GN Flashcards
FSGS causes?
idiopathic
Familial: NPHS1 (nephrin), NPHS2 (podocin), WT1
Infection: HIV, B19, SV40, CMV
Drug induced: Pamidronate, Sirolimus, heroin, interferon, Lithium, anabolic steroid, TKI
reduced renal mass: unilateral renal agenesis, oligomeganephroia, VLBW, renal dysplasia, reflux nephropathy, CAN, sequela to cortical necrosis, advanced renal disease
normal renal mass: HT, RAS, obesity, CRHD, sickle cell
FSGS sym?
HT, microhematuria, proteinuria (non selective), occ glucouria, aminoaciduria, PO4uria, conc defect
FSGS subtypes?
- NOS: accumulation of ECM that occlude glom capillary, forming discrete segmental solidifications
IF shows IgM, C3 - perihilar: SS and hyalinosis at vascular pole, usually in 2nd FSGS
- cellular: segmental endocapillary hypercellularity, usually 1st FSGS
- collapsing: at least 1 segmental or global collapse, prominent IFTA, commonly by HIV, B19, lupus podocytopathy, hemophagocytic syndrome, IF therapy, TKI pamidronate
- tip: adhesion to pole
- diffuse mesangial hypercellularity, IF IgM, C3 EM extensive foot process effacement; exclusively no children
C1qN: dominant or codominant C1q stain with LM FSGS or MCD like, need to exclude LN
Diff 1st and 2nd FSGS?
- HIV: tubular microcyst, EM tubuloreticular inclusion
- adaptive: glomerulomegaly, perihilar lesion, EM foot process effacement tends to be mild
- loss of renal mass: background global GS, IFTA, arteriosclerosis
- SCD: capillary congestion by sickled erythrocyte, double contour of GBM
FSGS prognosis?
some spontaneously remit, unresponsive case to ESRD in 5 - 20 years
worst for collapse, best for tip, NOS an cellular middle
FSGS Tx?
subnephrotic: BP < 125 / 75, ACEI, statin, low protein
nephrotic: + Pred 1mg/kg/d x 4 - 16wks then taper over 6m
SR or CI to steroid: CsA 3-5mg/kg/d x 4 - 6m, FK 2-4 bd x 4-6m, CYC 2mg/kg/d x 2-4m, MMF 1-1.5g bd x 4-6m
? RTX, Abatacept, ACTH
MN patho features?
LM: thickening of glom capillary wall, spike in silver stain
IF: diffuse finely granular IC IgG (IgG4, if other Ig suggest LN / 2nd cause) and EDD in subepithelial space, C3 common, C1q suggest LN, PLA2R suggest 1st, mesangial Ig present suggest 2nd
EM: subepithelial deposit without subendothelial
MN causes?
Anti PLA2R
Anti THSD7A
Autoimmune: Class V LN, uncommon RA, autoimmune thyroid, IgG4, Anti GBM, ANCA
Infection: HBV, common HCV, HIV, syphilis, schistosomiasis
malignancy: solid tumor, uncommon NHL, CLL, melanoma
Drug: NSAID, PPI, uncommon Hg, gold, D penicillamine
Other: sarcoidosis, GVHD, post transplant
MN typical age and sex?
M:F 2:1, peak 40s - 50s
MN features?
nephrotic, microscopic hematuria common but RBC cast rare, 10% HT, Cr n
MN Ix?
BP, RFT, urinalysis, 24hr uP, LDL, Anti PLA2R, HBV,HCV, ANA, dsDNA, C3, C4
doppler / MRA / CTA if frankl pain hematuria AKI
Anti GBM and ANCA if active urine
cancer screening if > 50y/o
NS ddx
DM, MCN, FSGS, MN, MPGN (IC or C3), amyloid / LCDD, LN
MN Tx?
BP 125 / 75 with ACEI
statin
low protein diet
anticoagulate if Alb < 25
immunosuppresant if uPCR > 4 without 50% decline over 6m despite ACEI (unless disabling or llife threatening sym or Cr rise 30% over 12m after r/o RVT / crescentic variant / AIN (or 3m if heavy NS >8g)
- Ponticelli: MP 1g x 3 days then pred 0.5mg/kg/d for 1,3,5m; CYC 2mg/kd/d 2,4,6m
- CNI: CsA 3.5-5mg/kg/d + 0.15mg/kg/d Pred x 6m, or FK 0.05-0.075mg/kg/d x 6m
? RTX / ACTH
Diff TTP and HUS?
TTP more severe low plt and less severe AKI
HUS causes?
typical:
- Shiga toxin bacteria (STE Coli, shigella)
- Strep pneumoniae (neuraminidase related)
Atypical:
- familial: CFH, C3, MCP, THBD, CFB, CHF / CHFR hybrid, DGKE
- sporadic
- idiopathic
- pregnancy related / HELLP
- Transplant
TTP cause?
congenital: homozygous / compound heterozygous mutation in ADAMTS13
Acquired: Anti ADAMTS13 AutoAb
TMA causes?
HUS / TTP Cobalamin C deficiency (MMACHC mutation) Drug induced: Ticlopidine and plavix: Anti ADAMTS13 BM / HSC transplant Malignancy HIV SLE, APS malignant HT scleroderma
TTP pentad?
fever, MAHA, fever, CNS AKI
Diff TMA from DIC?
normal PT, APTT, fibrinogen, coagulation factor
MIDD secondary cause?
MM, waldenstrom, CLL, NHL
MIDD sym?
hematuria, proteinuria may be NS, CKD or RPGN, hepatosplenomegaly, CHf, arrhythmia, neuropathy, GI upset, lung nodules, arthropathy
MIDD patho features?
eosinophilic tubular lesions, refractile, PAS+ ribbon like
or nodular GS
cresecent possible
arterial and ptc can have PAS+ deposit
IF mainly kappa
EM coarsely / fine granular EDD in tubular, BM or subendothial in GBM
MIDD Tx?
underlying cause
Melphalan +/- ASCT
Diff amyloid, fibrillary and Immunotactoid in patho?
congo red only in amyloid
size of deposit: amyloid 8 - 15nm, FGN 12-22, IGN > 30
alignment of deposit: only IGN are parallel
Ig: Amyloid LC lambda, FGN polychonal IgG4, IGN monoclonal IgGk or IgGL
extrarenal: amyloid systemic, FGN lung hemorrhage,
Asso with other disease: amyloid: MM, FGN: MM, IBD, SLE, IGN NHL, CLL
Tx: amyloid: mephalan + dexa, FGN steroid+/- CYC, IGN treat PLD
SLE Dx?
SLICC ACR Criteria: 4 of following, at least 1 clinical and 1 immunological criteria OR biopsy proven LN with ANA / dsDNA+
Clinical: acute / subacute cutaneous lupus, chronic cutaneous lupus, non scarring alopecia, oral / nasal ulcer, synovitis > 2 joints, serositis, renal disease (RBC cast / uPCR > 0.5g/d), neurological disorder, hemolytic anaemia, leukppenia OR lymphopenia, thrombocytopenia
Immunological criteria: ANA, dsDNA, APAb+, low C3 / C4, DAT+ without hemolytic anaemia,
Drug induced SLE?
procainamide, hydralazine, quinidine, Anti TNF
patho in LN?
I: normal LM, mesangial deposit in IF
II: LM mesangial hypercellularity
III: LM endocapillary or extracapillary GN in < 50% glom
IV: same as III with > 50%
V: GBM thickening with subepitheliam and mesangial IC
IV 90% sclersed
LN Tx?
III or IV:
PRed 0.5 - 1mg/kg/d titrate down in 6-12m +/- MP 1g 1-3days
NIH regime: IV CYC 0.5-1g/m2 monthly x 6
Euro-Lupus: IV CYC 500mg, Q2weeks x 3 months
PO CYC: 1-1.5mg/kd/d (Max 150mg/d) x 3 months
MMF up to 3g/d x 6m
If refractory: RITUXILUP: RTX 1g x 2,
FK / CsA, IVIG, TPE
? Abatacept CTLA4 fusion protein
maintainence: MAINTAIN: MMF 1-2g/d or AZA 1-2.5mg/kd/d or CsA 2.5-4mg/kd/d or FK to trough 4-6ng/ml
V and NS / AKI / persistently < 1g despite ACEI:
MMF 2-3g/d or AZA 1-2.5mg/kg/d +/- steroid x 6m
Alt use IV CYC 0.5-1g/,2 monthly x 6 / CsA 4-6mg/d x 12m / FK 0.1-0.2mg/kd/d x 12 m
CR / PR LN Def?
CR: < 0.5g/d proteinuria with no glom hematuria / RBC cast, normal GFR
PR: 50% reduction in proteinuria in subnephrotic range, stable GFR
what is C1q nephropathy
C1q predom in IF
can be MCN or FSGS spectrum
to r/o SLE
IRGN Tx?
Treat underlying infection
MP if extensive crescent or severe RPGN
type of cryoglobulemic GN?
I: monoclonal Ig - M>G>A>BJP: MM, CLL, Waldenstrom
II: mixed cryoglobulin with monoclonal Ig - M/G»_space; G/G: infection HCV, Sjogren, CLL, lymphoma)
III: Mixed polyclonal - M/G: Infection (HCV / HBV), SLE, RA, vasculitis, malignancy
Cryoglobulinemic GN sym?
palpable non puruitic pupura, arthralgia (not arthritis), PN, AKI
CHF, digital necrosis, lung infiltrate, mesenteric ischemica
type I usually asymptomatic
Ix for cryoglobulinemic GN?
low C3 with C3 normal or mildly low, RF+, 40% type II cryo -ve
cryoglobulinemic GN patho?
MPGN 80%, more macrophage than normal poliferative GN, intraluminal thrombi possible,
IF diffuse IgM
EM subendothelial deposit ‘fingerprint pattern of cryo[recipitate
Cryoglobulinmic GN Tx?
RP or organ threatening: MP + CYC / RTX
life threatening (lung hemorrhage, hyperviscosity) should have TPE
can IC first before treating HCV, but HIV / HBV should treat with antiviral first
MPGN type?
type I: subendothelial + mesangial
type II: intramembranous EDD + mesangial
type III: mesangial + subendothelial + subepithelial
Mayo clinic classification:
IC: infection HBV / HCV, IE, shunt, abscess, leprosy, meningiococcal, mycoplasma, malaria, haanta, schistsomiasis; autoimmune: SLe, sjogren, RA, PSC; neoplastic: monoclonal gammopathy
Complement related: C3 / DDD, due to CFH, CHI or C3NF
Non IC / complement: healing HUS / TTP, APS, POEMS, TMA, SCA, post transplant
Idiopathic
MPGN IgM predom causes?
Viral related, or RA / Sjrogren
usually IgG3 without LC restriction
MPGN Ix?
hepatitis serology, SPE, Ig pattern, FLC, septic workup, Echo
IF IgG + C3 ddx?
MPGN, MN, IRGN, CryoGN
IgAN Tx?
< 1g/d proteinuria: ACEI / ARB, BP control 130 / 70, statin, fish oil
> 1g/d despite ACEI x 6m and GFR > 60: 6m steroid
German STOP IgAN
Chinese TESTING
MMF in Chinese population, CsA maybe tried
Manno: Pred 0.8-1mg/kg/d x 2 months then reduce by 0.2mg/kg/d for next 4 months
Pozzi: MP 1g x 3d at month 1,3,5, followed by 0.5mg/kg/d alt day x 6m
IgAN association?
Rheumat: RA / AS GI: celiac disease hepatic: cirrhosis lung: sarcoid skin: dermatitis, herpetiformis Infection: HIV, HBV
IgAN Patho classification?
Oxford classification: MEST Mesangial hypercellulity Endocapillary hypecellularity Segmental sclerosis TI inflammation
Ddx of IgA in renal biopsy?
IgA / IgAV LN Alcoholic liver disease IgA monoclonal gammopathy IgA dominant SA associated GN
PCKD USG criteria
With FHx PKD1 (Ravine’s):
< 30, total 2 cyst
30 - 60, 2 in each kidney
> 60, 4 in each kidney
With FHx PKD unknown gene (Revised unified diagnostic criteria):
< 40, total 3 cyst
40 - 60, 2 in each kidney
> 60, 4 in each kidney
Rule out:
< 30/40: need MRI < 5 cyst
30 - 40: no renal cyst
> 40: 1 or 0 renal cyst
Without FHx:
> 10 cyst in each kidney
PCKD ddx
TSC, ARPKD, VNL, MCKD
PCKD prognostic factor?
Pro PKD: early HT / uro symptoms, truncating mutation / PKD2
TKV
PCKD association?
IC aneurysm PLD MVP diverticulum cervicocephalic / thoracic artery dissection
PCKD Tx:
fluid intake > 3L to keep Uosm < 250
Na restriction
MDRD: BP control ACEI MAP < 92
V2RA (SE polyuria , dLFT, high urate): - if Mayo classification 1C-E, - 18 - 55y/o with GFR 25 - 65 - PRO PKD > 6 kidney length > 16.5 TKV > 750ml
ALADIN: octreotide
Alport MOI?
80% XL, 15% AR, 5% AD
PCKD Comp?
cystic infection: septrin / FQ, aspirate if persistent
hemorrhage: conservative
Frank pain ddx: stone, hemorrhage, infection, tumor
stone: K citrate
PLD: avoid alcohol, caffine, OCP, ERT, somatostatin, H2RA
Aneurysm: monitor if < 5mm, surgery if > 5mm
alport cause?
XLAS: COL4A5 mutation
ARAS: COL4A3 / COL4A4
ADAS: COL4A3 / COL4A4 heterozygous
alport patho?
LM: mesangial hypercellularity, FSGS / IFTA
EM: variable thickening, thinning, lamellation of GBM, spliting of lamina densa
IF:
XLAS: no a3/a4/a5, a1/a2 normal
ARAS: GBM no a3/a4/a5, a5/a6 present in bowmen capsule / distal TBM
ADAS: normal staining
alport sym
hematuria, proteinuria
SNHL
anterior lenticonus, maculopathy, corneal endothelial vesicles
esophageal / tracheobronchial leiomyomatosis
clitoral hypertrophy
alport Tx
ACEI for proteinuria
Thin GBM dx?
GBM thickness < 250nm
Fabry cause?
alpha galactosidase A deficiency
Fabry sym?
arcoparasthesia ESRD MI / CVA autonomic: hypodidrosis, GI dysmotility skin: angiokeratoma at LL eye: verticulata (whitish discoloration radiation from center to cornea) lung: obstructive
Urine oval fat body, maltese cross configuration
fabry patho:
glomerular epithelial glycosphingolipid depositon / FSGS
EM lysosomal inclusion in epithelial
fabry dx?
male: a-galactosidase activity < 15%
female: genetic study
fabry Tx?
ERT
MCN Tx?
Pred 1mg/kg/d 4 - 16wks, titrate down over 6 months
if SR: rebiopsy
if FR / SD: CYC 2mg/kg/d x 3m or IV CYC 0.5-1g/m2
or CsA 4-6mg/kg/d air trough 50 - 150 x 1 year
MMF
RTX 1g x 2
stone Ix?
Hx: onset, hyperCa, gout, drug, UTI, FHx P/E: gouty tophi, RFT, CaPO4, PTH, Urate urine R/M, pH, biochem USG / KUB
stone urine biochem
Vol: 2-2.5 Ca < 0.1mmol/kg Oxalate < 0.36 urate < 4.5 (M) / 4.7 (F) citrate > 17 Ng < 2g PO4 < 35 cystine < 1.04 (usually 0.13)
stone Tx?
general: fluid > 2L Na restriction < 2g moderate protein intake moderate Ca diet
Oxalate stone:
- high UCa: thiazide, treat hyperCa
- high oxalate:
r/o primary hyperoxaluria (>0.7, can cause CMP, BM supp, CKD)
r/o enteric hyperoxaluria (Crohn, celiac, chronic pancreatitis, short bowel, post bariatric)
- hypocitrate (due to hypoK, metabolic acidosis, hypoMg, azetozolamide): K citrate
- RTA: K citrate
Urate stone:
- urine alkalinzation till urine pH > 6.5
- allopurinol
- acetozolamide if hyperK
Struvite stone:
- treat bacteruria till 3m sterile, remove stone
urease ihibitor: aceohydroxaic acid
chemolysis
Cystine stone:
urine alkalinzation > 7.5
tiopronin, D penicillamine
captopril
primary hyperoxaluria cause?
type 1: Alanine glyoxalate aminotransferase inactivation
type 2: impaired glyoxalate to glycolate
type 3
primary hyperoxaluria Tx?
pyridoxine, urine alkalinzation, citrate, Mg, orthophosphate
nephrocalcinosis cause?
medullary:
- hyperCa, hyperPTH
- Drug: acetozolamide, amphoB
- tubular: dRTA
- PCKD
cortical: cortical necrosis rejection GN TB Trauma
TTP Tx?
TPE
Pred ? 200mg, to 60mg/day then 5mg reduction per week
IVIG
RTX 375mg/m2/wk
RVH causes?
FMD
artherosclerotic
takayasu
coarctation and middle aortic syndrome
RVH Dx?
doppler PSV > 200
CT / MRA
RVH Tx?
FMD: balloon angioplasty artherosclerotic: ASTRAL 2009 STAR 2009 CORAL 2009 BP control / ACEI first, revascularization if fail
indication for revascularization in RVH?
Worsening kidney function in ischemic renal diease
uncontrolled HT
intolerance to media therapy
flash APO
RVT causes?
malignancy: tumor invasion NS: LN / MN complication of IVC / PICC line pyelonephritis, pancreatitis IBD inflammatory aortic aneurysm hypercoagulable state: APS, Factor V leiden, AT3 deficiency, Protein C/ S OCP high Plt / Hct post transplant surgicla compression pregnancy Behcet Bidd Chiari
RAT cause?
prothrombotic:
transplant, malignancy, APS, vascularitis, TTP, rejection
embolism:
AF. valvular, paradoxical embolism, cholesterol embolism, atheroemboli
ANCA AV TPE indication?
Anti GBM+
Cr > 350 or RRT dependent
lung hemorrhage
MEPEX: may enhance renal recovery
PEXIVAS trial: no different in death / ESRD
ANCA induction therapy?
MP 1g x 3 days, then 1mg/kg/d x 3-4m
+ IV CYC 0.5 - 0.75g/m2 monthly x 3m
or + PO CYC 2mg/kg/d x 3-6m
or + RTX 375mg/m2 x 4 week (RAVE vs PO CYC, RITUXVAS vs IV CYC
ANCA maintenance
Aza 2mg/kg/d MMF 1-2g/d MTX 0.3mg/kg/week if GFR > 60 RTX Q6 months septrin if upper airway disease
cast nephropathy Tx?
treat hyperCa
IVF to achieve 3L/d UO
bortezomib based chemo (CyBorD)
TPE or HCO controversal (EULITE: not useful)
AKI / CKD in HIV?
AKI:
Pre renal
Renal: ATN (sepsis, medication, pigment), TMA, HIV related GN (IgAN, MPGN, Cryoglobulimic, LN like, IRGN), AIN
Post renal
CKD:
HIVAN: Collapsing FSGS
ARTAN: AIN, crystaluria, fanconi
other causes: HT, DM
Cystinuria type?
AR
Type I • Obligate heterozygote Type I • Normal aminoaciduria • Associate with 2p21 deletion syndrome, hypotonia-cystinuria syndrome (HCS) & atypical HCS
- Type II and III
- Hyperexcretion of dibasic amino acid
- Very infrequently formation of cystine stones
Type A – Patient with 2 mutations of SLC3A1 gene
• Type B – Patient with 2 mutations of SLC7A9 gene
• Type AB – Patient with 1 mutation on both SLC3A1 and SLC7A9 genes
Cystinuria Tx?
low Na low protein high fluid
urine alkalinzation > pH 7
penicillinamine, Tioponin
Captopril
TTP Tx?
TPE
steroid
RTX
Caplacizumab
Drug induced TMA?
CNI, mTOR
Septrin
Quinine
Anti cancer
AIN causes?
Drug: beta lactam, sulfonamide, FQ, fibampicin, NSAID, PPI, diuretics, phenytoid, allopurinol, HARRT, TKI, ifosfamide, PD1, CTLA4, Aspirin
Infection: campylobacter, GNB, CMV, EBV, HIV, Brucella, toxoplasmosis, mycoplasma, chamydia
Systemic: sarcoidosis, Sjogren, SLE, IgG4, cryoglobulin
Malignancy: leukemia / lymphoma
TINU
AIN sym?
fever, MP rash, arthalgia, eosinophilia, hemolysis, hepatitis, high IgE,
granulomatous AIN ddx?
Infection (EBV, toxoplasmosis, Salmonella), sarcoidosis, Sjogren, GPA
AIN Ix?
eosinophiuria
gallium scan
AIN Tx?
Pred 1mg/kg/d x 4-6 wks if on RRT or RFT fail to improve after 1 week
cholesterol emboli patho?
needle-like or slit-like clefts in arterial
MCKD MOI?
AD
MCKD gene?
Uromodulin
REN
Mucin1
HNF1B
MCKD features?
strong family history
early onset gout
USG and urine normal
renal bx TIN, Eosinophilic “fluffy“/Fibrillar inclusions in tubule, EM shows TBM lamellation
MCKD Tx?
allopurinol
renal transplant
drug induced ANCA
hydralazine
PTU / carbimazole
minocycline, penacillamine
drug induced lupus
procainamide
hydralazine
penicillamine
