremarkable with serum IgG 12.2 g/l, IgA 5.8 g/l, IgM 2.7 g/l, C3 2.1 g/l and C4 0.44 g/l. There was no serum paraprotein or urinary BenceJones protein. Serum angiotensin converting enzyme was in the normal range.
The patient's renal function deteriorated rapidly requiring haemodialysis. A renal biopsy was performed, which showed collapsing glomerulosclerosis with widespread giant casts and tubular atrophy (Figures 1
and 2
). She had high-level CMV IgM antibodies (>400 arbitrary units/ml), low avidity CMV-specific IgG and was viraemic. Peak CMV DNA load reached 4900 copies per ml of plasma then declined to undetectable levels 6 months later. Plasma DNAemia was accompanied by accumulation of CMV DNA in leucocytes (1050-fold higher than in plasma) along with cell-associated CMV UL21.5 earlylate mRNA indicative of active CMV infection [6]. Furthermore, CMV DNA was detected in the renal biopsy at a level of 280 copies per 20 mg of paraffin-embedded tissue. No detectable plasma HIV-1 antibody or RNA, as well as serological evidence of HTLV-1, hepatitis B and C, were found in this patient. At the time of last follow-up the patient remained haemodialysis dependent.

View larger version (177K):
[in this window]
[in a new window]
|
Fig. 1. Renal biopsy. There is widespread tubular atrophy with some markedly dilated and cast-filled tubules. Moderate interstitial fibrosis and inflammation are present. H&E x100.
|
|

View larger version (156K):
[in this window]
[in a new window]
|
Fig. 2. Glomerular detail. The glomerular tuft has collapsed and is covered by a proliferation of visceral epithelial cells, many of which contain eosinophilic protein resorption droplets. PAS x400.
|
|
 |
Discussion
|
---|
This report describes the first case of CG with nephritic syndrome and rapid progression to end-stage renal failure associated with primary CMV infection. Several factors argue in favour of a causal relationship. The patient became unwell 3 weeks after her son developed symptoms of CMV infection. It is likely that the patient's renal pathology was acute in onset. She had had normal serum urea and electrolytes measured previously and a routine full blood count performed 10 weeks before admission was normal. She had no previously documented abnormal urinanalysis findings. Moreover, renal size was normal on ultrasound. There was no history of hypertension. She had been entirely well until 6 weeks before admission and only after hospital admission did her renal function deteriorate rapidly. The patient did not receive immunosuppressive drugs or steroids at any stage. Similarly, the possibility of a rare familiar immunodeficiency cannot explain the outcome of CMV infection in our patient. Both the patient and her son had no known comorbidities, developed acute CMV infection with comparable levels of viraemia and fully cleared the infection without treatment. However, while the son made an uncomplicated recovery his mother's infection led to severe end-organ damage that appeared to have been triggered by CMV infection.
Severe symptomatic CMV infection in previously healthy immunocompetent individuals is uncommon and cases resulting in end-organ failure are very rare [7,8]. Usually, however, these patients have identifiable underlying illnesses including pre-existing chronic renal failure [8]. Our case report describes acute, leading to end-stage, renal failure following primary CMV infection in an immunocompetent and otherwise healthy individual. As the first of its kind, it will complement case series of complications associated with acute CMV infection.
 |
Notes
|
---|
Correspondence and offprint requests to: Philip Rice, Department of Medical Microbiology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. Email: price{at}sghms.ac.uk 
 |
References
|
---|
- Weiss MA, Daquioag E, Margolin EG, Pollak VE. Nephrotic syndrome, progressive renal failure and glomerular collapse: a new clinicopathologic entity? Am J Kidney Dis1986; 7:2028[ISI][Medline]
- Detweiler RK, Falk RJ, Hogan SL, Jennette JC. Collapsing glomerulopathy: a clinically and pathologically distinct variant of focal segmental glomerulosclerosis. Kidney Int1994; 45:14161424[ISI][Medline]
- Laurinavicus A, Hurwitz S, Rennke HG. Collapsing glomerulopathy in HIV and non-HIV patients: a clinicopathological and follow-up study. Kidney Int1999; 56:22032213[CrossRef][ISI][Medline]
- Steel HM, Booth JC, Tryhorn YS, Stern H. A simple immunoalkaline phosphatase method for the rapid diagnosis of cytomegalovirus infection. Serodiagn Immunother Infect Dis1988; 2:193200[CrossRef][ISI]
- Boriskin YS. Quantitative nested PCR for human cytomegalovirus DNA: analysis using Nucleoscan 2001. New Microbiol2001; 24:19[ISI][Medline]
- Boriskin YS, Butcher PD. Human cytomegalovirus UL21.5 gene is expressed as an early-late gene in cultured human fibroblasts. Acta Virol2001; 45:185189[ISI][Medline]
- Eddleston M, Peacock S, Juniper M, Warrell DA. Severe cytomegalovirus infection in immunocompetent patients. Clin Infect Dis1997; 25:14871488[Medline]
- Kanno M, Chandrasekar PH, Bentley G, Vander Heide RS, Alangaden GJ. Disseminated cytomegalovirus disease in hosts without acquired immunodeficiency syndrome and without organ transplant. Clin Infect Dis2001; 32:313316[CrossRef][ISI][Medline]
Received for publication: 2. 7.01
Accepted in revised form: 8. 4.02