What Every Medical Student Needs to Know About ...

Renal Pathology
Roger S. Riley, M.D., Ph.D. November, 2001

Secondary Glomerular Diseases

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Acute proliferative glomerulonephritis Lupus nephritis Diabetic glomerulosclerosis Renal amyloidosis Chronic glomerulosclerosis

Patient Patient G.C. G.C.

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16 year old, female, student History: Weakness urine output x 2 days Recent history of sore throat, URI Physical: Mild peripheral edema Urinalysis: 2 protein

10 RBC/HPF Frequent RBC casts Few hyaline and granular casts

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Lab Data:

BUN - 45 mg/dL

Creatinine - 6.3 mg/dL H/H - 8.2/28.5

H&E H&E

IgG IgG

C3 C3

Acute Post-Streptococcal GN
Synonyms: Acute proliferative glomerulonephritis, acute post-infectious GN. Incidence: Etiology: Peak incidence in children (3-14). Sporatic, mostly winter and spring. Glomerular trapping of circulating antistreptococcal immune complexes. Group A, B-hemolytic streptococci, type 12. Acute nephritic syndrome post-strept pharyngitis or pyoderma. Other infections. Nephritic urine with RBC casts. Evidence of streptococcal infection or serologic evidence of recent infection. Decreased serum complement. Enlarged, hypercellular glomeruli with endothelial and mesangial cell proliferation. Acute inflammation. IgG and C3 in very coarsely granular pattern along GBMs. Discrete, subepithelial hump-like deposits. Children - Excellent prognosis. Adults Worse prognosis, some develop progressive disease.

Clinical: Lab:

Path:

Clinical Course:

Post-Streptococcal GN
CNS

Streptococcal Infection

+ Strep Assay Hypertension

Latent Period

Edema

Proteinuria

Acute Nephritis
Hematuria

Lupus Nephritis
Incidence: Common, autoimmune, multi-system disease. Black, female bias. Renal involvement in > 70% SLE patients, common cause of death. Autoimmune disorder with denatured DNA as the antigen. Skin, GI, and renal. May present as nephrotic or acute nephritic syndrome. Hematuria, RBC casts, some proteinuria. Positive assays for anti-nuclear and antiDNA antibodies. Six types of glomerular disease by WHO classification. (I) Normal glomeruli, (II) Pure mesangial alterations, (III) Focal segmental glomeuulonephritis, (IV) Diffuse glomerulonephritis, (V) Diffuse membranous glomerulonephritis, (VI) Advanced sclerosing glomerulonephritis. Poor disease prognosis with renal involvement. Crescent formation more omnious. Renal disease is cause of death in 30%. Recurs in transplanted kidneys. Etiology: Clinical Features: Lab:

Path:

Clinical Course:

Patient T.R.
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25 year-old auto mechanic History: urine output x 10 days Hematuria x 2 days

Headaches, myalgia, lassitude

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Physical: Obesity, mild HTN Urinalysis: 3 protein

Many RBCs, RBC casts

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Lab Data:

BUN - 102 mg/dL

Creatinine - 10.2 mg/dL Total protein 5.9 g/dL H/H - 12.5/28.4

The Biopsy showed anti-GBM Disease !

Anti-GBM Disease
Synonyms: Goodpastures Syndrome. Incidence: Etiology: Clinical Features: Primarily 2nd to 4th decade. Males. Anti-renal/pulmonary BM Abs. Inflammation and complement. Acute nephritic syndrome with very rapid disease progression Hemoptysis usually present. Frequent history of preceeding viral-like illness. History of exposure to volatile hydrocarbons in some patients. Nephritic urine with RBC casts. Positive assay for anti-GBM antibodies. Proliferative and necrotizing GN with crescent formation. Extensive interstitial inflammatory infiltrates. Diffuse, linear IgG deposits outlining GBMs. Progression to ESRD in 1-2 years in > 90% patients. High initial mortality rate. Aggressive Rx with steroids, plasmapheresis, and cytotoxic therapy mandatory.

Lab: Path:

Clinical Course:

Patient Patient L.M. L.M.

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65 year old female History: Recent anemia and proteinuria History of ASCVD & hypothyroidism History of adult-onset diabetes Physical: Moderate obesity Urinalysis: 4 protein 3-5 WBCs/HPF Few granular, hyaline casts Few WBC casts BUN - 49 mg/dL Creatinine - 4.8 mg/dL Hgb - 8.3 g/dL

Lab data:

H&E H&E

H&E H&E

PAS PAS

H&E H&E

H&E H&E

Mrs. M. has diabetic glomerulosclerosis!

Diabetic Glomerulosclerosis
Synonyms: Kimmelstiel-Wilson disease. Incidence: Common cause of renal failure in diabetics. 30-50% IDDM patients. Etiology: Renal disease secondary to diabetic microangiopathy, with thickening of BMs. Related to DM severity/duration. Clinical Features: Lab: Path: Proteinuria is major manifestation, nephrotic syndrome may develop. Hypertension and microscopic hematuria. Proteinuria hematuria. Elevated glucose, BUN, creatinine. Gross - Small, contracted kidneys with granular surface. Diffuse diabetic glomerulosclerosis - Increased mesangial matrix, thickened BMs, hyaline arteriosclerosis of afferent and efferent arterioles. Nodular diabetic glomerulosclerosis - Same as diffuse form + mesangial nodules (Kimmelstiel-Wilson lesion). Marked GBM thickening. Gradual progression to ESRD, usually within six years. Progression slowed with control of hyperglycemia. Transplantation is option. Nodular Diffuse

Clinical Course:

Patient Patient L.G. L.G.

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81 year old female History: Progressive L.E. edema x 5 mos. Multiple recent UTIs History of hypertension Physical: Pitting L.E. edema to mid-calf Urinalysis: 4 protein Hyaline casts and gitter cells 12 grams protein/24 hrs. Lab data : BUN - 35 mg/dL Creatinine - 2.0 mg/dL Serum total protein - 3.4 g/dL Serum cholesterol - 308 mg/dL ESR - 107 mm/hr

PAS PAS

PAS PAS

Anti-Lambda

Anti-Lambda

The biopsy Showed a myeloma kidney!

Renal Disease in Plasma Cell Dyscrasia

Synonyms: Myeloma kidney. Incidence: Common in patients with plasma cell dyscrasias. Etiology: Deposition of monoclonal immunoglobulins or Ig light chains in glomeruli or tubulointerstitium. Proteinuria, nephrotic syndrome, or renal insufficiency. Proteinuria, increased renal size, abnormal serum and/or urine protein electrophoresis. LM - Ig deposits, may be nodular. Light chains may deposit as amyloid or precipitate as hard casts. Membranous or proliferative pattern possible. Cryoglobulins produce microthrombi. IgM deposits in Waldenstroms. IF Autofluorescence. + kappa or lambda stain. EM - Amyloid may be identified. Poor prognosis. Transplantation contraindicated.

Clinical: Lab: Path:

Clinical Course:

Renal Amyloidosis
Incidence: Common in patients with amyloidosis. Etiology: Disorder of protein metabolism with extracellular deposits of amyloid. Amyloid is a proteinaceous material with a beta-pleated structure. Four biochemical forms of amyloid, all with identical light and ultrastructural features. Proteinuria, nephrotic syndrome, or renal insufficiency common, especially in primary (idiopathic) form. Hypertension. Proteinuria, increased renal size. Amyloid deposits in mesangium and small vessels, later in GBM. Congo red stain shows apple-green birefringence under polarized light. Small, nonbranched fibrils with criss-cross (felt-like) pattern, 7-10 nm. Poor prognosis, especially primary form. Death usually from other manifestations of amyloidosis. Transplantation contraindicated.

Clinical Features: Lab: Path:

Clinical Course:

Congo Congo Red Red

Chronic Glomerulosclerosis
Synonyms: End-stage renal disease, diffuse sclerosing glomerulonephritis Incidence: Etiology: Clinical Features: Lab: Path: End-stage of many renal diseases. The pathogenesis usually cannot be determined. Both sexes, all ages and races. A history of a preceeding renal disease is present in many patients. Severe renal failure. Uusually no diagnostic findings of a specific renal disease. Small contracted kidneys. Diffuse, global hyaline sclerosis of glomeruli accompanied by marked tubular atrophy, patchy interstitial fibrosis, and interstitial lymphocytic infiltrate. Irreversible, progressive renal failure. Treatment options are chronic dialysis or renal transplantation.

Clinical Course: