GlomerulonephritisGlomerulonephritis: Practical Approach: Practical Approachรศ.นพ. เถลิงศักดิ์ กาญจนบุษย

สาขาวิชาโรคไต ภาควิชาอายุรศาสตรหัวหนาศนูยวิจัยโรคไตและความผิดปกติทางเมตาบอลิซึม

จุฬาลงกรณมหาวิทยาลัย

JCMS 2009

Afferent arterioleEfferent arteriole

Endothelium

Podocyte

Pedicle

Bowman’s capsule

PCT

Endothelium

ก ข

ง

ก

ขค ง

ข

จ

GLOMERULAR GLOMERULAR DISEASEDISEASE

HematuriaHematuriaDysmorphic

Acanthocyte

RBC cast

ProteinuriaProteinuriaProteinuria > 2 gm/day

SaltSalt--water retentionwater retentionEdema

HT

GFR GFR ↓↓Azotemia

Oliguria

Helen Liapis, 2002

Endothelial cellEndotheliosisTMA/ Anti‐VEGF Ab

GBMLaminin 521 defect

PodocyteMost glomerulopathies

Loss perm-selectivity

Proteinuria

Defect Area

ก ก

ข

ค

ง

จ

ก

ฉ

จ

ง

ค

ข

AzotemiaOliguria

PPGCGC

PPTT

KKUFUF

GFR = snGFR x Nephron

snGFR = (PGC-PT) x KUF

MechanismGFR

Reabsorption

ManifestationsEdemaHT

Glomerular hematuria

Proteinuria usually < 3 gm/day

Less salt retention

RF over days/week; progessive

Glomerular hematuria

Proteinuria usually < 3 gm/day

Salt retention

Oliguria, Azotemia

Abrupt, usually self‐ limiting

AGN

RPGN

DPGN

IC mediatedAnti-GBMPauci-immune

GBM rupture

Acute self-limited inflammation

Proteinuria ≥ 3.5 gm/day/1.73 m2 ; UPCR > 3 gm/day + Lipiduria

Edema

Hyperlipidemia

Hypercoagulation

HT

Proteinuria > 2 gm/day

Renal insufficiency

Fit in CRF criteria

CGN

NS

IC mediatedNon-IC mediatedNon-immune

MCDFSGS IgM nephropathyMPGNMN

Progressive disease: ongoing, sclerosis

Podocyte injury, GBM charge loss

Gross hematuria

Hematuria > 2/HP

Proteinuria 0.15‐3.0

gm/day ±

Hematuria > 2/HP

Asymptomatic

Macroscopic hematuria

IgAStoneAIN&CTINLoin painhematuria

FSGS IgMMPGNMNIgA, Alport’sIC mediated

IgATBM/Alport’sPostinfectiousPost-GN

Less severe injury

GBM gaps

Case 1

A 43 year old female presented with 1 weeks of progressive facial edema, orthopnea, and PND . A day before admit, she developed sudden gross hematuria. PE reveals afebrile, BP 140/92 mm.Hg, and generalized edema. Laboratory evaluation reveals BUN 49 mg/dL, Cr 1.5 mg/dL, hypoalbuminemia, hyperkalemic wide-gap MAUrinalysis revealed sp.gr. 1.020, 2+ urinary protein, RBC 80-100/HP, WBC 5-7/HP.

1) Which glomerular syndrome is fit for the patient? 2) What additional laboratory tests should be performed in

this patient ?

5. Asymptomatic proteinuria / hematuria

4. Nephrotic syndrome

3. Chronic GN

2. Rapidly progressive GN

1. Acute GN

Nephritis

Nephrosis

Etiologies of Acute Glomerulonephritis

Low ComplementPrimary

Acute PSGN (>90%)MPGN

Type I (50‐80%)Type II (80‐90%)

SecondarySLE

Focal (75%)Diffuse (90%)

Acute‐subacute IE (90%)Visceral abscess“Shunt” nephritisCryoglobulinemia (85%)

Normal ComplementPrimary

IgA nephropathyIdiopathic CGN

Anti‐GBMPauci‐immune

SecondaryHypersensitivity vasculitisWGHSPGoodpasture syndrome

PSAGN, HUS

Infection related

MPGN II

‐ C3, CH50

+ C3 nephritic factor

Alternative

MPGN I

LN III, IV

‐ C3, C4, CH50Classical

Glomerular diseaseComplement changes

Pathway affected

C1q is also low↓C3, ± N C4Severe malnutrition

C1q levels are normal↓C3, ↓C4Severe liver disease

20‐40% of normals have one or two C4 null genes; higher incidence found in SLE

N C3, ±↓C4Inherited C4 deficiency

Subsides in a few days↓C3, ↓C4Acute pancreatitis

~50% of cases↓C3, ± ↓C4HUS/TTP

Esp. with shock↓C3, ↓C4Severe sepsis

Usually transient, mainly during acute embolism

↓C3, ± ↓C4Atheroembolism

CommentC’ levelsDisease

Case 1

A 43 year old female presented with 1 weeks of progressive facial edema, orthopnea, and PND . A day before admit, she developed sudden gross hematuria. PE reveals afebrile, BP 140/92 mm.Hg, and generalized edema. Laboratory evaluation reveals BUN 49 mg/dL, Cr 1.5 mg/dL, hypoalbuminemia, hyperkalemic wide-gap MAUrinalysis revealed sp.gr. 1.020, 2+ urinary protein, RBC 80-100/HP, WBC 5-7/HP.Further investigations found low C3 but normal C4, negative viral serologies, and UPCI 2.2

1) What is your final conclusion?2) How to confirm the diagnosis?3) How to manage the patient?

+

+++++Diffuse proliferative GN

+++++Crescentic GN

++++Acute PSGN

+++++MPGN

++++Mesangioproliferative GN

+++++Fibrillary GN

+++++FSGS

+++++MN

‐++++MCD

Nephritic FeaturesNephrotic Features

25<1Early mortality8325-40Azotemia204Nephrotic proteinuria43<5Dyspnea/heart failure5810-50Oliguria8360-80Hypertension7590Edema9280Proteinuria100100Hematuria

Elderly (%)Children (%)

Case 1

A 43 year old female presented with 1 weeks of progressive facial edema, orthopnea, and PND . A day before admit, she developed sudden gross hematuria. PE reveals afebrile, BP 140/92 mm.Hg, and generalized edema. Laboratory evaluation reveals BUN 49 mg/dL, Cr 1.5 mg/dL, hypoalbuminemia, hyperkalemic wide-gap MAUrinalysis revealed sp.gr. 1.020, 2+ urinary protein, RBC 80-100/HP, WBC 5-7/HP.Further investigations found low C3 but normal C4, negative viral serologies, and UPCI 2.2

1) What is your final conclusion?2) How to confirm the diagnosis?3) How to manage the patient?

ASO ~ 75% ASO ~ 75% AntiAnti--DNaseDNase B 90%B 90%AHA more sensitive for AHA more sensitive for pyodermapyodermaAntiAnti--GAPDH (GAPDH (NPlrNPlr))AntiAnti--SpeBSpeB/ / ZymogenZymogenDemonstrates streptococcal infection, but Demonstrates streptococcal infection, but does not predict development or severity does not predict development or severity of GNof GN

Case 1

A 43 year old female presented with 1 weeks of progressive facial edema, orthopnea, and PND . A day before admit, she developed sudden gross hematuria. PE reveals afebrile, BP 140/92 mm.Hg, and generalized edema. Laboratory evaluation reveals BUN 49 mg/dL, Cr 1.5 mg/dL, hypoalbuminemia, hyperkalemic wide-gap MAUrinalysis revealed sp.gr. 1.020, 2+ urinary protein, RBC 80-100/HP, WBC 5-7/HP.Further investigations found low C3 but normal C4, negative viral serologies, and UPCI 2.2

1) What is your final conclusion?2) How to confirm the diagnosis?3) How to manage the patient?

Proteinuria: 6 monthsHematuria: 12 months

Long term

Renal failure: 2 weeksHypertension or gross hematuria: 3 weeksLow C3: 6 weeks

Short term

Delayed resolution

Low antistreptococcal titerNormal C3Low C1q, C2 or C4

Lab

Short latent period Nephrotic syndrome or RPGNAnuriaMultiorgan involvement

Clinical

Atypical presentation

Get rid source

Corticosteroid & immunosuppressive agent

Some organisms still progress in spite of effective treatmentStaphylococcus aureusBrucellosisQuartan malariaSchistosomiasis

Case 2

A 43 year old year is found to have Scr of 1.6 mg/dland BUN of 32 mg/dl on her annual check up. Her urinalysis shows 3-4+ protein, a few rbc’s with some dysmorphic but no rbc casts. She is found to have 3.8 g proteinuria daily. PE reveals a BP 160/92 mm.Hg, and no edema. Further laboratory evaluation reveals WBC 50,000 /mm3, a reduced CH50, a borderline C3 level, and a reduced C4 level.

1) What is the differential diagnosis for renal diseases with nephrito-NS?

2) What additional laboratory tests should be performed in this patient ?

Classification of Glomerular Diseases

1o Glomerular Disease(idiopathic; renal‐limited)

MCDFSGSMesangial GN (IgA, IgM)MN MPGNCrescentic GNSclerosing GNUnclassified GN

2o Glomerular Disease(associated with multi‐system

disease)Systemic diseasesSystemic InfectionsVascular diseasesMetabolic & Deposition diseasesHereditary nephropathiesMiscellaneous

Mesangiocapillary GNDeposition diseases

Amyloidosis

Light‐chain deposition diseaseFibrillary GN and Immunotactoid GN

Hereditary disease: Alport’s syndromeSome cases of mesangial, focal and diffused proliferative GN

IgA nephropathy

Post‐infectious GNLupus nephritis

Diabetic nephropathy

Case 2

A 43 year old year is found to have Scr of 1.6 mg/dland BUN of 32 mg/dl on her annual check up. Her urinalysis shows 3-4+ protein, a few rbc’s with some dysmorphic but no rbc casts. She is found to have 3.8 g proteinuria daily. PE reveals a BP 160/92 mm.Hg, and no edema. Further laboratory evaluation reveals WBC 50,000 /mm3, a reduced CH50, a borderline C3 level, and a reduced C4 level.

1) What is the differential diagnosis for renal diseases with nephrito-NS?

2) What additional laboratory tests should be performed in this patient ?

Classification of Cryoglobulinemia

Collagen vascularChronic infections

•SBE•Leprosy•HBV•HCV

HCVHBVLymphoma

Multiple myelomaDysproteinmiasLymphoma

Associated disease

Occ. positivePositiveNegativeRF

pIgGpIgM(IgM – IgG)

pIgGmIgM(IgMk – IgG)

Single mIg (IgMk, IgGk, IgAk )

Ig content

Type IIIType IIType I

HCV

E 2

B B B

Polyclonal RF

t (14,18 )t Bcl 2*

overexpression

Oligoclonal RF

MC type IIIOther autoimmune

disorder

MC type II-IIIMC type II

B cell NHL

Unknown genetic and environmental factor

Clin Exp Rheumatol 2003; 21 (Suppl. 31)S78-S84.

CD 81

Evidence for HCV Virus in EMC

Anti-HCV antibidies (by RIBA) pressent in 91% of 45 pts with EMC(Ferri et al. Infection 1991; 19:417)

HCV RNA detected in 86% of 45 patients with EMC (Ferri et al. Clin Exp Rheumatol 1991; 9:621)

HCV RNA and anti-HCV Ab are concentrated in the cryoglobulins(Agnello et al. NEJM 1992; 327:1490)(Misiani et al. Ann Int Med 1992; 117:573)

Spectrum of HCV-Associated IC Disease

IC Size

MNMPGN ŝCryoglobulins

MPGN ĉCryoglobulins

EMC ĉMPGN

EMC

Case 3

A 66 year old, an accountant, develops cough, arthralgias, malaise, and weight loss. He is normotensive, and has no arthritis or edema. He is found to have a hazy LLLinfiltrate on his chest X-ray, a urinalysis with 2+ proteinuriaand 4+ heme, with many rbc’s and many dysmorphicacanthocytes, a BUN of 25 mg/dl and serum creatinine of 1.8mg/dl, and 24 hour urine shows 2.6 grams albuminuria daily. ANA is positive 1:80, and complement is WNL.

1) What is the differential diagnosis of “renal-pulmonary syndromes” ?

2) Which serologic tests are helpful in this case ?

With pulmonary edemaARF with hypervolemiaSevere cardiac failure

InfectiveSevere bacterial pneumonia (e.g. Legionella) with RFHantavirus infectionOpportunistic infections in the immunocompromised

OthersARDS with RF in multi‐organ failureParaquat poisoningRenal vein/IVC thrombosis with pulmonary emboliDisease associated with Anti‐GBM (20‐40% of cases) Goodpasture’s disease (spontaneous anti‐GBM disease)

Common

Anti-GBM Ab (20-40%)Goodpasture’s disease (spontaneous anti-GBM dis.)

Systemic vasculitis (60-80%)Wegener’s granulomatosisMicroscopic polyangiitisSystemic lupus erythematosusChurg Strauss syndromeHenoch‐SchÖnlein purpuraBehçet’s diseaseEssential mixed cryoglobulinemiaRheumatoid vasculitisDrugs: penicillamine, hydralazine, propylthiouracil

Case 2

A 66 year old, an accountant, develops cough, arthralgias, malaise, and weight loss. He is normotensive, and has no arthritis or edema. He is found to have a hazy LLLinfiltrate on his chest X-ray, a urinalysis with 2+ proteinuriaand 4+ heme, with many rbc’s and many dysmorphicacanthocytes, a BUN of 25 mg/dl and serum creatinine of 1.8mg/dl, and 24 hour urine shows 2.6 grams albuminuria daily. ANA is positive 1:80, and complement is WNL.

1) What is the differential diagnosis of “renal-pulmonary syndromes” ?

2) Which serologic tests are helpful in this case ?

DiagnosisFollow up

Remission: 80% ANCA ‐Relapse: 75% ANCA +No symptom: 1/4 ‐ 1/3 increasing titerLimitation:

ANCA testing represents several testsANCA‐vasculitis represents several diseasesVary in criteria dx of relapse

Predict outcome

99%66%4% (7/195)Hematuria, proteinuria, and Cr < 1.5 mg/dl

97%85%11% (36/311)Hematuria, proteinuria, and Cr 1.5‐3 mg/dl

89%95%30% (147/497)Hematuria, proteinuria, and Cr > 3 mg/dl

65%99%66% (82/124)RPGN

NPV for PI‐CGN

PPV for PI‐CGN

Prevalence of PI‐CGNClinical presentation

Age > 50 yr

Case 4A 29 year old. Female computer processor presents

with fever, lymphadenopathy, and diffuse arthritis of the small hand joints. She is found to have a WBC of 2,800, HCT 22%,platelets 168,000. Urinalysis shows 4+ protein, 20-30 rbc, and rbc casts; ANA 1:1280. A renal biopsy shows DPLN, WHO Class IV.

1) Which tests predict the best prognosis of this patient over the next decade ?

2) What serologic tests are the best guide to immediate therapy of this patient ?

3) If the patient had been taking minocycline for acne, what serologic tests might help in determining whether this is drug related disease ?

4) What medications can produce drug related SLE ? How is the diagnosis established ?

C4(mg/dL)

C3 (mg/dL)

Case 4A 29 year old. Female computer processor presents

with fever, lymphadenopathy, and diffuse arthritis of the small hand joints. She is found to have a WBC of 2,800, HCT 22%,platelets 168,000. Urinalysis shows 4+ protein, 20-30 rbc, and rbc casts; ANA 1:1280. A renal biopsy shows DPLN, WHO Class IV.

1) Which tests predict the best prognosis of this patient over the next decade ?

2) What serologic tests are the best guide to immediate therapy of this patient ?

3) If the patient had been taking minocycline for acne, what serologic tests might help in determining whether this is drug related disease ?

4) What medications can produce drug related SLE ? How is the diagnosis established ?

Clinical AssociationAg Specificity

dsDNA Marker for active disease; titers fluctuate with disease activity

ssDNA Non-specific

Ro/SSA Cutaneous lupus (75%), photosensitivity, neonatal lupus

La/SSB With La, low prevalence of renal disease, neonatal lupus (75%)

Sm Marker for disease; 15-30 % sensitivity, may be asso. with CNS disease

RNP (U1-RNP) MCTD, required for diagnosis; in SLE-mild, non-renal

Phospholipids Hypercoaqulable state in some, no significance in others; thrombocytopenia, latertrimester abortions

Histones >95% in drug-related lupus; present in RA> SLE, systemic sclerosis with pulmonary fibrosis

KU SLE, MCTD (Europeans/Americans): scleroderma/myositis overlap (Japanese)

Homogenous Peripheral

Speckle Nucleolar

DefiniteProcainamideHydralazineDiltiazemMinocyclinePenicillamineINHMethyldopaChlorpromazinePractolol

PossibleAnticonvulsants - phenytoinQuinidineAnti-thyroid drugsSulfonamidesLithiumBeta-blockersNitofurantoinPASCaptoprilInterferon alphaHCTZGlyburideCarbamazepineSulfasalazineHydralazine

Fever, Fever, myalgiasmyalgias, rash, , rash, arthralgiasarthralgias--arthritis, arthritis, serositisserositis, , hemotologichemotologic abnomalitiesabnomalitiesKidney disease and CNS uncommonKidney disease and CNS uncommonAntiAnti--DNA DNA AbAb and low C` uncommonand low C` uncommonSome with renal disease are ANCA + (antiSome with renal disease are ANCA + (anti--MPO + MPO + lactoferinlactoferin))

Clinical feature Spontaneous lupus Drug‐induced lupusUsual age 20‐40 50

Female to male ratio 9:1 1:1

Race All “No blacks”

Acetylation type Slow = Fast Slow

Onset of symptoms Gradual Abrupt

Constitutional symptoms 83 50

Arthralgia and arthritis 90 95

Pleuropericarditis(procainamide)

50 50

Hepatomegaly 25 25

Rash (all types) 74 10‐20

Discoid lesions 20 0

Malar erythema 42 2

Renal diseases 53 5

CNS disease Common Unusual

Immunologic abnormalitiesANA 95 95

LE cells 90 90

Anti‐RNP 40‐50 20

Anti‐Sm 20‐30 Rare

Anti‐DNA 80 Rare

Antihistone 80 90

Complement Reduced Normal

Immune complexes Elevated Normal

Present in > 95% drugPresent in > 95% drug--induced lupusinduced lupusCommon with Common with procainamideprocainamide, , hydralazinehydralazine, , chlorpromazine, chlorpromazine, quinidinequinidineCommon in native SLE ( but with AntiCommon in native SLE ( but with Anti--DNA DNA Abs, AntiAbs, Anti--SmSm AbAb, etc.), etc.)

Etiologies:Etiologies:HydralazineHydralazine

High dose (>200 mg/day High dose (>200 mg/day ±± cumulative > 100 gmcumulative > 100 gmFemaleFemaleSlow hepatic Slow hepatic acetylationacetylationHLAHLA--DR 4DR 4C4 def.C4 def.

MinocyclineMinocyclineANA 92%ANA 92%pp--ANCA 83%ANCA 83% Should not be used in SLE

ManifestationManifestationfrequent present with renalfrequent present with renalAntiAnti--dsDNAdsDNA++AntiAnti--histonehistone: may negative: may negativeHigh titer MPOHigh titer MPOlupuslupus--like, RPGN, PANlike, RPGN, PANMay need aggressive PX +drug withdrawalMay need aggressive PX +drug withdrawal

Case 5A 62 year old female housewife develops periorbital

edema in the AM followed by pedal and ankle edema later in the day, and a 6 kg weight gain. PE shows BP 142/84 mm.Hg, and edema only. Lab shows Urinalysis 4+ protein, 2-3 rbc, few oval fat bodies, BUN 18 mg/dl, creatinine 0.9 mg/dl, glucose 128 mg/dl, plasma albumin 2.4 g/dl, cholesterol 236 mg/dl, and 24 hour urinary protein 10 g/day.

1) Problem list and differential diagnosis?

2) Is the clinical finding related to hyperglycemia?

Problem List

Severe nephrotic syndromeIn an elderlyNew onset of HTMild renal insufficiency

DM

110.60.6Unknown

2.14.45.1Miscellaneous

001.2Congenital glomerulopathies

8.71.10Deposition diseases

8.77.83Post‐infectious GN

4.49.41DN

4.41.11.2LN

6.58.38.5Non‐IgA MesPGN

4.411.723IgAN

4.43.34.2MPGN

10.917.812.1MN

23.926.720FSGS

137.822.4MCD

Age > 60 yrsN = 46(%)

Age 36-60 yrsN = 180 (%)

Age 15-35 yrsN = 175 (%)

Histopathologic diagnosis

ARFHypovolemic

Nephrosarca

Intratubular obstruction by large proteinaceous cast

Renal vein thrombosis

Acute interstitial nephritisNSAIDs, Cox‐2 inhibitorsATBDiuretic

Chronic progressive diseaseSecondary FSGS, MN, MPGN

Assoc. vascular involvementDeposition diseases

APS

TMA (Sclerodema, Endotheliosis)

Nephrito‐NSMPGN

Fibrillary glomerulopathies

Hereditary nephritis (Alport’ssyndrome)

Some cases of mesangial, focal and diffuse proliferativeGN (e.g., LN, IgAN, PIGN)

Generalized edema Reduced GFR < 50 ml/min/1.73 m2

Proteinuria > 5 gm dailyPlasma albuminemia < 2 g/dLHyperlipidemia > 1.5 x UNLR/O other causes of RF, eg. CHF, sepsis

DDx of Severe Nephrotic Syndrome

MCDFSGSCollapsing glomerulopathyMembranous nephropathyDiabetic glomerulosclerosisAmyloidosisLight‐chain‐deposition disease

2) Is the clinical finding related to hyperglycemia?

HT start 2-yr after onset of microalbuminuriaRate 2.7 mmHg/yr

Case 5A 62 year old white female housewife develops

periorbital edema in the AM followed by pedal and ankle edema later in the day, and a 6 kg weight gain in 3 mo. PE shows BP 142/84 mmHg and edema only. Lab shows Urinalysis 4+ protein, 2-3 rbc, few oval fat bodies, BUN 28 mg/dl, creatinine 1.6 mg/dl, glucose 128 mg/dl, plasma albumin 1.9 g/dl, cholesterol 236 mg/dl, and 24 hour urinary protein 10 g/day.

Additional informationbilateral CTS, mild hepatomegaly, normochromic

normocytic anemia

Clinical and lab. Features in AL amyloidosis 474 pts

Initial symptoms

Fatigue 62%

Weight loss 52%

Pain 5%

Purpura 15%

Gross bleeding 3%

Physical finding

Palpable liver 24%

Palpable spleen 5%

Lymphadenopathy 3%

Macroglossia 9%

Kyle, RA, Semin Hematol 1995; 32: 45.

Laboratory findings

Increase plasma cell( BM> 6%) 56%

Anemia (Hb< 10 g/dL) 11%

Serum creatinine> 1.3 mg/dL 45%

Elevated alkaline phosphatase 26%

Hypercalcemia(>11 mg/dL) 2%

Proteinuria( > 1 g/24 hr) 55%

Urine light chain 73%

Ќ chain 23%

ג chain 50%

Syndrome at diagnosis in 229 pts with AL amyloidosis

Syndromes Without myeloma

(182 pts)

With myeloma

(47 pts)Nephrotic syndrome 37% 13%

Carpal tunnel syndrome 21% 38%

Congestive heart failure 23% 23%

Peripheral neuropathy 20% 6%

Orthostatic hypotension 16% 4%

Kyle, RA, Mayo Clin Proc 1983, 58:665

LVH & RVH with sparking appearance, no restrictionEF 60%Mild TR & MR

Echocardiography

Cardiac amyloidosis

ECG Decreased amplitude of the QRS complex in the limb lead,

Pseudoinfarct pattern across the anterior lead

Bone Survey

Case 6

A 48 year old female pharmacist has a history of DVT 4 yrs ago, and a PE 2 years ago. She is found to have an elevated Scr of 1.8 mg/dl, urinalysis 3+ protein 5-10 rbc’s 0 casts. Physical exam shows BP 150/92 mm.Hg, 1+ pedal edema, prominent P2, and livedo reticularis of the legs. 24 hr urinary protein excretion is 1.9 g/day, ANA+ 1:160, anti DNA antibody negative, serum complement WNL; wbc 6,200, HCT 36%, platelets 100,000.

1) What serologic tests might confirm the diagnosis here ?

2) What features in the history might help in the diagnosis ?

3) What other routine laboratory features are useful diagnostically while the definitive serologic tests are pending ?

Quiz) จงใหการวินิจฉัยโรค และบอกชื่อ sign ที่เห็นในรูป ?

TBM disease

Alport’s syndrome

Diffuse EP

GBM rupture

EP+GBM thickening

Mesangial proliferation

TMA

GBM weakness

AGNRPGNNephrito-NS CGNIsolated

Isolated hematuria

Inflammation

March’s disease

Loin pain syndrome ↑ Glomerular PIsolated

hematuria

TransientOrthostaticPhysiologicStress induced

PersistentOverflow Glomerular

FP

EF

Familial Amyloidosis

ADATTR : most commonRenal disease : less common than ALNeuropathy ( Sensori‐motor, ANS )GI : diarrhea, wt. lossNo macroglossiaCardiac involvement : Heart failure uncommon