HIV-associated nephropathy
1999; Elsevier BV; Volume: 56; Issue: 3 Linguagem: Inglês
10.1046/j.1523-1755.1999.00748.x
ISSN1523-1755
Autores Tópico(s)Cytomegalovirus and herpesvirus research
ResumoA 37-year-old African-American man, HIV seropositive since 1986 and a former injection drug user, was referred to the Division of Nephrology of Mt. Sinai Medical Center for evaluation of proteinuria and azotemia. He had been asymptomatic and never hospitalized until three years ago, when he presented to Mt. Sinai Medical Center for the first time with a fever and headache. Workup at that time included multiple blood cultures, CAT scan, and lumbar puncture. Significant findings included hypertension (160/100 mm Hg); oral thrush; serum creatinine, 1.2 mg/dl; urine protein, 700 mg/24 hrs; and a CD4 count of 30 cells/μl. His fever and headache resolved during hospitalization, and he was discharged on clotrimazole, fluconazole, and amlodipine with plans for followup in the AIDS clinic. He was not seen again until two years ago, when he presented to the AIDS clinic with weakness and pruritic skin lesions. The blood pressure was 140/105 mm Hg; CD4 count, 20 cells/μl; serum creatinine, 3.0 mg/dl; and 4+ proteinuria by dipstick. Therapy with AZT, 3TC (a reverse transcriptase inhibitor), and trimethoprim-sulfamethoxazole was initiated, and the patient was referred to the Nephrology Clinic. On examination in the Nephrology Clinic one month later, he complained of general malaise, weakness, fatigue, anorexia, and pruritus. Physical examination revealed a well-developed but ill-appearing black male. He was afebrile with a blood pressure of 170/100 mm Hg without orthostatic changes. Pertinent findings included trace edema, hyperpigmented and raised plaques on the upper body and arms, and cardiomegaly. Neither hepatosplenomegaly nor lymphadenopathy was present. Urinalysis revealed 4+ proteinuria and a negative sediment. Laboratory examination demonstrated a serum creatinine of 4.9 mg/dl and a CD4 count of 20 cells/μl. Red blood cell morphology, platelet count, and bleeding time were normal. A 24-hour urine collection contained 4.7 g of protein. Creatinine clearance was 15 cc/min. Antibodies to hepatitis B and C were negative; the ANA was negative and serum complement was normal. The HIV-1 RNA, quantitated by RT-PCR, was 1.4 × 103 copies/ml. A renal biopsy revealed collapsing focal glomerulosclerosis, extensive focal glomerulosclerosis, and extensive microcystic tubulointerstitial disease. There were no tubuloreticular structures, and immune complexes were not detected. The biopsy was consistent with HIV-associated nephropathy. The patient's serum creatinine rose to 6.7 mg/dl; a percutaneous vascular access was placed, a PTFE graft inserted, and hemodialysis initiated. The patient remained stable on hemodialysis. Four months after initiation of dialysis, saquinavir (a protease inhibitor) was added to the two reverse transcriptase inhibitors because of the persistently low CD4 count and viral burden. After six months of triple-drug therapy, the patient, on his own initiative, stopped taking all antiretroviral medications. One month later, when he returned to the clinic, the CD4 count was 30 cells/μl, and the plasma RNA level was 1.1 × 105 copies/ml. After lengthy discussions with his physicians, the patient restarted his triple-drug regimen. Shortly thereafter, he noticed that his urine output had increased, and he returned to the clinic one month later. His predialysis creatinine was stable at 4 mg/dl; the creatinine clearance was 30 ml/min. Dialysis was discontinued, and a repeat renal biopsy was essentially unchanged. The CD4 count was 20 cells/μl, and the viral load was 1.3 × 105/ml. The patient remains off dialysis, and his new antiretroviral regimen includes nelfinavir (a protease inhibitor), D4T (a reverse transcriptase inhibitor), and 3TC. Two months ago, his CD4 count was 80 cells/μl and his viral burden 2.8 × 103 copies/ml. Dr. PAUL E. KLOTMAN (Professor of Medicine, Chief, Division of Nephrology; Vice Chairman for Research, Department of Medicine, Mt. Sinai School of Medicine, New York, New York, USA): The patient today is similar in most ways to patients who present with human immunodeficiency virus (HIV)-associated nephropathy. He is a black male with a history of intravenous drug use from an urban center, New York City. He developed significant proteinuria and had a rapidly progressive clinical course. His only atypical clinical feature is the presence of hypertension; most patients with HIV-associated nephropathy (HIVAN) are volume depleted and tend to have normal or low systemic blood pressure. His CD4+ count of 30 cells/μl defines him as an AIDS patient relatively late in the course of his disease. His HIV RNA level of 2.8 × 103 copies/ml on the triple therapy represents a 2 log decrease from the untreated level, but he has never achieved an optimal response, suppression to nondetectable levels of viral RNA. His clinical course raises the possibility that antiviral agents were effective therapy for his HIVAN, but the patient might have had a reversible injury superimposed on a background of HIVAN that resolved spontaneously. This patient clearly demonstrates the need for controlled trials when proposing novel therapeutic interventions. This is not the first Nephrology Forum dedicated to HIVAN. In 1990, a Forum was dedicated to the renal complications of HIV-11.Bourgoignie J.J. Renal complications of human immunodeficiency virus type 1.Kidney Int. 1990; 37: 1571-1584Abstract Full Text PDF PubMed Scopus (131) Google Scholar. At that time, HIVAN was a rare disease; fewer than 200 cases were reported by the United States Renal Data System (USRDS). To put this case number in perspective, at the time of that Forum nine years ago, only 115,000 cases of AIDS had been reported by the Centers for Disease Control (CDC) in the entire United States. As of 1998, the City of New York alone reported just over 100,000 cases of AIDS (New York City Department of Health, Office of AIDS Surveillance). In the past nine years, the HIV epidemic has changed dramatically. Some of these changes have important implications for the demographics of renal disease in this country. Blacks and Hispanics have become the racial populations at greatest risk for AIDS in the United States. Heterosexual contact and intravenous drug use have become the most important routes for HIV infection. Thus, the population at greatest risk for the development of HIVAN has increased substantially and, not surprisingly, so have both the incidence of HIVAN and the prevalence of HIV-positive patients in the population with end-stage renal disease (ESRD). Since HIVAN is most often observed in the urban setting, nephrologists in other locations might be unaware of the profound impact that HIVAN has had on large population centers. This Forum is intended to persuade the reader that we are in the midst of a national epidemic of HIVAN and to address some important questions. (1) What is HIVAN? (2) Is HIVAN a significant problem? (3) What is the cause of HIVAN? (4) Is there any hope for effective therapy? In hospitals that serve communities with a high HIV-1 prevalence, the coexistence of seroposivity and/or AIDS with renal insufficiency is common. Not all of these patients, however, have HIVAN. Many patients, particularly those with AIDS, present with acute renal failure2.Bourgoignie J.J. Meneses R. Ortiz C. Jaffee D. Pardo V. The clinical spectrum of renal disease associated with immunodeficiency virus.Am J Kidney Dis. 1988; 12: 131-137Abstract Full Text PDF PubMed Scopus (130) Google Scholar, 3.Rao T.K. Friedman E.A. Nicastri A.D. The types of renal disease in the acquired immunodeficiency syndrome.N Engl J Med. 1987; 316: 1062-1068Crossref PubMed Scopus (269) Google Scholar, 4.Rao T.K. Clinical features of human immunodeficiency virus associated nephropathy.Kidney Int. 1991; 40: S13-S18PubMed Google Scholar, 5.Rao T.K. Acute renal failure syndromes in human immmunodeficiency virus infection.Semin Nephrol. 1998; 18: 378-395Crossref PubMed Scopus (640) Google Scholar. Patients with AIDS experience recurrent infections and are exposed to multiple drugs including potentially nephrotoxic antivirals6.Kopp J.B. Miller K.D. Mican J.A. Feuerstein I.M. Vaughan E. Baker C. Pannell L.K. Falloon J. Crystalluria and urinary tract abnormalities associated with indinavir.Ann Intern Med. 1997; 127: 119-125Crossref PubMed Scopus (263) Google Scholar, 7.Berns J.S. Cohen R.M. Silverman M. Turner J. Acute renal failure due to indinavir crystalluria and nephrolithiasis: Report of two cases.Am J Kidney Dis. 1997; 30: 558-560Abstract Full Text PDF PubMed Scopus (55) Google Scholar, 8.Vittecoq D. Dumitrescu L. Beaufils H. Deray G. Fanconi syndrome associated with cidofovir therapy (letter).Antimicrob Agents Chemother. 1997; 41: 1846PubMed Google Scholar, 9.Tashima K.T. Horowitz J.D. Rosen S. Indinavir nephropathy (letter).N Engl J Med. 1997; 336: 138Crossref PubMed Scopus (127) Google Scholar, 10.Chugh S. Bird R. Alexander E.A. Ritonavir and renal failure (letter).N Engl J Med. 1997; 336: 138PubMed Google Scholar, 11.Duong M. Sgro C. Grappin M. Biron F. Boibieux A. A Renal failure after treatment with ritonavir (letter).Lancet. 1996; 348: 693Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, and they are at great risk for developing acute renal failure from the many usual causes. In addition, AIDS patients tend to be volume depleted as a result of salt wasting, poor nutrition, nausea, or vomiting, and volume depletion is an important predisposing factor for acute renal injury from all causes2.Bourgoignie J.J. Meneses R. Ortiz C. Jaffee D. Pardo V. The clinical spectrum of renal disease associated with immunodeficiency virus.Am J Kidney Dis. 1988; 12: 131-137Abstract Full Text PDF PubMed Scopus (130) Google Scholar, 3.Rao T.K. Friedman E.A. Nicastri A.D. The types of renal disease in the acquired immunodeficiency syndrome.N Engl J Med. 1987; 316: 1062-1068Crossref PubMed Scopus (269) Google Scholar, 5.Rao T.K. Acute renal failure syndromes in human immmunodeficiency virus infection.Semin Nephrol. 1998; 18: 378-395Crossref PubMed Scopus (640) Google Scholar, 12.Gardenswartz M.H. Lerner C.W. Seligson G.R. Zabetakis P.M. Rotterdam H. Tapper M.L. Michelis M.F. Bruno M.S. Renal disease in patient in AIDS: Aclinicopathologic study.Clin Nephrol. 1984; 21: 197-204PubMed Google Scholar, 13.Soni A. Agarwal A. Chander P. Yoo J. Singal D. Salomon N. Robinson B. Treser G. Evidence for an HIV-related nephropathy: A clinicopathological study.Clin Nephrol. 1989; 31: 12-17PubMed Google Scholar, 14.Valeri A. Neusy A.J. Acute and chronic renal disease in hospitalizated AIDS patients.Clin Nephrol. 1991; 35: 110-118PubMed Google Scholar, 15.Appel G.B. Nicolaides M.N. Human immunodeficiency virus/acquired immunodeficiency syndrome nephropathy in the inner city.N Y State J Med. 1991; 91: 207-210PubMed Google Scholar, 16.Provenzano R. Kupin W. Santiago G.C. Renal involvement in the acquired immunodeficiency syndrome: presentation, clinical course, and therapy.Henry Ford Hosp Med J. 1987; 135: 38-41Google Scholar, 17.Frassetto L. Schoenfeld P. Humphreys M. The increasing incidence of human immunodeficiency virus associated nephropathy at San Francisco General Hospital.Am J Kidney Dis. 1991; 18: 655-659Abstract Full Text PDF PubMed Scopus (35) Google Scholar, 18.Seney Jr, Fd Burns D.K. Silva F.G. Acquired immunodeficiency syndrome and the kidney.Am J Kidney Dis. 1990; 16: 1-13Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 19.Cantor E.S. Kimmel P.L. Bosch J.P. Effect of race on expression of acquired immunodeficiency syndrome-associated nephropathy.Arch Intern Med. 1991; 151: 125-128Crossref PubMed Scopus (99) Google Scholar, 20.Marques L.P. Rioja L.S. De Oliveria C.A. Lopes G.S. Santos O.R. Kidney and HIV-infection (letter).Clin Nephrol. 1992; 37: 269-270PubMed Google Scholar, 21.Lopes G.S. Marques L.P. Rioja L.S. Basilio De Oliveira C.A. Oliveira A.V. Nery A.C. Santos O.R. Glomerular disease and human immunodeficiency virus infection in Brazil.Am J Nephrol. 1992; 12: 281-287Crossref PubMed Scopus (40) Google Scholar, 22.Rao T.K. Friedman E.A. Outcome of severe acute renal failure in patients with acquired immunodeficiency syndrome.Am J Kidney Dis. 1995; 25: 390-398Abstract Full Text PDF PubMed Scopus (55) Google Scholar. In contrast, HIVAN is a disease of progressive renal failure with both tubulointerstitial and glomerular components2.Bourgoignie J.J. Meneses R. Ortiz C. Jaffee D. Pardo V. The clinical spectrum of renal disease associated with immunodeficiency virus.Am J Kidney Dis. 1988; 12: 131-137Abstract Full Text PDF PubMed Scopus (130) Google Scholar, 12.Gardenswartz M.H. Lerner C.W. Seligson G.R. Zabetakis P.M. Rotterdam H. Tapper M.L. Michelis M.F. Bruno M.S. Renal disease in patient in AIDS: Aclinicopathologic study.Clin Nephrol. 1984; 21: 197-204PubMed Google Scholar, 23.D'agati V. Suh J.I. Carbone L. Cheng J.T. Appel G. Pathology of HIV-associated nephropathy: A detailed morphologic and comparative study.Kidney Int. 1989; 35: 1358-1370Abstract Full Text PDF PubMed Scopus (329) Google Scholar, 24.D'agati V. Appel G.B. HIV infection and the kidney.J Am Soc Nephrol. 1997; 8: 138-152PubMed Google Scholar, 25.D'agati V. Appel G.B. Renal pathology of human immunodeficiency virus infection.Semin Nephrol. 1998; 18: 406-421PubMed Google Scholar, 26.Chander P. Soni A. Suri A. Bhagwat R. Yoo J. Treser G. Renal ultrastructural markers in AIDS-associated nephropathy.Am J Pathol. 1987; 126: 513-526PubMed Google Scholar, 27.Pardo V. Aldana M. Colton R.M. Fischl M.A. Jaffe D. Moskowitz L. Hensley G.T. Bourgoignie J.J. Glomerular lesions in the acquired immunodeficiency syndrome.Ann Intern Med. 1984; 101: 429-434Crossref PubMed Scopus (240) Google Scholar, 28.Pardo V. Meneses R. Ossa L. Jaffe D.J. Strauss J. Roth D. Bourgoignie J.J. AIDS-related glomerulopathy: Occurrence in specific risk groups.Kidney Int. 1987; 31: 1167-1173Abstract Full Text PDF PubMed Scopus (133) Google Scholar, 29.Cohen A.H. Nast C.C. HIV-associated nephropathy: A unique combined glomerular, tubular, and interstitial lesion.Mod Pathol. 1988; 1: 87-97PubMed Google Scholar, 30.Glassock R.J. Cohen A.H. Danovitch G. Parsa K.P. Human immunodeficiency virus (HIV) infection and the kidney.Ann Intern Med. 1990; 112: 35-49Crossref PubMed Scopus (136) Google Scholar, 31.Humphreys M.H. Human immunodeficiency virus-associated glomerulosclerosis.Kidney Int. 1995; 48: 311-320Abstract Full Text PDF PubMed Scopus (91) Google Scholar, 32.Rao T.K. Filippone E.J. Nicastri A.D. Landesman S.H. Frank E. Chen C.K. Friedman E.A. Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome.N Engl J Med. 1984; 310: 669-673Crossref PubMed Scopus (478) Google Scholar. Thus, HIV-1-infected patients with acute renal failure should be approached like any patient with a change in renal function. The diagnosis of HIVAN, however, should be entertained in seropositive patients with proteinuria and evidence of declining GFR over time. The clinical course of HIVAN has changed very little from its early descriptions2.Bourgoignie J.J. Meneses R. Ortiz C. Jaffee D. Pardo V. The clinical spectrum of renal disease associated with immunodeficiency virus.Am J Kidney Dis. 1988; 12: 131-137Abstract Full Text PDF PubMed Scopus (130) Google Scholar, 32.Rao T.K. Filippone E.J. Nicastri A.D. Landesman S.H. Frank E. Chen C.K. Friedman E.A. Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome.N Engl J Med. 1984; 310: 669-673Crossref PubMed Scopus (478) Google Scholar, 33.Rao T.K. Friedman E.A. Renal syndromes in the acquired immunodeficiency syndrome (AIDS): Lessons learned from analysis over 5 years.Artif Organs. 1988; 12: 206-209Crossref PubMed Scopus (11) Google Scholar, 34.Bennett S.J. Rao T.K. Friedman E.A. Renal disease and the acquired immunodeficiency syndrome (letter).Ann Intern Med. 1985; 102: 274-275Crossref Scopus (1) Google Scholar, 35.Rao T.K. Clinical features of human immunodeficiency virus associated nephropathy.Kidney Int. 1991; 35S: 13-18Google Scholar, 36.Bourgoignie J.J. Pardo V. The nephropathy in human immunodeficiency virus (HIV-1) infection.Kidney Int. 1991; 40: S19-S23Google Scholar. Occurring almost exclusively in seropositive black patients, HIVAN occasionally affects Hispanics37.Mokrzycki M.H. Oo T.N. Patel K. Chang C.J. Human immunodeficiency virus-associated nephropathy in the Bronx: Low prevalence in a predominantly Hispanic population.Am J Nephrol. 1998; 18: 508-512Crossref PubMed Scopus (9) Google Scholar and very rarely, if ever, whites. Approximately 50% of HIVAN patients have a history of intravenous drug use. Most patients present with proteinuria and reduced renal function. The proteinuria can range from modest (0.5 to 1.5 g protein/24 hours) to nephrotic levels. In the early descriptions of HIVAN, the disease was thought to occur at any stage of HIV infection. Since the change in the diagnostic criteria for AIDS, however, most patients present late in the course of their HIV-1 infection38.Winston J.A. Burns G.C. Klotman P.E. The human immunodeficiency virus (HIV) epidemic and HIV-associated nephropathy.Semin Nephrol. 1998; 18: 373-377PubMed Google Scholar,39.Winston J. Klotman M.E. Klotman P.E. HIV-associated nephropathy is a late, not early, manifestation of HIV-1 infection.Kidney Int. 1999; 55: 1036-1040Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar. Most HIVAN patients already have experienced an AIDS-defining condition or already have a CD4+ cell count less than 250 cells/mm339.Winston J. Klotman M.E. Klotman P.E. HIV-associated nephropathy is a late, not early, manifestation of HIV-1 infection.Kidney Int. 1999; 55: 1036-1040Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar. Suggestive features of HIVAN include the presence of renal tubular epithelial cells in the urinary sediment and normal to enlarged echogenic kidneys despite significant renal insufficiency. Hypertension, although present in today's patient, is unusual despite the predicted prevalence in this predominantly black population. Thus the diagnosis of HIVAN would be distinctly unlikely in the presence of telescoped, highly active urinary sediment, in a white patient, and in patients with small end-stage kidneys. The value of renal biopsy in the diagnosis of HIVAN remains somewhat controversial in the general medical community but should be apparent to nephrologists. Although the patient's clinical course can be highly suggestive of HIVAN, biopsy confirmation is very important. Even when a patient presents with the “classic” clinical features of HIVAN, the clinical suspicion is only predictive of the biopsy diagnosis in 55% to 60% of patients25.D'agati V. Appel G.B. Renal pathology of human immunodeficiency virus infection.Semin Nephrol. 1998; 18: 406-421PubMed Google Scholar. Thus, to distinguish HIVAN from other forms of renal disease in HIV-seropositive patients, a renal biopsy is required. The key histopathologic features of HIVAN are the coexistence of focal segmental glomerulosclerosis (FSGS), often with glomerular collapse, and a distinctive tubulointerstitial disease that is termed microcystic Figure 1. Microcystic distortion involves enough tubule segments to increase kidney size by as much as 25% but does not lead to the massive enlargement of the kidney that is typical of macrocystic diseases like adult polycystic kidney disease. D'Agati and Appel recently reviewed in detail glomerular lesions associated with HIV infection25.D'agati V. Appel G.B. Renal pathology of human immunodeficiency virus infection.Semin Nephrol. 1998; 18: 406-421PubMed Google Scholar. Many glomeruli are globally sclerotic and are often seen interspersed among those that have segmental or collapsing sclerosis. Collapsing FSGS, however, is not pathognomonic for HIVAN, as it has been reported in patients who are HIV-1 seronegative40.Valeri A. Barisoni L. Appel G.B. Seigle R. D'agati V. Idiopathic collapsing focal segmental glomerusclerosis: A clinicopathologic study.Kidney Int. 1996; 50: 1734-1746Abstract Full Text PDF PubMed Scopus (219) Google Scholar. Similarly, FSGS is not exclusive to HIVAN and can be seen both as an idiopathic FSGS and in heroin nephropathy. The combination of FSGS (particularly the collapsing variant) with microcystic distortion in an HIV seropositive patient, however, establishes the diagnosis. As Table 1 illustrates, diagnoses other than HIVAN confirmed in HIV-1-positive patients include allergic interstitial nephritis, membranoproliferative glomerulonephritis, postinfectious glomerulonephritis, and many others23.D'agati V. Suh J.I. Carbone L. Cheng J.T. Appel G. Pathology of HIV-associated nephropathy: A detailed morphologic and comparative study.Kidney Int. 1989; 35: 1358-1370Abstract Full Text PDF PubMed Scopus (329) Google Scholar, 24.D'agati V. Appel G.B. HIV infection and the kidney.J Am Soc Nephrol. 1997; 8: 138-152PubMed Google Scholar, 25.D'agati V. Appel G.B. Renal pathology of human immunodeficiency virus infection.Semin Nephrol. 1998; 18: 406-421PubMed Google Scholar, 40.Valeri A. Barisoni L. Appel G.B. Seigle R. D'agati V. Idiopathic collapsing focal segmental glomerusclerosis: A clinicopathologic study.Kidney Int. 1996; 50: 1734-1746Abstract Full Text PDF PubMed Scopus (219) Google Scholar. Since specific therapy might be administered for some of these other renal diseases, the biopsy is particularly helpful in generating a rational therapeutic strategy.Table 1Glomerular diseases diagnosed by renal biopsy in 136 consecutive HIV-positive patients aAdapted from Ref.25Type of glomerular diseaseN = 127Type of tubulointerstitial diseaseN = 9Focal segmental sclerosis88Interstitial nephritis5Membranoproliferative GN13Acute tubular necrosis3Minimal change disease6Malignant lymphoma1Membranous glomerulopathy5Lupus-like nephritis4Amyloidosis4Acute postinfectious GN2Focal segmental necrotizing GN1Hemolytic-uremic syndrome1IgA nephropathy1Immunotactoid glomerulopathy1End-stage kidney1a Adapted from Ref.25.D'agati V. Appel G.B. Renal pathology of human immunodeficiency virus infection.Semin Nephrol. 1998; 18: 406-421PubMed Google Scholar Open table in a new tab Ancillary histologic studies provide some insight into pathogenesis. The immunofluorescence is most remarkable for the absence of specific findings. Occasionally, IgG, IgM, and/or C3 can be found in glomeruli, presumably as a result of protein trapping. Rare patients have been reported as having IgA deposition41.Kimmel P.L. Phillips T.M. Ferreira-Centeno A. Farkas-Szallasi T. Abraham A.A. Garrett C.T. Brief report: Idiotypic IgA nephropathy in patients with human immunodeficiency virus infection.N Engl J Med. 1992; 327: 702-706Crossref PubMed Scopus (125) Google Scholar, but this is a very unusual finding. Electron microscopy is similarly striking for its lack of findings; with rare exceptions41.Kimmel P.L. Phillips T.M. Ferreira-Centeno A. Farkas-Szallasi T. Abraham A.A. Garrett C.T. Brief report: Idiotypic IgA nephropathy in patients with human immunodeficiency virus infection.N Engl J Med. 1992; 327: 702-706Crossref PubMed Scopus (125) Google Scholar,42.Kimmel P. Phillips T. Ferreira-Centeno A. Farkas-Szallasi T. Abraham A. Garrett C. HIV-associated immune-mediated renal disease.Kidney Int. 1993; 44: 1327-1340Abstract Full Text PDF PubMed Scopus (134) Google Scholar, immune complexes are absent. Furthermore, the juxtaposition of glomerular basement membranes resulting from collapse of the capillary loops is easily visible at the light microscopic level. Thus HIVAN is not a disease generally associated with immune-complex deposition or complement activation, and the diagnosis can be established by standard light microscopy. Once HIVAN develops, it rapidly progresses to ESRD; renal survival is measured in weeks to months38.Winston J.A. Burns G.C. Klotman P.E. The human immunodeficiency virus (HIV) epidemic and HIV-associated nephropathy.Semin Nephrol. 1998; 18: 373-377PubMed Google Scholar. For patients on dialysis, the mortality rate approaches 50% per year38.Winston J.A. Burns G.C. Klotman P.E. The human immunodeficiency virus (HIV) epidemic and HIV-associated nephropathy.Semin Nephrol. 1998; 18: 373-377PubMed Google Scholar. Recent reports suggest a slightly slower progression to ESRD43.Ifudu O. Mayers J.D. Matthew J.J. Macey L.J. Brezsnyak W. Reydel C. McClendon E. Surgrue T. Rao T. Rao T.K. Friedman E.A. Uremic therapy in patients with end-stage renal disease and human immunodeficiency virus infection: Has the outcome changed in the 1990s?.Am J Kidney Dis. 1997; 29: 549-552Abstract Full Text PDF PubMed Google Scholar, and individual patients have been reported who have had little progression after as long as two years. These are exceptional cases, however, and recent studies continue to suggest a very aggressive disease process. For example, Burns et al reported that a group of patients with HIVAN progressed rapidly from relatively normal renal function (mean serum creatinine, 1.5 mg/dl) to ESRD within six months of diagnosis44.Burns G.C. Paul S.K. Toth I.R. Sivak S.L. Effect of angiotensin-converting enzyme inhibition in HIV-associated nephropathy.J Am Soc Nephrol. 1997; 8: 1140-1146PubMed Google Scholar. Whether this rapid progression represents the aggressiveness of the renal disease process or an effect of the underlying HIV infection remains unclear. Routine screening for proteinuria followed by a renal biopsy is not performed in most AIDS clinics and, as a result, we might be missing a large number of patients earlier in their clinical course whose pre-ESRD interval might be longer. In summary, HIVAN is a disease that affects predominantly HIV-seropositive blacks who present with proteinuria. The diagnosis, suggested by a low CD4+ cell count in patients with normal to enlarged kidneys, is made by renal biopsy and cannot be inferred from the clinical course alone. Histologically, patients often have the collapsing variant of FSGS with coexistent global glomerulosclerosis combined with microcystic tubulointerstitial disease. HIVAN progresses rapidly to ESRD and is associated with a very high mortality rate, probably reflecting the underlying, late stage of AIDS. The response to this question depends on one's geographic location. If the patient population comprises a significant number of black or Hispanic patients and AIDS is prevalent, the increase in HIVAN is well known to the nephrologists in that community. On the other hand, if the patient population is predominantly white and AIDS is a low-prevalence disease in the community, HIVAN appears only rarely if ever. Although concentrated in urban centers, HIVAN has emerged as a disease of national importance. According to the USRDS, the number of cases of HIVAN has increased at a rate of 30% each year, from 295 cases in 1991 to 951 cases in 199645.U.S. Renal Data System USRDS: Annual Data Report. MD, National Institutes of Health, NIDDK, Bethesda1997Google Scholar, the most recent year for which statistics have been reported. Even assuming that there is no underreporting of this disease, HIVAN is now the third leading cause of ESRD in blacks from the ages of 20 to 64, accounting for 10% of new cases of ESRD nationally38.Winston J.A. Burns G.C. Klotman P.E. The human immunodeficiency virus (HIV) epidemic and HIV-associated nephropathy.Semin Nephrol. 1998; 18: 373-377PubMed Google Scholar,39.Winston J. Klotman M.E. Klotman P.E. HIV-associated nephropathy is a late, not early, manifestation of HIV-1 infection.Kidney Int. 1999; 55: 1036-1040Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar. Not surprisingly, diabetes remains the leading cause of ESRD in this population, affecting 41% of the patients; hypertension is second at 28%. The fourth most common diagnosis, FSGS, a disease most would consider as common and important in blacks, represents only 3% of the new cases of ESRD and is now well behind HIVAN in incidence in this population. Because HIVAN cases occur in a segment of the population at risk for AIDS, we need to understand national trends in the AIDS epidemic to anticipate future trends in HIVAN. The CDC has carefully recorded the cumulative AIDS cases since the start of the epidemic in 1983. In 1983, AIDS was a disease almost exclusive to San Francisco and New York (Figure 2, top left). By 1985, other localized centers were in evidence including Los Angeles and Miami, but with few exceptions, the disease was bicoastal (Figure 2, top right). By 1989, most urban centers were reporting an increasing accumulation of cases (Figure 2, bottom left) and by 1995, almost every state with large urban centers reported significant numbers of accumulated cases of AIDS (Figure 2, bottom right). The incidence of new AIDS cases also varies dramatically by geographic location Figure 3. The Dakotas have a rate of less than 2/100,000 population, the lowest in the nation. This is in striking contrast to an incidence of 30.4 new cases/100,000 population in California, 33.5 in Georgia, 33.9 in Louisiana, 34.0 in Connecticut, 39.7 in Delaware, 44.7 in Maryland, 45.5 in New Jersey, 51.7 in Florida, 59.7 in Puerto Rico, and 68.3 in New York Figure 3. In urban centers the incidence is even more striking; Washington, DC, reported 227.7/100,000 population and some boroughs of New York City documented more than 2,000 new cases/100,000 population Figure 4.Figure 4Cumulative AIDS case rates per 100,000 population in New York City by zip code. Expressed per 100,000 population. Data are provided by the New York City Department of Health, Office of AIDS Surveillance.View Large Image Figure ViewerDownload (PPT) One of the major changes in the AIDS epidemic has been its
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