HIVAN (Nefropatía asociada al VIH) Evidencia al 2015

Nefropatía asociada al VIH

(HIVAN)

Dr. Cristhian Mauricio Bueno LaraEspecialista en Medicina Interna – Universidad Autónoma de Bucaramanga

Fellow en Nefrología – Universidad del Valle

HIVAN Historia

Patricio E. Ray. HIV-associated nephropathy: a diagnosis in evolution. Nephrol Dial Transplant (2012) 27: 3969–3972

1984 Nefropatía asociada a SIDA

1999 HIVAN – 3era causa de enfermedad renal estadio terminal

2004 Clasificación de Columbia – Glomerulopatía colapsante

2014

2014

HIVAN Definición/Patología

Christina M. Wyatt, MD. HIV-Associated Nephropathy: Clinical Presentation, Pathology, and Epidemiology in the

Era of Antiretroviral Therapy. Semin Nephrol. 2008 November ; 28(6): 513–522.

Microscopía de luz

Glomeruloesclerosis focal y segmentaria

Dilatación tubular microquística

Inflamación tubulointersticial

Figure 2.

The podocytes surrounding the collapsed tuft form a corona of hypertrophied cells with

numerous protein resorption droplets. Some of the podocytes appear detached from the tuft

and suspended in the urinary space (Jones methenamine silver, x400). [COLOR PRINT/

ONLINE]

Wyatt et al. Page 12

Semin Nephrol. Author manuscript; available in PMC 2009 November 1.

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Inmunofluorescencia

-Depósitos de IgM, C3, menos común C1 en

segmentos colapsantes




Microscopía electrónica

-Capilares colapsados, espacio urinario

obliterado, podocitos hiperplásicos

Figure 6.

The collapsed capillaries have wrinkled glomerular basement membranes and are surrounded

by hyperplastic visceral epithelial cells that obliterate the urinary space, in continuity with

adjacent parietal epithelial cells (electron micrograph, x3000).

Wyatt et al. Page 16

Semin Nephrol. Author manuscript; available in PMC 2009 November 1.

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NO HIVAN Enfermedad renal de complejos inmunes en VIH

Mediada por inmunocomplejos

Nefropatía por IgA

Glomerulonefritis similar a lupus

30% de las biopsias

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.

HIVAN Fisiopatología

Patricio E. Ray. HIV-associated nephropathy: a diagnosis in evolution. Nephrol Dial Transplant (2012) 27: 3969–3972

HIVAN Clínica

Proteinuria

Deterioro rápido de filtrado glomerular

Riñones hiperecogénicos en estudio ultrasonográfico



HIVAN Clínica

No HIVAN vs HIVAN

HR: 0.33 IC= 0.15 – 0.71, Valor P:0.0005

Inicio mas tardío de TRR en

pacientes con No HIVAN

2004

HIVAN Epidemiología



Prevalencia: 4.7-9.7%

Incidencia: 3.9-11.2 por 1000/año

Factores de riesgo

para HIVAN:• Mayor edad

• Mujeres

• Diabetes

• Hipertensión

• Drogas endovenosas

• Conteo CD4 bajo

• Medicamentos antiretrovirales

• Historia de lesión renal aguda

• Altos niveles de carga viral


HIV-associated chronic kidney

disease in sub-Saharan Africa

Reported prevalence of CKD has been as-

sessed on the presence of albuminuria and/or

eGFR (based on serum creatinine measure-

ments), and ranges from 6% to 48.5%. This

wide variation may be partly ascribed to dif-

ferences in study design, the populations

studied and definitions used for CKD, based

on dipstick proteinuria, quantitative measure

of proteinuria and/or serum creatinine.

Two screening studies have been performed

in South Africa; the first study screened 615

HIV-infected ambulatory patients; 6% had per-

sistent proteinuria and 30 renal biopsies were

done [18]. Histology showed HIVAN to be the

predominant lesion (83.3%) and the remain-

der comprised HIVAN + membranous glo-

merulonephritis (GN), membranoprolifera-

tive GN and interstitial nephritis. In the

second study, persistent proteinuria occurred

in 5.5% and 20 biopsies were performed [19].

HIV-associated immune complex disease

(HIV-ICD) was seen in 40%, HIVAN (5%), a

combination of HIVAN and ICD (5%) while

45% had mesangial and interstitial changes

that did not fulfill the current histological cri-

teria for HIVAN. This study showed a signifi-

cant improvement in eGFR and marked re-

duction or resolution of proteinuria mostly

within the first 6 months of commencing

ART. Athird study in South Africa of 99 renal

biopsies in hospitalized patients showed

HIVAN in 27%, HIV-ICD 21%, membranous

nephropathy in 13% as predominant lesions,

with the remaining comprising non-glomeru-

lonephritic renal disease, post-infectious or

mesangioproliferative glomerulonephritis and

IgA nephropathy [20].

A study in Nigeria described renal disease

(proteinuria or abnormal serum creatinine) in

38% of 400 patients. Of the 10 patients

biopsied, the majority had collapsing focal

segmental glomerulosclerosis (FSGS) [21].

In Cote D’Ivoire a study compared HIV-

infected patients in Paris with patients in

Abidjan and the prevalence of albuminuria

was higher in the cohort from Abidjan (26%

versus 5%, respectively) [22]. A Tanzanian

study found albuminuria to be more frequent

in an HIV-infected cohort, when compared

with a non-HIV-infected cohort (28.4% vs.

16.8%) [23]. In a Kenyan study, 216 anti-

retroviral-naïve patients with an average CD4

count of 383 cells/mm3 were screened: 25%

had eGFR < 90 ml/min, 2% had eGFR < 60

ml/min and 8% had proteinuria of > 1 g/day

[24]. A Ugandan study of 229 patients with

World Health Organization (WHO) clinical

Stage 3 disease showed eGFR < 80 ml/min in

48.5% of patients; 20% had proteinuria > 100

mg/dl [25]. In another study from Uganda

508 patients with HIV infection were evalu-

ated prior to ART; 8% had serum creatinine >

133 µmol/l and 20% had eGFR 25 – 50

ml/min. After 2 years on ART, median eGFR

increased by 21% [26]. In the DART study

(Development of Antiretroviral Therapy)

based on sites in Uganda and Zimbabwe that

included 3,316 participants, the eGFR was

60 – 90 ml/min/1.73 m2 in 45% and 30 – 60

ml/min/1.73 m2 in 7% of participants prior

to starting ART [27]. In Zambia 25,799

patients treated with ART showed that 33.5%

had renal dysfunction: 3.1% had eGFR

< 30 ml/min; 23.4% had eGFR of 30 –

59 ml/min and 73.5% had eGFR of 60 –

89 ml/min. Renal dysfunction was associated

with increased mortality after 90 days [27].

From the studies that have been pub-

lished, few renal biopsies have been per-

formed and most are cross-sectional. What is

Risk factors for the development of chronic kidney disease with HIV/AIDS S53

Table 1. Prevalence of CKD in HIV infection.

Country Prevalence (%)

United States [1] 11

Europe, Israel and

Argentina [2]3.5 – 4.7

Hong Kong [3] 18

Brazil [4] 1.1 – 5.6

Switzerland [5] 18

India [6] 27

Iran [7] 12.3

South Africa [8, 9] 5.5 – 6

Nigeria [10] 38

Cote d’Ivoire [11] 26

Tanzania [12] 28.4

Kenya [13] 25

Uganda [14, 15] 20 – 48.5

Zambia [16] 33.5

2010


2008

HR= 1.9 (1.2-2.8) HR= 17.7(2.5-127)

HIVAN Impacto de la enfermedad

Incidencia de lesión renal aguda: 2.8 a 5.9 casos por 100 personas-año



2010

HIVAN Implicaciones sobre terapia antiretroviral

2002


2009

Aumento de niveles de

proteínas fijadoras de retinol

en orina en grupo de Tenofovir




• En pacientes con VIH que tienen un filtrado glomerular < 60 ml/min/1.73 m2, evitar

tenofovir y otros medicamentos potencialmente tóxicos cuando sea posible. (Fuerte,

baja)

Recomendación IDSA 2014

HIVAN Seguimiento de función renal



• Medición de filtrado glomerular cuando TARGA sea iniciada o cambiada, al menos 2

veces al año, usando el mismo método de seguimiento durante el año. (Fuerte,

baja)


HIVAN Seguimiento de función renal

Performance of Creatinine and Cystatin C GFR Estimating

Equations in an HIV-positive population on Antiretrovirals

Lesley A INKER, MD, MS1, Christina WYATT, MD2, Rebecca CREAMER, BSN, RN, CCRC3,

James HELLINGER, MD1, Matthew HOTTA, BS2, Maia LEPPO, BS1, Andrew S LEVEY, MD1,

Aghogho OKPARAVERO, MD, MPH1, Hiba GRAHAM, PharmD4, Karen SAVAGE, BSN, RN,

CCRC3, Christopher H SCHMID, PhD1, Hocine TIGHIOUART, MS1, Fran WALLACH, MD2,

and Zipporah KRISHNASAMI, MD3

1Tufts Medical Center

2Mt Sinai School of Medicine

3University of Alabama at Birmingham

4Gilead Sciences, Inc

Abstract

Objective—To evaluate the performance of CKD-EPI creatinine, cystatin C and creatinine-

cystatin C estimating equations in HIV-positive patients.

Methods—We evaluated the performance of the MDRD Study and CKD-EPI creatinine 2009,

CKD-EPI cystatin C 2012 and CKD-EPI creatinine-cystatin C 2012 glomerular filtration rate

(GFR) estimating equations compared to GFR measured using plasma clearance of iohexol in 200

HIV-positive patients on stable antiretroviral therapy. Creatinine and cystatin C assays were

standardized to certified reference materials.

Results—Of the 200 participants, median (IQR) CD4 count was 536 (421) and 61% had an

undetectable HIV-viral load. Mean (SD) measured GFR (mGFR) was 87 (26) ml/min/1.73m 2. All

CKD-EPI equations performed better than the MDRD Study equation. All three CKD-EPI

equations had similar bias and precision. The cystatin C equation was not more accurate than the

creatinine equation. The creatinine-cystatin C equation was significantly more accurate than the

cystatin C equation and there was a trend toward greater accuracy than the creatinine equation.

Accuracy was equal or better in most subgroups with the combined equation compared to either

alone.

Conclusions—The CKD-EPI cystatin C equation does not appear to be more accurate than the

CKD-EPI creatinine equation in patients who are HIV-positive, supporting the use of the CKD-

EPI creatinine equation for routine clinical care for use in North American populations with HIV.

The use of both filtration markers together as a confirmatory test for decreased estimated GFR

based on creatinine in individuals who are HIV-positive requires further study.

Corresponding author and requests for single reprints: Lesley A Inker, MD MS, Division of Nephrology, Tufts Medical Center, 800Washington Street, Box #391, Boston, MA 02111; Tel: 617-636-2569; Fax: 617-636-8329, [email protected].

Conflicts of Interest:

The remaining authors declared no competing interests.

Preliminary results of this research were presented in abstract form at the Annual Meeting of the American Society of Nephrology in

Denver, CO, 18 November 2010.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

NIH Public AccessAuthor ManuscriptJ Acquir Immune Defic Syndr . Author manuscript; available in PMC 2013 November 01.

Published in final edited form as:

J Acquir Immune Defic Syndr . 2012 November 1; 61(3): 302–309. doi:10.1097/QAI.0b013e31826a6c4f.

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INKER et al. Page 15

Table 2

Performance of creatinine and cystatin C equations overall and across the range of GFR

Equation Overall Estimated GFR ml/min/1.73 m2

<60 60–90 >90

Bias, Median Difference (95% confidence intervals), ml/min per 1.73 m 2

MDRD Study 10.9 (8.0 – 14.0) 11.9 (7.9 – 18.7) 14.5 (11.2 – 17.1) 0.7 (−2.9 – 8.3)

CKD-EPI Creatinine 5.4 (2.7 – 7.9) 7.4 (5.0 – 14.6) 7.6 (3.5 – 13.0) 0.0 (−5.0 – 4.5)

CKD-EPI Cystatin C 4.3 (1.2 – 7.7) 13.1 (7.4 – 16.6) 6.5 (1.8 – 12.5) −5.4 (−10.9 – 0.5)

CKD-EPI Creatinine-cystatin 6.4 (3.1 – 9.3) 8.8 (2.7 – 12.5) 8.8 (4.7 – 13.4) 0.4 (−7.0 – 8.0)

Precision, Interquartile range of the difference (95% confidence intervals). ml/min per 1.73 m 2

MDRD Study 21.7 (18.6 – 25.8) 19.4 (14.3 – 25.7) 18.1 (13.9 – 27.2) 25.6 (15.6 – 34.8)

CKD-EPI Creatinine 22.7 (18.3 – 26.3) 18.1 (11.3 – 24.2) 23.1 (16.1 – 30.2) 22.8 (17.0 – 30.6)

CKD-EPI Cystatin C 25.7 (20.6 – 28.8) 17.2 (10.1 – 24.3) 22.9 (17.4 – 27.4) 24.6 (18.3 – 31.8)

CKD-EPI Creatinine-cystatin C 21.7 (18.1 – 24.4) 17.7 (9.5 – 20.2) 19.2 (14.4 – 24.2) 24.4 (20.1 – 30.4)

Accuracy, Percentage of estimates greater than 30% of measured GFR (95% confidence intervals), %

MDRD Study 20.0 (14.5 – 26.0) 33.3 (20.4 – 45.9) 15.7 (8.2 – 23.6) 13.0 (4.5 – 22.5)

CKD-EPI Creatinine 15.0 (10.5 – 20.0) 25.6 (12.8 – 38.7) 12.0 (5.2 – 19.3) 12.2 (5.1 – 20.0)

CKD-EPI Cystatin C 17.5 (12.5 – 22.8) 35.7 (21.4 – 50.0) 11.3 (4.9 – 18.7) 14.1 (6.7 – 22.2)

CKD-EPI Creatinine-cystatin C 10.0 (6.0 – 14.0) 18.4 (6.5 – 30.8) 5.9 (1.2 – 11.5) 10.4 (3.9 – 17.8)

MDRD, Modification of Diet in Renal Disease Study; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration

J Acquir Immune Defic Syndr . Author manuscript; available in PMC 2013 November 01.

CKD – EPI sobre MDRD

2012

Performance of Creatinine and Cystatin C GFR Estimating

Equations in an HIV-positive population on Antiretrovirals

Lesley A INKER, MD, MS1, Christina WYATT, MD2, Rebecca CREAMER, BSN, RN, CCRC3,

James HELLINGER, MD1, Matthew HOTTA, BS2, Maia LEPPO, BS1, Andrew S LEVEY, MD1,

Aghogho OKPARAVERO, MD, MPH1, Hiba GRAHAM, PharmD4, Karen SAVAGE, BSN, RN,

CCRC3, Christopher H SCHMID, PhD1, Hocine TIGHIOUART, MS1, Fran WALLACH, MD2,

and Zipporah KRISHNASAMI, MD3

1Tufts Medical Center

2Mt Sinai School of Medicine

3University of Alabama at Birmingham

4Gilead Sciences, Inc

Abstract

Objective—To evaluate the performance of CKD-EPI creatinine, cystatin C and creatinine-

cystatin C estimating equations in HIV-positive patients.

Methods—We evaluated the performance of the MDRD Study and CKD-EPI creatinine 2009,

CKD-EPI cystatin C 2012 and CKD-EPI creatinine-cystatin C 2012 glomerular filtration rate

(GFR) estimating equations compared to GFR measured using plasma clearance of iohexol in 200

HIV-positive patients on stable antiretroviral therapy. Creatinine and cystatin C assays were

standardized to certified reference materials.

Results—Of the 200 participants, median (IQR) CD4 count was 536 (421) and 61% had an

undetectable HIV-viral load. Mean (SD) measured GFR (mGFR) was 87 (26) ml/min/1.73m 2. All

CKD-EPI equations performed better than the MDRD Study equation. All three CKD-EPI

equations had similar bias and precision. The cystatin C equation was not more accurate than the

creatinine equation. The creatinine-cystatin C equation was significantly more accurate than the

cystatin C equation and there was a trend toward greater accuracy than the creatinine equation.

Accuracy was equal or better in most subgroups with the combined equation compared to either

alone.

Conclusions—The CKD-EPI cystatin C equation does not appear to be more accurate than the

CKD-EPI creatinine equation in patients who are HIV-positive, supporting the use of the CKD-

EPI creatinine equation for routine clinical care for use in North American populations with HIV.

The use of both filtration markers together as a confirmatory test for decreased estimated GFR

based on creatinine in individuals who are HIV-positive requires further study.

Corresponding author and requests for single reprints: Lesley A Inker, MD MS, Division of Nephrology, Tufts Medical Center, 800Washington Street, Box #391, Boston, MA 02111; Tel: 617-636-2569; Fax: 617-636-8329, [email protected].

Conflicts of Interest:

The remaining authors declared no competing interests.

Preliminary results of this research were presented in abstract form at the Annual Meeting of the American Society of Nephrology in

Denver, CO, 18 November 2010.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

NIH Public AccessAuthor ManuscriptJ Acquir Immune Defic Syndr. Author manuscript; available in PMC 2013 November 01.

Published in final edited form as:

J Acquir Immune Defic Syndr. 2012 November 1; 61(3): 302–309. doi:10.1097/QAI.0b013e31826a6c4f.

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HIVAN IECA & ARA2



• Uso de IECA o ARA 2, cuando sea clínicamente posible, en pacientes con VIH en quien

se halla confirmado HIVAN, o sospeche de este, o tengan albuminuria significativa (>

300 mg/día). (Fuerte, alta)


HIVAN IECA & ARA2

2003

44pacientes

Fosinopril10 mg/día

Aumento

sobrevida

HIVAN Acido acetilsalicílico



• Prescripción de aspirina (75-100 mg) para prevenir enfermedad cardiovascular en

pacientes infectados con VIH y con enfermedad crónica, sin embargo, el beneficio

de la aspirina debe ser balanceado con el riesgo individual de sangrado (Debil, alta)


HIVAN Acido acetilsalicílico

2009

Subgrupo

pacientes con VIH:

< 20% recibieron

aspirina con

indicación de

prescripción

HIVAN Estatinas



• Pacientes con infección por VIH con enfermedad renal crónica en pre-diálisis, sean

tratados con estatinas para prevenir enfermedad cardiovascular como es lo

apropiado para personas en alto riesgo cardiovascular (Fuerte, alta)


No hay estudios en pacientes con

VIH y pre-diálisis

HIVAN Corticoesteroides



• Considerar el uso de corticoesteroides como terapia adjunta de TARGA y IECA o ARA

2 in pacientes con biopsia confirmatoria de HIVAN. (Debil, baja)



2000

Corticoides No corticoides




• Prednisona 1 mg/Kg/día continuar por 2 a 11 semanas. Si hay respuesta antes de 4

semanas, continuar disminución de dosis por 2 a 26 semanas.

• Si no ha respuesta a la 4rta semana, iniciar disminución de dosis escalonadamente

de forma inmediata.


HIVAN Terapia de reemplazo renal

2003

6053Pacientes

1995-1999Tiempo de recolección

HR:1.01IC = 0.91 – 1.13 – IC 95%

HIVAN Terapia de reemplazo renal



• Para la elección de la diálisis debe

tenerse en cuenta:1. Preferencia del pacientes

2. Comorbilidades

3. Oportunidad de lograr un adecuado acceso de diálisis

HIVAN Trasplante renal



• Identificar pacientes en predialisis con la posibilidad de trasplante renal,

considerando historia de condiciones oportunistas, estatus inmune actual, y control

virológico del VIH con TARGA . (Fuerte, moderada)



2010


2015

93%1 año

84%3 años

84%5 años

84%1 año

84%3 años

75%5 años




Criterios de elección de candidatos para trasplante renal:

• Conteo de CD4 > 200 celulas/uL

• Carva viral sérica indetectable

• Sin historia de infecciones oportunistas

HIVAN (Nefropatía asociada al VIH) Evidencia al 2015

Health & Medicine

Transcript of HIVAN (Nefropatía asociada al VIH) Evidencia al 2015