Immune complex-mediated glomerular disease is usually more common in the Caucasian population, whereas HIVAN predominantly affects African Americans. therapy as the cornerstone of treatment for HIV-associated nephropathy, in the absence of prospective clinical trials. Adjunctive therapy for HIV-associated nephropathy includes ACE inhibitors or angiotensin receptor blockers, as well as corticosteroids in selected patients with significant interstitial inflammation or rapid progression. has been implicated in these changes, based on recent work demonstrating that expression impairs cytokinesis in tubular epithelial cells under the podocin promoter demonstrate expression of the cell cycle markers Ki-67 and phospho-Stat3 in podocytes.28 The relative contribution of podocytes and parietal cells to glomerular epithelial cell proliferation in HIVAN and other forms of collapsing glomerulopathy remains to be fully defined. Differential diagnosis of renal biopsy findings A biopsy picture of collapsing glomerulopathy is not specific for HIVAN. Differential diagnosis of the collapsing variant of FSGS includes main (idiopathic) FSGS,29 parvovirus B19 contamination,30 SV40 contamination,31 acute CMV contamination,32 erythrophagocytosis syndrome,33 interferon therapy,34 pamidronate toxicity,35 acute vaso-occlusive injury,36 rare familial forms,37 and glomerular injury in the renal allograft associated with microvascular disease.38 Renal biopsy in the HIV-infected patient is required to establish a diagnosis of HIVAN and exclude other causes of renal dysfunction and proteinuria, including a variety of HIV-related glomerular diseases, non-HIV-related renal diseases, and medication nephrotoxicity, many of which are reviewed in detail in companion articles. Other glomerular lesions encountered in the HIV-infected patient are outlined in Table 1. Immune complex-mediated glomerular disease is usually more common in the Caucasian populace, whereas HIVAN predominantly affects African Americans. It is particularly challenging for the renal pathologist to distinguish HIVAN from other forms of FSGS, including secondary FSGS from hypertensive arterionephrosclerosis or pre-existing main FSGS, which are also more common in black patients. Recent biopsy series in HIV-infected patients indicate an increasing prevalence of FSGS (NOS) in parallel with a reduction in HIVAN, suggesting modification of the collapsing pattern of HIVAN by ART.39,40 To illustrate the changing epidemiology of HIVAN, the renal biopsy incidence of HIVAN was 65% in a series of 112 patients reported in 1997,41 but only 35% in a recent series of 152 biopsies.39 Because endothelial tubulo-reticular inclusions also appear to be reduced by ART, the biopsy picture of HIVAN may be Rabbit Polyclonal to BRS3 attenuated in ART-treated patients, approximating the morphologic appearance of FSGS (NOS). In addition, as patients live longer with HIV contamination, they may develop other non-HIV-related kidney diseases common in the aging populace, such as diabetic nephropathy and arterionephrosclerosis of aging or hypertension, which may also exhibit focal sclerosing features. TABLE 1 GLOMERULAR LESIONS OCCURRING IN HIV-INFECTED PATIENTS HIVAN (collapsing glomerulopathy)Focal segmental glomerulosclerosis (FSGS), not otherwise specified (NOS)Minimal switch diseaseImmune complex-mediated glomerulonephritis?Lupus-like nephritis?IgA nephropathy?Membranoproliferative glomerulonephritis (associated with hepatitis C or B)?Membranous glomerulopathy (associated with hepatitis B or C, or neoplasia)?Acute post-infectious glomerulonephritisFibrillary and immunotactoid glomerulonephritis (often associated with hepatitis C)Diabetic nephropathyAmyloidosis, AA type (associated with IVDU)Thrombotic microangiopathy Open in a separate windows Treatment of HIV-associated nephropathy In the absence of randomized clinical trials, the treatment of HIVAN is based on small, uncontrolled studies, epidemiologic data, and pathogenic insights. The pathogenesis of HIVAN is usually examined in a companion article in this issue, and is known to involve direct HIV contamination and gene expression in renal epithelial cells, as well as host factors that impact susceptibility. Consistent with the direct pathogenic role of HIV contamination, the introduction of combination ART in 1996 was followed by a decline in the incidence of HIVAN42 43 and in the number of new cases of ESRD attributed to AIDS nephropathy in the United States (US).5 These suggestive epidemiologic data are supported by small, uncontrolled studies demonstrating improved renal survival with ART,44 45 and by case reports documenting renal recovery and histological improvement following the initiation of ART7 46. In a retrospective study of 42 patients with biopsy-proven HIVAN from 6 US academic medical centers, ART use was associated with delayed progression to ESRD (HR 0.24, 95% CI 0.07C0.84).44 A similar improvement in renal survival with ART was demonstrated in a single-center retrospective study of 36 patients with biopsy-proven HIVAN (HR 0.30, 95% CI 0.09C0.98).45 Although these estimates were adjusted for demographic and clinical characteristics, it is likely that there are also important unmeasured differences between patients who received ART and those who did not receive ART in these non-randomized studies. Realizing that randomized controlled trials comparing ART to placebo are no longer ethically tenable, recently updated expert guidelines consider HIVAN an indication for the initiation of ART, regardless of CD4 cell count. 47 48 The guidelines also recommend adjunctive therapy with ACE inhibitors or angiotensin receptor blockers as tolerated,47 based on evidence of benefit from cohort studies in patients with HIVAN and from randomized clinical trials in other glomerular diseases.49 The addition of corticosteroids may be considered in patients with aggressive disease or a prominent. The manuscript will undergo copyediting, typesetting, and review of the producing proof before it is published in its final citable form. in these changes, based on recent work demonstrating that expression impairs cytokinesis in tubular epithelial cells under the podocin promoter demonstrate expression of the cell cycle markers Ki-67 and phospho-Stat3 in podocytes.28 The relative MK-8719 contribution of podocytes and parietal cells to glomerular epithelial cell MK-8719 proliferation in HIVAN and other forms of collapsing glomerulopathy remains to be fully defined. Differential diagnosis of renal biopsy findings A biopsy picture of collapsing glomerulopathy is not specific for HIVAN. Differential diagnosis of the collapsing variant of FSGS includes main (idiopathic) FSGS,29 parvovirus B19 contamination,30 SV40 contamination,31 acute CMV contamination,32 erythrophagocytosis syndrome,33 interferon therapy,34 pamidronate toxicity,35 acute vaso-occlusive injury,36 rare familial forms,37 and glomerular injury in the renal allograft associated with microvascular disease.38 Renal biopsy in the HIV-infected patient is required to establish a diagnosis of HIVAN and exclude other causes of renal dysfunction and proteinuria, including a variety of HIV-related glomerular diseases, non-HIV-related renal diseases, and medication nephrotoxicity, many of which are reviewed in detail in companion articles. Other MK-8719 glomerular lesions encountered in the HIV-infected patient are outlined in Table 1. Immune complex-mediated glomerular disease is usually more common in the Caucasian populace, whereas HIVAN predominantly affects African Americans. It is particularly challenging for the renal pathologist to distinguish HIVAN from other forms of FSGS, including secondary FSGS from hypertensive arterionephrosclerosis or pre-existing main FSGS, which are also more common in black patients. Recent biopsy series in HIV-infected patients indicate an increasing prevalence of FSGS (NOS) in parallel with a reduction in HIVAN, suggesting modification of the collapsing pattern of HIVAN by ART.39,40 To illustrate the changing epidemiology of HIVAN, the renal biopsy incidence of HIVAN was 65% in a series of 112 patients reported in 1997,41 but only 35% in a recent series of 152 biopsies.39 Because endothelial tubulo-reticular inclusions also appear to be reduced by ART, the biopsy picture of HIVAN may be attenuated in ART-treated patients, approximating the morphologic appearance of FSGS (NOS). In addition, as patients live longer with HIV contamination, they may develop other non-HIV-related kidney diseases common in the aging population, such as diabetic nephropathy and arterionephrosclerosis of aging or hypertension, which may also exhibit focal sclerosing features. TABLE 1 GLOMERULAR LESIONS OCCURRING IN HIV-INFECTED PATIENTS HIVAN (collapsing glomerulopathy)Focal segmental glomerulosclerosis (FSGS), not otherwise specified (NOS)Minimal switch diseaseImmune complex-mediated glomerulonephritis?Lupus-like nephritis?IgA nephropathy?Membranoproliferative glomerulonephritis (associated with hepatitis C or B)?Membranous glomerulopathy (associated with hepatitis B or C, or neoplasia)?Acute post-infectious glomerulonephritisFibrillary and immunotactoid glomerulonephritis (often associated with hepatitis C)Diabetic nephropathyAmyloidosis, AA type (associated with IVDU)Thrombotic microangiopathy Open in a separate windows Treatment of HIV-associated nephropathy In the absence of randomized clinical trials, the treatment of HIVAN is based on small, uncontrolled studies, epidemiologic data, and pathogenic insights. The pathogenesis of HIVAN is usually reviewed in a companion article in this issue, and is known to involve direct HIV contamination and gene expression in renal epithelial cells, as well as host factors that impact susceptibility. Consistent with the direct pathogenic role of HIV contamination, the introduction of combination ART in 1996 was followed by a decline in the incidence of HIVAN42 43 and in the number of new cases of ESRD attributed to AIDS nephropathy in the United States (US).5 These suggestive epidemiologic data are supported by small, uncontrolled studies demonstrating improved renal survival with ART,44 45 and by case reports documenting renal recovery and histological improvement following the initiation of ART7 46. In a retrospective study of 42 patients with biopsy-proven HIVAN.
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