Glomerulonephritis 2

GLOMERULONEPHRITIS GLOMERULOPATHY By Mohamad A. Sobh, MD, FACP Prof. & Head of Nephrology Urology & Nephrology Center Mansoura University Egypt

Glomerulopathies and glomerulonephritis are group of diseases of inflammatory or non-inflammatory nature involving primeraly the renal glomeruli.

Etiology of Glomerulonephritis a. Primary or idiopathic b. Secondary: n Infection (bacteria, parasite, virus). n Colagen disease (SLE, PAN, Rhoid). n Drug

(Penicillamin, gold, Asprin, Paradion, heroin). n Metabolic diseases (DM, Amyloidosis). n Malignancy (Hodgkins lymphoma). n Heredofamilial (Alports Syndrome).

Histopathology of Glomerulonephritis 1. Minimal change (nil-change) disease. 2. Focal and segmental glomerulosclerosis 3. Membranous glomerulonephritis 4. Proliferative glomerulonephritis.  Mesangial proliferative GN.  Mesangiocapillary

(membranoproliferative) GN.  Crescentic GN.  IgA nephropathy.

Histopathology of Glomerulonephritis 1. Minimal change (nil-change) disease.

2. Focal and segmental glomerulosclerosis 3. Membranous glomerulonephritis 4. Proliferative glomerulonephritis. Mesangial proliferative GN.  Mesangiocapillary (membranoproliferative) GN.  Crescentic GN.  IgA nephropathy. 

Histopathology of Glomerulonephritis 1. Minimal change (nil-change) disease. 2. Focal and segmental glomerulosclerosis

3. Membranous glomerulonephritis 4. Proliferative glomerulonephritis.  Mesangial proliferative GN.  Mesangiocapillary

(membranoproliferative) GN.  Crescentic GN.  IgA nephropathy.

Histopathology of Glomerulonephritis 1. Minimal change (nil-change) disease. 2. Focal and segmental glomerulosclerosis 3. Membranous glomerulonephritis

4. Proliferative glomerulonephritis.  Mesangial proliferative GN.  Mesangiocapillary

(membranoproliferative) GN.  Crescentic GN.  IgA nephropathy.

Histopathology of Glomerulonephritis 1. Minimal change (nil-change) disease. 2. Focal and segmental glomerulosclerosis 3. Membranous glomerulonephritis 4. Proliferative glomerulonephritis.  Mesangial proliferative GN.  Mesangiocapillary

(membranoproliferative) GN.  Crescentic GN.  IgA nephropathy.

Histopathology of Glomerulonephritis

1. Minimal change (nil-change) disease. 2. Focal and segmental glomerulosclerosis 3. Membranous glomerulonephritis 4. Proliferative glomerulonephritis.  Mesangial proliferative GN.  Mesangiocapillary

(membranoproliferative) GN.  Crescentic GN.  IgA nephropathy.

Histopathology of Glomerulonephritis 1. Minimal change (nil-change) disease. 2. Focal and segmental glomerulosclerosis 3. Membranous glomerulonephritis 4. Proliferative glomerulonephritis.  Mesangial proliferative GN.  Mesangiocapillary

(membranoproliferative) GN.  Crescentic GN.  IgA nephropathy.

Histopathology of Glomerulonephritis 1. Minimal change (nil-change) disease. 2. Focal and segmental glomerulosclerosis 3. Membranous glomerulonephritis 4. Proliferative glomerulonephritis.  Mesangial proliferative GN.  Mesangiocapillary

(membranoproliferative) GN.  Crescentic GN.  IgA nephropathy.

Clinical Manifestations of Glomerulonephritis 1. Nephrotic Syndrome. 2. Acute Nephritic Syndrome. 3. Rapidly Progressive GN. 4. Chronic Nephritic Syndrome. 5. Asymptomatic Urinary Abnormalities.

Nephrotic Syndrome 1. Insidious onset of massive oedema. 2. Heavy proteinuria. 3. Hypoalbuminaemia. 4. Hyperlipidemia.

Acute Nephritic (Acute Nephritis) 1. Rapid onset of oedema, smooky urine,

oliguria and hypertension. 2. Urine shows red cell casts, proteinuria. 3. Serum creatinine may be high, but

albumin and lipids usually normal. 4. Prognosis is usually good and recovery

occurs.

Rapidly progressive Glomerulonephritis (RPGN) 1. Rapid

onset of nephritis development of uraemia.

with

2. Urine shows nephritic sediment. 3. Serum creatinine is high. 4. If

untreated aggressively, prognosis is poor.

the

Chronic nephritic Syndrome 1. Slowly

progressive (mon., years) uraemia.

2. Urine shows proteinuria, hematuria,

broad casts, no urine concentration. 3. Serum creatinine is high as well as

other stegmata of uraemia.

Asymptomatic Urine Abnormalities 1. Microscopic hematuria or proteinuria

or both. 2. Serum creatinine is normal. 3. Prognosis is usually excellent.

Nephrotic Syndrome A syndrome characterized by: •

Heavy proteinuria (> 3.5 gm/1.73 m2/d.)

•

Massive oedema.

•

Hypoalbminaemia.

•

Hyperlipidaemia.

Etiology of Nephrotic Syndrome 1. Primary (idiopathic) N. S. 2. Secondary N. S.       

Post infection. Drug induced Metabolic Collagen and autoimmune. Malignancy. Renal vein thrombosis. Congenital.

Pathology of Nephrotic Syndrome    

Minimal change nephritis. Focal and segmental glomerulosclerosis. Membranous glomerulonephritis. Proliferative glomerulonephritis.    

Mesangial proliferative. Mesngiocapillary. Crescentic GN. IgA nephropathy.

Pathogenesis of Hypoalbuminaemia in N. S. •

Protenuria

•

Decrease influx from GIT (poor intake and poor absorption)

•

Increased tubular filtered albumin.

•

Sometimes decreased rate of hepatic biosynthesis.

catabolism

of

Glomerular damage Proteinuria Hypoalbuminaemia Decreased plasma oncotic pressure Water retention • increased angiotensin, aldosteron • Decreased ANP

Water retention

Oedema Decreased effective circulating blood volume • increased Pathogenesis of Oedema in N. S.

ADH

Hyperlipidemia in N. S.  ↑ Cholesterol, VLDL, LDL 

triglycerids, ↓ HDL.

 ↑ Hepatic synthesis  ↓ Peripheral utilization.  Urinary loss of HDL.

Hypercoagulability in N. S.  Venous stasis.  Abnormal

platelets endothelium.

and

vascular

 Urinary loss of anti-thrombin III,

protein C, and protein S.  More in membranous G. N. & MPGN.

Other Urinary Losses in N. S.  Transferrin  TBG  25-OHD3  IgG, C1q

Clinical Features of N. S. 1. Oedema 2. Hypertension 3. Lassitude, anorexia, loss of appitite,

pallor. 4. Manifestations of the etiologic cause. 5. Manifestations of complications.

Complications of N. S. 1. 2. 3. 4. 5. 6. 7. 8. 9.

Subnutritional state. Infection. Clotting episodes (DVT) and pulmonary embolism. Premature atherosclerosis. Hypovolaemia. Drug related complications. Acute renal failure. Bone disease. Anaemia.

Investigations of Nephrotic Syndrome 1. Urine

analysis for proteinuria, microscopic hematuria, pyuria, and casts.

2. Blood analysis for creatinine, albumine

and lipid profile. 3. Investigations for diagnosis of the etiology

in secondary N.S. such as DM, SLE, malignancy. 4. Kidney biopsy.

Treatment of N. S. 1. Treatment of the cause in 2ry cases. 2. Treatment of complications. 3. Rest in bed during exacerbations and early

ambulation with remissions. 4. Diet:

 Salt restricted  Protein content equal 1 g/kg/d plus urinary

losses

5. Diuretics, mainly loop diuretics. 6. Human salt free albumin in

certain

situations. 7. Steroid, CsA, and other immunosuppressive drugs.

Acute Glomerulonephritis  Post streptococcal (post infection).  MPGN, mesangial proliferative G.N.  IgA nephropathy.  SLE, systemic vasculitis, cryoglobulinemia

endocarditis, Henoch- Schonlein purpura.

Acute post-Streptococcal GN



Occurs after infection with nephritogenic strain of group A, Bhaemolytic streptococci.



Ether pharyngeal or skin infection.



Latent period is 1-3 weeks.



Children are affected more than adults.

Clinical Features Of PostStreptococcal GN 

1-3 weeks after streptococcal infections patient presents with acute nephritis (oliguria, smooky urine, oedema, headache, high blood pressure, ⇑ S.Cr.).



20% of cases presents with NS.



5% of cases present with RPGN.



Some cases may be asymptomatic.

Post streptococcal G.N. (Laboratory)



Urine:  



Red & White blood cell casts. Proteinuria ( < 3 gm./4h. In 75%, <0.5% gm in 50%). Rarely –ve.

Pharyngeal and skin cultures  ASLO, AH.  Hypocomplementemia C3 < C1, C4 CH50 

Postreptococcal G.N. (Histopathology) Light microscopy G.N.

Diffuse

proliferative

Crescents I. F.

C3, C1q, IgG, IgM, IgA.

E. M.

Humps

Complications Of Acute Nephritis 1. Encephalopathy. 2. Heart failure. 3. Acute renal failure.

Prognosis 

85% of the cases recover completely.



5% die-in the acute phase.



10% develop CRF.



Signs of bad prognosis.

Treatment

1. Irradication of infection. 2. Rest 3. salt restricted diet.

4. Hypotensive drugs. 5. Diuretics. 6. Dialysis treatment if renal failure develop. 7. Steroids and immunosuppressives for cases with RPGN.

Rapidly Progressive Glomerulonephritis “Crescentic Glomerulonephritis” “Extracapillary Proliferative G. N.” “Subacute Glomerulonephritis” • Goodpasture’s syndrome. - Type I

- Type II

- Type III

• Idiopathic. • Postinfection. • SLE. • Henoch-Schonlein purpura. • Systemic vasculitis. • Cryoglobulinemia. • Idiopathic.

Asymptomatic Urinary Abnormalities 

Any type of nephropathy.



Berger’s disease.



Mild mesangial proliferative G. N.



Post infection G. N.



IgM nephropathy.



Hereditary nephritis.

Isolated Proteinuria



 





> 150 mg/24 hr., < 3 gm/24 hr, almost always 1 gm/24 hr, occur in 0.6- 8.8% of healthy young adults. All lab tests and clinically are OK. Orthostatic or constant, persistent or transient. 70% with persistent, constant isolated proteinuria have abnormal biopsies, while in only 10-15% of those with persistent arthostatic. Ten-years prognosis is excellent.

Isolated Proteinuria 

Also with vigorous exercise, stress, fever, C. H. F., and hypertension.