A patient with HIV infection presenting with diffuse membranous glomerulonephritis in a country with a low HIV prevalence-remarkable remission with therapy

(1)

JournalofInfectionandPublicHealth(2012)5,207—210

SHORT

COMMUNICATION

A

patient

with

HIV

infection

presenting

with

diffuse

membranous

glomerulonephritis

in

a

country

with

a

low

HIV

prevalence—–Remarkable

remission

with

therapy

Selda

Aydin

a

,

Bilgül

Mete

a

,

Mesut

Yilmaz

b,∗

,

Gulsah

Yenidünya

c

,

Res

¸at

Zaras

a

,

Aydın

Tunckale

c

,

Fehmi

Tabak

a

a_Istanbul_University,_Cerrahpasa_Medical_Faculty,_Infectious_Diseases_and_Clinical_{Microbiology,}_Istanbul,

Turkey

b_Istanbul_Medipol_University,_Infectious_Diseases_and_Clinical_{Microbiology,}_Istanbul,_Turkey c_Istanbul_University,_Cerrahpasa_Medical_Faculty,_Internal_Medicine,_Istanbul,_Turkey

Received11October2011 ;receivedinrevisedform19December2011;accepted23December2011

KEYWORDS

HIV;

Nephropathy; Membranous glomerulonephritis

Summary ThemostcommonmanifestationofHIVinthekidneyisHIV-associated nephropathy(HIVAN).Inthisreport,wedescribetheﬁrstdocumentedcaseof mem-branousglomerulonephritisinanHIV-positiveindividualinTurkey,thecountrywith thelowestHIVprevalenceintheregion.ThecaseoccurredinanHIV-positive, hepati-tisC(HCV)-negative,andhepatitisB(HBV)-negativeCaucasianmale,whopresented withnephrotic-rangeproteinuria.The patienthadafavorableresponsetoHAART andanangiotensin-receptorblocker.

Introduction

HIV-associated nephropathy (HIVAN) is character-izedclinicallybyproteinuria, oftenwitha sudden onset, with rapidly progressive renal dysfunction

∗_{Corresponding}_author_at:_Istanbul_Medipol_University,

Infec-tious Diseases and Clinical Microbiology, Unkapani, Ataturk BulvariNo.:27,34083Fatih,Istanbul,Turkey.

Tel.:+902124534856;fax:+902125317555.

E-mailaddress:myilmaz@medipol.edu.tr(M.Yilmaz).

resulting in end-stage renal disease (ESRD) over the course of several months [1]. The pathology ofHIVAN is characterized by the triad of collaps-ing focal glomerular sclerosis (FGS), microcystic tubulardilation, and endothelial cell tubuloretic-ular inclusions [2]. HIVAN was initially described in 1984 by Rao et al., who reported a pattern ofsclerosing glomerulopathyin HIV-1-seropositive patients in New York City [3]. Although approx-imately half of the patients were asymptomatic andhadnotsufferedfromopportunisticinfections

doi:10.1016/j.jiph.2011.12.003

Downloaded for Anonymous User (n/a) at Istanbul Medipol University from ClinicalKey.com by Elsevier on April 08, 2020. For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.

(2)

208 S.Aydinetal. at the time of diagnosis, all had CD4 cell counts

of less than 200cells/mm3_. _These _patients _may

presentwithnephrologicaldisorders.HIVANis espe-cially prevalentamongHIV-1-seropositive patients of African descent [4,5]. Herein, we present the ﬁrstwell-documentedcaseofanHIV-1-seropositive Caucasianmalepatientwithmembranous glomeru-lonephritis but without coinfections associated with membranous nephropathy in Turkey, the country with the lowest HIV prevalence in the region.

Case

report

A 55-year-old man was admitted to our hospi-tal with proteinuria exceeding 3.5g per day as determinedbyurineanalysisduringaroutine labo-ratory evaluation. He had no further complaints, although HIV seropositivity had been detected 3 months previously. The physical examination was normal. Laboratoryﬁndings were asfollows: Hgb: 11.0g/dL, Na: 126mequiv/L, albumin: 1.4g/dL, creatinine:1.8mg/dL,CD4:75/mm3,andHIVRNA: 547,000copies/ml. He tested negative for toxo-plasma,syphilisandmalaria.Theurinarysediment revealed severe proteinuria. The glomerular ﬁl-tration rate (GFR) was found to be 77ml/min as predicted by the 24-h creatinine excretion rate. Proteinuria of 6.7g per day was detected by 24-h measurements and urine analysis. The serum complement levels were normal. Serum protein electrophoresis showed a broad-basedincrease in the levels of gamma globulins. ANA was slightly positive; cANCA and pANCA were negative. The patientwasalsonegativeforHCVandHBV.Further investigation excluded malignancies and possi-ble exposure to drugs. Urinary ultrasonography revealed increased parenchymal echogenicity in therightkidney.

A renal biopsy was performed, and a total of 18 glomeruli were observed on the slides. Three of these glomeruli were globally sclerotic. The other glomeruli were normocellular, but the cap-illary basementmembranes weresigniﬁcantly and diffusely thickened. The mesangial regions were slightly expanded and hypercellular in some seg-ments. The interstitium was expanded in the subcapsular region with mononuclearcell inﬁltra-tion (Fig. 1). The histopathological abnormalities observedintherenalbiopsyspecimenwere consis-tentwithmembranousglomerulonephritis.

A treatment regimen of HAART (consisting of lopinavir/ritonavir+lamivudine+zidovudine) and valsartan (40mg/day) was commenced. A dietary

Figure 1 Diffuse membranous glomerulonephritis (H&E).

protein range of 0.6—0.8g/kg/day was suggested as a further means of reducing the proteinuria. After 6 weeks oftreatment, his serum creatinine level was 1.28mg/dL, and urineanalysis revealed 0.825g/day of proteinuria. The patient was dis-charged for follow-up.The patient is currently in the second year of treatment with 15mg/day of protein in the urine, a serum creatinine level of 1.04mg/dL, a GFR of 110ml/min, a CD4 level of 350/mm3andnoexpressionofHIVRNA.

Discussion

Turkey has one of the lowest prevalences of HIV/AIDS in central Europe. By the end of June 2009,a totalof 3898cases had been identiﬁedin our country, which has a population of 70 million

[6].

HIV-infected people exhibit a wide spectrum of kidney histopathologies. Although HIVAN is now a well-characterized renal disease present-ing with collapsing focal glomerulosclerosis, an

(3)

HIVinfectionwithdiffusemembranousglomerulonephritis 209 ever-increasingnumberof otherglomerulopathies

includingamyloidosis,minimalchangedisease, dia-betic nephropathy, allergic interstitial nephritis, and cryoglobulinemiaare described in association withHIVinfection[1,3,7].PatientswithHIVAN usu-allypresentwithsymptomsofchronicrenalfailure accompaniedbyproteinuria[1,3,4].

Membranous nephropathy has been reported previouslyinHIV-infectedpatients[8,9].However, HIV-associated nephropathies including membra-nous glomerulopathyhave beenrecently reported tooccursigniﬁcantlymorefrequentlyinindividuals coinfected with hepatitisC thanin those who are not coinfected [10]. Our patientdid nothave any coinfections or comorbidities typically associated withmembranousnephropathy.Hepresentedwith massiveproteinuriawithatleast3monthsofknown HIVseropositivity.Hewasasymptomaticandhadno detectableopportunisticinfections.Unfortunately, the demonstration of viral antigens could not be performedbyelectron microscopyor immunoﬂuo-rescence.

Renalechogenicitymaybe increasedduringthe ultrasonographic examination [4]. Both increased echogenicityoftherightkidneyanddiffuse mem-branous glomerulonephritis were observed in our case.

HAART prevents the progression of HIVAN to end-stage renal failure. Furthermore, HAART decreases the development of HIVAN by 60% in risk groups [4,11,12]. Angiotensin-converting enzyme (ACE) inhibitors were also implicated in the prevention of HIVAN in some studies [1,4]. Although steroids maycause signiﬁcant decreases in serum creatinine levels, recurrences were observed after the cessation of therapy [4,13]. We began to treat our patient with both HAART and anangiotensin-receptorblockerand observed the regression of proteinuria at the 6th week of follow-up. No immunosuppressive agent was used.

In conclusion, HIV infection can lead to func-tionaland structural abnormalities in renal tissue at any stage ofthe disease. HIV-associated mem-branous nephropathy should be considered in Caucasianpatientswith HIVinfectioncomplicated by nephrotic syndrome and renal failure even in the absence of other coinfections and comor-bidities typically associated with membranous nephropathy. The management of HIV-associated kidneydiseasesrequiresclosecollaborationamong infectious disease specialists and nephrologists. New combination therapies including protease inhibitors, determination of HIV disease stage by viral load detection and the management of infections and renal diseases at early stages are

promisingmodalitiesin thereversalofprogression toend-stagerenalfailure.

Funding

Nofundingsources.

Competing

interests

Nonedeclared.

Ethical

approval

Notrequired.

References

[1]Conaldi PG,BottelliA, BajA, SerraC,FioreL, Federico G, et al. Human immunodeﬁciency virus-1 tat induces hyperproliferation and dysregulation of renal glomerular epithelialcells.AmJPathol2002;161:53—61.

[2]Wyatt CM, Klotman PE, D’Agati VD. HIV-associated nephropathy: clinical presentation, pathology, and epi-demiology in the era of antiretroviral therapy. Semin Nephrol2008;28:513—22.

[3]RaoTK,FilipponeEJ,NicastriAD,LandesmanSH,FrankE, ChenCK,etal.Associatedfocaland segmental glomeru-losclerosisintheacquiredimmunodeﬁciencysyndrome.N EnglJMed1984;310:669—73.

[4]LuTC,RossM.HIV-associatednephropathy:abriefreview. MtSinaiJMed2005;72:193—9.

[5] WilliamsDI,WilliamsDJ,WilliamsIG,UnwinRJ,Grifﬁths MH,MillerRF.Presentation,pathology,andoutcomeofHIV associatedrenaldiseaseinaspecialistcentreforHIV/AIDS. SexTransmInfect1998;74:179—84.

[6]Turkey-CountryProgressReport.2010[lastaccesseddate 19.12.2011];Availablefrom:[http://data.unaids.org/pub/ Report/2010/turkey2010countryprogressreporten.pdf]. [7]HailemariamS,WalderM,BurgerHR,CathomasG,Mihatsch M, BinswangerU, etal. Renal pathologyand premortem clinicalpresentationofCaucasian patientswithAIDS:an autopsystudyfromtheerapriortoantiretroviraltherapy. SwissMedWeekly2001;131:412—7.

[8]ChenYM,MarcosLA,LiapisH,SteinbergTH,MorrisonAR. Anunusualcauseofmembranousglomerulonephritisina patientwithHIV.IntUrolNephrol2011.

[9]NebuloniM,BarbianodiBelgiojosoG,GenderiniA,TosoniA, RianiLN,etal.GlomerularlesionsinHIV-positivepatients:a 20-yearbiopsyexperiencefromNorthernItaly.ClinNephrol 2009;72:38—45.

[10]GeorgeE,NadkarniGN,EstrellaMM,LucasGM,SperatiCJ, AttaMG,et al.TheimpactofhepatitisCcoinfectionon kidney diseaserelated tohuman immunodeﬁciencyvirus (HIV):abiopsystudy.Medicine2011;90:289—95.

[11]AbbottKC,HypoliteI,WelchPG,AgodoaLY.Human immun-odeﬁciency virus/acquired immunodeﬁciency syndrome-associatednephropathyatend-stage renaldiseaseinthe UnitedStates: patientcharacteristicsandsurvivalin the

(4)

210 S.Aydinetal.

pre highly active antiretroviral therapy era. J Nephrol 2001;14:377—83.

[12]LaiCF,HuangJW,LinWC,HungCC,ChuTS.Human immun-odeﬁciency virus-associated nephropathy. J Formos Med Assoc2006;105:680—4.

[13]Szczech LA, Edwards LJ, Sanders LL, van der Horst C, Bartlett JA, Heald AE, et al. Protease inhibitors are associated with a slowed progression of HIV-related renal diseases. Clin Nephrol 2002;57: 336—41.

Availableonlineatwww.sciencedirect.com