Prof.Dr.P.Vijayaraghavan’s UnitDr.C.R.Rajkumar

GLOMERULAR DISEASESDEFINITION; Abnormalites of glomerular funtion can be

caused by damage to the major components of the glomerulus: Epithelium (podocytes), Basement membrane, capillary endothelium, mesangium.

Damage manifested by an inflammatory process. Specific histologic pattern of glomeruli injury can

be seen on renal biobsy through light microscopy, Electron microscopy.

Pathogenesis of glomerular injury Antibody mediated injuryIn situ immune complex deposition Fixed intrinsic tissue antigens NC1 domain of collagen type4 antigen [anti

GBM-nephritis] Heymann antigen [membranous

nephropathy] Mesangial antigens Circulating immune complex deposition Endogenous antigen[DNA,Nuclear

proteins,immunoglobulins,igA] Exogenous antigen [infectiousagents,drugs]Cytotoxic antibodiesCell mediated immune injuryActivation of alternative complement pathway

Clinical manifestation of glomerular injuryAsymptomatic

Macroscopic hematuria

Nephrotic Syndrome

Nephritic syndrome

Rapidly Progressive glomerular nephritis

Chronic Nephritic Syndrome

GLOMERULAR DISEASE WITH NEPHRITIC SYNDROMEPost streptococcal glomerular nephritisOther post infectious diseases Endocarditis Abscess ShuntIg A nephropathySystemic lupus

Glomerular diseases with acute nephritis

Acute Proliferative Glomerulonephritis Acute post-streptococcal (post-infectious) GN. children age 3-14 . Immune complexes and planted bacterial antigens

with activation of alternative complement pathway

oliguria, hematuria or tea-colored urine, edema, hypertension, and eventually renal failure 1-4 weeks post-infections.

protenuria,RBC cast Positive, streptococcal serology and decreased C3 complement

Subepithelial deposits of IgG and C3 complement in coarsely granular ("lumpy-bumpy" or "hump-like") pattern along capillary loops.

good prognosis, rarely renal failure

Glomerular diseases with primary haematuria

IgA Nephropathy (Berger’s Disease] Most common primary glomerular disease. Mostly adolescents and young adults

1.gross hematuria occurring coincidentally with or immediately following (24-48 hours), a viral upper respiratory infection, flu-like illness, gastrointestinal syndrome

2.episodes of gross hematuria,

3.microscopic hematuria. Focal and segmental glomerular mesangial

proliferation, with IgA deposits. Increased serum IgA. Normal C3 complement. Prognosis – Generally benign 20% progress to renal insufficiency in 10 years. recurs after renal transplantation.

Glomerular disease presenting as nephrotic syndromeMinimal change diseaseFSGNMembranous nephropathyMPGN type 1MPGN type 2Cryoglobulinemic MPGNAmyloid diabetic nephropathy

Minimal Change Disease (Lipoid nephrosis, foot process disease)

80%- childhood nephrotic syndrome 20% - adult nephritic syndrome. Idiopathic . Pathogenesis is loss of net negative

charge on capillary basement membrane. Nephrotic syndrome, may be severe. History of

recent URI in 30%. Association with Hodgkin’s lymphoma in some patients.

Heavy proteinuria with minimal or only modest urinary sediment (cells and casts).

Normal light microscopy. Foot process fusion on electron microscopy.

Course & Prognosis – Most children show complete remission with steroid treatment. Adults are more resistant to steroid therapy and have a higher incidence of complications.

Glomerular Diseases with Nephrotic Syndrome

Focal segmental glomerulo sclerosis

80% < 35 years 10-15% of cases of nephrotic syndrome in childhood. Idiopathic Chronic ureteral reflux or heroin abuse in some

patients. Nephrotic syndrome with many patients showing hematuria, hypertension, and/or renal insufficiency.

Focal and segmental sclerosis initially, progressing to global sclerosis of the glomerulus.

Course & Prognosis - Slowly progressive ,25% -of patients developing renal insufficiency in 5

years, 50%-80% within 10 years. Usually steroid resistant. Recurrence after renal transplantation is very

common.

Membrano proliferative glomerulo nephritis (MPGN)Mesangiocapillary glomerulonephritis OR lobar

glomerulonephritis 5-30 years Immune complex disease Associated conditions: Chronic infections (especially hepatitis C),

cancer, heroin abuse, SLE, etc Usually nephrotic syndrome, less often acute nephritic syndrome.

Recent history of URI in many patients. Hypertension and/or renal insufficiency may occur.

Decreased serum complement levels. Hepatitis C serology should be obtained

Glomerular hypercellularity with capillary basement membrane thickening and splitting[TRAM-TRACKING]. Subendothelial deposits of C3 complement and sometimes IgG

. Prognosis Progressive deterioration of renal function; Many patients develop end-stage renal insufficiency within 10

years.

Schematic representation of MPGN type I & II

MPGN 2Dense deposit disease causes ; Idiopathic C3 nephritic factor associated Partial lipodystrophyLow serum c3 and thickening of the GBM

containing ribbons of dense deposits and C3 -intra membranous deposit

Membranous Glomerulonephritis (MGN 4th-6th decade50% - most common cause of nephrotic

syndrome in adults. idiopathic. Associated conditions: Carcinoma, chronic

infections, heavy metal exposure, drugs. Nonselective proteinuria ± hematuria Nephrotic syndrome in most patients +

microscopic hematuria. Systemic disease may be present, especially colon and lung carcinoma.

Renal vein thrombosis is a common complication (50%).

Thickened basement membranes with subepithelial deposits of IgG and C3 complement. Four pathologic stages.

Good prognosis in children, 20-30% of adults progress to ESRD in a few years

in spite of steroids

Glomerular disease presenting as RPGN Goodpasture’s syndromeVasculitis Wegner’s granulomatosis Microscopic polyangitis Pauci immune crecentric glomerulonephritisImmune complex disease SLE Post steptococcal glomerulo nephritis IgA nephropathy/henoch –schonlein purpuraendocarditis

Anti-Glomerular Basement Membrane Disease (Goodpasture’s Syndrome)2nd-4th decades, usually males. The GBM and alveolar basement membrane

becomes antigenic. Deposited antibodies activate complement system and damage membranes.

Hemoptysis with coincident or subsequent acute renal failure.

Anti-GBM antibodies in 90% cases. Crescents in >50% of glomeruli. Diffuse,

linear IgG outlining capillary loops. 90% progress to end-stage renal insufficiency

in 1-2 years. Prognosis may depend on pulmonary complications. Frequently recurs after renal transplantation.

Renal Manifestations of Systemic Disease

Renal Manifestations of SLE (Lupus Nephritis)

common, multisystem disease. 10:1, F:M an autoimmune disorder in which denatured

DNA functions as the antigen nephritis or nephrotic syndrome.

proteinuria, Hematuria in severe cases with red and white blood cells, hyaline, granular, and broad casts ("telescoped" urinary sediment). Decreased serum complement levels, false positive test for syphilis, antinuclear antibodies,

Prognosis – Renal failure in about 40% of

patients. Related to histologic sub-class. Crescent formation more ominous.

)diabetic glomerulosclerosis

(Kimmelstiel-Wilson Syndrome) Most common glomerular disease. multifactorial. >20%-40% - type I diabetes mellitus in approximately 20

years 20%-30% - type II DM proteinuria full-blown nephrotic syndrome Microscopic hematuria and hypertension Hypertension and retinopathy Microalbuminuria is an early sign of diabetic

nephropathy, usually about 10 years after onset of disease..

initially diffuse diabetic glomerulosclerosis later becomes nodular diabetic glomerulosclerosis, Kimmelstiel-Wilson kidney)

Prognosis – Gradual progression to ESRD. Commonly recurs after renal transplantation.

Renal Amyloid Primary [AL ]amyloidosis – associated with

multiple myeloma. Secondary[AA] amyloidosis – chronic infectious

diseases (i.e., TB, osteomyelitis, leprosy) and chronic inflammatory diseases (i.e., rheumatoid arthritis, ankylosing spondylitis).

Proteinuria, nephrotic syndrome, Hypertension is usual Amyloid deposited first in mesangium, small

vessels, and later in glomerular capillary wall. "Apple" green birefringence of vessels and

glomeruli when stained with Congo Red and polarized.

Prognosis – Usually progresses to renal failure. secondary amyloidosis (e.g. cure of TB),

improvement may occur. Renal failure is common cause of death in

primary amyloidosis.

TUBULOINTERSTITIAL DISEASES Primary tubulointerstitial disease of the

kidney characterized by histologic and functional abnormalities that involve the tubules and interstitium to a greater degree than glomeruli and renal vasculature

Acute tubular necrosisAcute interstitial nephritisChronic interstitial nephritis

ACUTE INTERSTITIAL NEPHRITIS

DRUGSAntibiotics[betalactams,sulphonamides,vancomycin,

erythromycin,minocycline] NSAID and cyclooxygenase 2inhibitor Diuretics [thiazides,frusemide,triamterine] Anti convulsions

[phenytoin,phenobarbitol,CBZ,volproic acid] Misscelleneous [captopril,H2blockers,proton pump

inhibitor] INFECTIONBacteriaVirusesmiscellaneous IDIOPATHICTubulointerstitial nephritis –uveitis syndromeAcute –tubule basement membrane diseasesarcoidosis

CHRONIC INTERSTITIAL NEPHRITISCAUSESKIDNEYS MACROSCOPICALLY NORMALDrugs[lithim,cyclosporine,tacrolimus,indinavir,cisplatin]Metabolic[hyperuricemia,hypokalemia,hypercalcemia,hypero

xaluria,cystinosis]Heavy metals [lead,cadmium,arsenic,mercury,gold,uranium]RadiationBalkan nephropathyImmunemediated[SLE,sjogrens

syndrome,sarcoidosis,wegner’s granulomatosis,other vasculitis]

Vascular diseases [athero sclelotic kidney disease]Hematologic disturabances[multiple myeloma,light chain

deposition disease, lymphoma, SCD,PNH]Progressive glomerular disease of all

etiologies[glomerulonephritis, diabetes, hypertension]idiopathic

KIDNEYS MACROSCOPICALLY ABNORMAL

Analgesic nephropathyChronic obstructionHereditary

[nephronophtisis , medullary cystic disease , familial juvenile hyperuricemic nephropathy , ADPKD , ARPKD]

Infection Chronic pylonephritis, malacoplakia,xanthogranulomatous pylonephritis]

FUNCTIONAL CONSEQUENCES OF TUBULO INTERSTITIAL DISEASEDEFECT CAUSES

REDUCED GFR OBLITERATION OF microvasculature and obstruction of tubules

FANCONI SYNDROME DAMAGE OF PROXIMAL TUBULAR REABSORBTION OF GLUCOSE , AMINOACIDS, PHASPHATE ,AND BICORBANATE

HYPERCHOREMIC ACIDOSIS 1.REDUCED AMMONIA PRODUCTION2.INABILITY TO ACIDIFY THE COLLECTING DUCT [DISTAL RTA]3.PROXIMAL BICORBANATE WASTING

TUBULAR OR SMALL MOLECULAR WEIGHT PROTENURIA

FAILURE OF PROXIMAL TUBULE PROTEIN REABSORBTION

POLYURIA ,ISOTHENUIA DAMAGE TO MEDULLARY TUBULES AND VASCULATURE

HYPERKALEMIA POTTASIUM SECRETARY DEFECTS INCLUDING ALDOSTERONE RESISTANCE

Analgesic nephropathyHeavy users of analgesics mixtures

containing phenacetin combination with aspirin acetoaminophen,or coffeine,.

Clinical features; renal insufficiency,non nephrotic proteinuria,or sterile pyuria

Hypertension, anemia and impaired urinary concentration –renal insufficiency

Flank pain and hematuria-pappillary necrosis

Diagnosis ;1]history

2]CT-signs decreased renal size pappillary calcificationsMore prone for transitional cell carcinoma

Thank You.