Study guide
9.2 Glomerular Disorders & Nephrotic Syndrome
ABIM Internal Medicine Exam
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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy
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2 Chapter 1: Cardiovascular Disease (14% of Exam)
1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection
3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)
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6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations 6.2 Antirheumatic Pharmacotherapy & the Spondyloarthropathies 6.3 Gout: Pathophysiology & Acute Management 6.4 Urate-Lowering Therapy & Calcium Pyrophosphate Deposition Disease 6.5 Osteoarthritis 6.6 Systemic Lupus Erythematosus 6.7 Systemic Sclerosis, Sjogren Syndrome & Inflammatory Myopathies 6.8 The Vasculitides 6.9 Regional Musculoskeletal Syndromes, Back Pain & Sports Injuries 6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease 6.11 Osteonecrosis & Metabolic Bone Disease
8 Chapter 7: Hematology (6% of Exam)
7.1 Approach to Anemia & the Microcytic Anemias 7.2 Macrocytic, Normocytic & Hemolytic Anemias 7.3 Hemoglobinopathies, Thalassemias & Paroxysmal Nocturnal Hemoglobinuria 7.4 Platelet Disorders, Thrombocytopenia & the Bleeding Patient 7.5 Coagulation Factor Disorders, Thrombophilia & Anticoagulant Reversal 7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms 7.7 Lymphomas & Plasma Cell Disorders 7.8 Myelodysplastic Syndrome, Myeloproliferative Neoplasms & Porphyria 7.9 Transfusion Medicine & Late Complications of Transplantation
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10 Chapter 9: Nephrology & Urology (6% of Exam)
9.1 Acute Kidney Injury: Staging, Etiology & Urine Microscopy 9.2 Glomerular Disorders & Nephrotic Syndrome 9.3 Nephritic Syndromes, RPGN & Indications for Renal Replacement Therapy 9.4 Chronic Kidney Disease: Staging & Progression Retardation 9.5 Complications of Chronic Kidney Disease: Anemia, CKD-MBD & Acidosis 9.6 Hyponatremia, Hypernatremia & Water Balance 9.7 Potassium Disorders & Systematic Acid-Base Analysis 9.8 Renal Tubular Acidosis & Nephrolithiasis 9.9 Prostate Disorders, Urinary Incontinence & Other Urologic Conditions 9.10 Cystic Kidney Disease, Obstructive Uropathy, Tubulointerstitial Disease & Hematuria
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13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications
15 Chapter 14: Geriatric Syndromes (3% of Exam)
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16 Chapter 15: Allergy & Immunology (2% of Exam)
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17 Chapter 16: Preventive Medicine, Immunization & Clinical Epidemiology
16.1 The USPSTF Framework & Evidence-Based Cancer Screening 16.2 Cardiovascular & Metabolic Screening and Primary Prevention 16.3 Adult Immunization & Vaccines in Special Populations 16.4 Clinical Epidemiology, Biostatistics & Study Design
18 Chapter 17: Miscellaneous - Ethics, Patient Safety & Quality Improvement (2% of Exam)
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19 Chapter 18: Perioperative Medicine & Medical Consultation
18.1 Preoperative Cardiovascular Risk Assessment 18.2 Preoperative Pulmonary Risk & Perioperative Medication Management 18.3 Perioperative Anticoagulation, Bridging & Postoperative Complications
20 Chapter 19: Ophthalmology (1% of Exam)
19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease
21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)
20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders
9.2 Glomerular Disorders & Nephrotic Syndrome
Key Takeaways Explain This Topic AI
Lupus nephritis, minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, membranoproliferative glomerulonephritis, IgA nephropathy and anti-glomerular basement membrane disease are enumerated glomerular topics.
Nephrotic syndrome is defined by proteinuria exceeding 3.5 grams per day with hypoalbuminemia, edema and hyperlipidemia.
Membranous nephropathy carries the highest thrombotic risk of the nephrotic syndromes, and renal vein thrombosis presents with flank pain and gross hematuria.
Primary membranous nephropathy is associated with anti-phospholipase A2 receptor antibodies, whose presence can obviate biopsy in selected patients.
Focal segmental glomerulosclerosis has primary and secondary forms whose treatment differs, since secondary disease is managed by addressing the underlying driver rather than with immunosuppression.
Last updated: August 2026
1. Glomerular Diseases: Nephrotic vs. Nephritic Spectrum
Glomerular diseases are categorized into primary nephrotic syndromes (characterized by podocyte injury and massive proteinuria) and nephritic syndromes (characterized by inflammatory endocapillary proliferation and glomerular basement membrane rupture).
Comparison of Nephrotic vs. Nephritic Syndromes
Feature Nephrotic Syndrome Nephritic Syndrome
Defining Proteinuria >3.5 g / 24 hours (or Spot Urine Protein-to-Creatinine Ratio UPCR >3.5 g/g; Urine Albumin-to-Creatinine Ratio UACR >3000 mg/g) Sub-nephrotic ( <3.5 g / 24 hours , typically 0.5–2.0 g/day)
Serum Albumin Severe hypoalbuminemia ( <3.0 g/dL ) Normal or mildly decreased
Edema Marked, generalized, anasarca (periorbital, peripheral, ascites, pleural effusions) Mild-to-moderate dependent edema (facial/periorbital and pretibial)
Urinary Sediment Bland, oval fat bodies, fatty casts, "Maltese cross" birefringence under polarized light Active sediment: Dysmorphic RBCs (acanthocytes) , RBC casts , WBCs
Hematuria / Urine Color Microscopic or absent (clear / yellow urine) Macroscopic or microscopic ( coca-cola / tea-colored / smoky urine )
Blood Pressure Usually normal (except in secondary forms like diabetic nephropathy) Hypertension (due to fluid retention and impaired natriuresis)
Renal Function Initially preserved GFR (unless severe intravascular depletion or ATN) Rapidly declining GFR / Acute Kidney Injury (Oliguria)
- 2. Nephrotic Syndromes: Subtypes & Clinical Pearls
- Complications of Nephrotic Syndrome
Hypercoagulability & Thromboembolism: Urinary loss of endogenous anticoagulant proteins ( Antithrombin III , protein C, protein S) combined with hepatic overproduction of prothrombotic factors (fibrinogen, factor V, factor VIII) and thrombocytosis. Highest risk in Membranous Nephropathy with serum albumin <2.0–2.5 g/dL. Manifests as Renal Vein Thrombosis (sudden flank pain, gross hematuria, worsening proteinuria, acute GFR decline; left renal vein > right due to anatomical drainage into the IVC), deep vein thrombosis, and pulmonary embolism. Prophylactic anticoagulation (e.g., Warfarin or DOAC) is indicated for high-risk patients with albumin <2.0–2.5 g/dL.
Infection Susceptibility: Urinary loss of immunoglobulins (IgG) and complement factors (properdin factor B) leads to impaired opsonization of encapsulated organisms ( Streptococcus pneumoniae , Haemophilus influenzae ). Patients require pneumococcal and influenza immunizations.
Severe Hyperlipidemia & Accelerated Atherosclerosis: Hypoalbuminemia stimulates generalized hepatic protein synthesis, resulting in elevated total cholesterol, LDL, and VLDL, and reduced lipid catabolism (decreased lipoprotein lipase activity).
Primary & Secondary Nephrotic Subtypes
Minimal Change Disease (MCD):
Epidemiology: Accounts for ~85–90% of pediatric nephrotic cases and ~10–15% of adult nephrotic syndrome.
Histopathology: Light microscopy (LM) appears completely normal ; Immunofluorescence (IF) is negative ; Electron microscopy (EM) demonstrates diffuse effacement of visceral epithelial cell (podocyte) foot processes .
Secondary Causes: Hodgkin lymphoma and other hematologic malignancies, NSAID use.
Treatment: High-dose oral corticosteroids ( Prednisone 1 mg/kg/day up to 80 mg/day for 8–16 weeks in adults). Adults have a slower initial response than children (up to 12–16 weeks required for full remission) and high relapse rates (~50%; treated with repeated steroids, cyclophosphamide, calcineurin inhibitors, or rituximab).
Focal Segmental Glomerulosclerosis (FSGS):
Epidemiology: Most common primary cause of nephrotic syndrome in African American adults. Strongly linked to APOL1 risk alleles (G1/G2 variants) which provide evolutionary protection against Trypanosoma brucei rhodesiense sleeping sickness but predispose podocytes to lysosomal injury.
Primary FSGS: Mediated by a circulating podocyte permeability factor (e.g., suPAR). Presents with acute, explosive nephrotic syndrome, severe hypoalbuminemia, and diffuse foot process effacement (>80%) on EM. Treatment: High-dose oral prednisone (1 mg/kg/day for >=16 weeks) +/- Calcineurin Inhibitors (Cyclosporine, Tacrolimus).
Secondary FSGS (Adaptive / Maladaptive Hyperfiltration): Due to structural nephron loss or hemodynamic overload:
Causes: Advanced obesity, sickle cell nephropathy, severe solitary kidney hyperfiltration, chronic reflux nephropathy, HIV-associated nephropathy (HIVAN, classic collapsing glomerulopathy variant), IV heroin nephropathy, anabolic steroid abuse.
Features: Slow, insidious onset of proteinuria, normal or near-normal serum albumin, absence of severe anasarca, and patchy/focal foot process effacement on EM.
Treatment: Treat underlying etiology, strict blood pressure control, maximum tolerated ACE inhibitor / ARB , and SGLT2 inhibitor. Immunosuppression is contraindicated in secondary FSGS .
Membranous Nephropathy (MN):
Epidemiology: Most frequent cause of primary nephrotic syndrome in non-diabetic white adults >40 years of age.
Primary Membranous (~75–80%): Autoantibodies against the M-type Phospholipase A2 Receptor (anti-PLA2R) expressed on podocytes (detected by ELISA or indirect immunofluorescence); ~5% against THSD7A (Thrombospondin type-1 domain-containing 7A).
Secondary Membranous (~20–25%): Must be ruled out before establishing primary diagnosis:
Infections: Chronic Hepatitis B, Hepatitis C, Syphilis.
Malignancy: Solid organ carcinomas (colon, lung, prostate, breast, stomach; age-appropriate cancer screening is mandatory).
Autoimmune: Systemic Lupus Erythematosus (Class V Lupus Nephritis; "full-house" IF), Hashimoto thyroiditis.
Drugs: NSAIDs, penicillamine, gold salts.
Renal Biopsy: LM reveals diffuse thickening of the glomerular basement membrane; Silver stain shows characteristic "spike and dome" appearance (subepithelial basement membrane projections surrounding immune deposits); IF shows granular capillary wall staining for IgG and C3 ; EM reveals subepithelial electron-dense deposits .
Treatment Strategy:
Low Risk (normal eGFR, non-nephrotic proteinuria <3.5 g/d, anti-PLA2R low/negative): Conservative supportive therapy with ACEi/ARB, SGLT2i, statin, and blood pressure control for 6 months.
Moderate-to-High Risk (persistent proteinuria >4 g/d, declining eGFR, or high anti-PLA2R titers): Immunosuppressive therapy with Rituximab (375 mg/m2 weekly x 4 or 1000 mg on days 1 and 15; now preferred first-line via MENTOR trial) or Cyclical Corticosteroid + Cyclophosphamide regimen (Modified Ponticelli Regimen) for 6 months.
Diabetic Nephropathy:
Characterized by mesangial expansion, nodular glomerulosclerosis ( Kimmelstiel-Wilson nodules ), arteriolar hyalinosis, and GBM thickening. Progresses from microalbuminuria (30–300 mg/g) to overt macroalbuminuria (>300 mg/g) and GFR decline.
Renal Amyloidosis:
Deposition of insoluble beta-pleated fibrillar protein sheets. Congo red stain shows pathognomonic apple-green birefringence under polarized light. Electron microscopy confirms randomly oriented non-branching 7.5–10 nm fibrils. Subdivided into AL Amyloidosis (clonal plasma cell light chains; treated with Daratumumab + CyBorD) and AA Amyloidosis (serum amyloid A in chronic inflammation: RA, Crohn's, osteomyelitis, familial Mediterranean fever; treated by controlling underlying disease).