SINDROME NEFROTICO

SINDROME NEFROTICO DRA. ALEJANDRA AGUILAR KITSU FEBRERO 2015 CASO CLINICO •  PREESCOLAR MASCULINO DE 3 AÑOS DE EDAD •  INICIO EDEMA FACIAL Y POSTERIORMENTE GENERALIZADO •  ANTECEDENTE DE INFECCION RESPIRATORIA ALTA Síndrome nefróGco SINDROME NEFROTICO CLASIFICACION ! SECUNDARIO (10%-15%)
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Púrpura de Henoch-Schönlein
Lupus eritematoso sistémico
Infecciones sistémicas
Anemia de células falciformes
Diabetes mellitus
Medicamentos y drogas
Neoplasias
SINDROME NEFROTICO CLASIFICACION ! PRIMARIO (85-90%)
-  Cambios mínimos
-  Glomerulonefritis crónica
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Glomeruloesclerosis focal y segmentaria
Glomerulonefritis membranosa
Glomerulonefritis membranoproliferativa
Proliferación mesangial difusa
-  Síndrome Nefrótico Congénito
IMAGEN HISTOLOGICA EN SINDROME NEFROTICO (ISKDC) Imagen
histológica
Cambios
mínimos
Glomeruloesclerosis
focal y segmentaria
Glomerulonefritis
membranoproliferativa
Proliferación
mesangial difusa
Glomerulonefritis
membranosa
Total de pacientes 471 Pacientes
(%)
Corticosensibles (%)
77
93.1
7.8
29.7
6.2
6.9
1.9
55.6
1.3
0
J Pediatr 1981; 98:561-‐4 CLAVES DIAGNOSTICAS •  SINDROME NEFROTICO DE CAMBIOS MINIMOS •  SEXO –  MAS FRECUENTE EN HOMBRES 2:1 A 3:1 •  EDAD –  EDAD DE PRESENTACION MAS FRECUENTE EN PREESCOLARES 3-‐5 AÑOS •  EDEMA –  FACILMENTE LLEGA A ANASARCA –  EDEMA EN GENITALES –  ASCITIS EXAMENES DE LABORATORIO •  EXAMENES CONFIRMAN DIAGNOSTICO –  ALBUMINA SERICA –  COLESTEROL SERICO –  TRIGLICERIDOS –  PROTEINURIA –  PLAQUETAS •  EXAMENES RENALES –  CREATININA SERICA –  EXAMEN GENERAL DE ORINA –  ELECTROLITOS SERICOS –  PROTEINAS EN ORINA 24 HORAS O INDICE PROTEINAS/
CREATININA CLAVES DIAGNOSTICAS •  PROTEINURIA –  MAYOR A 40 MG/M2/H –  INDICE PROTEINAS/CREATININA MAYOR A 2 –  EXAMEN GENERAL DE ORINA +++ A ++++ •  HIPOALBUMINEMIA •  HIPERLIPIDEMIA •  PLAQUETOSIS PROTEINURIA • 
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NORMAL <4 MG/M2/H NEFROTICA > 40 MG/M2/H EJEMPLO -‐ SUPERFICIE CORPORAL 1 METRO –  VOLUMEN 1000 ML –  24 HORAS DE RECOLECCION –  PROTEINAS 40 MG/DL –  40 MG POR CADA 100 ML –  400 MG DE PROTEINAS EN ESTA RECOLECCION –  400/24/1 –  16 MG/M2/H Core Curriculum in Nephrology
Parietal
epithelial cell
Fisiopatología Urinary Space
Slit
diaphragm
Filtration slit
(40 nm)
Podocyte
Cell body
Subpodocyte
space
Podocyte
Foot processes
GBM
Endothelial
cell
Glycocalyx
Fenestrae
Glomerular Capillary Lumen
Am J Kid Dis 2011 TRATAMIENTO •  PREDNISONA –  PRIMER ESQUEMA •  60 MG/M2/DIA POR SEIS SEMANAS •  40 MG/M2/48 HORAS POR SEIS SEMANAS •  MAXIMO 80 MG/DIA •  RECOMENDACIÓN K DIGO 60 MG/DIA CLAVES TRATAMIENTO •  ESTABLECER SI EL PACIENTE ES CORTICOSENSIBLE –  90% DE LOS NEFROTICOS PRIMARIOS SON CORTICOSENSIBLES –  NO HAY PROGRESION A INSUFICIENCIA RENAL •  10% PACIENTES CORTICORRESISTENTES –  50% EVOLJUCIONAN A INSUFICIENCIA RENAL EN 10 AÑOS CORTICOSENSIBLE •  ESQUEMA COMPLETO •  GUIAS K DIGO REQUIERE DE POR LO MENOS 8 SEMANAS DE TRATAMIENTO CON ESTEROIDES •  80% NIÑOS CORTICOSENSIBLES RESPONDEN A LAS 2 SEMANAS DE TRATAMIENTO •  95% A LAS 4 SEMANAS •  100% A LAS 8 SEMANAS TRATAMIENTO •  PREDNISONA ISKDC –  PRIMER ESQUEMA •  60 MG/M2/DIA POR 4 SEMANAS •  40 MG/M2/48 HORAS (3 DE CADA 7) POR 4 SEMANAS Tratamiento de SNCM Periodo más corto APN 1988 # Ensayo clínico controlado al azar # Esquema corto vs tradicional # Esquema corto # 60 mg/m2/día hasta proteinuria negaGva # 40 mg/m2/3er. día hasta proteinuria negaGva # Dosis total prednisona 50% # Recayeron el doble de pacientes # Recaídas más tempranas # A largo plazo igual dosis de prednisona total (J Pediatr 1988) Tratamiento de SNCM Periodo más largo # Ensayo clínico controlado al azar # Primer episodio de síndrome nefróGco # Esquema tradicional vs largo # Esquema largo # Prednisona 60 mg/m2/día por 6 semanas # Prednisona 40 mg/m2/3er. día por 6 semanas # Dos veces más probable remisión # Menos pacientes: recaídas frecuentes # Efectos colaterales por esteroides: igual (Eur J Pediatr 1993) ESQUEMA DE REDUCCION •  RECOMENDACIÓN KDIGO –  CONTINUAR DESPUES DEL ESQUEMA REDUCCION POR LO MENOS 3 A 6 MESES •  DISMINUCION PAULATINA –  DISMINUIR NUMERO DE RECAIDAS –  SOLO 25% DE LOS NIÑOS PRESENTAN UN SOLO EPISODIO Disease in Children (ISKDC) regime.
recently in evolution and is
ment for variables including
agethis,
andfully SSNS
is considered
to be a benign
Theemerged
results
show that the number of 87: 169–175.
Despite
half of patients
will
frequent
and the this
otherholds
half
major
riskrelapses,
disease,
true for only half of
relapses per patient-year was 1.33 in the dose, younger age was the have
whoalthough
do not relapsethe
or have
only infrepatients.
Prolonged and repeated
6-month
therapy
group
in factor for frequent relapses,
see clinical
trial on
pagesvs.
2171.25
and 225
quent relapses may be overtreated. The
Japanese
courses
of
steroids
have many side
the 2-month group. After 24 months, this was a post hoc analysis. The
KDIGO recommendations end with a
the impact
and second-line and third-line
relapses occurred in 58 of 122 (48%) trial results did not supportresearch
call for effects,
quality randomized
controlled
trials with
adequate
was not
therapy
is power,
often necessary throughout
versus 54 of 124 (44%) and frequent of age, but again, the study
sufficient and
follow-up,
and appropriate
childhood
and often into adulthood.
relapses in 37 vs. 37%, respectively. The designed to answer this question,
monitoring to answer these questions.
to of Kidney
SomeInternational,
patients have a lifelong disease, so
median time to reach the frequently age was not used to stratify patients
In this issue
it
cannot
really
relapsing nephrotic syndrome (FRNS) risk groups.
two large randomized prospective
trials be called benign. Ster5,6
on
the
efficacy
of
prolonged
corticosIn contrast, other reports strongly oids cannot be considered to have cured
status was shorter at 799 days (26
teroid therapy
treatment
theinitial
disease
in these circumstances; they
months) in the 6-month treatment argue that age may be a predictor
of the for the
of SSNS in children are published.3,4
contribute
to restoration of defective
group, hazard ratio
0.86
(90%
conseverity
of
the
disease,
that
is,
frequent
One group from India3 and another
1
Peter
F.
Hoyer
4
filter and podocyte function.
fidence interval, 0.64–1.16). The final relapses, steroid dependence,from
andJapan,
respo-both glomerular
with long-standing
experience
in doing
collaborative
Frequent
relapses
as well as steroid
conclusion
is
that
2
months
of
therapy
nse
to
cyclophosphamide
therapy.
Time
The best initial therapy for steroid-sensitive nephrotic syndrome (SSNS) multicenter trials, have addressed the
is not
inferioris to
6 months.
to first relapse
been described as dependence should be taken as a clinical
in children
subject
to ongoing
debate. Systematic
reviewshas
andalso
metaquestion of the validity of extending the
Kidney
International
(2015)
87,
17–19.
doi:10.1038/ki.2014.354
Interestingly,
these
two
randomized
analyses have concluded that at least 3 months and up to 7 months
initial steroid therapy up to 6 months.
trials
came towould
the reduce
same conclusion,
The Indian study group conducted a
of treatment
the number of relapses by 30%. But
blinded 1:1 placebo-controlled trial
although
a head-to-head
comparison
summarizing
small underpowered
studies cannot eliminate the basic
100
flaws insome
design. differences
Two well-powered
randomized prospective
trials now enrolling 181 patients 1–12 years old
shows
between
with a first episode of SSNS. Eligible
to thePatients
oppositefrom
conclusion,
thecome
studies.
India and
werethese results should impact the patients were treated with 2 mg/kg
Modifying
management
children
withbody
SSNS.size
younger,
and of
their
mean
75
body weight of prednisone
perfactors:
day
age
at
onset,
early
relapse
Kidney International (2015) 87, 17–19. doi:10.1038/ki.2014.354
for
6
weeks
followed
by
1.5
mg/kg
body
was below the norm. Initial therapy,
weight every other day for another
believed
by some to be of great imporFor more than 40 years corticosteroids cal experience and50
a scattering of small 6 weeks. Thereafter, patients were
tance,
TheofJapanese
P = NS
have was
been different.
the treatment
choice forgroup
prospective randomized trials. There randomized to receive either placebo
used
thetreatment
old 2-month
ISKDC regime.
initial
of steroid-sensitive
are no agreed optimal
dose
and
duraor
prednisone
in
decreasing
doses
of
1,
25
nephrotic syndrome
(SSNS) in children;
tion of treatment. The Cochrane group 0.75, and 0.5 mg/kg on alternate days
It resulted
in a cumulative
prednisone
however, there is no pathophysiological
has tried to shed light on the dilemma for 1 month each. The results show that
dose
of 2240 mg/m2, compared with
rationale for the treatment, and all by publishing several
0 updates of meta- the number of relapses per patient-year
therecommendations
Indian study are
group,
who
used the
based on
empirianalyses on this topic.1 The current was 1.01±1.04 in the 6-month treat0
4 6 8
12
24
52
104
recommendations say that extending ment group versus 1.13±1.01 in the
3-month regime with a cumulative
2
1
treatment
followed
by 3-month
Time
after start
of initial
treatment (weeks)
Zentrum fu¨r KinderJugendmedizin,
Klinik . the
prednisone
doseund of
2792 mg/m
In initial treatment with prednisone 3-month
beyond 2 months is beneficial in reduc- placebo group. Relapses occurred in
fu¨r Kinderheilkunde II, Universita¨t Duisburg-Essen,
contrast,
in
the
Japanese
trial
in
the
Essen, Germany
ing the number of relapses as well as 66.7 vs. 70.2% and frequent relapses in
Correspondence:
Peter treatment
F. Hoyer, Zentrum
fu¨r
6-month
initial
arm
the
frequent relapses. Recent Kidney Disease: 48.6 vs. 53.7%, respectively. Mean time
Kinder- und Jugendmedizin, Klinik fu¨r KinderheilkImproving Global Outcomes (KDIGO) to first relapse was 9.6 vs. 6.6 months,
cumulative
prednisone
dose was
¨t Duisburg-Essen, Hufelandunde II, Universita
2
2
guidelines2 have adopted these conclu- and to frequent relapse status 23 vs.
strasse
55,
D-45122
Essen,
Germany.
3885 mg/m , vs. 3530 mg/m in the
sions, recommending initial treatment 17.6 months (P ¼ not significant). The
E-mail: [email protected]
1 Indian long-treatment cohort. HowPrednisone
Prednisone
Zentrum
fu¨r87KinderdailyKlinikalternate days
ever,
the und
medianJugendmedizin,
Kidney after
International24
(2015)months
17
dose
including
relapse
treatment
in
Figure
| Lack of effect of extending initial prednisone treatment on long-term freedom
¨t 1Duisburg-Essen,
fu¨r Kinderheilkunde II, Universita
the short-treatment arm in Japan was from frequent relapses. NS, not significant.
analyses have concluded that at least 3 months and up to 7 month
ofNew
treatment
would
reduce the number of relapses by 30%. But
lessons from
randomized
trials in steroid-sensitive
summarizing
small underpowered studies cannot eliminate the bas
nephrotic syndrome: clear
flaws
in design.
randomized prospective trials n
evidence
againstTwo
long well-powered
steroid
come
to the opposite conclusion, and these results should impact
therapy
management of children with SSNS.
Initial prednisone
regime
Survival free of frequent
relapses (%)
For more than 40 years corticosteroids
have been the treatment of choice for
initial treatment of steroid-sensitive
nephrotic syndrome (SSNS) in children;
however, there is no pathophysiological
rationale for the treatment, and all
recommendations are based on empiri-
Essen, Germany
cal experience and a scattering of s
prospective randomized trials. T
are no agreed optimal dose and d
tion of treatment. The Cochrane gr
has tried to shed light on the dilem
by publishing several updates of m
analyses on this topic.1 The cur
recommendations say that extend
the initial treatment with prednis
beyond 2 months is beneficial in red
ing the number of relapses as we
SINDROME NEFROTICO PRONOSTICO Recaídas -‐  25% una recaída -‐  33% recaídas ocasionales -‐  50% evolucionan a corGcodependencia RECAIDAS FRECUENTES •  2 O MAS RECAIDAS EN LOS PRIMEROS SEIS MESES DE TRATAMIENTO •  3 O MAS RECAIDAS EN CUALQUIER PERIODO DE 12 MESES •  CORTICODEPENDIENTES –  RECAEN AL DISMINUIR LA DOSIS –  RECAEN EN LAS PRIMERAS DOS SEMANAS DE HABER SUSPENDIDO TRATAMIENTO TRATAMIENTO RECAIDAS •  PREDNISONA 60 MG/M2/DIA POR 4 SEMANAS •  PREDNISONA 40MG/M2/48 HORAS POR 4 SEMANAS •  REDUCCION PAULATINA MOTIVOS DE ENVIO • 
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INCREMENTO DE LA CREATININA SERICA CORTICORRESISTENTE, CORTICODEPENDIENTE RECAIDAS FRECUENTES EDAD DIAGNOSTICO MENOR DE UN AÑO O MAYOR DE 8 AÑOS EDAD DE PRESENTACION •  MENOR DE UN AÑO –  SINDROME NEFROTICO PRIMER AÑO DE VIDA •  TIPO FINLANDES •  ESCLEROSIS MESANGIAL DIFUSA •  NO RESPONDEN A TRATAMIENTO •  MAYORES DE 8 AÑOS –  80% de los casos de sindrome nefróGco de cambios minimos se presentan antes de los 6 años CLAVES MANEJO •  EVALUAR REMISION A LAS 4 SEMANAS DE TRATAMIENTO CON PROTEINURIA •  ENVIO TEMPRANO AL NEFROLOGO •  ASOCIACION CON INFECCIONES RESPIRATORIAS –  TRATAMIENTO SINUSITIS –  TRATAMIENTO CARIES •  CONTROL DE ASMA O ALERGIAS COMPLICACIONES •  Infecciones por organismos capsulados –  PeritoniGs primaria –  CeluliGs •  Trombosis –  Periféricas –  Cerebrales –  Renales

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