5. Glomerulonephritis, Nephrotic Syndrome

How much albumin do normal nephrons excrete?

8-10 mg/day

**Increases with glomerular injury

Conditions that cause chronic glomerulosclerosis

- Genetic mutations

- HTN and atherosclerosis

- Malignant HTN

- Diabetic nephropathy

Major cause of non-diabetic ESRD in AA population

Focal segmental glomerulosclerosis (chronic glomerular disease)

Onset of focal segmental glomerulosclerosis

Young adult with advanced CKD

Malignant HTN & chronic glomerulosclerosis

Necrosis of arterioles and glomeruli

Diabetic nephropathy & chronic glomerulosclerosis

Acquired injury with thickening of GBM

Conditions that cause acute glomerular diseases

- Cytokine-mediated

- Autoantibodies

- Vasculitis (inflammatory cell mediated)

- Infiltrative disease

Presentation of nephritic/nephrotic syndrome

AKI or CKD

Nephritic syndrome

1-2g/day proteinuria, hematuria, RBC casts, reduced GFR (increased Cr)

Nephrotic syndrome

HEAVY >3g/day proteinuria, microscopic hematuria, hypoalbumin with edema/anasarca, gradual decline of GFR

UA findings with glomerulocephritis

- Asymptomatic hematuria (micro)

- RBC casts

- Proteinuria with microalbuminuria OR frank

Microalbuminuria value

30-300 mg/day

Frank proteinuria value

>300 mg/day

RBC casts in urine is associated with...

Glomeronephritis

Foamy urine is associated with...

Proteinuria

Benign, non-sustained proteinuria value + possible causes

Pathologic conditions associated with proteinuria

Nephritic, nephrotic, tubular, CKD

Quantification of proteinuria for AKI, AGN & nephrotic syndrome

Urine dipstick then spot P/Cr ratio + 24hr urine protein (for accuracy)

Quantification of proteinuria for CKD screen/monitor

Urine dipstick & spot albumin/Cr ratio + 24hr urine protein (for accuracy)

Quantifying proteinuria (grading)

1+ → 200-500 mg/24h

2+ → 0.5-1.5 g/24h

3+ → >2-3 g/24h

Acute nephritic syndromes AKA

Acute glomerulonephritis (AGN)

Common presentation of acute nephritic syndromes

- Reduced GFR with increase Cr

- Fluid retention/edema

- Mild-moderate proteinuria

- Hematuria/pyuria

- RBC cast

- Progressive

Post-streptococcal GN

Circulating immune complexes, strep antigens, activation of complement → deposition in glomeruli, endothelial, epithelial sites

Risk factors for post-streptococcal GN

- Developing countries → age 2-14

- ANY strep infection

Onset of post-streptococcal GN

1-6 weeks after strep infection

S/S of post-streptococcal GN

Oliguric renal failure, edema, HTN

UA with micro hematuria, pyuria, RBC cast

Anorexia, flank pain d/t swelling of renal capsule

Diagnostic workup for post-streptococcal GN

Anti-streptolysin titer

Management of post-streptococcal GN

Supportive, ABX for strep infection

Endocarditis-associated GN

Immune complex deposition in kidney

Onset of endocarditis-associated GN

10-14 days after infection

Cause of endocarditis-associated GN

Untreated subacute endocarditis with potentially negative blood sultures

S/S of endocarditis-associated GN

Rapid loss of renal function → AKI/RPGM

Diagnostic workup & findings for endocarditis-associated GN

- Elevated ESR

- Rheumatoid factor

- Positive cryoglobins & ANCA

+ dx of endocarditis with blood cultures/echo

Management of endocarditis-associated GN

Address infection

Serious complication of systemic lupus erythematosus

Lupus nephritis

Lupus nephritis

Deposition of circulating immune complexes

Demographic associated with severe lupus nephritis

Female AA adolescent

Presentation of renal disease in Lupus

Common to have renal disease with diagnosis of SLE

MC lupus nephritis sign on workup

Proteinuria

Diagnostic workup of patients with know lupus OR suspected lupus for lupus nephritis

Macro + micro UA, BUN, Cr

Diagnostic workup of lupus nephritis

- UA with renal involvement → Renal biopsy to classify severity

- Serology testing → Anti-dsDNA Ab

Management of class I & II lupus nephritis

Not required

Management of class III lupus nephritis

Steroids if small % of glomeruli involvement

Management of class IV+ lupus nephritis

High dose steroids and immunosuppression + maintenance therapy

Management of lupus nephritis progressed to ESRD

Dialysis, consider transplant

Anti-glomerular BM disease

Antibodies against GBM antigens & BM in lungs

Good pasture syndrome

Lung hemorrhage & glomerulonephritis — Pulmonary-renal syndrome

Diagnostic workup of good pasture syndrome

Urgent renal biopsy & anti-GBM Ab serology

What worsens prognosis of anti-glomerular BM disease?

Biopsy with advanced fibrosis, serum Cr >5, renal replacement therapy required

Management of anti-glomerular BM disease/good pasture syndrome

Steroids, plasmphoresis, cyclophosphamide (immunosuppressant)

When can a transplant be considered for anti-glomerular BM disease/good pasture syndrome?

Serum antibodies undetectable x6 months

IgA nephropathy

Immune complex-mediated, diffuse mesangial IgA deposits & mesangial hypercellularity

Common cause of GN in Asia

IgA nephropathy

Presentation of IgA nephropathy

Recurrent macroscopic hematuria during/after URI +/- proteinuria

Diagnosis of IgA nephropathy

Renal biopsy with mesangial proliferation

Prognosis of IgA nephropathy

Generally benign; slow progression

Management of IgA nephropathy

ACEI +/- corticosteroids

ANCA AKA

Antineurtrophil cytoplasmic antibody

ANCA vasculitis

Leukocyte and monocytes damage small vessel; associated with anti-proteinase 3 and anti-myeloperoxiade

Examples of ANCA vasculitis

- Granulomatosis with polyangiitis

- Microscopic polyangiitis

- Eosinophilic granulomatosis with polyangiitis

- Renal-limited vasculitis

Prognosis of ANCA vasculitis

High mortality w/o treatment — High relapse (maintenance immunosuppressants up to a year)

Management of ANCA vasculitis

URGENT induction therapy with high-dose (pulse-dose) glucocorticoids + cyclophosphamide or rituximab

What is indicated for rapid worsening of renal function OR pulmonary hemorrhage with management of ANCA vasculitis?

Plasmapheresis

Granulomatosis with polyangiitis (GPA) AKA

Wegener's granulomatosis

Classic presentation of granulomatosis with polyangiitis (GPA)

- Fever, purulent rhinorrhea, nasal ulcers, sinus pain

- Polyarthralgias, hemoptysis, SOB

- Microscopic hematuria, proteinuria

How much proteinuria is expected with GPA?

0.5-1 g/day

Diagnostic workup & findings associated with granulomatosis with polyangiitis (GPA)

CXR: Nodules, persistent infiltrates

Lung biopsy: Small vessel vasculitis

Kidney biopsy: Necrotizing glomerulonephritis w/o immune deposits

Eosinophilic granulomatosis with polyangiitis (EGPA) AKA

Churg-Strauss

Eosinophilic granulomatosis with polyangiitis (EGPA)

Small vessel vasculitis with pulmonary and renal involvement

S/S associated with eosinophilic granulomatosis with polyangiitis (EGPA)

Cutaneous purpura, asthma, allergic rhinitis & lung inflammation → cough, pulmonary infiltrates, exudative effusion with eosinophils

Diagnostic workup & findings associated with eosinophilic granulomatosis with polyangiitis (EGPA)

- Renal biopsy → small vessel vasculitis

- Peripheral eosinophilia

Membranoproliferative GN

Immune-mediated with thickening of GBM & mesangioproliferative changes

Associations with type I membranoproliferative GN

Hep C & B, lupus, cryglobulinemia, neoplastic disease

Associations with type II & III membranoproliferative GN

Idiopathic

Diagnostic workup & findings associated with membranoproliferative GN

- Low complement levels

- Proteinuria, hematuria

Either rapid or gradual decline in renal function

Management of membranoproliferative GN

RAAS, transplant

Which renal disease has high organ rejection rates with transplant?

Membranoproliferative GN

S/S of nephrotic syndrome

- HypOalbuminemia

- PrOteinuria

- Odema (edema)

- Fatty acid casts / fat bodies

- Hypercholesteremia

What is proteinuria in nephrotic syndrome dependent on?

Degree of GFR decline

Management of nephrotic syndrome

- Lipid-lowering

- Diuresis for salt retention (edema)

- AC for hypercoag state

- RAAS inhibition

Primary cause of nephrotic syndrome in children

Minimal change disease

Associations with minimal change disease in adults

Hodgkin lymphoma, allergies, NSAID

Renal biopsy findings with minimal change disease

No glomerular lesion light microscopy, no deposits on immunofluorescent microscopy

Diagnostic workup of minimal change disease

Electron microscopy → effacement of foot processes, weakening of slit-pore membranes

S/S of minimal change disease

- Abrupt edema → anasarca, periorbitial edema

- Severe hypoalbumin

- Protein UA >10g

Management of minimal change disease

- Steroids

- If non-responsive → biopsy

What is considered remission for minimal change disease?

Urine protein

Which nephrotic syndrome has highest likelihood of renal vein thrombosis, DVT, and PE? Management?

Membranous nephropathy → AC for ALL (low bleeding risks)

Demographic associated with membranous nephropathy

Male age 30-50

Associated conditions with membranous nephropathy

Malignancy: Breast, lung, colon

Infection: Malaria, hepatitis B/C

Rhematologic disease: Lupus

Autoantibodies with membranous nephropathy

To PLA2R

Management of membranous nephropathy with persistent proteinuria despite treatment of underlying

Immunosuppressive drugs

Glomerular deposition diseases

MULTIPLE MYELOMA — light chain deposit in glomeruli and renal tubules → heavy proteinuria & renal failure

Amyloidosis — amyloid protein fragment deposition

Diagnostic workup of glomerular deposition diseases

- Urine protein electrophoresis & immunofixation

- Serum protein electrophoresis & immunofixation → M-spike

- Serum free light chain assay for circulating Kappa and Lambda free light chains → Elevated FLC assay with abnormal ratio indicating monoclinal plasma cell proliferation

- Renal biopsy

Renal biopsy findings with amyloidosis

Amyloid fragments on Congo Red Stain

Renal biopsy findings with multiple myeloma

Granular deposits on electron microscopy

Management of MM with glomerular deposition disease

Oncologist referral