This document discusses sickle cell nephropathy and provides information over several slides. It begins with basic renal anatomy and physiology concepts. It then covers the pathophysiology of sickle cell nephropathy including hyperfiltration, albuminuria, tubular abnormalities, and hematuria. Epidemiology statistics for sickle cell nephropathy are presented. Clinical manifestations such as hematuria, nocturia, polyuria, acute kidney injury, chronic kidney disease, and nephrotic syndrome are outlined. Methods for diagnosis including basic tests, glomerular filtration rate equations, and newer biomarkers are reviewed. Treatment options are explored including hydroxyurea, ACE inhibitors, blood transfusions, erythropoies

1. Nefropatía De Células Falciformes
Dr. Cristhian Mauricio Bueno Lara
Especialista en Medicina Interna – Universidad Autónoma de Bucaramanga
Fellow en Nefrología – Universidad del Valle

2. 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)

3. Conceptos básicos fisiología renal
1. Comprenhensive clinical nephrology 4th edition 2010

4. Fisiopatología
1. Claire C. Sharpe and Swee L. Thein. Sickle cell nephropathy – a practical British Journal of Haematology, 155, 287–297
2. Comprenhensive clinical nephrology 4th edition 2010
Hipoxia relativa, acidosis e hiperosmolaridad

5. Fisiopatología
1. Claire C. Sharpe and Swee L. Thein. Sickle cell nephropathy – a practical British Journal of Haematology, 155, 287–297
2. Comprenhensive clinical nephrology 4th edition 2010

6. 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

7. 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
1. Claire C. Sharpe and Swee L. Thein. Sickle cell nephropathy – a practical British Journal of Haematology, 155, 287–297

8. 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
1. Claire C. Sharpe and Swee L. Thein. Sickle cell nephropathy – a practical British Journal of Haematology, 155, 287–297
Albuminuria y proteinuria

9. 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 parvovirusB19 infection and nephroticsyndrome
in patients with sickle cell disease
LynnQuek,1
ClaireSharpe,2,3
Neelanjana
Dutt,4
SueHeight,1
MarleneAllman,1
Moji Awogbade,1
David CRees,1,3
Mark
Zuckerman5
and SweeLay Thein1,3
1
Department of Haematological Medicine,
2
Department of Renal Medicine, 3
King’sCollege
LondonSchool of Medicine, Division of Geneand
Cell BasedTherapy, 4
Department of
Summary
AcuteHuman Parvovirus B19 (HPV B19) infection isthemajor cause of
transient red cell aplasia(TRCA) and acuteanaemiain patientswith sickle
celldisease(SCD).Wereport threecasesofpatientswhodevelopednephrotic
syndrome (NS) with chronic sequelae after initially presenting with HPV
B19-associated TRCA. Therewasno correlation between evidenceof HPV
short report
2010
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-
to below steady-statelevelsof morethan 30 g/l associated wit
a very low reticulocyte count.
Of the37individuals(median age8 years; range2–27 years
with acuteHPV B19 infection presenting with acutecrisisan
TRCA, 29 were children below the age of 16 years, and eigh
were patients over the age of 16 years. Thirty-two (25 below
16 yearsold and 7over age16 years) of the37patientshad th
HbSS genotype, two HbSC and three HbSb thalassaemi
genotypes. Three patients developed NS within 4 months o
acuteHPV B19 infection and TRCA; Patient 1 at 17, Patient
at 26, and Patient 3 at 11 years of age at diagnosis.
Patient 1 had stable HbSC disease with a steady-stat
haemoglobin level of 130–140 g/l and serum creatinine leve
of between 70 and 80 l mol/l. In May 2004 he was admitte
with acute pain and dyspnoea. Investigations confirmed a
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 parvoviru
First published online 7 January 201
ª 2010 Blackwell Publishing Ltd, British Journal of Haematology, 149, 289–291 doi:10.1111/j.1365-2141.2009.08062.
Microalbuminuria y proteinuria
No es posible establecer una relación directa entre el
síndrome nefrótico y parvovirus B19

10. Fisiopatología
• Hipostenuria en anemia de células falciformes.
• Alteraciones túbulos proximales y distales.
Anormalidades tubulares
1. Claire C. Sharpe and Swee L. Thein. Sickle cell nephropathy – a practical British Journal of Haematology, 155, 287–297
• Desde hematuria microscópica a macroscópica dolorosa.
• Excluir otras causas de hematuria.
Hematuria

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

12. 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

13. 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

14. 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
116
Pacientes con anemia de células
falciformes

15. 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.

16. Tratamiento
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
Hidroxyurea y Nefropatía por células falciformes
2006
Sin Tto
Enalapri
l
+ Hidroxiurea
La combinación de terapias
debe ser efectuada en
pacientes con nefropatía por
células falciformes

17. 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) inhibitorsfor
proteinuria and microalbuminuria in people with sickle cell
disease (Review)
Sasongko TH, NagallaS, BallasSK
2014
5 ensayos
clínicos
controlados
Captopril
Vs
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

18. 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
Antagonistas SRAA y Nefropatía por células falciformes
2014
Recomendación:
Para adultos con albuminuria sin otra causa aparente, iniciar
terapia con IECA (Nivel de evidencia 2B)

19. Tratamiento
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
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.

20. Tratamiento
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
Terapia de reemplazo renal y Nefropatía por células falciformes
2002
Mortalidad en HD
HR: 1.52 (IC= 1.27 – 1.82)
Mortalidad en TR
HR: 1.1 (IC= 0.82 – 1.48)

21. 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
Antagonistas SRAA y Nefropatía por células falciformes
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)

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

23. Pronóstico
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
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.