Nephrology Dialysis Transplantation Crescentic IgA nephropathy and ...

Nephrol Dial Transplant (1996) 11: 2320-2323

Nephrology Dialysis Transplantation

Case Report

Crescentic IgA nephropathy and acute renal failure in an HIV-positive patient with enteric salmonella infection W.-S. Hsieh1, S. Szukala2, D. N. Howell2 and P. J. Conlon3 'Department of Medicine, Duke University Medical Center, Durham, and 2Department of Pathology, 3Division of Nephrology, Duke University and Durham VA Medical Centers, Durham, NC, USA

Key words: IgA nephropathy; salmonella; HIV infection; ARF; crescents

Case report

f 1996 European Renal Association-European Dialysis and Transplant Association

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A 30-year-old black male with a history of HIV infection since 1984 presented to Duke University Medical Center with a 2-day history of fevers, chills, Introduction abdominal pain, diarrhoea, nausea, and vomiting. The patient had been incarcerated at a federal penitentiary The association of HIV with renal disease has been for more than 5 years. He had no previous episodes well documented since the early days of the epidemic of opportunistic infections. He had persistently refused [1]. Heavy proteinuria and rapid progression to renal antiretroviral therapy. Shortly after the patient became failure are described as clinical characteristics in most ill he began to notice the presence of haematuria. He cases arising in HIV-infected patients. On renal biopsy had no other significant past medical history. On many of these patients have been shown to have a physical examination he had a fever of 39°C and had distinctive combination of focal segmental glomerulo- mild generalized abdominal tenderness. sclerosis (FSGS), cystic tubular damage, and extensive Biochemical abnormalities included a BUN of collections of tubular reticular inclusions (TRI) in a 37 mg/dl and creatinine of 3.4 mg/dl, and white blood variety of cell types [1,2]. This constellation of findings cell count of 10.2 x 103/cm3, with 78% neutrophils/12% has been termed 'HIV-associated nephropathy' by some authors. However, there is a wide spectrum of bands. Urinalysis showed 3 + blood, 3 + protein, with clinical manifestations of renal disease in patients with greater than 50 red cells per high-power field, and HIV infection [2]. In addition to the characteristic numerous red cell casts. Blood and urine cultures were histopathological findings of mesangial expansion sterile. The patient was empirically commenced on and/or FSGS, immune complex glomerulonephropath- intravenous cefazolin lg t.i.d. He remained febrile to 40°C and his creatinine rose to 8.1 mg/dl over the next ies have also been described in patients with HIV. 36 h despite vigorous hydration. A renal ultrasound A significant proportion of these cases consist of examination showed normal sized kidneys and no HIV-positive patients with IgA nephropathy [3-6]. evidence of obstruction. In view of the acute renal There are rare reports of crescentic IgA nephropathy failure and active urinary sediment a renal biopsy was associated with HIV infection [3,7,8]. performed. Other investigations of note revealed that Most cases of crescentic IgA nephropathy are idio- he had an elevated creatinine kinase at 920 iU/cm3 and pathic and no precipitating cause for nephropathy is a CD4 + Tcell count of 104/cm3. Antineutrophil cytoever identified. We report here the case of a young plasmic antibodies were negative and his complement black male with a 10-year history of HIV infection levels were within the normal range. Stool cultures who presented with an acute febrile illness secondary obtained on the day of admission subsequently grew to Salmonella typhimurium enteritis who developed a Salmonella typhimurium. crescentic IgA glomerulonephritis with acute renal By 48 h after admission the patient's fever had failure. The patient's renal failure resolved completely with treatment of the infection and a short course resolved and he was empirically commenced on oral prednisone 60 mg/day. By day 6 his renal function of steroids. began to improve and he was discharged with a serum creatinine of 3.5 mg/dl. When the patient was seen in the clinic 4 weeks later he had remained well with no Correspondence and offprint requests to: Peter J. Conlon. Box 3014, Division of Nephrology, Department of Medicine, Duke University more fevers or diarrhoea and he had a serum creatinine of 1 mg/dl. He was rapidly tapered off of prednisone. Medical Center, Durham, NC 27710, USA.

IgA nephropathy and ARF in an HIV-positive patient with enteric salmonella

Renal pathology

Two cores of renal tissue were obtained and processed in a standard fashion [9]. Light-microscopic examination of the biopsy tissue demonstrated numerous red blood cell casts present within tubular lumina. The interstitium contained a patchy mononuclear infiltrate as well as mild fibrosis. Glomeruli exhibited mild to moderate hypercellularity and mesangial expansion with 50% of the glomeruli demonstrating cellular crescents (Figure 1A). The tubules demonstrated focally flattened, regenerative appearing tubular epithelium, which occasionally contained granular, coarse brown pigment. Direct immunofluorescence analysis showed moderate coarse granular staining for IgA (Figure IB), Ig kappa, and Ig lambda in the glomerular mesangium.

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Minimal staining was detected for other immunoglobulin and complement components, and no significant capillary loop staining was seen. Transmission electronmicroscopy demonstrated expansion of the glomerular mesangium by abundant immune complex deposits (Figure 1C). A few subendothelial electron-dense deposits were noted, mostly adjacent to mesangial areas. No subepithelial or intramembranous deposits were identified. Numerous tubuloreticular inclusions were noted within endothelial cells (Figure ID). A biopsy diagnosis of crescentic IgA nephropathy was made. The degree of tubular injury was felt to be unexpectedly severe. Though some degree of tubular injury can accompany acute glomerulonephritis, the extent of the tubular changes in the biopsy most


Fig. 1. A Light-micrograph of renal cortex showing two glomeruli. Mild mesangial expansion and hypercellularity are present; in addition the glomerulus on the right shows a well-developed cellular crescent (arrowheads) (H&E). Bar= 100 um. B Immunofluorescence-micrograph of glomerulus stained for IgA; coarse granular mesangial staining is present. Bar=100um. C Medium-power electron-micrograph of glomerular capillary loop (L) and adjacent mesangial area. Large mesangial immune complex deposits are present (arrowheads). Bar = 1 um. D High-power electron-micrograph of capillary loop; a large tubuloreticular inclusion is present within the endothelial cell cytoplasm (arrowhead). Bar=l um.

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probably reflected an additional aetiological factor. Possibilities include ischaemic damage as a result of volume depletion and/or a mild component of myoglobinuria.


necrosis. It should be noted that several features of the biopsy, including tubular injury, mesangial hypercellularity, and the presence of tubuloreticular inclusions (TRI), are shared by HIVAN [20,21]. The latter item in particular is a potential source of confusion, since TRI have been emphasized as a key feature for Discussion distinguishing the glomerular sclerosis of HIVAN from other forms of sclerosing glomerulopathy, including Herein we have reported a case of crescentic IgA heroin-associated nephropathy and idiopathic focal glomerulonephritis associated with acute renal failure segmental glomerulosclerosis [21]. TRI are by no in a patient with severe Salmonella typhimurium infec- means specific for HIVAN, however; they can be seen tion and coincident HIV infection. The acute renal in patients with HIV infection regardless of renal status failure reversed completely with resolution of the sal- [2,22], including HIV-infected patients with IgA nephropathy [3], and also in a number of other nonmonella infection and a short course of steroids. Since the original description of IgA nephropathy HlV-related renal diseases [23]. more than 25 years ago our understanding of the This case demonstrated a variety of renal patholodisease has broadened [10]. The IgA nephropathies gical lesions, including crescentic IgA nephropathy and constitute a diverse group of renal disorders that resolving acute tubular necrosis, in a patient with HIV may accompany a number of underlying diseases. infection. We believe it emphasizes the need for early Gastrointestinal symptoms are common in many forms renal biopsy in patients with HIV infection and renal of IgA nephropathy such as Berger's disease, failure, when the clinical characteristics are in any way Henoch-Schoenlein purpura, and IgA nephropathy different from those that would be expected for HIVassociated with coeliac disease [11]. What the patho- associated nephropathy, as was recently stressed by genesis of both the renal disease and the intestinal Winston and Klotman [24]. upset are is not well understood; it appears that the gastrointestinal disease may act as a precipitating event, similar to the observation that upper respiratory infections may act as a precipitating event. There have References been previous reports of a number of different gastroin1. Rao TK, Filippone EJ, Nicastri AD et al. Associated focal and testinal infections precipitating acute crescentic IgA segmental glomerulosclerosis in the acquired immunodeficiency syndrome. N Engl J Med 1984; 310: 669-673 nephritis [12-15]. We are unaware of previous reports describing the development of IgA nephropathy associ- 2. Bourgoignie JJ, Pardo V. The nephropathology in human immunodeficiency virus (HIV-1) infection. Kidney Int 1991; 40 ated with salmonella infection. [suppl. 35]: S19-S23 An increasing number of cases of immune complex 3. Katz A, Bargman JM, Miller DC, Guo JW, Ghali VS, Schoeneman MJ. IgA nephritis in HIV-positive patients: a new glomerulonephropathies have been described in associHIV-associated nephropathy? Clin Nephrol 1992; 38: 61-68 ation with HIV. Large series report that as many as 4. Schoeneman MJ, Ghali V, Lieberman K, Reisman L. IgA 20% of HIV positive patients with renal related sympnephritis in a child with human immunodeficiency virus: a toms have biopsy proven immune complex renal disunique form of human immunodeficiency virus-associated nephropathy? Pediatr Nephrol 1992; 6: 46-49 ease [16]. A recent post-mortem examination of 5. Trachtman H, Gauthier B, Vinograd A, Valderrama E. IgA material from a group of patients without overt renal nephropathy in a child with human immunodeficiency virus disease by Beaufils et al. [17] showed that 8% had type 1 infection. Pediatr Nephrol 1991; 5: 724-726 evidence of diffuse IgA mesangial deposits, suggesting 6. Kimmel PL, Philips TM, Ferreira-Centeno A, Farkas-Szallasi T, that IgA deposition is not an uncommon phenomenon Abraham AA, Garrett CT. Brief report: Idiopathic IgA nephropathy in patients with human immunodeficiency virus infection. in HIV-positive patients. N Engl J Med 1992; 327: 702-706 Several aspects of this patient's clinical course are 7. Jindal KK, Trillo A, Bishop G, Hirsch D, Cohen A. Crescentic at variance with the clinical findings reported for a IgA nephropathy as a manifestation of human immune defimajority of patients with HIV-associated nephropathy ciency virus infection. Am J Nephrol 1991; 11: 147-150 (HIVAN). Like our patient, individuals with HIVAN 8. Kenouch S, Delahousse M, Mery J, Nochy D. Mesangial IgA deposits in two patients with AIDS-related complex. Nephron typically experience rapidly progressive renal failure 1990; 54: 338 [18,19], although HIVAN is typically associated with 9. Pirani CL. Evaluation of kidney biopsy specimens. In: Tisher heavy proteinuria. In contrast, our patient experienced CC, Brenner BM, eds. Renal Pathology with Clinical and a nephritic syndrome manifested by haematuria and Functional Correlations. 2nd edn. Lippincott, Philadelphia, 1989; 11-42 passage of numerous erythrocyte casts. A more important difference is that the majority of patients with 10. Berger J, Hinglais N. Les depots intercapillaires d"IgA-IgA. Urol Nephrol (Paris) 1968; 74: 694-695 HIVAN progress inexorably to end-stage renal failure, 11. JClarkson AR, Woodroffe AJ, Bannister KM, Lomax-Smith JD, while our patient recovered normal renal function. Aarons I. The syndrome of IgA nephropathy. Clin Nephrol 1984; 21: 7-14 Renal biopsy is of great value in distinguishing HIVAN from other renal disorders with more favour- 12. Carter JE, Cimolai N. IgA nephropathy associated with Campylobacter jejuni enteritis. Nephron 1991: 58: 101-102 able prognosis and/or potential for treatment. Our 13. Lind KM, Gaub J, Pedersen RS. Henoch-Schonlein purpura patient's biopsy showed unequivocal evidence of IgA associated with Campylobacter jejuni enteritis. Case report. Scand nephropathy accompanied by resolving acute tubular J Urol Nephrol 1994: 28: 179-181

IgA nephropathy and ARF in an HIV-positive patient with enteric salmonella 14. Rasmussen NH. Henoch-Schdnlein purpura after yersinia infection. Arch Dis Child 1982; 52: 322-323 15. Roza M, Galbe M, Gonzalez-Baschwitz C. Henoch-Schoenlein purpura after shigellosis. Clin Nephrol 1983; 20: 269-270 16. Nochy D, Glotz D, Dosquet P el al. Renal disease associated with HIV infection: a multicentric study of 60 patients from Paris hospitals. Nephrol Dial Transplant 1993; 8: 11-19 !7. Beaufils H, Jouanneau C. Katlama C, Sazdovitch V, Hauw JJ. HIV-associated IgA nephropathy—a post-mortem study. Nephrol Dial Transplant 1995; 10: 35-38 18. Carbone L, D'Agati V, Cheng J, Appel GB. Course and prognosis of human immunodeficiency virus associated nephropathy. Am J Med 1989; 87: 389-395 19. Rao TK. Clinical features of human immunodeficiency virus associated nephropathy. Kidney Int 1989; 40 [suppl 35]: S13-S18

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20. D'Agati V, Suh JI, Carbone L, Cheng JT, Appel G. Pathology of HIV-associated nephropathy: a detailed morphologic comparative study. Kidney Int 1989; 35: 1358-1370 21. Cohen AH, Nast CC. HIV-associated nephropathy. A unique combined glomerular, tubular, and interstitial lesion. Modern Pathol 1988; 1: 87-97 22. Grimley PM, Kang JH, Fredrick W. Interferon-related leukocyte inclusions in the acquired immunodeficiency syndrome. Am J Clin Pathol 1984; 81: 147-155 23. Bariety D, Richer DD, Appay MD, Grossetete J. Callard P. Frequency of intraendothelial 'viruslike' particles: an electron microscopy study of 376 human renal biopsies. J Clin Pathol 1973; 26: 21-24 24. Winston JA, Klotman PE. Are we missing an epidemic of HIVassociated nephropathy. Am J Kidney Dis 1996; 1-7 Received for publication: 2.7.96 Accepted: 4.7.96
