HIV-associated nephropathy (HIVAN) was once the most common cause of glomerular disease in HIV-infected patients but has been overtaken by focal segmental glomerulosclerosis (FSGS) associated with metabolic and cardiovascular risk factors. HIVAN remains strongly associated with severe renal failure, black race, and low CD4 counts. While renal biopsy is needed for definitive diagnosis, certain clinical factors such as black race, low CD4, and rapid renal progression suggest HIVAN. Treatment includes antiretroviral therapy and corticosteroids, with the latter showing benefit in slowing renal disease progression in some studies. Renal replacement therapy is an option for end-stage renal disease, with peritoneal dial

1. M R 2 O S C A R M A L P A R T I D A T A B U C H I
E N F E R M E D A D E S I N F E C C I O S A S Y
T R O P I C A L E S
H N G A I - U P C H
1 1 D E J U L I O 2 0 1 5
Servicio de nefrologia HNGAI
Unidad Investigación y docencia
Nefropatía asociada al HIV

3. Introducción
 35 millones infectados con HIV en el mundo
 24.7 millones en SAA
 12.9 (37% en TARV)

4. Definición: HIVAN (clásico)
 Es una forma de glomerulopatía colapsante
(glomeruloscerosis FS)
 Relacionada HIV-1
 Más común en raza negra, estadios avanzados
 Otras enfermedades HIVICK, microangiopatía y
alteraciones/toxicidad por ARV.

5. Perla clínica HIVAN
“Paciente joven, ascendencia
africana, CV-HIV elevada,
enfermedad renal de rápida
progresión a ESRD, riñones
grandes”

6. Efecto de TARV
 HIVAN asociado a inmunosupresión severa
 EEUU: 60% disminución de ERC-V en era post
TARV
 TARV/envejecimiento produce nuevo patrón de CKD
(inflamación crónica)
 Nefrotoxicidad asociada a TARV: Tenofovir y
cristaluria/litiasis asociada a IP

7. Histopatología
 HIVAN clásico: glomerulopatía colapsante
 Enfermedades renales asociadas a HIV tienen un
amplio espectro histológico
 Alteraciones glomerulares, tubulointersticiales
 Asociado a TARV
 Comorbilidades asociadas (HCV, CV, DM, CMV)

8. Histopatología HIVAN
 Colapso de capilares glomerulares
 Epiteliosis visceral glomerular
 Hipertrofia y proliferación podocitos
 Hipercelularidad y prominencia mesangial
 Inclusiones tubuloreticulares endoteliales TRI

9. Histopatología
 HIVAN clásico puede verse en cualquier grupo
etáreo y estadio
 Más común en estadios avanzados y descendientes
África Occidental (2º Hispano)
 HIVICK y formas no colapsantes luego de TARV
 HIVICK en poblaciones europeas

10. Background. Treatment and co-morbidities of human immunodeficiency virus (HIV)-
infected individuals have changed dramatically in the last 20 years with a potential impact on
renal complications. Our objective was to assess the change in distribution of the glomerular
diseases in HIV patients.
 Methods. We retrospectively analysed demographic, clinical, laboratory and renal
histopathological data of 88 HIV-infected patients presenting with a biopsy-proven
glomerular disease between 1995 and 2007.
 Results. In our study including 66% Black patients, HIV-associated nephropathy (HIVAN)
was observed in 26 cases, classic focal segmental glomerulosclerosis (FSGS) in 23 cases,
immune complex glomerulonephritis in 20 cases and other glomerulopathies in 19 patients.
HIVAN decreased over time, while FSGS emerged as the most common cause of
glomerular diseases (46.9%) in HIV-infected individuals undergoing kidney biopsy in
the last 2004–07 period. Patients with HIVAN were usually Black (97%), with CD4
<200/mL (P = 0.01) and glomerular filtration rate <30 mL/min/1.73m2 (P < 0.01).
Compared to HIVAN, patients with classic FSGS were less often Black (P < 0.01), have been
infected for longer (P = 0.03), were more often co-infected with hepatitis C virus (P = 0.05),
showed more often cardiovascular (CV) risk factors (P < 0.01), had less often CD4 <200/mL
(P = 0.01), lower HIV viral load (P = 0.01) and tended to be older (P = 0.06).
 Conclusions. Classic FSGS associated with metabolic and CV risk factors has overcome
HIVAN in HIV-infected patients. Compared with other glomerulopathies, HIVAN remains
strongly associated with severe renal failure, Black origin and CD4 lower than 200/mL at
presentation.

11. Histopatología

12. Etiopatogenia
 HIVAN: cDNA-HIV y proteínas virales en células
renales
 Inducen muerte celular y apoptosis
 HIVICK (?)
 APOL1 en ascendencia africana.
 Entrada?
 CD209 podocitos/células dendríticas
 Ag linfocitario 75 (DEC205), c. tubulares

13. Etiopatogenia

14. Screening y detección temprana
Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With
HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America
 HIV asociado a mayor riesgo de ERC
 PA, SrCr (eGFR y albuminuria en TDF)
 Proteinuria/creatinuria + albuminuria/creatinuria
 Se debe tamizar para e. renal incipiente: HIVAN, y
otras glomerulo-tubulopatías
 Cuándo?
 Al diagnóstico
 Antes de iniciar TARV
 Dos veces al año en pacientes estables o que modifican TARV

16. Utilidad Biopsia renal
Berliner A.R. · Fine D.M. · Lucas G.M. · Rahman M.H. · Racusen L.C. · Scheel P.J. · Atta M.G. Observations
on a Cohort of HIV-Infected Patients Undergoing Native Renal Biopsy Am J Nephrol 2008;28:478–486
 No toda ERC con proteinuria y disminución en
función renal es HIVAN
 Hallazgos (eco, proteinuria, CD4) no predicen de
forma confiable su presencia
 Decisión terapéutica es guiada por histopatología
(TARV probado en HIVAN, en otras?)
 Dependerá de posibilidad de diagnósticos
alternativos, que puedan cambiar terapia y de
riesgo/beneficio

17. AIMS:
 This study aims to explore the spectrum of renal disease in HIV-infected patients, identify clinical
predictors of HIV-associated nephropathy (HIVAN), and investigate the performance of renal biopsy in
HIV-infected patients.
 METHOD:
 Of 263 HIV-infected patients with renal disease evaluated between 1995 and 2004, 152 had a renal biopsy,
while 111 had not. A group comparison was performed.
 RESULTS:
 The leading biopsy diagnoses were HIVAN (35%), noncollapsing focal segmental glomerulosclerosis
(22%), and acute interstitial nephritis (7.9%), amongst over a dozen others. There was a trend of
decreasing yearly incidence of HIVAN diagnoses, paralleling the use of antiretroviral therapy. By
multivariate logistic regression, CD4 counts >200 cells/mm(3) and higher estimated glomerular filtration
rate were strong negative predictors of HIVAN. HIVAN patients were more likely to require dialysis (p <
0.0001) and had worse overall survival (p = 0.02). Younger age and lower estimated glomerular filtration
rate were significant predictors of renal biopsy in multivariate regression analysis. More biopsied patients
progressed to dialysis (51 vs. 25%, p = 0.001) and death (15 vs. 5.4%, p = 0.001), despite more frequent
corticosteroid treatment (29 vs. 3.6%, p = 0.001).
 CONCLUSION:
 These findings may reflect more severe acute and/or chronic disease at the time of biopsy
and suggests that earlier renal biopsy may be warranted in HIV-infected patients, especially
in light of the changing spectrum of renal disease in this group.

18. Tratamiento
 ARV
 Manejo de enfermedades renales asociadas
 Terapia de reemplazo renal
 Transplante

19. TARV
 Antes de era TARV, HIVAN progresaba
inexorablemente a ESRD
 HIVAN es una indicación de TARV (CD4)
 Beneficio en HIVICK, microangiopatía trombótica
 Se ha observado mejora de eGFR en pacientes en
TARV y ERC

22. Manejo adicional
1. Corticoides
 En los primeros años de la epidemia se utilizaron
corticoides con resultados modestos
 Información con alto poder estadístico escasa
 PDN 1mg/kg/día
 IO vs necrosis avascular
 Escasa información era TARV (beneficio añadido?)

23.  Cohort study of the treatment of severe HIV-associated nephropathy with corticosteroids.
 Background
 Human immunodeficiency virus-associated nephropathy (HIVAN) results in rapidly progressive azotemia.
The effectiveness and safety of corticosteroids in the treatment of HIVAN, however, remains controversial.
 Methods
 We conducted a retrospective cohort study of patients with biopsy-proven HIVAN and progressive azotemia
who were eligible for corticosteroid treatment and who had no clinical or histologic evidence of an
alternative cause of acute renal failure. Selected patients were treated with 60 mg of prednisone for one
month, followed by a several-month taper.
 Results
 Twenty-one eligible patients were identified. Thirteen subjects had received corticosteroid treatment,
whereas eight had not. The mean serum creatinine was 6.2 and 6.8 mg/dL, respectively (P > 0.05). The
relative risk (95% CI) for progressive azotemia with corticosteroid treatment at three months was 0.20
(0.05, 0.76, P < 0.05). This association remained significant despite adjustment in separate logistical
regression analyses for baseline creatinine, 24-hour proteinuria, CD4 count, history of intravenous drug
use, hepatitis B, and hepatitis C. In an additional logistic regression model, using backward stepwise
selection of the previously mentioned covariates, only corticosteroid treatment (P = 0.02) and baseline
serum creatinine (P = 0.10) were retained within the model. In the corticosteroid-treated group, the mean
level of proteinuria decreased by 5.5 g/24 hour (P= 0.01). On long-term follow-up, there was no significant
difference in the incidence of hospitalizations (1 per 2.1 vs. 1 per 2.3 patient months) or of serious infections
(1 per 2.6 vs. 1 per 2.3 patient months), but there was a significantly longer duration of hospitalization in the
corticosteroid-treated group (3.2 vs. 2 days per patient month). At six months, only one of the non–
corticosteroid-treated patients but seven of the corticosteroid-treated group continued to have independent
renal function (P = 0.06). Three of the corticosteroid-treated group continued to have independent function
at two years of follow-up.

24. Regimen recomendado
Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With
HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America
 PDN 1mg/kg/día por 1-4 semanas y si responden se
prolonga hasta 11 semanas y luego retirados en 2-26
semanas

25. Manejo adicional
2. IECA/ARB
Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With
HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America
 ATI- ATII tienen un rol
patogénico directo in
vivo en modelos
animales

26. Manejo adicional
3. Medidas generales
Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With
HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America
 Control de PA<140/90
 Evitar nefrotóxicos
 Pérdida de peso en obesos
 No fumar

27. Terapia de reemplazo renal
Recommendations for Preventing Transmission of Infections Among Chronic Hemodialysis Patients
CDC 2001
 Pacientes con TARV en TRR (HD-PD) tienen tasas
de supervivencia similares a controles
 HD vs PD no hay diferencia en morbi-mortalidad
 Infecciones CAPD ? No parece haber mayor riesgo…
 Precauciones universales para prevención de
infecciones en HD

28.  Abstract
 Background
 Controversy continues concerning the morbidity and mortality of HIV-infected ESRD patients on the two
dialysis options. This article presents our experience with complications and survival rate among our HIV-
infected ESRD patients on peritoneal dialysis and hemodialysis. We reviewed the literature on this subject.
 Methods
 The charts of seven and eight HIV-infected ESRD patients on peritoneal dialysis and hemodialysis
respectively, between January 1989 and November 2004, were reviewed retrospectively for specific clinical
and demographic data. Their survival was calculated using the Kaplan-Meier method.
 Results
 Total follow-up of HIV-infected PD and HD patients was 248.3 and 207 patient months, respectively.
There was no significant difference in hospitalization rate between HIV-infected PD and HD patients (1.01
and 1.39 admission/year, respectively, P = NS). Survival of HIV-infected patients on PD at one, two and
three years was 100, 83, and 50%, and for HD patients was 75, 33, and 33%, respectively. HIV-infected
patients on HD had more prevalent advanced HIV disease. Two out of seven PD patients were on PD for
more than five years and one of the HD patients was on that form of dialysis for more than nine years.
Median survival of patients with advanced (Stage IV) AIDS (both HD and PD) was 15.1 months (range 1.6–
17.3) while this value for non-advanced (Stage II, III) patients was 61.2 months (range 6.8–116.6).
 Conclusion
 Type of renal replacement therapy does not have a significant effect on the morbidity and mortality of
HIV-infected ESRD patients. Survival is worse in patients with advanced HIV disease. Both dialysis
options provide similar results in HIV patients; hence, the choice of dialysis modality should be based on
patient’s preference and social conditions.

29. Transplante renal
Outcomes of kidney transplantation in HIV-infected
recipients. NEJM 2010
 Se puede realizar en HIV
 150 casos en EEUU
 Mayores tasas de rechazo agudo (31%)
 Supervivencia del injerto a los 2 y 3 años de 88.2-
73.7% respectivamente

32.  GRACIAS