Dr.

Mario Alberto Lara Aramil

08/03/2023
 INTRODUCCIÓN
• Las glomerulopatías o GN son entidades que implican
patogénesis inmune o inflamatoria.
• Dx clínico y por laboratorio
• Biopsia: clasificación y pronóstico

Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,

2010.
 Adecuado estudio de biopsia:

• Microscopia de luz
• Microscopia electrónica
• Inmunofluorescencia
• Técnicas de inmunoperoxidasa

Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,

2010.
 • En las GN el factor dominante es la lesión a nivel
glomerular, sin embargo no son los únicos afectados

Focal

Difusa
Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,
2010.
 Segmentaria

Global

Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,

2010.
 Proliferativa

Exudativa

Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,

2010.
 MECANISMOS DE LESIÓN
GLOMERULAR

PROTEINURIA
• Sello de la enfermedad glomerular
• Glucocálix endotelial, la MBG y los podocitos repelen las
proteínas

Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,

2010.
Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,
2010.
• Lesión en hendidura diafragmática o en los podocitos.
 ANTIGENOS Y ANTICUERPOS
Lesión glomerular por complejos inmunes

2 mecanismos:
• GN mesangioproliferativa
• GN membranoproliferativa

Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,

2010.
Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,
2010.
 COMPLEMENTO
• El sistema del complemento puede activarse en algunas
enfermedades glomerulares

• Nefritis lúpica

Clásica • GNMP I
• GNMP crioglobulinémica

• Nefropatía por IgA

Alterna • PSGN
• Nefropatía membranosa

Manosa • Nefropatía por IgA

Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,

2010.
 MECANISMOS INMUNOLÓGICOS DE
LESIÓN GLOMERULAR
• Dos mecanismos principales

ØPoca eficacia en la eliminación de antígenos

ØMecanismo autoinmunes
Ø Pérdida de la tolerancia celular
Ø Toxinas o procesos infecciosos
Ø Mimetismo celular ACTIVACIÓN
Ø Liberación de citocinas y linfocinas DE CÉLULAS
Ø MHCII de novo en células renales T

Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,

2010.
 Activación de células glomerulares
• Células epiteliales, mesangiales y endoteliales
• Células mesangiales à c. similares a miofibroblastos à
MEC
• Lesión en c. endoteliales à moléculas de adhesión
leucocitaria y activación de la coagulación
• Podocitos à proteinuria y glomeruloesclerosis

Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,

2010.
Jurgen Floege, Richard J. Johnson, Comprehensive Clinical Nephrology, Elsevier, 4ed,
2010.
GLOMERULOPATIAS
PRIMARIAS
Enfermedad por cambios mínimos
Glomeruloesclerosis focal y segmentaria
Glomerulopatia membranosa
Glomerulonefritis membranoproliferativa
Enfermedad por Cambios mínimos
Definición:

• Caracterizado por síndrome nefrótico

Biopsia renal:
• No lesiones glomerulares en microscopia de luz
• Inmunoflurescencia negativa
• Borramiento de procesos podocitarios en
microscopia electrónica

J Am Soc Nephrol 24: 702–711, 2013

• En niños representa el 90% de los casos de síndrome
nefrótico.

• La biopsia renal en niños es raramente realizada ya que

responden a esteroides.

• En adultos la representa el 10-25% de los casos de

síndrome nefrótico

J Am Soc Nephrol 24: 702–711, 2013

Patofisiologia
• Poco entendida

• El modelo animal que reproduce MCD es la nefrosis por

puromicina aminonucleosidos.

• Origina la producción de especies reactivas del oxígeno y

daño directo a DNA

• Histológicamente origina alteración en los procesos

podocitarios y separación de la membrana basal
glomerular
J Am Soc Nephrol 24: 702–711, 2013
 Proteins of the Podocyte Slit Diaphragm
Involved in Proteinuria

!-Actinin 4 TRPC6
Podocin
CD2AP CD2AP
Nephrin
Nephrin

NEPH 1
P-Cadherin
FAT

gure 16-5 Proteins of the podocyte Comprehensive

slit diaphragm involved
Clinical Nephrology. in
Fifth Edition 2015
• Células T involucradas en daño de membrana basal
glomerular

• Deficiencia de células T reguladoras (Treg).

• Defecto en proteínas CD80 y angioproteina parecida a

proteínas 4 (Angptl4)

• CD80 (B7-1) proteína de células presentadoras de

antígenos

J Am Soc Nephrol 24: 702–711, 2013

Presentación clínica

• Edema
• Proteinuria en rangos nefróticos
• Hipoalbuminemia
• Hiperlipidemia
• Hematuria microscópica 10-30%

En adultos considerar etiologías secundarias

• Linfoma de Hodgkin´s y timoma
• AINES
• Litio
• Infecciones (estrongiloides)
J Am Soc Nephrol 24: 702–711, 2013
• Lesión renal aguda en 25% de los casos

• AKI mas frecuente en adultos de edad avanzada,

hombres, hipertensión, bajos niveles de albumina.

• Enfermedad renal crónica no frecuente.

• Experimentan recaídas en en 30% de los casos y llegan a

ser corticodependientes

J Am Soc Nephrol 24: 702–711, 2013

Histopatologia

Figure 17-1 Podocyte foot process fusion in minimal change disease.

Tratamiento

• Los corticoesteroides originan remisión completa hasta

en el 80% de los casos.

Adultos
• Tiempo de respuesta mas lento que en niños

• 50% responden en 4 semanas y un 10-25%requieren 12-

16 semanas

J Am Soc Nephrol 24: 702–711, 2013

mg/m2 for 3 consecutive days per week up (mean follow-up=46 months,
for 4 weeks) or slow taper (prednis- 34.5% versus 5.9%). The slow-taper CORTICOSTEROID-RESISTANT
olone=40 mg/m2 every other day for 4 group initially received a 35% higher ste- MCD
weeks followed by a slow taper over 5 roid dose than the rapid-taper group,
months). There was a higher incidence but the total cumulative steroid dose at Steroid-resistant (SR) MCD is defined
of FR and/or SD in the rapid- versus last follow-up was similar between as failing 16 weeks of corticosteroid

Table 1. Available treatment regimens and published response rates for the initial episode and infrequent relapse of adult
MCD
Medication Regimen Remission Rates (Complete + Partial)
Initial episode without
contraindication to steroids
Prednisone Dose: 1 mg/kg per day (maximum 80%–90%
80 mg/day) or 2 mg/kg every other day (maxium
120 mg every other day), for a minimum of 4 weeks,
and a maximum of 16 wks (as tolerated). After remission,
taper over a total period of corticosteroid exposure
of at least 24 weeks.
Initial episode with
contraindication to steroids
Oral CYC 2–2.5 mg/kg per d38 wk 75%
Cyclosporine 3–5 mg/kg per d in divided doses31–2 yr 75%
Tacrolimus 0.05–0.1 mg/kg per d in divided doses31–2 yr Unknown
Infrequent relapse
Same as initial medication Same as initial regimen Unknown—thought to be
similar to initial remission rate

J Am Soc Nephrol 24: 702–711, 2013 Adult Minimal Change Disease 705

J Am Soc Nephrol 24: 702–711, 2013

 Esteroide oral diario vs días alternos www.jasn.org BRI

groups. These data suggest

dose and longer taper of ster
improved outcomes in ch
MCD.
In adults, no studies com
versus slow steroid taper exi
case series reports, steroids
tapered by 5–10 mg/wk afte
has been achieved for a tot
corticosteroid exposure of
weeks.16, 18,19

ALTERNATIVE REGIMEN
THE INITIAL EPISODE

The data for the use of ster

regimens in the treatment o
MCD episode are limited to
and case series. These tre
reserved for patients who h
contraindications (severe hy
or steroid-induced psycho
Figure 2. Time to first remission in MCD adults treated with daily versus alternate-day unwilling to take steroids.
steroids. QD, daily; QOD, every other day. Modified from reference 18, with permission. phamide 23,39–42 and cycl
have been used with respo
approximately 75% with t
J Am Soc Nephrol 24: 702–711, 2013
4 weeks. They were then randomized to slow-taper group at both 6 months experience (Table 1).
either rapid taper (prednisolone=40 (51.7% versus 17.6%) and last follow-
Definiciones de respuesta a tramiento

• Resistencia a esteroide
Ausencia de respuesta después de 16 semana de
tratamiento

•Corticodependencia
2 o mas recaídas dentro de los 15 días posterior a
diminución de dosis de esteroide

•Recaída frecuente
2 recaídas en 6 meses o 4 recaídas en 1 año
J Am Soc Nephrol 24: 702–711, 2013
 www.jasn.org BRIEF REVIEW

Table 3. Published experience for the treatment of steroid-resistant, SD, and FR MCD in adults
Remission Rates Relapse Rates
Medication Evidence Regimen
SRa SD FR SRa SD FR
Oral CYC Observational series; 2–2.5 mg/kg per 50%–80% 50%–80% 50%–80% 50% 25%–56% 25%–56%
one RCT in adults d38 wk
iv CYC Two small RCTs in adults 750 mg/m2 per 50% 77% NA 14% 40% NA
mo36 mo + steroids
Cyclosporine 6 Large observational 3–5 mg/kg per d in 45%–92% 45%–92% 45%–92% NA 62%–75% 62%–75%
prednisone series data; one small divided dose31–2 yr
RCT in children and
one RCT in adults
Tacrolimus 6 Small observational 0.05–0.1 mg/kg per d in 79%–100% 91%–100% NA 40% 50% NA
prednisone series; two small divided dose31–2 yr
RCTs in adults
Mycophenolate Small observational 1–2 g/d in divided dose 25% 80%–100% 58% NA 20%–50% 20%–50%
mofetil series; one small
RCT in children
In many studies, the outcomes for these groups are combined. NA, data not available; RCT, randomized controlled trial.
a
In steroid-resistant cases, review of the initial biopsy and a repeat biopsy may be considered to evaluate for FSGS.

J Am Soc Nephrol 24: 702–711, 2013

to achieve trough level of 4–8 ng/ml) or Although a small case series in chil- (5 mg/kg per day) for 9 months followed
intravenous CYC (n=14; CYC dose=750 dren showed the use of chlorambucil in by a 3-month taper to withdrawal. At 9
Glomeruloescerosis Focal y segmentaria
• Enfermedad renal progresiva

• Caracterizada por proteinuria marcada y daño

podocitario.

• Mutaciones en genes estructurales de podocitos.

• Alto riesgo de recurrencia en el trasplante.

• Factores circulantes de permeabilidad vinculados a

patogénesis
Nat Rev Nephrol. 2015 February ; 11(2): 76–87
 CHAPTER 18 Primary and Secondary (Non-Genetic) Causes of Focal and Segmental Glomerulosclerosis 219

Etiologic Classification of Focal Segmental Glomerulosclerosis

Primary (Idiopathic) FSGS Pamidronate
Probably mediated by circulating/permeability factor(s) Sirolimus
Secondary FSGS Anabolic steroids
1. Familial/Genetic* 4. Mediated by Adaptive Structural-Functional Responses
Mutations in nephrin (NPHS1) Reduced renal mass
Mutations in podocin (NPHS2) Oligomeganephronia
Mutations in α-actinin 4 (ACTN4) Very low birth weight
Mutations in transient receptor potential cation channel (TRPC6) Unilateral renal agenesis
Mutations in Wilms tumor suppressor (WT1) Renal dysplasia
Mutations in inverted formin-2 (INF2) Reflux nephropathy
Mutations in phospholipase C epsilon 1 (PLCE1) Sequela to cortical necrosis
Risk alleles for apolipoprotein L1 (APOL1) Surgical renal ablation
Chronic allograft nephropathy
2. Virus Associated
Any advanced renal disease with reduction in functioning
HIV-1 (“HIV-associated nephropathy”) nephrons
Parvovirus B19 Initially normal renal mass
Simian virus 40 (SV40) Hypertension
Cytomegalovirus (CMV) Atheroemboli or other acute vaso-occlusive processes
3. Drug Induced Obesity
Heroin (“heroin-nephropathy”) Increased lean body mass
Interferon Cyanotic congenital heart disease
Lithium Sickle cell anemia

Box 18-1 Etiologic classification of focal segmental glomerulosclerosis (FSGS). *For complete list of genetic causes see Chapter 19. HIV, Human
immunodeficiency virus.

Comprehensive Clinical Nephrology. Fifth Edition 2015

plasma of some FSGS patients. The presence of such permeability obesity related, there is initially glomerular hypertrophy and a high
Patogénesis
Fogo Page 22

Figure 2.
Nat to
Possible pathways for regeneration of podocytes from PEC migration Rev
theNephrol. 2015
glomerular tuftFebruary ; 11(2): 76–87
Cuadro clínico

• Causa mas común de síndrome nefrótico en adultos.

• Representa el 4% de enfermedad renal estadio 5/5

KDIGO

• El síndrome nefrótico responde menos a esteroides que

la enfermedad de cambios mínimos.

• Responden un 50% esteroides

Nat Rev Nephrol. 2015 February ; 11(2): 76–87

• Síndrome nefrótico 50-70%

• Hipertensión en 30-50%

• Microhematuria 25-75%

• Deterioro en función renal 20-30%

• Complemento e inmunológicos sin alteraciones

Nat Rev Nephrol. 2015 February ; 11(2): 76–87

Variantes histopatológicas

Variantes morfológicas
GEFS no especifica
GESFS perihiliar
GESFS celular
GESFS punta
GESFS variante colapsante

Comprehensive Clinical Nephrology. Fifth Edition 2015

 Tratamiento
CHAPTER 18 Primary and Secondary (Non-Genetic) Causes of Focal and Segmental Glomerulosclerosis

Therapeutic Options in FSGS

• Optimal BP control (!125/75 mm Hg)

Subnephrotic proteinuria • Therapy with ACE inhibitor/ARB
without symptoms • Therapy with statins
• Avoid high-protein diet

• Optimal BP control (!130/80 mm Hg)

• Therapy with ACE inhibitor/ARB
• Therapy with statins
Nephrotic syndrome, • Avoid high-protein diet
symptomatic, high risk of
complications of plus
nephrotic syndrome • Predniso(lo)ne 1 mg/kg/day or 2 mg/kg qod
for 4–16 weeks with subsequent dose tapering and
continued therapy until remission or up to 6 months

Alternative therapy for Oral cyclosporine 3–5 mg/kg/day for 4–6 months
steroid-resistant patients
or for patients with Oral cyclophosphamide 2 mg/kg/day for 2–4 months
contraindications to
steroid therapy Oral MMF 1–1.5 g bid for 4–6 months

-19 Therapeutic options in focal segmental glomerulosclerosis. Treatment of secondary FSGS should be directed at the unde
Comprehensive
ossible. For HIV-associated nephropathy, treatment with highly active antiretroviral Clinical
therapy Nephrology.
(HAART); Fifth Editionnephrotoxicity,
for pamidronate 2015
tion; and for obesity-related glomerulopathy, weight loss. ACE, Angiotensin-converting enzyme; ARB, angiotensin receptor blocke
Respuesta a tratamiento

• Resistencia a esteroide
Ausencia de respuesta después de 16 semana de
tratamiento

•Corticodependencia
2 o mas recaídas dentro de los 15 días posterior a
diminución de dosis de esteroide

Advances in Chronic Kidney Disease, Vol 21, No 5 (September),

2014: pp 434-441
 Treatment of FSGS in Adults 437

h FSGS at 5
y remission
ntal glomer-
from Troya-

Advances in Chronic Kidney Disease, Vol 21, No 5 (September), 2014: pp 434-441

Tratamiento recaídas
Corticodependencia o corticorresistencia

• Ciclosporina 3-5 mg/kg respuesta hasta 80%

• Tacrolimus+ prednisona respuesta entre 67-73%

• Micofenolato de mofetilo 1-3 gramos resultados muy

variables

• Rituximab 375 m2 x 4 dosis respuesta 30-40%

• Plasmaféresis en trasplante renal

Advances in Chronic Kidney Disease, Vol 21, No 5 (September), 2014: pp 434-441
 Nefropatía membranosa

• Es una lesión glomerular especifica caracterizada por

engrosamiento de la pared capilar glomerular.

• El engrosamiento es resultado de depósito de complejos

inmunes subepiteliales o la formación in sittu de
complejos inmunes

Clin J Am Soc Nephrol 9: 609–616, 2014.

 Formación in situ CHAPTER 20 Membranous Nephropathy 241

Intrinsic Podocyte Antigens

urinary space

Podo

GBM

Endo

sms of in situ im-

ion in experimen-
nous nephropathy
ntibodies may cross Neutral endopeptidase (NEP) – alloimmune antenatal MN
wall and bind to Phospholipase A2 receptor (PLA2R) – Primary MN
ns exposed on the Megalin – Heymann nephritis in rats
ann nephritis in rats Anti-NEP, anti-PLA2R or anti-megalin
N (neutral endopep- A
(PLA2R). Endo, Glo-
; GBM, glomerular Comprehensive Clinical Nephrology. Fifth Edition 2015
Extrinsic Planted Antigens
B, Certain extrinsic
 of in situ im-
in experimen-
us nephropathy
Neutral endopeptidase (NEP) – alloimmune antenatal MN

Depósito extrinseca
odies may cross
all and bind to Phospholipase A2 receptor (PLA2R) – Primary MN
exposed on the Megalin – Heymann nephritis in rats
nephritis in rats Anti-NEP, anti-PLA2R or anti-megalin
eutral endopep- A
A2R). Endo, Glo-
BM, glomerular Extrinsic Planted Antigens
Certain extrinsic
d bovine serum
ites in the GBM
gens and form
body. urinary space

Podo

GBM

Endo

Cationized BSA – rabbit and mouse models, childhood MN

B Anti-BSA

Comprehensive Clinical Nephrology. Fifth Edition 2015

 240 SECTION IV Glomerular Disease

Causas Classification and Causes of Membranous

Nephropathy
Clinical Features of Membra
Rare in children: less than 5% of total c
Primary syndrome
Anti-PLA2R associated (70%-80%) Common in adults: 15% to 50% of tota
Idiopathic (20%-30%) syndrome, depending on age; increas
Males > females in all adults groups
Secondary Common Uncommon
Caucasians > Asians > African American
Autoimmune Class V lupus Rheumatoid arthritis
diseases nephritis Autoimmune thyroid disease Nephrotic syndrome in 60% to 70%
IgG4-related systemic disease Normal or mildly elevated blood pressu
Anti-GBM and ANCA- “Benign” urinary sediment
associated crescentic
glomerulonephritis Nonselective proteinuria
Tendency to thromboembolic disease*
Infections Hepatitis B Hepatitis C virus (HCV)
Human immunodeficiency Other features of secondary causes: inf
virus (HIV) systemic lupus erythematosus
Syphilis
Schistosomiasis Box 20-1 Clinical features of membra
venous thrombosis, renal vein thrombosis, an
Malignancy Solid tumors (colon, Non-Hodgkin lymphoma
stomach, lung, Chronic lymphocytic
prostate) leukemia (CLL)
Melanoma MN in childhood is more often second
Drugs or Nonsteroidal Mercury-containing Primary MN is the most common cause
toxins anti-inflammatory compounds nondiabetic Caucasian adults, with an est
drugs and Gold salts 8 to 10 cases per 1 million population in W
cyclooxygenase-2 D-Penicillamine, bucillamine association with certain human leukoc
(COX-2) inhibitors
immune response genes indicated a
Miscellaneous Sarcoidosis primary MN is not a familial disease, e
Anticationic bovine serum more than one affected family member.22
albumin
became more evident after the discove
Alloimmune antigen, when studies from Korea and Ta
Graft-versus-host disease following hematopoietic stem cell cant association with non-synonymous
transplantation phisms (SNPs)23,24 in the first C-type lec
De novo membranous nephropathy in renal allograft
PLA2R (Fig. 20-3), a region that is known
Fetomaternal alloimmunization to neutral endopeptidase
changes, as well as another in CTLD7. A
Table 20-1 Classification of conditions and agents associated with association study conducted by a Euro
Comprehensive Clinical Nephrology.
membranous nephropathy. The list excludes conditions for which only a Fifth with
strong associations Edition 2015
a noncoding SN
single case has been reported or the lesions were atypical of membranous
and another in HLA-DQA1 (rs2187668)
2 grupos de edad

• 3ra y 4ta década de la vía etiologías primarias

• 6ta década de la vida descartar etiologías secundarias

Clin J Am Soc Nephrol 9: 609–616, 2014.

Cuadro clínico
• 70-80% debutan con síndrome nefrótico.

• 20-30% con proteinuria subnefrotica asintomática.

• Hematuria microscópica es común en 30-40%

• En etiologías primarias anti-PLA2R positivo en 75% a

80%
• Complemento sérico normal a pesar de activación de
complemento intraglomerular

• 10-20% hipertensión arterial

Clin J Am Soc Nephrol 9: 609–616, 2014.
Histopatología
244 IV
SECTION Glomerular Disease

A
B

Comprehensive Clinical Nephrology. Fifth Edition 2015

SpikesA B

Figure 20-4 Lig

thy (MN). A, Ear
nephrotic syndro
ripheral capillary
B, Morphologica
ness of glomerul
with no increase
cally advanced M
matrix emanating
brane (arrow), in
methenamine sta
reaction; ×400.) (

membrane–like
Comprehensive Clinical Nephrology. Fifth Edition 2015
 BM

Complejos Inmunes microscopia

CL B
electrónica
A

GEC

US
CL

BM

C
Figure 20-6 Electron microscopy in membranous nephropathy
Comprehensive (MN). A,Fifth
Clinical Nephrology. Early (stage
Edition 2015 II) M
deposits on the subepithelial surface of the basement membrane (BM) corresponding to granular d
 Etiologías secundarias
Clin J Am Soc Nephrol 9: 609–616, March, 2014 Membranous Nephropathy, Ponticelli and Glassock 611

Table 1. Investigations suggested to detect/exclude an underlying cancer in a patient with apparently idiopathic (primary) MN and
repeatedly negative serologic tests for anti-PLA2R1 autoantibody and/or absence of PLA2R1 or IgG4 in glomerular deposits

Cancer Type Young Adult Older Patient

Lung Chest x-ray Computed tomography

Kidney Ultrasonography, malignant cells in the urine Ultrasonography, malignant cells in the urine
Breast Physical examination Mammography
Stomach Fecal occult blood? Gastroscopy
Colon Fecal occult blood? Colonoscopy
Prostate Rectal digital examination, percentage PSA Ultrasonography, prostate biopsy
Uterus Gynecologic examination Colposcopy

In young patients, fecal occult blood is usually searched for only in the case of anemia. MN, membranous nephropathy; PLA2R1,
phospholipase A2 receptor 1; PSA, prostate specific antigen.

uterus. An evaluation for underlying cancer is recommen- prolonged exposure to the nephrotic state, including dis-
ded for patients with MN, particularly for older individu- abling edema, proatherogenic hyperlipidemia and coronary
als (Table 1). heart disease, the prothrombotic milieu, malnutrition, and
Treatment of secondary MN depends on the etiology. enhanced risk of infection. Thus, a wait-and-see attitude might
Children with MN secondary to HBV infection do not re- be justified in patients with proteinuria ,4 g/d, in those
quire specific treatment because they often undergo spon- with a steadilyClindiminishing
J Am Soc Nephrol 9: 609–616,
magnitude of 2014.
proteinuria
taneous remission of renal disease within 1 year from over time, and in asymptomatic patients with normal renal
 Tratamiento
SECTION IV Glomerular Disease

MN Treatment Algorithm

Moderate proteinuria Heavy proteinuria

>4 <8 g/day >8 g/day
GFR normal + ↓ GFR

Mild proteinuria BP <125/75 BP <125/75

<4 g/day ACEi/ARB, diet ACEi/ARB, diet
GFR normal Monitor about 6 mo Monitor up to 3 mo

BP <125/75 *Persistent *Persistent

ACEi/ARB Proteinuria >4 g/day Proteinuria >8 g/day
Monitor

Cytotoxic + steroids ***CNI ↓ GFR and

or **CNI **Cytotoxic + steroids proteinuria >8 g/day

*Risk reduction
strategies **ACTH **Rituximab **Cytotoxic + steroids
**Consider drug risks
***See reference 71
e 20-7 Algorithm for treatment of the patient with membranous nephropathy (MN). Details of possible therapies are discussed in t
Angiotensin-converting enzyme inhibitor; ACTH, adrenocorticotropic hormone; Comprehensive
ARB, angiotensinClinical blocker; BP, Fifth
receptorNephrology. bloodEdition
pressure; CNI, ca
2015
or; GFR, glomerular filtration rate.
 Guías KDIGO Regimen Ponticelli
chapter 7

3
Table 15 | Cyclical corticosteroid/alkylating-agent therapy
of for IMN (the ‘‘Ponticelli Regimen’’)
f Month 1: i.v. methylprednisolone (1 g) daily for three doses, then oral
d methyprednisolone (0.5 mg/kg/d) for 27 days
- Month 2: Oral chlorambucil (0.15–0.2 mg/kg/d) or oral cyclophosphamide
(2.0 mg/kg/d) for 30 daysa
d Month 3: Repeat Month 1
s Month 4: Repeat Month 2
o Month 5: Repeat Month 1
Month 6: Repeat Month 2
IMN, idiopathic membranous nephropathy.
a
Monitor every 2 weeks for 2 months, then every month for 6 months, with serum
creatinine, urinary protein excretion, serum albumin, and whiteSupplements
Kidney International blood cell count.
(2012) If
2, 186–197
a total leukocyte count falls to o3500/mm , then hold chlorambucil or cyclophos-
3
Guías KDIGO

• Se puede iniciar manejo con inhibidores de calcineurina

• Ciclosporina : 3.5- 5 mg/kg/d en dos dosis divididas cada

12 horas + prednisona .15 mg/kg/día por 6 meses

• Tacrolimus .05-.075 mg/kg/d en dos dosis divididas cada

12 horas sin prednisona por 6-12 meses

Kidney International Supplements (2012) 2, 186–197

and intravenous corticosteroids and an oral alkylating monotherapy, without concomitant steroids (37).
agent (cyclophosphamide is better tolerated than chloram- Mycophenolate mofetil (MMF) has also been used.
bucil). Such a treatment requires monitoring of leukocyte Negative results have been reported by a French trial
counts every 7–10 days during alkylating agent adminis- (38), in which 36 patients were randomized to receive
tration to help modulate the dosage to avoid serious leu- MMF as monotherapy (2 g/d for 12 months) or symptom-
copenia. This regimen may be contraindicated in a number atic therapy. No difference in remission was seen between
of patients affected by comorbidities such as diabetes or the two groups. Better results were reported by a retro-
prior malignancy. Concerns over the possible cosmetic spective study in which MMF was combined with oral

Table 2. Possible treatment choices in patients with idiopathic (primary) membranous nephropathy

Treatment Results Notes

Steroids alone No benefit Although ineffective, frequently used by practitioner

Steroids-alkylating Can significantly increase the The results are confirmed by randomized controlled
agents probability of complete or trials. Risk of side effects (infection, leucopenia).
partial remission. Protect renal Avoid frequent repetitions (risk of oncogenic or
function in the long term gonadotoxic effects)
CNI Can significantly reduce the amount Relapse of proteinuria is frequent after CNI
of proteinuria and increase the withdrawal. Risk of hypertension, nephrotoxicity.
probability of complete or partial Little information about long-term safety
remission. Little information about
their effects on renal function
Mycophenolate Ineffective when given alone. Can Only small-sized studies with short-term follow-up
salts reduce proteinuria when given are available. High relapse rate. No information
together with steroids about the long-term safety and efficacy
ACTH Can reduce proteinuria Only few small-sized studies with short-term
follow-up are available. A randomized controlled
trial is in progress
Rituximab Can reduce proteinuria Large observational studies available. No
head-to- head comparison with other treatments

CNI, calcineurin inhibitors; ACTH, adrenocorticotropic hormone.

Clin J Am Soc Nephrol 9: 609–616, 2014.

 Glomerulonefritis membranoproliferativa
• También llamada glomerulonefritis mensagiocapilar

• Representa 7-10% de las glomerulonefritis

• Entidad previamente clasificada como primaria y

secundaria.

• La primaria se subdividía en tres grupos

• Tipo I (complejos subendoteliales)
• Tipo II (depósitos densos)
• Tipo II (complejos subendoteliales y subepiteliales)

Nat. Rev. Nephrol. 8, 634–642 (2012)

Reclasificación
REVIEWS

MPGN or other proliferative GN (e.g. mesangioproliferative GN or crescentic GN) on LM co

im
in
C3 + immunoglobulin on IF C3 alone on IF tr
o

Immune-complex-mediated GN C3 glomerulopathy: complement a

alternative pathway-mediated GN
d
ti
p
Mesangial and intramembranous highly Mesangial, subendothelial, subepithelial,
electron-dense deposits on EM and/or intramembranous deposits on EM (C
T
ti
DDD C3GN la
c
Figure 1 | The reclassification of MPGN has led to the emergence of a new
Nat. Rev. Nephrol. 8, 634–642 (2012) p
 Etiología
254 SECTION IV Glomerular Disease

Etiology of Membranoproliferative Glomerulonephritis and Dense Deposit Disease

Type Secondary Causes
MPGN Type I
With mixed (type II or III) cryoglobulinemia Hepatitis C virus (70%-90% of patients)
Other infections: bacterial endocarditis, chronic hepatitis B viral infection
Collagen vascular disease: systemic lupus erythematosus, Sjögren syndrome
Malignancy: chronic lymphocytic leukemia, non-Hodgkin lymphoma
Without cryoglobulinemia Bacterial infections: endocarditis, abscess, infected ventriculoatrial shunt
Viral infections: hepatitis B, C, and G; human immunodeficiency virus; hantavirus
Malarial (Plasmodium malariae)
Collagen vascular disease (systemic lupus erythematosus, hypocomplementemic urticarial vasculitis)
Hereditary complement deficiency (C1q, C2, C4, or C3)
Acquired complement deficiency (presence of C4 nephritic factor)
Chronic liver disease: especially associated with hepatitis B or C infection, chronic schistosomal
infection, with splenorenal shunt for liver fibrosis, and with α1-antitrypsin deficiency
Sickle cell disease
Malignancy: chronic lymphocytic leukemia, lymphoma, thymoma, renal cell carcinoma
Dense Deposit Disease (MPGN Type II)
Associated with C3 nephritic factor (C3 Nef) With or without partial lipodystrophy and retinal abnormalities
Associated with factor H defect Inherited mutations of factor H (deficiency)
Autoantibodies to factor H
MPGN Type III
Secondary causes similar to MPGN type I (hepatitis C or B, and others)

Table 21-1 Etiology of membranoproliferative glomerulonephritis.

Comprehensive Clinical Nephrology. Fifth Edition 2015

 Medical Progress

Patofisiología A Normal

B Immune-complex–mediated
MPGN

N Engl J Med 2012;366:1119-31.

Presentación clínica
• La presentación clínica es muy variable

• Glomerulonefritis rápidamente progresiva 20%

• Pueden presentar hematuria microscopica y proteinuria no

nefrótica 35%

• Pueden presentar síndrome nefrótico 35%

• Hipertensión arterial 50-80%

• Pueden llegar a enfermedad renal crónica

• Pueden presentar síndrome nefrítico- nefrótico

N Engl J Med 2012;366:1119-31.

 258 IV Glomerular Disease
Histopatologia SECTION

Figure 21-9 “Tram tracks” in MPGN type I. Silver staining shows a

double contouring of the glomerular basement membrane (GBM) can be
Comprehensive Clinical Nephrology. Fifth Edition 2015
observed in MPGN type I, resembling tram tracks.
Abordaje Medical Progress

MPGN

Capillary wall and mesangial immuno- Negative immunoglobulin, mesangial

globulin and C3 deposits and capillary wall C3 deposits

Immunoglobulin-positive, Immunoglobulin-negative,
complement-positive MPGN complement-positive MPGN

Electron microscopy
Circulating immunoglobulin
or immune complexes
C3GN DDD

Autoimmune or Monoclonal
Infections
rheumatologic gammopathy
diseases (dysproteinemia) Dysregulation of the alternative pathway
of complement

Mutations or antibodies to complement

factors or complement-regulating proteins

Figure 5. Pathophysiology of MPGN.

On the basis of the immunofluorescence findings, MPGN can be broadly divided into immunoglobulin-positive,
complement-positive MPGN and immunoglobulin-negative, complement-positive MPGN. The presence of immuno-
Glomerulonephritis in Children and Adults Treatment options in mixed cryoglobulinemia with renal involve-
For patients with normal renal function and asymptomatic non- ment include corticosteroids, cytotoxic drugs such as cyclophospha-
nephrotic–range proteinuria, supportive antiproteinuric and antihy- mide, rituximab, and antiviral therapy (see Chapter 57). Subcutaneous
pertensive measures only are required (see Chapter 80). Close administration of pegylated interferon alfa-2a or alfa-2b often
follow-up every 3 to 4 months is recommended.22 In adults or chil- improves extrarenal manifestations associated with reduced levels of

Tratamiento
dren with presumed idiopathic MPGN accompanied by nephrotic
syndrome and a progressive decline of kidney function, oral cyclo-
phosphamide or mycophenolate mofetil (MMF) plus low-dose
viremia, but relapse is common after cessation of therapy. The current
treatment of choice in patients with HCV-associated MPGN or cryo-
globulinemic MPGN with moderate proteinuria and nonrapid but
alternate-day or daily corticosteroids has been suggested, with initial progressive renal failure is pegylated interferon alfa-2a (180 μg every
therapy limited to less than 6 months.23 These drugs in combination week) or alfa-2b (1.5 μg kg−1 every week) and ribavirin (800 to
with high-dose pulse corticosteroids have also been administered 1200 mg/day in two divided doses), adapting the dose to the stage

Suggested Management of Membranoproliferative Glomerulonephritis

Type Treatment
All types Supportive therapy following recommendations discussed in Chapter 80
Idiopathic MPGN in Non-nephrotic proteinuria, normal renal function: follow with 3-month visits
children Normal renal function and moderate proteinuria (>3 g/day): prednisone 40 mg/m2 on alternate days for 3 months
Nephrotic or impaired renal function: prednisone 40 mg/m2 on alternate days (maximum 80 mg) for 2 years, tapering to
20 mg on alternate days for 3-10 years
Idiopathic MPGN in Non-nephrotic, normal renal function: follow with 3-month visits
adults Nephrotic or impaired renal function: 6-month course of corticosteroid with/without cyclophosphamide, cyclosporine,
tacrolimus, or mycophenolate (MMF)
Rapidly progressive renal failure with diffuse crescents: treat as for renal-limited pauci-immune crescentic GN (see Chapter 25)
In the presence of heavy proteinuria: ACE inhibitors
MPGN associated Non-nephrotic, normal renal function: treat with interferon alfa (see Chapter 57) based on severity of liver disease (diagnosed
with HCV or by biopsy)
cryoglobulinemia Nephrotic syndrome, reduced renal function, or signs of cryoglobulinemia: pegylated interferon alfa-2b (1 μg/kg weekly) and
ribavirin (15 mg/kg/day) for 12 months, followed by short-term course of low-dose corticosteroids; if relapse occurs,
consider high-dose interferon alfa (10 million U daily for 2 weeks, then every other day for 6 more weeks).
Rapidly progressive renal failure or severe symptoms of vasculitis (heart failure, pulmonary disease): methylprednisolone (1 g/
day) for 3 days, followed by oral prednisone (60 mg/day) with slow taper over 2-3 months
Cyclophosphamide (2 mg/kg/day with adjustment for renal function) and cryofiltration may be added as adjunctive therapy;
when prednisone reduced to 20 mg/day and cyclophosphamide discontinued, add interferon alfa.
MPGN in renal or liver transplant recipient: consider course of oral ribavirin (0.6-1 g/day).

Table 21-3 Suggested management of membranoproliferative glomerulonephritis (MPGN).

N Engl J Med 2012;366:1119-31.

 VASCULITIS DE PEQUEÑO VASO:
GRANULOMATOSIS CON POLIANGEITIS
ENFERMEDAD ANTIMEMBRANA BASAL
GLOMERULAR
2012 Revised International Chapel Hill Consensus Conference Nomenclature of
Vasculitides

J. C. Jennette,1 R. J. Falk,1 P. A. Bacon,2 N. Basu,3 M. C. Cid,4 F. Ferrario,5 L. F. Flores-Suarez,6 W. L. Gross,7

L. Guillevin,8 E. C. Hagen,9 G. S. Hoffman,10 D. R. Jayne,11 C. G. M. Kallenberg,12 P. Lamprecht,13
C. A. Langford,10 R. A. Luqmani,14 A. D. Mahr,15 E. L. Matteson,16 P. A. Merkel,17 S. Ozen,18 C. D. Pusey,19
N. Rasmussen,20 A. J. Rees,21 D. G. I. Scott,22 U. Specks,16 J. H. Stone,23 K. Takahashi,24 and R. A. Watts25

Introduction our understanding of vasculitis, another International

Chapel Hill Consensus Conference (CHCC2012) was
The goals of the first International Chapel Hill
convened to improve the CHCC1994 nomenclature,
Consensus Conference on the Nomenclature of Sys-
change names and definitions as appropriate, and add
temic Vasculitides (CHCC1994) were to reach consen-
important categories of vasculitis that were not included
sus on names for the most common forms of vasculitis
in CHCC1994. As in the original CHCC, the emphasis
and to construct a specific definition for each (1). An
was on making changes only when justified. Herein we
effort was made to adopt names and definitions that
report the CHCC2012 revised nomenclature for vascu-
were already widely accepted. Because of advances in
litides.
CHCC is a nomenclature system (nosology). It is
1
J. C. Jennette, MD, R. J. Falk, MD: University of North neither a classification system that specifies what findings
Carolina, Chapel Hill; 2P. A. Bacon, MD: University of Birmingham, must be observed in a specific patient to classify that
Birmingham, UK; 3N. Basu, MBChB, PhD: University of Aberdeen, patient for clinical research nor a diagnostic system that
Aberdeen, UK; 4M. C. Cid, MD: University of Barcelona Hospital
Clinic, Barcelona, Spain; 5F. Ferrario, MD: University of Milan– directs clinical management (Table 1). A disease nomen-
Biocca, Milan, Italy; 6L. F. Flores-Suarez, MD, PhD: Instituto Nacio- clature system specifies the name that should be used for
nal de Enfermedades Respiratorias, Mexico City, Mexico; 7W. L. a specifically defined disease process. A nomenclature
Gross, MD: Klinikum Bad Bramstedt, Bad Bramstedt, Germany;
8
L. Guillevin, MD: Hôpital Cochin, AP-HP, Paris, France; 9E. C. Vol.
system 65, No. based
is constructed 1, January
on the state2013, pp 1–11
of knowledge at
Box 1. Systemic Vasculitis Nomenclature ANCA Antibodies
ANCAs are autoantib
Small-vessel vasculitis (SVV)
• Antineutrophil cytoplasmic antibody (ANCA)–associated antigens expressed in
vasculitis (AAV) and the lysosomes o
> Microscopic polyangiitis (MPA) granules contain a
> Granulomatosis with polyangiitis (Wegener) (GPA) including lysozyme,
> Eosinophilic granulomatosis with polyangiitis (Churg- (PR3, elastase, and c
Strauss) (EGPA) (cathepsin B and D).
• Immune complex SVV any of these proteins,
> Anti–glomerular basement membrane (anti-GBM) disease are directed against M
> Cryoglobulinemic vasculitis (CV)
of disease, ANCAs are
> Immunoglobulin A (IgA) vasculitis (Henoch-Scho €nlein)
but other immunogl
(IgAV)
described.
> Hypocomplementemic urticarial vasculitis (HUV) (anti-C1q
vasculitis)
ANCA Testing
Medium-vessel vasculitis (MVV) Many laboratories use
• Polyarteritis nodosa (PAN) (IIF) as a screening tes
• Kawasaki disease (KD) PR3 are found in pr
Large-vessel vasculitis staining patterns are s
• Takayasu arteritis (TA) lution of primary gran
• Giant cell arteritis (GCA) to the negatively ch
perinuclear pattern
Variable vessel vasculitis (VVV)
• Behçet disease (BD)
distributed in a cyto
• Cogan syndrome (CS) positive IIF result is
Based on 2012 International Chapel Hill Consensus Conference (see Jennette
confirmed by an antig
et al in Additional Readings). linked immunosorbe
consensus statement o
Vasculitis de pequeño vaso

Es una poliangeitis necrotizante que afecta

predominantemente capilares, vénulas y arteriolas

A nivel glomerular principalmente los capilares glomerulares

Anticuerpos contra citoplasma de neutrófilo

• ANCA-P o ANCA-C negativos en un 30% en presencia de

vasculitis

Anticuerpos contra proteína 2 Liposomal (LAMP-2)

Vol. 65, No. 1, January 2013, pp 1–11

ASOCIACIONES

Am J Kidney Dis. 2013;62(6):1176-1187

 CHAPTER 25 Renal and Systemic Vasculitis 293

ANCA in Small-Vessel Vasculitis

Frequency (%)
Proteinase 3 Myeloperoxidase
Disorder (PR3, usually c-ANCA) (MPO, usually p-ANCA) Negative
Granulomatosis with polyangiitis (Wegener) 70 25 5
Microscopic polyangiitis 40 50 10
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) 5 40 55
Renal-limited pauci-immune crescentic GN 20 70 10

Table 25-3 Antineutrophil cytoplasmic antibody (ANCA) in small-vessel vasculitis. Approximate frequency of ANCA with specificity for proteinase
3 (PR3/c-ANCA) and for myeloperoxidase (MPO/p-ANCA) in patients with different categories of pauci-immune small-vessel vasculitis and crescentic glomeru-
lonephritis. GN, Glomerulonephritis.

Comprehensive Clinical Nephrology. Fifth Edition 2015

GRANULOMATOSIS CON
POLIANGEITIS

(WEGENER)
Datos clínicos

Am J Kidney Dis. 2013;62(6):1176-1187

CRITERIOS DX ACR 1990
Diagnostico Histopatológico
 TRATAMIENTO INDUCCIÓN REMISIÓN
chapter 13

Table 30 | Recommended treatment regimens for ANCA vasculitis with GN

Agent Route Initial dose
Cyclophosphamidea i.v. 0.75 g/m2 q 3–4 weeks.
Decrease initial dose to 0.5 g/m2 if age 460 years or GFR o20 ml/min per 1.73 m2.
Adjust subsequent doses to achieve a 2-week nadir leukocyte count 43000/mm3.
Cyclophosphamideb p.o. 1.5–2 mg/kg/d, reduce if age 460 years or GFR o20 ml/min per 1.73 m2.
Adjust the daily dose to keep leucocyte count 43000/mm3.
Corticosteroids i.v. Pulse methylprednisolone: 500 mg i.v. daily " 3 days.
Corticosteroids p.o. Prednisone 1 mg/kg/d for 4 weeks, not exceeding 60 mg daily.
Taper down over 3–4 months.
Rituximabc i.v. 375 mg/m2 weekly " 4.
Plasmapheresisd 60 ml/kg volume replacement.
Vasculitis: Seven treatments over 14 days If diffuse pulmonary hemorrhage, daily until the bleeding stops, then every
other day, total 7–10 treatments.
Vasculitis in association with anti-GBM antibodies: Daily for 14 days or until anti-GBM antibodies are undetectable.
ANCA, antineutrophil cytoplasmic antibody; GBM, glomerular basement membrane; GFR, glomerular filtration rate; GN, glomerulonephritis; i.v., intravenous; p.o., orally.
a
Given with pulse and oral steroids. An alternative i.v. cyclophosphamide dosing schema is 15 mg/kg given every 2 weeks for three pulses, followed by 15 mg/kg given every
3 weeks for 3 months beyond remission, with reductions for age and estimated GFR.705
b
Given with pulse and oral steroids.
c
Given with pulse and oral steroids.
d
Not given with pulse methylprednisolone. Replacement fluid is 5% albumin. Add 150–300 ml fresh frozen plasma at the end of each pheresis session if patients have
pulmonary hemorrhage, or have had recent surgery, including kidney biopsy.
Kidney International Supplements (2012) 13, 233–242
TRATAMIENTO FASE DE
MANTENIMIENTO DE REMISIÓN

ARTHRITIS & RHEUMATISM Vol. 65, No. 1, January 2013, pp 1–11

Plasmaférisis

Ante evidencia de creatinina sérica > 5.6 mg/dl, o

hemorragia alveolar. De 5-7 sesiones en 14 días

Rituximab
TRIAL: RITUXVAX y RAVE

Dosis de Rituximab 375 m2 x 4 dosis VS ciclofosfamida

No diferencia en remisión

Ventaja de Rituximab sobre ciclofosfamida en recaídas

Kidney International Supplements (2012) 13, 233–242
 SECTION IV Glomerular Disease

Treatment Options for AAV

Induction therapy

No life-threatening or Life-threatening or organ-

organ-threatening disease threatening disease

Rituximab with prednisone 6 mo or Methylprednisolone and/or plasma

cyclophosphamide IV Q mo × 3 mo, exchange, cyclophosphamide IV Q
prednisone × 16 wk mo × 3–6 mo, prednisone × 16 wk

Remission Remission
Treatment
following following
resistance
rituximab cyclophosphamide

Follow patient Remission

Rituximab or oral
closely to detect maintenance with
Remission cyclophosphamide
disease early relapse azathioprine

Relapse Relapse

Following 12–18 mo in remission,

Rituximab ± prednisone if relapse caught early or
maintenance immunosuppression
cyclophosphamide IV monthly with prednisone for
may be discontinued with close
life/organ-threatening disease
follow-up

25-11 Algorithm of recommended treatment for ANCA-associated vasculitis.

Comprehensive Clinical Nephrology. Fifth Edition 2015
ENFERMEDAD ANTI
MEMBRANA BASAL
GLOMERULAR
Pregunta…......

• Síndrome Good-Pasture=Riñon-Pulmon = Enfermedad

anti membrana basal glomerular.

¿?
Figure 24-2 Type IV collagen structure. A, The type IV collagen network makes a “chicken w
genes, COL4A1 to COL4A6, encode type IV collagen monomers α1 to α6. These associate in two
terminal domains of α3:α4:α5 shown in C, to form three recognized networks shown in D, α1:α2

Definiciones
is the major constituent of GBM and is a significant component of alveolar basement membrane and
skin, esophagus, and other locations.

Anti–Glomerular Basement Membrane (GB

Term Definition
Pulmonary renal syndrome Renal and respiratory failure
Goodpasture syndrome RPGN and alveolar hemorrhage
Anti-GBM disease Disease associated with antibodies specific for (any)
components of GBM
Goodpasture disease Disease associated with autoantibodies specific for α3(IV)NC1
May include RPGN, lung hemorrhage, or both
Alport syndrome Glomerulonephritis associated with anti-GBM antibodies
post-transplant developing after renal transplantation in Alport syndrome
anti-GBM disease patients

Table 24-1 Definition of terms associated with anti-GBM disease and Goodpasture synd

Comprehensive Clinical Nephrology. Fifth Edition 2015

 1 caso por cada 2 millones por año

Responsable de 1-5% de las GMN

Responsable de 10-20% GMN con semilunas

Más común Europeos Caucásicos

Mayor pico de incidencia 3ª y 6ª década

Hemorragia pulmonar más común en hombres

jóvenes

Enfermedad renal aislada más común en edades

avanzadas

Factores ambientales
 Factores predisponentes asociados
Eventos que probablemente producen respuesta autoinmune
Vasculitis de pequeños vasos afectando al glomérulo
Nefropatía Membranosa
Litotripsia
Obstrucción urinaria
Precipitantes de hemorragia pulmonar
Fumadores de cigarros
Exposición a hidrocarburos
Infección pulmonar
Sobrecarga de volumen
Manifestaciones Clínicas
Ø Fiebre
Ø Malestar general
Ø Pérdida de peso
Ø Artralgias
Ø GMN Rápidamente progresiva
Ø Hemorragia pulmonar
ØAnemia
Hemorragia pulmonar
ØSe presenta en el 70% de los casos y en ocasiones
precede la enfermedad renal por meses o años.

ØLa presencia de hemoptisis no se correlaciona con la

cantidad de hemorragia pulmonar.

Ø Ocurre casi exclusivamente en fumadores.

ØPuede ser precipitada por infecciones o sobrecarga de volumen.
- Palidez
Difusión de monóxido de
- Dificultad respiratoria
carbono incrementada
- Estertores
(DLCO2)
- Signos de Consolidación
Manifestaciones Renales
Ø GMN rápidamente progresiva
Ø Hematuria macroscópica con formación de cilindros
hemáticos
Ø Hematuria con dolor lumbar
Ø Proteinuria subnefrótica (< 3g/24hr)
Ø Falla renal progresiva à Oliguria
ØPeor pronóstico
ØSobrecarga de volumen
ØSobreinfección pulmonar
Comprehensive Clinical Nephrology. Fifth Edition 2015
Comprehensive Clinical Nephrology. Fifth Edition 2015
• Anticuerpos anti-MBG
• Dos epítopes residuos 17-31 y 127-141 del α3(IV)NC1 de la
colágena tipo IV

• Biopsia renal
• Microscopía electrónica
• inmunofluorescencia
Biopsia Renal

Expansión mesangial
e hipercelularidad Formación de
semilunas compuesta
por células epiteliales
Glomerulonefritis focal parietales
Nefritis Intersticial,
y segmentaria con cicatrización y ERC
infiltración de
leucocitos Destrucción de la MBG
(Mismo estadio de
evolución)
Necrosis segmentaria
con ruptura de MBG
Inmunohistoquímica

Depósitos lineales de inmunoglobulina a lo largo de la

Ø
MBG

Ø Usualmente IgG
Ø En ocasiones (10-15%) con IgA o IgM, raramente IgA sola

Ø Depósitos lineales de C3 en el 75% de las biopsias

Membrane Disease and Goodpasture Disease
A 281

A B
Figure 24-5 Renal biopsy in Goodpasture disease. A, Glom
a patient with Goodpasture disease showing a recent, mostly c
cent. B, Direct immunofluorescence study showing ribbon-like lin
tion of IgG along the glomerular basement membrane. The glom
is slightly compressed by cellularClinical
Comprehensive proliferation
Nephrology.(exhibiting no imm
Fifth Edition 2015
cence), forming a crescent (arrows). (Courtesy Dr. Richard Herriot
 Tratamiento
Iniciar inmunosupresión con corticosteroides + plasmaféresis
excepto en aquellos dependientes de diálisis y con 100% de
semilunas (1B)

Iniciar tratamiento una vez se haya confirmado el diagnóstico.

Si el diagnóstico es altamente sugestivo iniciar dosis alta de
corticosteroides y plasmaféresis mientras se confirma (NG)

Se recomienda no mantener terapia de inmunosupresión (NG)

Diferir el trasplante renal hasta que los anticuerpos anti-MBG

se encuentren indetectables por un mínimo de 6 meses
Kidney International Supplements (2012) 13, 233–242
Kidney International Supplements (2012) 13, 233–242
Predictores de sobrevida renal
ØCreatinina sérica a la presentación

ØNecesidad de diálisis a la presentación

ØPorcentaje de semilunas
Ø Recurrencia hasta en un 50%

Ø Por lo general no lleva a pérdida del injerto renal

Ø Tratamiento a base de PF, CF, PD

Ø La misma inmunosupresión mantiene niveles bajos de

anticuerpos