Nefropatia de celulas falciformes

Nefropatía De Células Falciformes

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

Fellow en Nefrología – Universidad del Valle

Contenido

• Conceptos básicos de anatomía renal (Diapositiva 2)

• Fisiopatología de la nefropatía de células falciformes (Diapositiva 3 –10)

• Epidemiología (Diapositiva 11)

• Manifestaciones clínicas (Diapositiva 12)

• Diagnóstico y detección temprana (Diapositiva 13 - 15)

• Tratamiento (Diapositiva 16 – 22)

• Pronóstico (Diapositiva 23)

Conceptos básicos fisiología renal

1. Comprenhensive clinical nephrology 4th edition 2010

Fisiopatología

1. Claire C. Sharpe and Swee L. Thein. Sickle cell nephropathy – a practical British Journal of Haematology, 155, 287–297


Hipoxia relativa, acidosis e hiperosmolaridad

Fisiopatología



Fisiopatología

Hiperfiltración

2012

Elevada tasa de filtración glomerular en la línea

de base del estudio en infantes con media de

edad de

13.7 años

1. Courtney D. Thornburg, Beatrice A. Files, Zhaoyu Luo, Scott T. Miller, Ram Kalpatthi, Rathi Iyer, Phillip Seaman, Jeffrey

Lebensburger, Ofelia Alvarez,9 Bruce Thompson, Russell E. Ware, and Winfred C. Wang, for the BABY HUG Investigators. Impact of

hydroxyurea on clinical events in the BABY HUG trial. Blood. 2012;120(22):4304-4310

Fisiopatología

• Aumento de la filtración glomerular por la fase vasodilatadora de la NCF.

• Aumento de la secreción tubular de creatinina al filtrado.

• Aumento del gasto cardiaco.

• Desaparición de la hiperfiltración posterior a los 30 años.

Hiperfiltración


Fisiopatología

• Aumento de la tasa de incidencia de albuminuria con la edad.

• Un 4% de los pacientes con anemia de células falciformes progresan a

síndrome nefrótico.

• Asociación entre infección por parvovirus B19 y síndrome nefrótico


Albuminuria y proteinuria

Fisiopatología

1. Lynn Quek, Claire Sharpe, Neelanjana Dutt, Sue Height, Marlene Allman, Moji Awogbade,1David C Rees, Mark Zuckerman and Swee

Lay TheinAcute. Human parvovirus B19 infection and nephrotic syndrome in patients with sickle cell disease. British Journal of

Haematology, 149, 289–291

Acute human parvovirus B19 infect ion and nephrot ic syndrome

in pat ients w ith sickle cell disease

Human Parvovirus B19 (HPV B19) infection causessignificant

morbidity in patients with sickle cell disease (SCD) (Serjeant

et al, 1993, 2001; Smith-Whitley et al, 2004) and is a major

cause of transient red cell aplasia (TRCA) (Goldstein et al,

1987). It has also been previously suggested as a trigger of

nephrotic syndrome (NS) in patients with SCD (Wierenga

et al, 1995). The possible association between acute HPV B19

infection and NS was investigated in our cohort of SCD

patients. Information was gathered on (i) 37 individuals with

SCD of all ages admitted to King’s College Hospital (KCH)

with acute HPV B19 infection between November 2002 and

July 2008 and (ii) baseline HPV B19 status and indices of

proteinuria and renal function in a cohort of 317 adult SCD

patientswho attended thespecialist clinic between January and

December 2008.

The diagnosis of acute parvovirus B19 infection in aplastic

crisis was based on positive HPVB19 IgM, with or without

positive IgG, and past exposure to parvovirus infection based

on positive HPV B19 IgG. HPV B19 IgM and IgG antibodies

were detected by using antibody sandwich enzyme immuno-

assays (EIAs) according to manufacturers’ instructions. Red

cell aplasia wasdefined as a fall in haemoglobin concentration

to below steady-state levels of more than 30 g/l associated with

a very low reticulocyte count.

Of the37 individuals (median age8 years; range2–27 years)

with acute HPV B19 infection presenting with acute crisis and

TRCA, 29 were children below the age of 16 years, and eight

were patients over the age of 16 years. Thirty-two (25 below

16 yearsold and 7 over age16 years) of the37 patientshad the

HbSS genotype, two HbSC and three HbS b thalassaemia

genotypes. Three patients developed NS within 4 months of

acute HPV B19 infection and TRCA; Patient 1 at 17, Patient 2

at 26, and Patient 3 at 11 years of age at diagnosis.

Patient 1 had stable HbSC disease with a steady-state

haemoglobin level of 130–140 g/l and serum creatinine level

of between 70 and 80 l mol/l. In May 2004 he was admitted

with acute pain and dyspnoea. Investigations confirmed an

aplastic crisiswith ahaemoglobin level of 75 g/l and avery low

reticulocyte count of 5Æ3 · 1012 per litre (normal 50–

150 · 1012 per litre) associated with an acute parvovirus

Lynn Quek,1 Claire Sharpe,2,3 Neelanjana

Dutt,4 Sue Height,1 Marlene Allman,1

Moji Awogbade,1 David C Rees,1,3 Mark

Zuckerman5 and Swee Lay Thein1,3

1Department of Haematological Medicine,2Department of Renal Medicine, 3King’sCollege

London School of Medicine, Division of Gene and

Cell Based Therapy, 4Department of

Histopathology, and 5Department of Virology,

King’sCollege Hospital NHS Trust, Denmark

Hill, London, UK

Received 20 October 2009; accepted for

publication 28 November 2009

Correspondence: Swee L. Thein, King’s College

London School of Medicine, James Black

Centre, 125 Coldharbour Lane, London SE5

9NU, UK.

E-mail: [email protected]

Regrettably, Dr N Dutt died after submission of

the manuscript.

Summary

Acute Human Parvovirus B19 (HPV B19) infection is the major cause of

transient red cell aplasia (TRCA) and acute anaemia in patients with sickle

cell disease(SCD). Wereport threecasesof patientswho developed nephrotic

syndrome (NS) with chronic sequelae after initially presenting with HPV

B19-associated TRCA. There was no correlation between evidence of HPV

B19 infection and impaired renal function in our cohort of adult sickle cell

patients. This is consistent with a view that although NSis potentially a rare

complication of symptomatic acute HPV B19 infection, exposure to HPV

B19 is not associated with an increased risk of renal disease.

Keywords: parvovirus B19, nephrotic syndrome, sickle cell.

short report

First published online 7 January 2010

ª 2010 Blackwell Publishing Ltd, British Journal of Haematology, 149, 289–291 doi:10.1111/j.1365-2141.2009.08062.x

2010

Acute human parvovirus B19 infection and nephrotic syndrome

in patients with sickle cell disease

Human ParvovirusB19 (HPV B19) infection causessignificant

morbidity in patients with sickle cell disease (SCD) (Serjeant

et al, 1993, 2001; Smith-Whitley et al, 2004) and is a major

cause of transient red cell aplasia (TRCA) (Goldstein et al,

1987). It has also been previously suggested as a trigger of

nephrotic syndrome (NS) in patients with SCD (Wierenga

et al, 1995). The possible association between acute HPV B19

infection and NS was investigated in our cohort of SCD

patients. Information was gathered on (i) 37 individuals with

SCD of all ages admitted to King’s College Hospital (KCH)

with acute HPV B19 infection between November 2002 and

July 2008 and (ii) baseline HPV B19 status and indices of

proteinuria and renal function in a cohort of 317 adult SCD

patientswho attended thespecialist clinic between January and

December 2008.

The diagnosis of acute parvovirus B19 infection in aplastic

crisis was based on positive HPVB19 IgM, with or without

positive IgG, and past exposure to parvovirus infection based

on positive HPV B19 IgG. HPV B19 IgM and IgG antibodies

were detected by using antibody sandwich enzyme immuno-

assays (EIAs) according to manufacturers’ instructions. Red

cell aplasia wasdefined asa fall in haemoglobin concentration

to below steady-state levelsof morethan 30 g/l associated with

a very low reticulocyte count.

Of the37 individuals (median age8 years; range2–27 years)

with acuteHPV B19 infection presenting with acute crisisand

TRCA, 29 were children below the age of 16 years, and eight

were patients over the age of 16 years. Thirty-two (25 below

16 yearsold and 7over age16 years) of the37 patientshad the

HbSS genotype, two HbSC and three HbSb thalassaemia

genotypes. Three patients developed NS within 4 months of

acuteHPV B19 infection and TRCA; Patient 1 at 17, Patient 2

at 26, and Patient 3 at 11 years of age at diagnosis.

Patient 1 had stable HbSC disease with a steady-state

haemoglobin level of 130–140 g/l and serum creatinine level

of between 70 and 80 l mol/l. In May 2004 he was admitted

with acute pain and dyspnoea. Investigations confirmed an

aplastic crisiswith ahaemoglobin level of 75 g/l and avery low

reticulocyte count of 5Æ3 · 1012 per litre (normal 50–

150 · 1012 per litre) associated with an acute parvovirus

Lynn Quek,1Claire Sharpe,2,3Neelanjana

Dutt,4 Sue Height,1 Marlene Allman,1

Moji Awogbade,1 David C Rees,1,3 Mark

Zuckerman5 and Swee Lay Thein1,3

1Department of Haematological Medicine,2Department of Renal Medicine, 3King’sCollege

London School of Medicine, Division of Geneand

Cell Based Therapy, 4Department of

Histopathology, and 5Department of Virology,

King’sCollege Hospital NHSTrust, Denmark

Hill, London, UK

Received 20 October 2009; accepted for

publication 28 November 2009

Correspondence: Swee L. Thein, King’sCollege

London School of Medicine, James Black

Centre, 125 Coldharbour Lane, London SE5

9NU, UK.

E-mail: [email protected]

Regrettably, Dr N Dutt died after submission of

the manuscript.

Summary

Acute Human Parvovirus B19 (HPV B19) infection is the major cause of

transient red cell aplasia (TRCA) and acute anaemia in patients with sickle

cell disease(SCD). Wereport threecasesof patientswho developed nephrotic

syndrome (NS) with chronic sequelae after initially presenting with HPV

B19-associated TRCA. There was no correlation between evidence of HPV

B19 infection and impaired renal function in our cohort of adult sickle cell

patients. This isconsistent with a view that although NSispotentially a rare

complication of symptomatic acute HPV B19 infection, exposure to HPV

B19 is not associated with an increased risk of renal disease.

Keywords: parvovirus B19, nephrotic syndrome, sickle cell.

short report

First published online 7 January 2010

ª 2010 Blackwell Publishing Ltd, British Journal of Haematology, 149, 289–291 doi:10.1111/j.1365-2141.2009.08062.x

Microalbuminuria y proteinuria

No es posible establecer una relación directa entre el

síndrome nefrótico y parvovirus B19

Fisiopatología

• Hipostenuria en anemia de células falciformes.

• Alteraciones túbulos proximales y distales.

Anormalidades tubulares


• Desde hematuria microscópica a macroscópica dolorosa.

• Excluir otras causas de hematuria.

Hematuria

Epidemiología


2. Fabio D. Pereira, M.D.1, Isabel Sáenz, T.M.. Hemoglobinopatías en niños. Colombia Med 1996; 146- 149

3. Richard Gargiulo, DO, Mauna Pandya, MD, Amber Seba, MD, Rami Y. Haddad, MD, Edgar V. Lerma, MD. Sickle cell nephropathy.

Disease-a-Month 60 (2014) 494–499

70.000 – 100.000

25%Nefropatía por Células

Falciformes 1% Población de raza negra de Tumaco

1996

Manifestaciones clínicas

1. ichard Gargiulo, DO, Mauna Pandya, MD, Amber Seba, MD, Rami Y. Haddad, MD, Edgar V. Lerma, MD. Sickle cell nephropathy.

Disease-a-Month 60 (2014) 494–499

Hematuria

Nicturia

Poliuria

Lesión renal aguda (5 a 10%)

Enfermedad renal crónica

Síndrome nefrótico

Hipertensión

Diagnóstico

1. Geraldo Bezerra da Silva Junior, Alexandre Braga Libório, Elizabeth De Francesco Daher. New insights on pathophysiology, clinical

manifestations, diagnosis, and treatment of sickle cell nephropathy. Ann Hematol (2011) 90:1371–1379

Exámenes básicos

Uroanálisis

Depuración de creatinina de 24 horas

Ecuaciones para evaluar filtrado glomerular

Diagnóstico

Ecuaciones de filtrado glomerular

1. Nambirajan Sundaram, Michael Bennett, Jamie Wilhelm, Mi-Ok Kim, George Atweh, Prasad Devarajan, and Punam Malik. Biomarkers

for early detection of sickle nephropathy. Am. J. Hematol. 86:559–566, 2011

2011

116Pacientes con anemia de células

falciformes

Diagnóstico

1. E Voskaridou, E Terpos, S Michail, E Hantzi, A Anagnostopoulos, A Margeli, D Simirloglou, D Loukopoulos and I Papassotirio. Early

markers of renal dysfunction in patients with sickle cell/b-thalassemia. Kidney International (2006) 69, 2037–2042

Otros marcadores de nefropatía por células falciformes

Cistatina C

β2 - Microglobulina

2006

Cistatina C y β2 – Microglobulina sérica muestra una fuerte

relación con la creatinina y la edad del paciente.

Tratamiento


Disease-a-Month 60 (2014) 494–499

Hidroxyurea y Nefropatía por células falciformes

2006

Sin TtoEnalapri

l+ Hidroxiurea

La combinación de terapias

debe ser efectuada en

pacientes con nefropatía por

células falciformes

Tratamiento

1. Sasongko TH, Nagalla S, Ballas SK. Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in

people with sickle cell disease (Review)

Antagonistas SRAA y Nefropatía por células falciformes

Angiotensin-converting enzyme (ACE) inhibitors for

proteinuria and microalbuminuria in people with sickle cell

disease (Review)

Sasongko TH, Nagalla S, BallasSK

Thisisareprint of aCochranereview, prepared and maintained byTheCochraneCollaboration and published in TheCochraneLibrary

2013, Issue3

http://www.thecochranelibrary.com

Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease (Review)

Copyright © 2013 The Cochrane Collaboration. Published by John W iley & Sons, Ltd.

2014

5 ensayos

clínicos

controlados

CaptoprilVs

Placebo

6 meses

seguimiento

pacientes con

proteinuria

Albuminuria

Proteinuria

No diferencias en estadísticamente

significativas en proteinuria y

albuminuria

Diferencias significativas en descenso

de cifras tensionales

Tratamiento

Management of Sickle Cell Disease Summary of the 2014 Evidence-Based Report by Expert Panel Members. JAMA. 2014;312(10):1033-

1048. doi:10.1001/jama.2014.10517


2014

Recomendación:

Para adultos con albuminuria sin otra causa aparente, iniciar

terapia con IECA (Nivel de evidencia 2B)

Tratamiento


Disease-a-Month 60 (2014) 494–499

Transfusión de hemoderivados y Nefropatía por células falciformes

• Mantener la Hb < a 10 gr/dL y evitar aumentos de hematocrito mayores al

2% cada semana.

• El uso de agentes estimulantes de la eritropoyesis no se recomienda de

rutina en pacientes con nefropatía de células falciformes.

Tratamiento


Disease-a-Month 60 (2014) 494–499

Terapia de reemplazo renal y Nefropatía por células falciformes

2002

Mortalidad en HDHR: 1.52 (IC= 1.27 – 1.82)

Mortalidad en TRHR: 1.1 (IC= 0.82 – 1.48)

Tratamiento

Management of Sickle Cell Disease Summary of the 2014 Evidence-Based Report by Expert Panel Members. JAMA. 2014;312(10):1033-

1048. doi:10.1001/jama.2014.10517


2014

Recomendación:

La terapia de reemplazo renal (Hemodiálisis, diálisis peritoneal y/o

trasplante renal) debe ser usada en pacientes con nefropatía por

células falciformes que la requieran (Nivel de evidencia 1C)

1. Jon I Scheinman. Sickle cell disease and the kidney.. doi:10.1038/ncpneph1008

Tra

tam

iento

Pronóstico


Disease-a-Month 60 (2014) 494–499

Terapia de reemplazo renal y Nefropatía por células falciformes

• Sobrevida = 4 años posterior a inicio de hemodiálisis.

• Riesgo de muerte es similar entre los pacientes con nefropatía y los

pacientes con enfermedad cerebrovascular.

Nefropatia de celulas falciformes

Health & Medicine

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