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
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Introduction |
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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 (haematoxylineosin 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.
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Case |
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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 1.21.3 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 1.
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Discussion |
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The association of the glomerular lesions found in our case might not be coincidental. Minimal-change disease has been found in 47% 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 1.
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 1). 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.
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References |
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