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Kidney Disease in HIV-Positive Children

Mignon I. McCulloch, MBBCh(Wits), DCH(SA), MRCP(Lon), DTM&H(Lon), MRCPCH(Lon),FCP(Paed)SA,* and Patricio E. Ray, MD†

Summary: Before the era of highly active antiretroviral therapy, more than 40% of humanimmunodeficiency virus (HIV)-infected children experienced renal complications. In sub-Saharan Africa, approximately 2.1 million children are infected with HIV-1. In the absence ofantiretroviral therapy, young African children frequently died of AIDS-related complicationsbefore renal diseases could be manifested or diagnosed. As antiretroviral therapy has becomemore available, and their survival has increased, our experience in treating kidney disease inHIV-infected children has improved. This article discusses relevant clinical and pathologicfindings related to kidney disease in HIV-infected children.Semin Nephrol 28:585-594. © 2008 Published by Elsevier Inc.Keywords: HIV-infected children, pediatric AIDS, childhood HIV-associated nephropathy,immune complex renal diseases, HIV-HUS, South Africa

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t the end of 2007 there were 33.2 millionindividuals infected with human immu-nodeficiency virus (HIV)-1, of whom ap-

roximately 2.1 million were children youngerhan 15 years of age.1 More than 85% of allIV-infected children live in sub-Saharan Africa

Fig. 1). Considering new infections, unreportedases, and the increased survival of childreneceiving appropriate antiretroviral therapyART), this number probably will increase. Inhe absence of ART, approximately 40% of allIV-infected children living in the United Statesxperienced renal complications leading tooor growth, accelerated progression of ac-uired immune deficiency syndrome (AIDS),nd/or premature death.2 In contrast, the pres-nce of renal disease in HIV-infected Africanhildren not treated with ART is overshadowedy the high prevalence of diarrheal and respi-atory diseases, including Pneumocystis ji-oveci (previously known as Pneumocystis ca-

Red Cross Children’s Hospital, School of Child and Adolescent Health,University of Cape Town, Cape Town, South Africa.

Children’s Research Institute, Children’s National Medical Center, Depart-ment of Pediatrics, The George Washington University, Washington, DC.

upported by National Institutes of Health grants R0-1 DK-49419, R0-1HL55605, and R21 NICAN-AT-002278 (P.E.R.).

ddress reprint requests to Patricio E. Ray, MD, Robert Parrott Professor ofPediatrics, Children’s Research Institute, Children’s National Medical Cen-ter, The George Washington University, 111 Michigan Ave NW, Washing-ton, DC 20010. E-mail: Pray@cnmc.org

270-9295/00/$ - see front matter

m2008 Published by Elsevier Inc. doi:10.1016/j.semnephrol.2008.09.001

eminars in Nephrology, Vol 28, No 6, November 2008, pp 58

inii) pneumonia.3-5 Without access to standardherapy, African children younger than 2 yearsf age frequently died from diarrhea-inducedehydration or respiratory infections, even be-ore renal diseases could be manifested or diag-osed.4,5 As ART and other supportive treat-ents have become more available, the survi-

al of African children has increased, and ournowledge and experience in treating child-ood HIV-associated renal diseases has im-roved. This article discusses relevant clinicalnd pathologic renal findings in HIV-infectedhildren, and compares the experience in chil-ren from South Africa and the United States.

IV-INFECTED CHILDREN INOUTH AFRICA AND THE UNITED STATES

n mid-2006 there were approximately 300,000hildren in South Africa with HIV infection, andore than 21,000 were receiving ART.1,4,5 Therovision of ART for children varies throughoutouth Africa. Coverage of children in urgenteed of therapy is highest in the Northern andestern Cape, approaching 60%. The Western

ape has an estimated 11,000 children; how-ver, at the end of April 2008 there were only,898 children receiving ART.4,5 Currently 40%o 60% of all pediatric admissions to hospitals inouth Africa may be HIV-related.4,5 The epide-

iology and pathogenesis of HIV-associated re-

5-594 585

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al diseases is not yet well documented amongfrican children, but with the growing availabil-

ty of ART, this information has become moremportant for appropriate management.

In contrast to African countries, the Unitedtates has a small percentage of the world’shildren living with HIV/AIDS. At the end of theear 2005, the World Health Organization esti-ated that approximately 9,000 children youn-

er than 15 years of age were living with HIV/IDS in North America (Fig. 1). However, ithould be acknowledged that for each pediatricIDS case reported, there might be as many asunreported cases.1,6 African American chil-

ren represent approximately 65% of all HIV-nfected children living with HIV/AIDS in thenited States.6,7

ISTORY OF HIV-ASSOCIATED PEDIATRICENAL DISEASES IN THE UNITED STATES

he first cases describing an HIV-associated ne-hropathy (HIVAN) in African American chil-ren were reported by Strauss et al8,9 fromiami, and confirmed almost simultaneously in

hildren from New York.10 These pediatrictudies were published approximately 3 yearsfter HIVAN was described in adult patientsrom New York and Miami.11,12 It should be

igure 1. World Health Organization assessment of theermission from UNAIDS.1

oted, however, that the focal segmental glo- a

erulosclerosis (FSGS) lesions described in therst adult cases of HIVAN were considered sim-

lar to the glomerular lesions seen in the settingf heroin use.11,12 What were considered uniqueeatures of HIVAN were the rapid progressionf the disease and the combination of FSGSith tubular microcystic changes.11,12 The diag-osis of FSGS in young children with HIV infec-ion provided key evidence to support the no-ion that HIV-1 was capable of inducing renalisease independent of drug use.8-10

During the early years of the AIDS epidemic,merican children frequently died of nonrenalIDS-related complications.2,7-10 Autopsy repo-ts frequently described and attributed renal tubu-ar-interstitial lesions to acute tubular necrosis.ubsequently, with the recognition of the renalistology of HIVAN, this renal disease was identi-ed in perinatally infected children at 2 to 3 yearsf age.2,7-10 Although the presence of renal diseaseontributed to poor quality of life and prematureeath, these children usually died before theyeveloped end-stage renal disease (ESRD).2,7-10,13

ince the widespread establishment of ART in996, the clinical outcome of HIV-infected chil-ren in the United States has improved dramati-ally.7-10,14 HIVAN is diagnosed at an older age,nd the pool of HIV-infected children surviving

er of children infected with HIV-1. Figure reprinted with

numb

nd requiring dialysis or transplantation has in-

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Kidney disease in children with HIV 587

reased considerably.7,14,15 It is anticipated thats ART becomes available to more children inesource-limited settings, a similar epidemio-ogic and clinical pattern will be seen in Africa.

LINICAL FEATURES OF HIV-SSOCIATED PEDIATRIC RENAL DISEASES

hildren with HIV disease may present withenal manifestations, which can be exacerba-ions of common renal conditions or may bepecific to HIV-1 viral activity in the kidney.

rinary Tract Infections

rinary tract infections may be diagnosed withncreased frequency in children with HIV, buthis often reflects difficulties in collecting a rep-esentative urine sample that is not contami-ated in the face of diarrheal disease (the mostommon presentation of HIV infection in manynfants) or severe napkin dermatitis. Severe uri-ary tract infections and pyelonephritis wereeen in 23% of a group of 60 children with HIVnd renal involvement studied in Johannesburg,outh Africa.4

cute Renal Failure and HIV-ssociated Hemolytic Uremic Syndrome

cute renal failure caused by dehydration re-ains a problem, especially in infants, requiring

ehydration by oral, nasogastric, or intravenousoutes. Intravenous fluids may not be easilyvailable in some resource-poor areas.

HIV-infected children also can develop antypical, fatal form of hemolytic uremic syn-rome (HUS) defined by the presence of mi-roangiopathic hemolytic anemia, thrombocy-openia, and acute renal failure.2,13 Unlike thelassic form of Shiga-toxin–induced HUS, HIV-US is characterized by an insidious clinicalnset, preserved urine output, and the absencef preceding diarrhea. Rapid progression toSRD or death from infectious or bleeding com-lications is common.2,13 The presence of throm-otic microangiopathic (TMA) glomerular le-ions is characterized by the accumulation ofbrin and often is associated with microcysticubular changes (Fig. 2A). The pathogenesis ofhildhood HIV-HUS is not clearly understood. It

ppears that HIV-HUS is triggered by infectious w

gents that induce endothelial injury leading tohe development of renal TMA lesions.2,13 Theresence of proteinuria and high viral load inIV-infected children are risk factors for theevelopment of HIV-HUS.2,13 Alternatively, someIV-infected children may develop renal TMA le-

ions without clinical symptoms of HUS,2,8 buthe prevalence of asymptomatic TMA lesions inIV-infected children is unknown. In South Af-

ica, HIV-HUS typically is seen in childrenounger than 2 years of age, who usuallyresent in critical condition, often too sick tondergo renal biopsy, but with the classic clin-

cal symptoms of HUS. These children arereated with supportive therapy and peritonealialysis, but often die from overwhelming sep-is without the growth of any specific organ-sm. Because of the high mortality rates associ-ted with HIV-HUS, it is necessary to be awaref this syndrome, and to make an early diagno-is to prevent its fatal complications.2,13

ephropathy

IV-infected children can present with the clas-ic clinical features of the nephrotic syndrome,ncluding heavy proteinuria, edema, and hy-oalbuminemia. Alternatively, the renal diseaseay be manifested clinically by persistent and

solated proteinuria. Thus, some programs arettempting to screen for proteinuria in childrennown to have HIV disease. There is a widepectrum of renal diseases that occur in theetting of HIV infection. Although a clinicaliagnosis can be made in some cases, renaliopsy studies show varying frequencies of his-ologic patterns.16-18 Biopsy diagnosis can revealhe typical histologic features of minimal changeephrotic syndrome, mesangioproliferative glo-erular lesions, and “lupus-like” renal lesi-

ns.2,8-16 Other patients show renal changesonsistent with the diagnosis of HIVAN orIV-immune complex disease (HIVICK) (Fig.B-D).17,18 Thus, performing a renal biopsy ishe only way to establish a definitive diagnosis.

HIVAN is the most widely recognized causef heavy proteinuria in HIV-infected Africanmerican children,2,8-10 and black race is anstablished risk factor for the development ofIVAN.7-12 In adults, HIVAN usually presents

ith the classic histologic findings of collapsing

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588 M.I. McCulloch and P.E. Ray

SGS and tubular microcystic changes.17,18 Inontrast, HIV-infected children more freque-tly show mesangial hyperplasia and/or clas-ic FSGS in combination with the microcysticubular lesions.2,8-10 Children with mesangialyperplasia show a slower rate of progressionf their renal disease when compared with chil-ren with classic or collapsing FSGS.2,9 Al-hough unproven, it has been argued that mes-ngial hypercellularity may be an early sign ofSGS.9

Studies from the United States have shownhat HIVAN is a common cause of chronic kid-ey disease in HIV-infected adults.18-20 Earlytudies in children and adults suggested thatIVAN usually develops during the late stagesf HIV disease, in association with a high viral

igure 2. Representative photomicrographs of renal seight microscopy renal section from a child with HIV-HUell fragments and tubular microcysts. The black arrowragments and intramural thrombosis (hematoxylin-eosinith HIVAN. The black arrows show a shrunken glome

ilver stain, 200�). Figure 2B courtesy of Dr. William Barom a child with HIVICK showing mesangial prominencelomerular basement membrane (black arrow) (Jonesicroscopy from a glomerular capillary in a child with HI

igure 2C and D courtesy of Drs. Stewart Goetch and P

oad and a low CD4� cell count.2,8-10,19,20 A s

ecent study has found that reduction of theIV viral load by ART may prevent progressionf proteinuria and improve the clinical out-ome of HIV-infected children.14

Studies in HIV-infected patients from Africaave found a variety of renal diseases.5,20-22 Onetudy from South Africa examined 99 adult bi-psy specimens and showed the presence oflassic HIVAN and HIVICK in approximately7% and 21%, respectively.21 These renal dis-ases play an important role in the develop-ent of chronic kidney disease. Renal biopsy

pecimens with HIVICK may show subepithe-ial immune deposits inducing a “ball-in-cup”lomerular basement membrane reaction.21

he renal histologic lesions found in 2 pediatricenal biopsy studies from South Africa are

from children with HIV-HUS, HIVAN, and HIVICK. (A)ing collapsed glomerular capillary loops with red bloodan arteriole with luminal narrowing owing to red cell

, 200�). (B) Light microscopy renal section from a childnd microcystic tubular dilatation (Jones methenamined Dr. Peter Nourse. (C) Light microscopy renal sectionglomerular tuft is lobulated with double contours of thenamine silver stain, 700�). (D) Transmission electronThe black arrows show subepithelial deposits (4.000�).or Udai Kala.

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Kidney disease in children with HIV 589

ubulopathy

he presence of renal tubular disorders inIV-infected African American children was

ecognized during the early years of the HIVpidemic.2,9 A more recent study from Venezu-la found that renal tubular disorders also areommon in HIV-infected Hispanic children.23

ypercalciuria was seen most frequently, withpotential for nephrocalcinosis, but crystallu-

ia, hyperchloremia, and metabolic acidosislso are seen. These metabolic complicationsay be in part responsible for the growth im-airment frequently seen in HIV-infected chil-ren.2,9 Tubular disorders may induce sodium,otassium, and phosphate wasting states, whichlso mistakenly could be attributed to gastroin-estinal diseases. Renal tubular disorders oftenre identified when electrolyte abnormalitieso not improve after diarrhea or other gastro-

ntestinal complications have resolved. Treat-ent can be clinically difficult because a large

ral intake of supplements is required. Thisherapy can have side effects such as diarrhea,n the case of phosphate, which could perpet-ate an ongoing cycle of electrolyte losses. Inddition, the renal concentration ability of HIV-nfected children might be impaired, and thenfusion of intravenous hypotonic or isotonicolutions must be monitored closely to preventhe development of acute dysnatremic disor-

Table 1. Renal Histologic Findings in Two StudLiving in South Africa

Number of Pediatric Patients

HIVICKFSGS/HIVANMesangioproliferative glomerulonephritisMinimal change diseaseSevere interstitial nephritisInfectious changes (including TB)Acute tubular necrosisKaposi’s sarcomaBladder stonesData from Kala et al5 and Nourse et al.22

ers causing severe neurologic complications b

r death.2,24 Finally, tubular disorders also coulde related to nephrotoxic effects of medica-ions, such as antibiotics or the antiretroviralgent tenofovir.25

hronic Kidney Disease

nsidious onset of renal failure is usually the normf HIV-infected children are not screened for theresence of renal diseases. Early onset proteinuria

s a useful clinical clue indicating the presence ofenal disease. Symptoms such as polyuria, poly-ipsia, fatigue, headache, seizures, and hyperten-ion together with unexplained severe acidosisan be suggestive of chronic kidney disease. How-ver, many patients in resource-limited areas mayresent only with marked proteinuria, or evenith oliguria and ESRD.

IAGNOSIS OF HIV-ASSOCIATEDENAL DISEASE IN CHILDREN

linical features of HIV infection such oral can-idiasis, failure to thrive, and lymphadenopa-hy may be observed on physical examinationefore the diagnosis of HIV infection is estab-

ished. The interpretation of blood tests con-rming HIV infection is age-dependent, especia-

ly in young children, and should be discussedith an infectious disease expert.The initial renal evaluation should include

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rolytes, and urine electrolytes to evaluate forubulopathies. The urinary sediment can pro-ide important clues such as the presence oflusters of renal epithelial cells forming cyst-ike structures, which are seen in children withIVAN and HIV-HUS.2,26 All HIV-infected chil-ren should be screened for proteinuria at leastnce a year. Proteinuria is not always detected

n diluted urine samples during the early stagesf HIVAN or in the presence of tubular disor-ers.2 Although hypertension is not a typicalnding in the early stages of HIVAN, the bloodressure should be monitored regularly. Theresence of (1) hypertension, (2) macroscopicematuria, (3) microscopic hematuria withoutroteinuria, (4) increased blood urea nitrogenr serum creatinine values without significantroteinuria, and (5) persistent proteinuria inhite children, are all clinical features not typ-

cal of HIVAN, and should be a clear indicationo search for an alternative etiology of the renalisease.2 Ultrasound examination should beerformed to assess renal size and echogenicitynd exclude obstruction or anatomic pathol-gy, with renal biopsy to follow if indicatedwing to the presence of proteinuria. If clini-ally indicated, infections such as tuberculosisTB) should be excluded. Further investigationsay be limited according to resource availabil-

ty in some settings.

REATMENT OF HIV-SSOCIATED RENAL DISEASE IN CHILDREN

efore the introduction of ART, treatment con-isted only of supportive symptomatic therapy.n one study, children with HIV-related kidneyisease who were on corticosteroids for treat-ent of lymphocytic interstitial pneumonitis

howed a variable response of the renal diseaseo corticosteroids.2 The short-term effects oforticosteroids may be well tolerated,2,9,27,28

ut their long-term risks in HIV-infected chil-ren are unknown, especially in countries withhigh prevalence of TB. Moreover, in the ab-

ence of appropriate ART, corticosteroids haveeen unable to prevent the progression of HIV-ssociated childhood renal diseases.2,9,10

Diuretics, angiotensin-converting enzyme in-ibitors, and angiotensin-receptor blockers are

ther forms of supportive therapy available for b

IV-related kidney disease in children.2,9,27-29

hese agents should be used with caution inIV-infected children with nephrotic syndrome,

evere hypoalbuminemia, tubular disorders cau-ing salt wasting, and diarrhea or other gastro-ntestinal problems.2,9 These clinical situationsnduce extracellular volume contraction and ac-ivate the renin-angiotensin system. Blocking theenin-angiotensin system under clinical condi-ions in which the renal perfusion pressure isependent on high levels of angiotensin II willecrease the glomerular filtration rate, and can

nduce acute renal failure if these changes areot recognized in a timely manner.

The introduction of ART has revolutionizedhe clinical management of HIV-associated renalisease.14,27-30 The use of ART is associated withmarked improvement of HIVAN, resulting in

lower progression to ESRD,28,29 or even in re-overy from dialysis-dependent renal failure30

rovided the kidney damage is not too severe.In resource-limited countries with a high

revalence of HIV infection, chronic renal fail-re often presents late in the course of the

llness. Onset of this condition often is undetec-ed because renal disease screening, such asrine testing and blood pressure monitoring, isot performed routinely. These children mayresent with nonspecific signs such as anemia,

ailure to thrive, poor appetite, and lack ofnergy. ESRD with fluid overload and hyperten-ion are often the presenting signs. Renal ultra-ound may show large kidneys consistent withIVAN, or in the case of long-standing kidneyisease, already may show signs of fibrosis withmall kidneys.

ialysis

n the early days of managing HIV-related renalisease, dialysis was thought to be contraindi-ated because of poor survival and concernbout the infection rate on dialysis. With time,enal replacement therapy was shown to beossible, especially in pediatric patients inhom dialysis therapies have offered improved

urvival.7,9,14,31 A debate still remains as to whichodality, peritoneal or hemodialysis, is the most

ppropriate for children. Peritoneal dialysisay be associated with increased infections,

ut is more readily available than hemodialysis

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Kidney disease in children with HIV 591

n resource-poor countries, and may presentess risk for health care professionals. Neverthe-ess, the peritoneal fluid contains HIV-infected

ononuclear cells and should be handled withll the necessary precautions to prevent theransmission of HIV-1 to health care workers.2

n the United States, hemodialysis is the pre-erred modality in perinatally infected childrenecause of the availability of resources and ex-ertise for this treatment, as well as the addedurden of peritoneal dialysis for the familyembers who are often managing their ownIV disease as well as that of the child.7,14,31 It

s important to reduce the HIV viral load ofhildren undergoing dialysis as much a possi-le, to improve their quality and length of life,nd to make them eligible candidates for kidneyransplant.

ransplantation

n the early years of the AIDS epidemic, HIVnfection was considered an absolute contrain-ication to kidney transplantation because theombination of transplantation plus immuno-uppression appeared to shorten the AIDS-freeime in HIV-infected patients, compared withemophiliac control groups.32 Subsequently,

mprovements in HIV-related morbidity andortality with ART have prompted a re-evalua-

ion of renal transplantation in this popula-ion.33 For example, studies in adherent adultsave suggested that adult patients with HIV

nfection do better after transplantation than onialysis. The immunosuppressant drugs usedre similar to those used in non-HIV transplants.enal transplantation in adults can be success-

ul, provided there is stable maintenance ofRT, the HIV viral load is undetectable for at

east 6 months, and the CD4 cell count isreater than 200 cells/mm3.

In a group of HIV-positive patients receivingolid-organ transplants in the 1980s, who werenfected either preoperatively or postopera-ively, the best survival results (70%) were inact shown in the pediatric group.33 The selec-ion of children for transplantation, and thessessment of their immune status, should takento consideration the age and weight of thehild, as well as different parameters for CD4

ounts33,34: (1) younger than 1 year of age: aim a

o get to 1 year or 10 kg on dialysis, (2) 1 to 6ears of age: CD4% greater than 25%, takingnto account the absolute CD4 count, and (3)lder than 6 years of age: CD4 count greaterhan 200 cells/�L.

To date, very few pediatric nephrology unitsorldwide have transplanted a significant num-er of HIV-infected children, but this clinicalxperience is expected to increase as moreIV-infected children undergo this procedure.

n addition to the challenges faced by adultransplant recipients, additional problems spe-ific to pediatric patients include the need forooperative providers and families to supervisehe double-compliance required for both ARTnd immunosuppressive regimens. This is par-icularly concerning in adolescents, both inerms of risk-taking behavior and poor compli-nce associated with this age.31 Poor compli-nce with ART can lead to increased HIV resis-ance patterns and complicate management.verall, renal transplantation in adults, and

eemingly in children, can be successful in HIV-ositive patients provided the HIV disease isnder control.

In children who are immunosuppressed bothy HIV as well as the use of immunosuppres-ant medications, there remains concern thatverwhelming infections will occur, includingypical nosocomial bacteria, viruses such as cy-omegalovirus and Epstein-Barr virus, and atyp-cal organisms. Tuberculosis remains a signifi-ant problem in many parts of Africa, and therevalence has escalated with the HIV epidemic.B was an important cause of pediatric sys-emic illness in 2 South African studies. Thirty-hree percent of pediatric renal patients in aohannesburg study had or were currently be-ng treated for pulmonary TB,5 and renal TB wasbserved in 2 of 14 (14%) pediatric patients inCape Town study.22 In a separate review fromape Town, among 150 HIV-negative pediatric

enal transplants, the incidence of TB acquiredosttransplantation was 9.8%. This was com-ared with 9.7% of liver transplant patients inhe same center, illustrating the high preva-ence of TB in this community.35 Multidrug-esistant TB and extensively drug-resistant TBave become a major concern. In addition,

nti-TB medications can induce liver enzymes

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592 M.I. McCulloch and P.E. Ray

hat affect the metabolism and serum levels ofome immunosuppressant agents and otherrugs, complicating the clinical management ofransplant recipients.36

In addition to the potential for infectiousomplications, the transplantation of HIV-in-ected children also raises ethical concerns. Thecarcity of organs for transplantation may forcergans to be allocated to the best-possible-out-ome recipient without concomitant risk fac-ors. In Africa, HIV infection itself has resultedn a reduction in the number of suitable donors,

ith resultant lower organ availability and in-reased waiting times. Ideas have circulatedbout using HIV-positive donors for HIV-posi-ive recipients, but significant controversy hasrisen around this topic. In particular, there isoncern about different HIV viral strains andssociated drug resistance.

Ethical aspects of living donor transplanta-ion are also important, especially in children,n whom pre-emptive transplantation may avoidhe physical and psychologic stress of dialysisnd improve retarded growth. Judgment thenlso arises between the values of life in childrenersus adults. In these circumstances, commer-ialism may be considered and should be pre-ented according to the Ethical Council of theransplantation Society for both ethical andedical reasons. The risk is very high, not only

or donors but for transplant recipients as well,ecause there may be poor screening not onlyor HIV-1 but also for other infectious agents.37

CREENING FOR RENALISEASE IN HIV-INFECTED CHILDREN

any HIV-associated renal diseases are asymp-omatic during their early stages, thus recom-endations have been made that all individuals

e assessed for the presence of kidney diseaset the time of HIV diagnosis.29,38 This screenings even more important in children, who mayave a longer life expectancy if treated appro-riately. Screening should include urinalysisnd serum creatinine levels to estimate renalunction.38,39

A South African study screened 615 HIV-in-ected adults who were not receiving ART forroteinuria, in an attempt to make an early

iagnosis of HIVAN.39 Renal biopsy was per- m

ormed in 30 patients with proteinuria or mi-roalbuminuria, and 25 of 30 (83%) of theseenal biopsies revealed histologic features con-istent with HIVAN. Microalbuminuria wasound to be an early manifestation of HIVAN.hese findings suggest that screening HIV-in-

ected patients for microalbuminuria might fa-ilitate the early diagnosis of HIVAN.39,40 Givenhe large number of HIV-infected people in Af-ica, the early detection and treatment ofIVAN should become a major priority.

ONCLUSIONS

n children, initiation of ART with reduction ofiral load and restitution of the immune systemurrently provides the most promising treat-ent to prevent the progression of childhoodIVAN to ESRD.7,14 Hopefully in the near fu-

ure, better education, prevention, and treat-ent programs will lead to the eradication

f this fatal childhood disease. However, atresent, HIV disease, including renal disease,emains a major problem in sub-Saharan Africa,here other health priorities may prevail,35 re-

ources are lacking, and, most importantly,here is lack of ART availability.

cknowledgmentshe authors thank Professor Brian Eley, Head ofaediatric Infectious Disease and HIV Service, Redross Children’s Hospital, Cape Town, for assistanceith up to date HIV population statistics locally inediatric patients; Dr. William Bates, Division ofnatomical Pathology, Department of Pathology, Na-

ional Health Laboratory Service (NHLS) and Facultyf Health Sciences, University of Stellenbosch, andr. Peter Nourse, Department of Pediatric Nephrol-gy, Tygerberg Hospital and University of Stellen-osch (Cape Town) for providing a light microscopyicture from a child with HIVAN (Fig. 2B); and Drs.tewart Goetch (Department of Histopathology) androfessor Udai Kala, Head of Pediatric Nephrology,rom Baragwanath Hospital, University of Witwa-ersrand (Johannesburg), for providing the light andlectron microscopy pictures from children withIVICK (Fig. 2C and D). Finally, the authors would

ike to thank Dr. Christina Wyatt from Mount Sinaichool of Medicine, New York, for reading the

anuscript and providing very helpful suggestions.

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4. McCulloch MI. Introduction to pediatric HIV disease[abstract]. Pediatr Nephrol. 2007;22:1438:298.

5. Kala U, Petersen K, Faller G, Goetsch S. Spectrum ofsevere renal disease in children with HIV/Aids atChris Hani Baragwanath Hospital, Johannesburg [ab-stract]. Pediatr Nephrol. 2007;22:1439:301.

6. Fauci SA. HIV-1 and AIDS. 20 years of science. NatMed. 2003;9:839-43.

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