Printer Friendly

Focal segmental glomerulosclerosis and parvovirus B19.

Focal segmental glomerulosclerosis (FSGS) is a glomerular disease with a characteristic pathologic presentation that includes segmental scarring involving some but not all glomeruli. On immunofluorescence, deposits of immunoglobulin (Ig) M and C3 may be found in the areas of segmental scarring. Electron microscopy typically demonstrates difluse epithelial cell foot process effacement and focal areas of retraction of glomerular basement membrane with collapse of the involved tuft (1). Due to the focal nature of the process, it is sometimes challenging to recognize this lesion in the biopsy specimen. Accordingly, special attention needs to be directed at the corticomedullary regions of the kidney where FSGS is more likely to be found. Otherwise, an errant diagnosis of minimal change disease could be made. Once underlying causes of this particular glomerular presentation are ruled out (such as obesity, sleep apnea, heroin abuse, reflux nephropathy, and HIV), one is left with a diagnosis of primary or idiopathic FSGS. It is important to identify patients who present with nephrotic-range proteinuria and have FSGS because early treatment of these patients may alter the course of the disease and prevent relentless progression to terminal renal failure (2).

The collapsing form of FSGS, which occurs more commonly in African American patients than in Caucasians, carries a particularly poor prognosis with respect to renal survival (3). This variant is morphologically similar to the glomerular lesion often associated with HIV infection. However, the term idiopathic collapsing glomerulopathy is reserved for patients who are HIV negative.

Collapsing glomerulopathy has been associated with non-HIV-related pathologies. These include associations with medications like pamidronate and interferon-alfa and with viral infections like parvovirus B19, cytomegalovirus, and hepatitis C (4, 5). Rarely, multiple myeloma has been associated with this lesion (6, 7). A case of collapsing FSGS in a patient with parvovirus B19 infection is presented with review of the known literature.

CASE PRESENTATION

A 56-year-old African American man with a history of hypertension, hyperlipidemia, and chronic kidney disease, with a baseline serum creatinine of 1.9 mg/dL 4 months earlier, presented to the hospital with worsening fatigue and malaise. Renal laboratory results had deteriorated, with a creatinine of 17 mg/dL and blood urea nitrogen of 94 mg/dL. He denied any recent use of nonsteroidal antiinflammatory drugs or herbal supplements and reported compliance with his medications, which included metoprolol 50 mg twice daily and verapamil (dose unknown). Physical examination was remarkable only for a blood pressure of 170/88 mm Hg and bilateral lower extremity edema. Urinanalysis revealed 3+ proteinuria, 1+ blood, and hyaline casts. The spot urine protein/creatinine ratio was 5.2 (normal, <0.2). Renal ultrasound revealed normal-sized kidneys with increased echogenicity. Tests for HIV by enzyme-linked immunosorbent assay and polymerase chain reaction were negative, as were tests for hepatitis B surface antigen and hepatitis C antibody and urine drug screens. Serum protein electrophoresis, urine protein electrophoresis, and urine immunofixation revealed no monoclonal protein. Tests for parvovirus antibodies were positive, with titers of IgM 5.2 and IgG 4.5, indicative of active infection.

A renal biopsy revealed collapsing FSGS glomerulopathy with patchy tubular dilatation (Figure 1). The patient's clinical course was characterized by nonoliguric renal failure and difficult-to-control hypertension. However, his renal function gradually improved with no specific therapy, with his serum creatinine falling to 4 mg/dL. Subsequent parvovirus IgM and IgT titers fell, indicating a resolution of his viral infection.

DISCUSSION

It is postulated that in collapsing glomerulopathy, unlike other podocytopathies, the podocyte dedifferentiates, and this results in a dysregulated phenotype (8). Diseased podocytes exhibit a loss of differentiation and gain of proliferation. Podocytes have been described to "transdifferentiate" towards a macrophage-like cell (9-13) (Figure 2).

Patients with FSGS usually present with nephrotic-range proteinuria, hypertension, and decreased renal function. The collapsing variant of FSGS was first recognized and described by Schwartz and Lewis (14) and was later confirmed by Weiss et al (15), Detwiler et al (16), and Valeri et al (17). These patients are likely to have higher levels of proteinuria, are more commonly African American, and have a poor prognosis with more rapid progression to terminal renal failure.

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

Parvovirus B19 infection is a common disease, with 50% to 80% of adults having parvoviral-specific IgG. The infection is usually minimally symptomatic, but aplastic anemia can occur in patients with sickle cell disease and other chronic hemolytic disorders. Parvovirus B19 can evolve into a chronic infection in patients who are immunosuppressed. Clinical symptoms of active disease include skin rash and arthralgias.

FSGS has been described as a clinical consequence of parvovirus B19 infection (18-20). Moudgil et al presented a series of 23 patients with collapsing glomerulopathy, and 18% of these cases revealed parvovirus B19 DNA in the renal specimens. In another series, 10 more cases of collapsing FSGS were reported by Tanawattanacharoen et al, where 90% of the cases had DNA evidence of parvovirus B19 in renal tissue (21). It has been speculated that some patients have a predisposition that makes them susceptible to defects in their ability to generate a cellular and humoral immune response to clear this virus. The persistence of viremia increases the infectivity and has a possible impact on a variety of clinical disease presentations.

The collapsing variety of FSGS is rare. African Americans are hyperproducers of transforming growth factor B, a cytokine associated with fibrosis, which could contribute to excessive proliferative and sclerosing in response to a viral insult. In certain individuals, this may initiate a cascade of events in the kidney, which results in collapsing glomerulopathy (16, 18, 22, 23). However, other individuals may have resistance to this viral infection due to lack of the viral receptor (in the erythrocytes and/or kidney tissue), which protects their renal epithelial cells from parvovirus infection. In our patient, there was a temporal relationship between active parvovirus B19 infection and the development of collapsing FSGS, with clinical improvement as the viral infection resolved.

No evidence-based therapy exists for collapsing FSGS. Current therapies are based on empiric experience and have been extrapolated from treatments used for FSGS. Treatments utilized include steroids, cyclophosphamide, and cyclosporine (9). The usual recommended course ofsteroid therapy is 6 months of daily or alternate daily prednisone. Unfortunately, despite aggressive therapy, remission is uncommon. Various studies have reported full remission rates of 9.6% and partial remission rates of 15.2%. Furthermore, Crenshaw et al, in their retrospective series, did not find a beneficial effect of steroids in African Americans (3, 24). For patients who are intolerant of prednisone, various immunosuppressives have been tried, again with variable success. A recent report presented a patient with cyclosporine-resistant collapsing FSGS who was successfully treated with rituximab and achieved a complete remission. Therefore, this agent may emerge as yet another therapeutic option for patients with refractory collapsing FSGS (25).

Treatment of hypertension is an important aspect of treatment for all patients with renal disease, regardless of etiology, and angiotensin-converting enzyme inhibitors (ACEIs) are considered first-line drugs for this purpose. ACEIs control systemic hypertension and simultaneously reduce intraglomerular pressure and hence decrease proteinuria (3). Prasher et al assessed the efficacy of enalapril in controlling proteinuria in steroid-resistant idiopathic nephrotic syndrome and found that enalapril exerted a long-lasting effect (26). Also, a randomized controlled trial of losartan therapy in 23 normotensive patients with primary FSGS who were refractory to immunosuppressive therapy showed a reduction in proteinuria compared with the control group after 1 year of treatment (27).

In summary, a rare subtype of FSGS called collapsing FSGS is reported. This glomerulopathy, often associated with active HIV infection, has a very aggressive course leading to terminal renal failure. In this case a coexistent acute parvovirus B19 infection was identified. The patient's clinical presentation and renal biopsy findings are indistinguishable from those features in patients with HIV nephropathy. This finding raises the possibility that parvovirus B19 may be the precipitating or causative etiologic agent for this form of FSGS. This possibility is further supported by the patient's marked clinical improvement as the parvovirus B19 infection resolved.

(1.) Korbet SM. Primary focal segmental glomerulosclerosis. J Am Soc Nephrol 1998;9(7):1333-1340.

(2.) Chun MJ, Korbet SM, Schwartz MM, Lewis EJ. Focal segmental glomerulosclerosis in nephrotic adults: presentation, prognosis, and response to therapy of the histologic variants. J Am Soc Nephrol 2004;15(8): 2169-2177.

(3.) Tucker JK. Focal segmental glomerulosclerosis in African Americans. Am J Med Sci 2002;323(2):90-93.

(4.) Tomlinson L, Boriskin Y, McPhee I, Holwill S, Rice P. Acute cytomegalovirus infection complicated by collapsing glomerulopathy. Nephrol Dial Transplant 2003;18(1):187-189.

(5.) di Belgiojoso GB, Ferrario F, Landriani N. Virus-related glomerular diseases: histological and clinical aspects. J Nephrol 2002;15(5):469-479.

(6.) Schwimmer JA, Markowitz GS, Valeri A, Appel GB. Collapsing glomerulopathy. Semin Nephrol 2003;23(2):209-218.

(7.) Markowitz GS, Nasr SH, Stokes MB, D'Agati VD. Treatment with IFN-alpha, -beta, or -gamma is associated with collapsing focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2010;5(4):607-615.

(8.) Albaqumi M, Barisoni L. Current views on collapsing glomerulopathy. J Am Soc Nephrol 2008;19(7):1276-1281.

(9.) Albaqumi M, Soos TJ, Barisoni L, Nelson PJ. Collapsing glomerulopathy. J Am Soc Nephrol 2006;17(10):2854-2863.

(10.) Bariety J, Nochy D, Mandet C, Jacquot C, Glotz D, Meyrier A. Podocytes undergo phenotypic changes and express macrophagic-associated markers in idiopathic collapsing glomerulopathy. Kidney Int 1998;53(4): 918-925.

(11.) Barisoni L, Kriz W, Mundel P, D'Agati V. The dysregulated podocyte phenotype: a novel concept in the pathogenesis of collapsing idiopathic focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 1999;10(1):51-61.

(12.) Barisoni L, Mokrzycki M, Sablay L, Nagata M, Yamase H, Mundel P. Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies. Kidney Int 2000;58(1):137-143.

(13.) Shankland SJ, Eitner F, Hudkins KL, Goodpaster T, D'Agati V, Alpers CE. Differential expression of cyclin-dependent kinase inhibitors in human glomerular disease: role in podocyte proliferation and maturation. Kidney Int 2000;58(2):674-683.

(14.) Schwartz MM, Lewis EJ. Focal segmental glomerular sclerosis: the cellular lesion. Kidney Int 1985;28(6):968-974.

(15.) Weiss MA, Daquioag E, Margolin EG, Pollak VE. Nephrotic syndrome, progressive irreversible renal failure, and glomerular "collapse": a new clinicopathologic entity? Am J Kidney Dis 1986;7(1):20-28.

(16.) Detwiler RK, Falk RJ, Hogan SL, Jennette JC. Collapsing glomerulopathy: a clinically and pathologically distinct variant of focal segmental glomerulosclerosis. Kidney Int 1994;45(5):1416-1424.

(17.) Valeri A, Barisoni L, Appel GB, Seigle R, D'Agati V. Idiopathic collapsing focal segmental glomerulosclerosis: a clinicopathologic study. Kidney Int 1996;50(5):1734-1746.

(18.) Moudgil A, Nast CC, Bagga A, Wei L, Nurmamet A, Cohen AH, Jordan SC, Toyoda M. Association of parvovirus B19 infection with idiopathic collapsing glomerulopathy. Kidney Int 2001;59(6):2126-2133.

(19.) Markenson AL, Chandra M, Lewy JE, Miller DR. Sickle cell anemia, the nephrotic syndrome and hypoplastic crisis in a sibship. Am J Med 1978;64(4):719-723.

(20.) Wierenga KJ, Pattison JR, Brink N, Griffiths M, Miller M, Shah DJ, Williams W, Serjeant BE, Serjeant GR. Glomerulonephritis after human parvovirus infection in homozygous sickle-cell disease. Lancet 1995;346(8973):475-476.

(21.) Tanawattanacharoen S, Falk RJ, Jennette JC, Kopp JB. Parvovirus B19 DNA in kidney tissue of patients with focal segmental glomerulosclerosis. Am J Kidney Dis 2000;35(6):1166-1174.

(22.) Suthanthiran M, Khanna A, Cukran D, Adhikarla R, Sharma VK, Singh T, August P. Transforming growth factor-beta 1 hyperexpression in African American end-stage renal disease patients. Kidney Int 1998;53(3):639-644.

(23.) Brown KE, Hibbs JR, Gallinella G, Anderson SM, Lehman ED, McCarthy P, Young NS. Resistance to parvovirus B19 infection due to lack of virus receptor (erythrocyte P antigen). N Engl J Med 1994;330(17):1192-1196.

(24.) Crenshaw G, Bigler S, Salem M, Crook ED. Focal segmental glomerulosclerosis in African Americans: effects of steroids and angiotensin converting enzyme inhibitors. Am J Med Sci 2000;319(5):320-325.

(25.) Kaito H, Kamei K, Kikuchi E, Ogura M, Matsuoka K, Nagata M, Iijima K, Ito S. Successful treatment of collapsing focal segmental glomerulosclerosis with a combination of rituximab, steroids and ciclosporin. Pediatr Nephrol 2010;25(5):957-959.

(26.) Prasher PK, Varma PP, Baliga KV Efficacy of enalapril in the treatment of steroid resistant idiopathic nephrotic syndrome. J Assoc Physicians India 1999;47(2):180-182.

(27.) Usta M, Ersoy A, Dilek K, Ozdemir B, Yavuz M, Gullulu M, Yurtkuran M. Efficacy of losartan in patients with primary focal segmental glomerulosclerosis resistant to immunosuppressive treatment. J Intern Med 2003;253(3):329-334.

Catalina Sanchez, MD, Andrew Fenves, MD, and John Schwartz, MD

From the Division of Nephrology, Department of Internal Medicine, Baylor University Medical Center at Dallas.

Corresponding author: Andrew Fenves, MD, Division of Nephrology, Department of Internal Medicine, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, Texas 75246 (e-mail: Andrew.Fenves@BaylorHealth.edu).
COPYRIGHT 2012 The Baylor University Medical Center
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2012 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Sanchez, Catalina; Fenves, Andrew; Schwartz, John
Publication:Baylor University Medical Center Proceedings
Article Type:Clinical report
Geographic Code:1USA
Date:Jan 1, 2012
Words:2136
Previous Article:Comments on Darwinism.
Next Article:Echinococcus granulosus infection presenting as right upper-quadrant abdominal pain.
Topics:

Terms of use | Copyright © 2018 Farlex, Inc. | Feedback | For webmasters