Steroid-responsive nephrotic syndrome with minimal-change disease and IgA deposits in a HIV-infected patient

Evangelina Boix1, Francisco Rivera2, Carmen-María Gil1, Javier Pérez-Contreras1 and Jesús Olivares1

2 Servicio de Nefrología, Hospital General Universitario de Alicante and 1 Departamento de Medicina Clínica, Facultad de Medicina, Universidad Miguel Hernandez, Elche, Spain

Correspondence and offprint requests to: Dr F. Rivera, Servicio de Nefrología, Hospital General Universitario de Alicante, c/ Pintor Baeza, s/n. E-03010 Alicante, Spain.

Keywords: human immunodeficiency virus; IgA nephropathy; steroid-responsive nephrotic syndrome



   Introduction
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 Introduction
 Case
 Discussion
 References
 
Several types of glomerulopathy have been described in patients with HIV infection. Although HIV-associated nephropathy, namely `focal collapsing glomerulosclerosis' and related mesangiopathies, has been considered to be the most specific renal lesion, other immune-mediated renal diseases, such as membranous nephropathy, membranoproliferative glomerulonephritis, lupus-like nephritis and haemolytic–uraemic syndrome can be found in HIV-positive patients [1].

The association of minimal-change disease with nephrotic syndrome in HIV-infected patients has been described previously [1,2]. However, mesangial IgA nephropathy has also been reported [3]. In both situations the relationship between HIV infection and glomerular damage is not coincidental because viral products play a direct role in HIV-related renal diseases [4,5].

We describe the case of an HIV-positive man who presented with hypertension, moderate renal insufficiency and full-blown nephrotic syndrome with minimal-change disease (haematoxylin–eosin staining) and mesangial IgA deposits. He was steroid-responsive although he relapsed. He was also treated with lisinopril, nifedipine and three antiretroviral drugs, with a favourable outcome for a 1.5-year follow-up.



   Case
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 Introduction
 Case
 Discussion
 References
 
A 58-year-old white Spanish male was admitted to our hospital in December 1997 because of a 4-week history of oedema of the face, hands and lower extremities. He also complained of headache and blurred vision. His past clinical history was unremarkable and the only symptom he remembered was headaches many years before. He denied intravenous drug abuse or blood transfusions. Physical admission revealed a supine blood pressure of 200/120 mmHg, grade III-IV retinopathy and generalized oedema without adenopathies. The remainder was normal. Laboratory studies showed: haemoglobin 13 g/dl, white cell count 4800/µl, platelet count 313000/µl, ESR 92 mm/h. Serum creatinine 1.6 mg/dl, creatinine clearance (CCr) 47 ml/min, albumin 26 g/l, cholesterol 471 mg/dl, triglycerides 288 mg/dl. Serum bilirubin, alanine and aspartate transaminases and alkaline phosphatases were normal. IgG 864 mg/dl, IgA 425 mg/dl, IgM 155 mg/dl, complement C3 155 mg/dl and complement C4 47 mg/dl. Tests for antinuclear antibodies, c-ANCA, p-ANCA and anti-MBG were negative. The tests for serum antibodies to hepatitis C virus (RIBA 2) and hepatitis B surface antigen were negative but hepatitis B surface antibodies were 574 U/l. Renal ultrasonography revealed normal kidneys. Twenty-four hour urine protein was 15 g. Urinary sediment revealed 30 red cells per high-power field. Urine culture was sterile. HIV screening using the enzyme immunoassay method was highly positive at 1415 (abs indexx100). Immunoblotting (Western blot) revealed antibodies to p18, p34, p36 and gp41. A percutaneous renal biopsy revealed, in haematoxylin–eosin sections, four glomeruli with a mild increase in mesangial matrix and cellularity. Immunofluorescence studies showed mesangial staining for IgA and C3. The interstitium, blood vessels and tubuli were not damaged.

The patient was started on prednisone, 1 mg/kg/day, with remission of proteinuria in 12 weeks. The prednisone regimen was then changed from a daily dose to an alternate-day, slowly tapering schedule. Seven months later, when steroids were stopped he relapsed. Prednisone was restarted at the same dose, with prompt remission. He developed steroid-induced diabetes mellitus that was controlled with diet and Candida esophagitis, treated with oral fluconazole. During follow-up hypertension was treated with lisinopril 20 mg/day and for several weeks nifedipine GITS 30 mg/day. He partially recovered renal function but moderate renal insufficiency persisted during follow-up (serum creatinine 1.2–1.3 mg/dl). Following the diagnosis of HIV infection he received antiretroviral therapy with two nucleotide analogue reverse transcriptase inhibitors (zidovudine and lamivudine) and the proteinase inhibitor indinavir. His pre-treatment CD4 count (flow cytometry) was 387/mm3 and plasma HIV RNA levels (PCR) 165x1000 copies/ml. The evolution of renal function, proteinuria, serum cholesterol, peripheral CD4 count, plasma viral load and treatment is shown in Table 1Go.


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Table 1. Evolution of clinical and analytical data
 


   Discussion
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 Introduction
 Case
 Discussion
 References
 
We describe an HIV-positive white Spanish man who presented with nephrotic syndrome and minimal-change disease with mesangial IgA deposits. To our knowledge the combination of these two entities in the same HIV-infected patient has not been described previously. It indicates the low incidence of typical HIV-associated nephropathy in infected patient in Europe, where other types of glomerulonephritis appear to predominate [6].

The association of the glomerular lesions found in our case might not be coincidental. Minimal-change disease has been found in 4–7% of HIV-positive patients with glomerular involvement [1,6] and some of them evolved towards typical collapsing focal segmental glomerulosclerosis, suggesting the possibility of transformation between these histopathological subtypes, similar to what has been proposed for the idiopathic nephrotic syndrome [1].

IgA nephropathy is an immune complex-mediated glomerulonephritis which has been reported in HIV-infected patients [1,3,7]. Most of the cases with IgA deposits and HIV infection are normotensive with non-nephrotic proteinuria and preserved renal function [7].

In our case, it would be tempting to suggest that HIV infection may simultaneously precipitate an episode of steroid-responsive nephrotic syndrome and an increased load of nephritogenic IgA immune complexes. In fact, HIV could stimulate cytokine production by monocytes and lymphocytes. Furthermore, IgA rheumatoid factors directed toward HIV viral antigens can be deposited in glomeruli, either by passive deposition or `in situ' formation [4,5].

The role of glucocorticoids in the management of HIV infection remains a matter of debate. Several uncontrolled studies suggest that glucocorticoids ameliorate proteinuria and renal insufficiency in HIV-infected patients, but may also cause an important number of opportunistic infections [8]. Although we initiated this treatment before knowing HIV serology, the histological findings encouraged us to maintain glucocorticoids, because of the high probability of remission, as effectively observed in this case. In spite of a relapse several months later, the reintroduction of prednisone was effective. The complications of this treatment (steroid-induced diabetes and Candida esophagitis) were managed easily. Furthermore, HIV infection stage did not progress, as shown in Table 1Go.

Although most patients with typical HIV-associated nephropathy have no arterial hypertension, treatment with angiotensin-converting enzyme inhibitors (ACEI) appears to have beneficial effects on proteinuria and renal function [8,9]. Independent of their haemodynamic intrarenal effects, ACEI decrease renal tissue expression of TGF-ß and have several immune and antiviral effects. During follow-up the patient required antihypertensive drugs (lisinopril and nifedinipine) to obtain an optimal control of hypertension. Although these drugs, particularly lisinopril, probably help to decrease proteinuria, the global evolution was clearly dependent on glucocorticoid treatment. Moreover, the second relapse appeared in the presence of antihypertensive treatment, and proteinuria remitted after the reintroduction of prednisone.

Finally, the possible effect of antiretroviral drugs in the evolution of HIV-related renal disease must also be considered. It appears that these drugs are beneficial [10]. In the present patient we observed a decrease in plasma viral load after treatment with antiretroviral drugs (Table 1Go). However, the proteinuria appeared to respond only to steroid treatment. In contrast, the relapse took place when plasma viral load was undetectable and proteinuria remitted after the reintroduction of steroids.

In summary, HIV-positive patients with nephrotic syndrome may have minimal-change disease and IgA deposits simultaneously. Treatment with steroids is effective, although a potential additive effect of ACEIs and antiretroviral drugs cannot be ignored.



   References
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 Introduction
 Case
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 References
 

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Received for publication: 19. 7.99
Accepted in revised form: 20.10.99