Unusual course of nephrotic syndrome associated with atypical pneumonia

(Section Editor: K. Kühn) Supported by an educational grant from

Michael Imgrund1,, Rolf Rohrbach2, Mehmet-Özer Öksüz3 and Wolfgang Grotz1

1 Department of Medicine IV, 2 Department of Pathology and 3 Department of Radiology, Albert-Ludwigs University Freiburg, Germany

Keywords: nephrotic syndrome; pneumonia

Introduction

Focal segmental glomerulosclerosis (FSGS) is the most common cause of idiopathic nephrotic syndrome. As secondary forms may have a better prognosis than the primary form of FSGS [1,2] it is important to exclude an underlying disease.

Case report

A 28-year-old man presented in March 2000 with a 1-week history of increasing leg oedema. Surprisingly, he had also experienced an involuntary weight loss of 6 kg during the preceding weeks. There was no relevant medical past history. Physical examination revealed a slightly elevated blood pressure of 145/90 mmHg and marked pretibial oedema. As laboratory values included a proteinuria of 14.5 g/day, a serum albumin of 1.85 g/dl, and a serum cholesterol of 357 mg/dl, a nephrotic syndrome was diagnosed. Serum creatinine was 0.9 mg/dl and creatinine clearance 148 ml/min. The urinary sediment showed no abnormalities.

Kidney biopsy revealed obliteration of the glomerular capillary lumen in segmental parts of some of the glomerula and adhesions of portions of the glomerular tufts to the Bowman's capsule (Figure 1Go), establishing the diagnosis of FSGS. The immunofluorescence revealed segmental IgM deposits in one of the visualized glomerula. Electron microscopy showed marked foot process fusions of the podocytes in a light microscopically normal glomerulum.



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Fig. 1.  Kidney biopsy of the patient. An affected glomerulum shows segmental sclerosis in the left lower part. A smaller segment of sclerosis, combined with adhesion of the visceral epithelium to Bowman's membrane, is visible in the middle of the upper part. PAS staining, original magnification x650.

 
Serum electrolytes and differential blood count were unremarkable. Screening for hepatitis B and C, and HIV was negative and an immunoserologic workup failed to show any abnormalities despite a moderately elevated C-reactive protein (2.0 mg/dl). The initial chest X-ray showed pneumonia in the right upper lung field and right mediastinal enlargement (Figure 2Go). Computed tomographs visualized multiple mediastinal and retroperitoneal lymphnodes (Figure 3Go). Therefore, mediastinoscopic biopsy was performed. Morphology revealed the presence of Hodgkin's disease of the nodular-sclerosing type (clinical stage III2B). Chemotherapy was started according to the enhanced BEACOPP-protocol [3], including procarbacine, etoposide, cyclophosphamide, doxorubicine, vincristine, bleomycine, and prednisone. As renal function was normal, no dose reduction of the drugs was necessary. The patient had no major side effects despite hair loss. Four months after the start of therapy a control CT was performed and showed a remarkable regression of the pathological lymphnodes (Figure 4Go). Furthermore, the proteinuria decreased after 4 months of therapy (0.41 g/day), leg oedema were absent and the patient was feeling well.



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Fig. 2.  Initial chest X-ray of the patient showing right mediastinal enlargement and infiltration in the right upper lung field.

 


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Fig. 3.  Initial chest CT with pathologic mediastinal lymph nodes. Because active kidney disease was present at that time, CT was performed without contrast medium.

 


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Fig. 4.  Contrast-enhanced chest CT performed four months after the initial CT. After application of the chemotherapy, mediastinal lymph nodes are no longer detectable.

 

Discussion

The primary form of focal-segmental glomerulosclerosis has an acute onset and usually presents with a persistant nephrotic syndrome and hypertension as was the case in our patient. Secondary forms of FSGS can be associated with intravenous drug abuse, lithium therapy, HIV-infection, malignancy or Hodgkin's disease. Usually, Hodgkin's disease rarely affects the kidney. Minimal change nephropathy occurs in only 0.4% of these patients and amyloidosis, as a later complication of Hodgkin's disease, in 0.1%. The association of FSGS and Hodgkin's disease seems to be more uncommon [1]. From a pathogenic point of view, a circulating T-cell derived factor seems to play a role in the pathogenesis of FSGS [4]. Hodgkin's disease is a B-cell derived tumour, but polyclonal T-cells are present in close vicinity to the malignant B-cells [5]. Those T-cells may produce a ‘soluble factor’ targeted to glomerular cells, thereby causing glomerulopathy. This factor might be a chemokine which induces inflammation and subsequent scarring, leading to enhanced protein-permeability of the glomerulum [6].

Nephrotic syndrome can be associated with several complications. Loss of clotting inhibitors and particular immunoglobulins makes the patient prone to complications like thrombosis and infection. Our patient presented with a clinically silent pneumonia (Figure 2Go), which may have been promoted by the nephrotic syndrome.

A high-proteinuric state as it was present in our patient is associated with a particularly bad prognosis in idiopathic FSGS. The initial therapy of FSGS is prednisone, which is only able to induce a remission in 20% of cases [2]. In secondary FSGS, the discovery of an underlying disease can change the therapeutic approach and therefore improve the prognosis of the nephrotic syndrome as in our case.

Teaching point

In a patient with focal-segmental glomerulosclerosis (FSGS), a secondary form of FSGS should be considered.

It is necessary to establish the diagnosis of an underlying disease like Hodgkin's lymphoma as early as possible since therapeutic intervention can induce a remission of the nephrotic syndrome.

Notes

Correspondence and offprint requests to: Dr M. Imgrund, Department of Medicine IV, Albert-Ludwigs-University Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany. Email: imgrund{at}med1.ukl.uni\|[hyphen]\|freiburg.de Back

References

  1. Dabbs DJ, Striker LM, Mignon F, Striker G. Glomerular lesions in lymphomas and leukemias. Am J Med1986; 80: 63–70.[ISI][Medline]
  2. Korbet SM, Schartz MM, Lewis EJ. Primary focal segmental glomerulosclerosis: clinical course and response to therapy. Am J Kidney Dis1994; 23: 773–83.[ISI][Medline]
  3. Diehl V, Franklin J, Hasenclever D et al. BEACOPP: a new regimen for advanced Hodgkin's disease. Ann Oncol1998; 9 [Suppl. 5]: S67–71.[Medline]
  4. Sharma M, Sharma R, McCarthy ET, Savin VJ. ‘The FSGS factor’: enrichment and in vivo effect of activity from focal segmental glomerulosclerosis plasma. J Am Soc Nephrol1999; 10: 552–61.[Abstract/Free Full Text]
  5. Van den Berg A, Visser L, Poppema S. High expression of the CC Chemokine TARC in Reed-Sternberg cells: a possible explanation for the characteristic T-Cell infiltration in Hodgkin's lymphoma. Am J Pathol1999; 154: 1685–1691.[Abstract/Free Full Text]
  6. Kühn K, Felten F, Nock U, Herth F. Glomerulonephritis as a secondary disease. Clinical significance. Internist1995; 36: 207–217.[ISI][Medline]




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