glomerular diseases , podocytopathies,mpgn,igA,psgn,rpgn,alports

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What are the 6 major presentations of glomerular disease?

1. Asymptomatic 2. Macrohematuria 3. Nephrotic syndrome 4. Nephritic syndrome 5. RPGN 6. CKD/chronic glomerulonephritis.

What are biopsy indications in asymptomatic urine abnormalities?

Proteinuria >500 mg/24 h + microhematuria ≥3 RBC/HPF; OR proteinuria alone >1 g/24 h.

What is the 40/5/1 rule for macrohematuria?

≥40% dysmorphic RBCs; ≥5 acanthocytes; ≥1 RBC cast.

What are the criteria for nephrotic syndrome in adults?

Nephrotic-range proteinuria + hypoalbuminemia <3 g/dL + edema/extravascular edema.

What is nephrotic-range proteinuria in adults?

3.5 g/24 h.

What is nephrotic-range proteinuria in children?

50 mg/kg/day.

What urine protein:creatinine ratio corresponds to nephrotic-range proteinuria?

Adults ≥3000 mg/g; children ≥2000 mg/g.

What are the 3 major components of nephrotic syndrome?

Proteinuria + hypoalbuminemia + edema.

In childhood nephrotic syndrome, is edema predominantly extra- or intravascular?

Extravascular > intravascular.

What causes hypoalbuminemia in nephrotic syndrome?

Urinary loss of albumin with inadequate hepatic compensation.

What is Muehrcke's line associated with?

Hypoalbuminemia.

What is the underfill theory of edema?

Hypoalbuminemia → ↓ capillary oncotic pressure → fluid shifts into interstitium → ↓ effective circulating volume → secondary RAS activation → aldosterone → Na+/water retention.

What is the overfill theory associated with?

Nephritic syndrome.

What mechanism of overfill is mentioned in PSGN?

β-hemolytic streptococci → plasmin → activates ENaC → primary RAS activation → Na+/water retention → intravascular edema.

What is ANP resistance associated with?

Edema in nephrotic syndrome.

What percentage of childhood nephrotic syndrome is due to MCD according to the notes?

85–90%.

What percentage of adult nephrotic syndrome is due to MCD?

10–15%.

What is the typical age of peak presentation of MCD?

2–7 years.

Is MCD more common in boys or girls?

Boys > girls.

What is the classic presentation of MCD?

Nephrotic syndrome without hypertension, AKI or significant microhematuria.

What is the defining podocyte change in MCD?

Effacement of foot processes.

What changes in podocyte proteins contribute to protein leakage in MCD?

↑ CD80 expression and ↑ angiopoietin-like 4 peptide → loss of negative charge → protein leakage.

What type of proteinuria occurs in MCD?

Selective proteinuria—mainly albumin and transferrin.

What is the treatment response of MCD?

Steroid responsive in ~95%; biopsy usually has no role.

What features argue against MCD?

RBC casts, hypertension and renal failure.

What are important secondary causes of MCD?

NSAIDs, interferon-α, gold, atopic conditions, Hodgkin disease, Sézary syndrome, CLL and post-immunization.

What defines steroid-resistant nephrotic syndrome (SRNS) in the notes?

Persistent proteinuria despite a full steroid dose for 4 weeks.

What is an important biopsy indication in a child with SRNS?

Biopsy to look for FSGS.

What genetic form of FSGS is specifically mentioned in SRNS?

Podocin mutation.

What is the treatment of genetic FSGS?

Renal transplantation.

What is the duration of calcineurin inhibitor therapy mentioned for MCD?

6 months; maximum 2 years.

What tacrolimus dose is mentioned?

0.1 mg/kg/day.

What adverse effects of tacrolimus are listed?

Neuropathy, diabetes mellitus and alopecia.

What adverse effects of cyclosporine are listed?

Hirsutism and gingival hyperplasia.

What defines frequently relapsing nephrotic syndrome (FRNS)?

≥2 relapses within 6 months OR ≥4 relapses within 1 year.

What defines steroid-dependent nephrotic syndrome (SDNS)?

≥2 consecutive relapses during steroid tapering or within 14 days after stopping steroids.

Which steroid-sparing drug is preferred for FRNS according to the notes?

Oral cyclophosphamide.

Which drugs are mentioned for steroid-dependent nephrotic syndrome?

Mycophenolate mofetil (MMF) and rituximab.

At what serum albumin level is thrombosis particularly concerning?

What causes the hypercoagulable state in nephrotic syndrome?

Urinary loss of antithrombin III; urinary loss of protein C/S; ↑ platelet aggregation; ↑ fibrinogen; ↓ plasminogen.

What thrombotic complications are mentioned?

Renal vessel thrombosis, CVT and DVT.

What albumin correction target is mentioned?

2 g/dL.

What albumin preparation is mentioned?

20% albumin, 20 g/100 mL; dose 0.5 g/kg.

What other options besides albumin are mentioned?

FFP and egg white.

What is the common cause of death associated with ascites in childhood nephrotic syndrome according to the notes?

Pneumococcal peritonitis.

What is FSGS?

Focal segmental glomerulosclerosis.

What does 'focal' mean histologically?

What does 'segmental' mean?

Only a portion of an involved glomerulus is affected.

What is sclerosis histologically?

Eosinophilic hyaline material obliterating the glomerulus.

What causes secondary FSGS according to the notes?

Pamidronate, anabolic steroids, heroin, sirolimus, dasatinib, IFN-α, HIV, parvovirus B19, EBV, CMV, sickle-cell anemia, obesity and congenital cyanotic heart disease.

What is the 75/25 rule for FSGS?

75% present with nephrotic syndrome; 25% have asymptomatic nephrotic-range proteinuria.

What should NOT be given in secondary FSGS due to diabetes?

Immunosuppression.

Which FSGS variant has the worst prognosis?

Collapsing FSGS.

What is collapsing FSGS associated with?

HIVAN, heroin, IFN-α, parvovirus B19 and pamidronate.

What is the morphology of collapsing FSGS?

Complete collapse of glomeruli with podocyte hypertrophy/pseudocrescents; dilated tubules and microcysts may occur.

What is the treatment sequence for FSGS in the notes?

Steroid → CNI/MMF if resistant → CKD → transplant.

Can FSGS recur after renal transplantation?

Yes—transplant recurrence is possible.

What is the commonest cause of nephrotic syndrome in adults listed?

Membranous nephropathy.

What is the major primary antibody association in membranous nephropathy?

Anti-PLA₂R antibody.

What is the classic LM finding in membranous nephropathy?

Uniform thickening of the glomerular capillary wall/GBM.

What is seen on EM in membranous nephropathy?

Effacement of podocytes + subepithelial deposits + spikes between deposits.

What is the rule of 1/3 in membranous nephropathy?

1/3 spontaneous remission; 1/3 persistent heavy proteinuria with normal kidney function; 1/3 CKD.

What are important secondary causes of membranous nephropathy?

Drugs, infections, autoimmune disease and malignancy.

Which drugs are associated with secondary MN?

Gold, NSAIDs, D-penicillamine, captopril and mercury.

Which infections are associated with MN?

HBV, syphilis and schistosomiasis.

Which malignancy is specifically highlighted?

Solid-organ adenocarcinoma, especially colorectal carcinoma.

What percentage of MN patients have nephrotic syndrome vs asymptomatic disease according to the notes?

70% nephrotic syndrome; 30% asymptomatic microhematuria/proteinuria.

What is the classic LM appearance of MPGN?

Mesangiocapillary proliferation with lobular appearance.

What is Type I MPGN associated with on IF?

IgG + IgM + C3.

What is Type II MPGN also called?

C3 glomerulonephritis.

What is the recurrence rate after transplant for Type I vs Type II MPGN?

Type I: 80%; Type II: 100%.

What is the EM appearance of Type I MPGN?

Train-track/double-contour appearance due to subendothelial + mesangial deposits.

What is the EM finding in Type II/C3 GN?

Intramembranous + mesangial deposits.

What are major secondary causes of MPGN?

Monoclonal gammopathy/malignancy, infections, shunts and autoimmune diseases.

What infections are listed as secondary causes of MPGN?

Hepatitis virus, infective endocarditis, leprosy and quartan malaria.

What autoimmune conditions are listed?

SLE, Sjögren syndrome and scleroderma.

What is IgA nephropathy also called?

Berger disease / Henoch–Schönlein nephritis in the notes.

What is the commonest glomerular disease mentioned?

IgA nephropathy.

Where is polymeric IgA produced?

MALT/mucosa-associated lymphoid tissue.

What happens to polymeric IgA normally?

It is normally cleared by the liver.

What is the characteristic biopsy finding in IgA nephropathy?

Mesangial proliferation with IgA deposition in the mesangium.

What are poor prognostic biopsy findings in IgA nephropathy?

IgA deposits outside mesangium; proliferation other than mesangial; non-IgA deposits; endocapillary hypercellularity; segmental sclerosis; tubular atrophy; crescents/RPGN.

What is the rule of 1/3 for IgA nephropathy?

1/3 spontaneous resolution; 1/3 near-normal RFT/stable course; 1/3 develop CKD.

What is the value of serum C3/C4 in IgA nephropathy according to the notes?

No value.

What is the value of serum IgA in IgA nephropathy?

No value.

What organism causes PSGN?

Group A β-hemolytic Streptococcus.

Which strains are associated with sore throat vs skin infection?

Sore throat: strains 1, 4, 12. Skin infection: strains 47, 49, 55, 57.

What is the incubation period after streptococcal infection?

Sore throat: 7–10 days. Skin infection: 4–6 weeks.

What is the classic triad of PSGN?

Cola-colored urine + hypertension + oliguria.

What happens to C3 in PSGN?

↓ C3.

What antibody is associated with PSGN after skin infection?

Anti-DNase B.

What is the classic IF pattern in PSGN?

Granular 'starry sky' pattern with IgG + C3 in capillary walls/mesangium.

What is the EM finding in PSGN?

Subepithelial 'hump' deposits.

When is renal biopsy indicated in PSGN according to the notes?

C3 remains low after ~8 weeks OR recurrent episode to evaluate an alternative diagnosis.

What is the usual prognosis of PSGN according to the notes?

Good; recovery occurs in ~99% within 3–5 days with prompt treatment.

What is RPGN histologically?

Diffuse proliferative glomerulonephritis with crescents.

What is the key biopsy feature determining prognosis in RPGN?

Number of crescents.

What is seen on LM in RPGN?

Crescentic glomerulonephritis with proliferation of parietal epithelial cells and fibrin.

What are the 3 immunofluorescence types of RPGN?

Type I: linear; Type II: granular; Type III: pauci-immune.