Crescentic IgA nephropathy and acute renal failur ien an HIV … · 2013-03-12 ·...

Nephrol Dial Transplant (1996) 11: 2320-2323

Case Report

NephrologyDialysis

Transplantation

Crescentic IgA nephropathy and acute renal failure in an HIV-positivepatient 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 ofNephrology, Duke University and Durham VA Medical Centers, Durham, NC, USA

Key words: IgA nephropathy; salmonella; HIV infec-tion; ARF; crescents

Introduction

The association of HIV with renal disease has beenwell documented since the early days of the epidemic[1]. Heavy proteinuria and rapid progression to renalfailure are described as clinical characteristics in mostcases arising in HIV-infected patients. On renal biopsymany of these patients have been shown to have adistinctive combination of focal segmental glomerulo-sclerosis (FSGS), cystic tubular damage, and extensivecollections of tubular reticular inclusions (TRI) in avariety of cell types [1,2]. This constellation of findingshas been termed 'HIV-associated nephropathy' bysome authors. However, there is a wide spectrum ofclinical manifestations of renal disease in patients withHIV infection [2]. In addition to the characteristichistopathological findings of mesangial expansionand/or FSGS, immune complex glomerulonephropath-ies have also been described in patients with HIV.

A significant proportion of these cases consist ofHIV-positive patients with IgA nephropathy [3-6].There are rare reports of crescentic IgA nephropathyassociated with HIV infection [3,7,8].

Most cases of crescentic IgA nephropathy are idio-pathic and no precipitating cause for nephropathy isever identified. We report here the case of a youngblack male with a 10-year history of HIV infectionwho presented with an acute febrile illness secondaryto Salmonella typhimurium enteritis who developed acrescentic IgA glomerulonephritis with acute renalfailure. The patient's renal failure resolved completelywith treatment of the infection and a short courseof steroids.

Correspondence and offprint requests to: Peter J. Conlon. Box 3014,Division of Nephrology, Department of Medicine, Duke UniversityMedical Center, Durham, NC 27710, USA.

Case report

A 30-year-old black male with a history of HIVinfection since 1984 presented to Duke UniversityMedical Center with a 2-day history of fevers, chills,abdominal pain, diarrhoea, nausea, and vomiting. Thepatient had been incarcerated at a federal penitentiaryfor more than 5 years. He had no previous episodesof opportunistic infections. He had persistently refusedantiretroviral therapy. Shortly after the patient becameill he began to notice the presence of haematuria. Hehad no other significant past medical history. Onphysical examination he had a fever of 39°C and hadmild generalized abdominal tenderness.

Biochemical abnormalities included a BUN of37 mg/dl and creatinine of 3.4 mg/dl, and white bloodcell count of 10.2 x 103/cm3, with 78% neutrophils/12%bands. Urinalysis showed 3 + blood, 3 + protein, withgreater than 50 red cells per high-power field, andnumerous red cell casts. Blood and urine cultures weresterile. The patient was empirically commenced onintravenous cefazolin lg t.i.d. He remained febrile to40°C and his creatinine rose to 8.1 mg/dl over the next36 h despite vigorous hydration. A renal ultrasoundexamination showed normal sized kidneys and noevidence of obstruction. In view of the acute renalfailure and active urinary sediment a renal biopsy wasperformed. Other investigations of note revealed thathe had an elevated creatinine kinase at 920 iU/cm3 anda CD4+ Tcell count of 104/cm3. Antineutrophil cyto-plasmic antibodies were negative and his complementlevels were within the normal range. Stool culturesobtained on the day of admission subsequently grewSalmonella typhimurium.

By 48 h after admission the patient's fever hadresolved and he was empirically commenced on oralprednisone 60 mg/day. By day 6 his renal functionbegan to improve and he was discharged with a serumcreatinine of 3.5 mg/dl. When the patient was seen inthe clinic 4 weeks later he had remained well with nomore fevers or diarrhoea and he had a serum creatinineof 1 mg/dl. He was rapidly tapered off of prednisone.

f 1996 European Renal Association-European Dialysis and Transplant Association

IgA nephropathy and ARF in an HIV-positive patient with enteric salmonella 2321

Renal pathology

Two cores of renal tissue were obtained and processedin a standard fashion [9]. Light-microscopic examina-tion of the biopsy tissue demonstrated numerous redblood cell casts present within tubular lumina. Theinterstitium contained a patchy mononuclear infiltrateas well as mild fibrosis. Glomeruli exhibited mild tomoderate hypercellularity and mesangial expansionwith 50% of the glomeruli demonstrating cellular cres-cents (Figure 1A). The tubules demonstrated focallyflattened, regenerative appearing tubular epithelium,which occasionally contained granular, coarse brownpigment. Direct immunofluorescence analysis showedmoderate coarse granular staining for IgA (Figure IB),Ig kappa, and Ig lambda in the glomerular mesangium.

Minimal staining was detected for other immunoglob-ulin and complement components, and no significantcapillary loop staining was seen. Transmission electron-microscopy demonstrated expansion of the glomerularmesangium by abundant immune complex deposits(Figure 1C). A few subendothelial electron-densedeposits were noted, mostly adjacent to mesangialareas. No subepithelial or intramembranous depositswere identified. Numerous tubuloreticular inclusionswere noted within endothelial cells (Figure ID).

A biopsy diagnosis of crescentic IgA nephropathywas made. The degree of tubular injury was felt to beunexpectedly severe. Though some degree of tubularinjury can accompany acute glomerulonephritis, theextent 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 additionthe glomerulus on the right shows a well-developed cellular crescent (arrowheads) (H&E). Bar= 100 um. B Immunofluorescence-micrographof glomerulus stained for IgA; coarse granular mesangial staining is present. Bar=100um. C Medium-power electron-micrograph ofglomerular 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 ofvolume depletion and/or a mild component ofmyoglobinuria.

Discussion

Herein we have reported a case of crescentic IgAglomerulonephritis associated with acute renal failurein a patient with severe Salmonella typhimurium infec-tion and coincident HIV infection. The acute renalfailure reversed completely with resolution of the sal-monella infection and a short course of steroids.

Since the original description of IgA nephropathymore than 25 years ago our understanding of thedisease has broadened [10]. The IgA nephropathiesconstitute a diverse group of renal disorders thatmay accompany a number of underlying diseases.Gastrointestinal symptoms are common in many formsof IgA nephropathy such as Berger's disease,Henoch-Schoenlein purpura, and IgA nephropathyassociated with coeliac disease [11]. What the patho-genesis of both the renal disease and the intestinalupset are is not well understood; it appears that thegastrointestinal disease may act as a precipitatingevent, similar to the observation that upper respiratoryinfections may act as a precipitating event. There havebeen previous reports of a number of different gastroin-testinal infections precipitating acute crescentic IgAnephritis [12-15]. We are unaware of previous reportsdescribing the development of IgA nephropathy associ-ated with salmonella infection.

An increasing number of cases of immune complexglomerulonephropathies have been described in associ-ation with HIV. Large series report that as many as20% of HIV positive patients with renal related symp-toms have biopsy proven immune complex renal dis-ease [16]. A recent post-mortem examination ofmaterial from a group of patients without overt renaldisease by Beaufils et al. [17] showed that 8% hadevidence of diffuse IgA mesangial deposits, suggestingthat IgA deposition is not an uncommon phenomenonin HIV-positive patients.

Several aspects of this patient's clinical course areat variance with the clinical findings reported for amajority of patients with HIV-associated nephropathy(HIVAN). Like our patient, individuals with HIVANtypically experience rapidly progressive renal failure[18,19], although HIVAN is typically associated withheavy proteinuria. In contrast, our patient experienceda nephritic syndrome manifested by haematuria andpassage of numerous erythrocyte casts. A more import-ant difference is that the majority of patients withHIVAN progress inexorably to end-stage renal failure,while our patient recovered normal renal function.

Renal biopsy is of great value in distinguishingHIVAN from other renal disorders with more favour-able prognosis and/or potential for treatment. Ourpatient's biopsy showed unequivocal evidence of IgAnephropathy accompanied by resolving acute tubular

W.-S. Hsieh et al.

necrosis. It should be noted that several features ofthe biopsy, including tubular injury, mesangial hyper-cellularity, and the presence of tubuloreticular inclu-sions (TRI), are shared by HIVAN [20,21]. The latteritem in particular is a potential source of confusion,since TRI have been emphasized as a key feature fordistinguishing the glomerular sclerosis of HIVAN fromother forms of sclerosing glomerulopathy, includingheroin-associated nephropathy and idiopathic focalsegmental glomerulosclerosis [21]. TRI are by nomeans specific for HIVAN, however; they can be seenin patients with HIV infection regardless of renal status[2,22], including HIV-infected patients with IgAnephropathy [3], and also in a number of other non-HlV-related renal diseases [23].

This case demonstrated a variety of renal patholo-gical lesions, including crescentic IgA nephropathy andresolving acute tubular necrosis, in a patient with HIVinfection. We believe it emphasizes the need for earlyrenal biopsy in patients with HIV infection and renalfailure, when the clinical characteristics are in any waydifferent from those that would be expected for HIV-associated nephropathy, as was recently stressed byWinston and Klotman [24].

References

1. Rao TK, Filippone EJ, Nicastri AD et al. Associated focal andsegmental glomerulosclerosis in the acquired immunodeficiencysyndrome. N Engl J Med 1984; 310: 669-673

2. Bourgoignie JJ, Pardo V. The nephropathology in humanimmunodeficiency virus (HIV-1) infection. Kidney Int 1991; 40[suppl. 35]: S19-S23

3. Katz A, Bargman JM, Miller DC, Guo JW, Ghali VS,Schoeneman MJ. IgA nephritis in HIV-positive patients: a newHIV-associated nephropathy? Clin Nephrol 1992; 38: 61-68

4. Schoeneman MJ, Ghali V, Lieberman K, Reisman L. IgAnephritis in a child with human immunodeficiency virus: aunique form of human immunodeficiency virus-associatednephropathy? Pediatr Nephrol 1992; 6: 46-49

5. Trachtman H, Gauthier B, Vinograd A, Valderrama E. IgAnephropathy in a child with human immunodeficiency virustype 1 infection. Pediatr Nephrol 1991; 5: 724-726

6. Kimmel PL, Philips TM, Ferreira-Centeno A, Farkas-Szallasi T,Abraham AA, Garrett CT. Brief report: Idiopathic IgA nephro-pathy in patients with human immunodeficiency virus infection.N Engl J Med 1992; 327: 702-706

7. Jindal KK, Trillo A, Bishop G, Hirsch D, Cohen A. CrescenticIgA nephropathy as a manifestation of human immune defi-ciency virus infection. Am J Nephrol 1991; 11: 147-150

8. Kenouch S, Delahousse M, Mery J, Nochy D. Mesangial IgAdeposits in two patients with AIDS-related complex. Nephron1990; 54: 338

9. Pirani CL. Evaluation of kidney biopsy specimens. In: TisherCC, Brenner BM, eds. Renal Pathology with Clinical andFunctional Correlations. 2nd edn. Lippincott, Philadelphia,1989; 11-42

10. Berger J, Hinglais N. Les depots intercapillaires d"IgA-IgA.J Urol Nephrol (Paris) 1968; 74: 694-695

11. Clarkson AR, Woodroffe AJ, Bannister KM, Lomax-Smith JD,Aarons I. The syndrome of IgA nephropathy. Clin Nephrol1984; 21: 7-14

12. Carter JE, Cimolai N. IgA nephropathy associated withCampylobacter jejuni enteritis. Nephron 1991: 58: 101-102

13. Lind KM, Gaub J, Pedersen RS. Henoch-Schonlein purpuraassociated with Campylobacter jejuni enteritis. Case report. ScandJ Urol Nephrol 1994: 28: 179-181

IgA nephropathy and ARF in an HIV-positive patient with enteric salmonella 2323

14. Rasmussen NH. Henoch-Schdnlein purpura after yersinia infec-tion. Arch Dis Child 1982; 52: 322-323

15. Roza M, Galbe M, Gonzalez-Baschwitz C. Henoch-Schoenleinpurpura after shigellosis. Clin Nephrol 1983; 20: 269-270

16. Nochy D, Glotz D, Dosquet P el al. Renal disease associatedwith HIV infection: a multicentric study of 60 patients fromParis hospitals. Nephrol Dial Transplant 1993; 8: 11-19

!7. Beaufils H, Jouanneau C. Katlama C, Sazdovitch V, HauwJJ. 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 andprognosis of human immunodeficiency virus associated nephro-pathy. Am J Med 1989; 87: 389-395

19. Rao TK. Clinical features of human immunodeficiency virusassociated nephropathy. Kidney Int 1989; 40 [suppl 35]: S13-S18

20. D'Agati V, Suh JI, Carbone L, Cheng JT, Appel G. Pathologyof HIV-associated nephropathy: a detailed morphologic compar-ative study. Kidney Int 1989; 35: 1358-1370

21. Cohen AH, Nast CC. HIV-associated nephropathy. A uniquecombined glomerular, tubular, and interstitial lesion. ModernPathol 1988; 1: 87-97

22. Grimley PM, Kang JH, Fredrick W. Interferon-related leukocyteinclusions in the acquired immunodeficiency syndrome. AmJ Clin Pathol 1984; 81: 147-155

23. Bariety D, Richer DD, Appay MD, Grossetete J. Callard P.Frequency of intraendothelial 'viruslike' particles: an electronmicroscopy study of 376 human renal biopsies. J Clin Pathol1973; 26: 21-24

24. Winston JA, Klotman PE. Are we missing an epidemic of HIV-associated nephropathy. Am J Kidney Dis 1996; 1-7

Received for publication: 2.7.96Accepted: 4.7.96