- IgA nephropathy is the most common cause of primary glomerulonephritis worldwide, typically presenting in young adults with a male predominance. - Mesangial IgA deposition is seen in 3-16% of healthy individuals, suggesting there is a large, undiagnosed population with "latent" IgA nephropathy. - On biopsy, IgA nephropathy shows mesangial proliferation and matrix expansion. Electron microscopy shows electron-dense deposits primarily in the mesangium. - Clinically, 40-50% present with visible hematuria after upper respiratory infections. 30-40% have microscopic hematuria and mild proteinuria. Less than

1. IG A NEPHROPATHY
GAYATHRI THAMPATTY
PGY2

3. • MOST COMMON LESION FOUND TO CAUSE
PRIMARY GLOMERULONEPHRITIS THROUGHOUT
MOST DEVELOPED COUNTRIES OF THE WORLD
• MAY PRESENT AT ANY AGE, PEAK INCIDENCE IN THE
SECOND AND THIRD DECADES OF LIFE. THERE IS
APPROXIMATELY A 2:1 MALE TO FEMALE
PREDOMINANCE IN NORTH AMERICAN AND
WESTERN EUROPEAN POPULATIONS

4. • THE REPORTED INCIDENCE OF MESANGIAL IGA DEPOSITION IN APPARENTLY
HEALTHY INDIVIDUALS RANGES FROM 3 TO 16 PERCENT . THESE CASES HAD
NO CLINICAL FEATURES OF NEPHRITIS BUT THEIR RENAL BIOPSY WAS
CONSISTENT WITH IGA NEPHROPATHY.
• THIS OBSERVATION RAISES THREE IMPORTANT POINTS:
●THERE IS A LARGE COHORT OF UNDIAGNOSED "LATENT" IGA
NEPHROPATHY IN THE GENERAL POPULATION.
●THIS MUST BE TAKEN INTO ACCOUNT WHEN GENETIC STUDIES ARE
UNDERTAKEN COMPARING GENE POLYMORPHISMS IN IGA NEPHROPATHY
WITH NORMAL "HEALTHY" POPULATIONS.
●PROCESS OF MESANGIAL IGA DEPOSITION IS LIKELY TO BE SEPARATE
FROM THE INDUCTION OF GLOMERULAR INJURY AND IGA DEPOSITION DOES
NOT NECESSARILY NEED TO BE FOLLOWED BY NEPHRITIS-

5. IGA DEPOSITION IN OTHER FORMS OF
GLOMERULONEPHRITIS- THIN BASEMENT MEMBRANE
NEPHROPATHY, LUPUS NEPHRITIS, MINIMAL CHANGE
DISEASE, AND DIABETIC NEPHROPATHY. MOST PROBABLY
DUE TO CHANCE ASSOCIATIONS, SINCE IGA DEPOSITION IS
COMMON IN THE GENERAL POPULATION
LUPUS NEPHRITIS COULD ALSO HAVE ASSOCIATED
PROMINENT MESANGIAL IGA DEPOSITION. LUPUS CAN BE
DISTINGUISHED FROM IGA NEPHROPATHY
HISTOLOGICALLY BY THE MORE PROMINENT DEPOSITION
OF IGG THAN IGA AND THE PRESENCE OF SUBSTANTIAL
C1Q DEPOSITION, INDICATING ACTIVATION OF THE
CLASSIC COMPLEMENT PATHWAY, AS OPPOSED TO THE
ALTERNATE PATHWAY ACTIVATION IN IGA NEPHROPATHY

6. LIGHT MICROSCOPY
• MAJOR FINDING - FOCAL (INVOLVING LESS THAN 50
PERCENT OF GLOMERULI) OR MORE OFTEN
DIFFUSE MESANGIAL PROLIFERATION AND MATRIX
EXPANSION

7. ELECTRON MICROSCOPY
• ELECTRON-DENSE DEPOSITS THAT ARE
PRIMARILY LIMITED TO THE MESANGIUM (WHICH
ARE OUTSIDE OF MESANGIAL CELLS IN THE
MESANGIAL SPACES) BUT MAY ALSO OCCUR IN
THE SUBENDOTHELIAL AND SUBEPITHELIAL
SPACES. THE NUMBER AND SIZE OF THESE
DEPOSITS GENERALLY CORRELATES WELL WITH
THE SEVERITY OF CHANGES SEEN ON LIGHT
MICROSCOPY

8. CLINICAL FEATURES
• APPROXIMATELY 40 TO 50 PERCENT - ONE OR RECURRENT EPISODES
OF VISIBLE HEMATURIA, USUALLY FOLLOWING A URI (SYNPHARYNGITIC
HEMATURIA). PATIENTS MAY COMPLAIN OF FLANK PAIN, LOW GRADE
FEVER- MIMIC URINARY TRACT INFECTION OR UROLITHIASIS. MOST
PATIENTS HAVE ONLY A FEW EPISODES OF VISIBLE HEMATURIA AND
EPISODES USUALLY RECUR FOR A FEW YEARS AT MOST.
• 30 TO 40 PERCENT HAVE MICROSCOPIC HEMATURIA AND USUALLY MILD
PROTEINURIA, AND ARE INCIDENTALLY DETECTED ON A ROUTINE
EXAMINATION . THESE PATIENTS, THE DISEASE IS OF UNCERTAIN
DURATION. GROSS HEMATURIA WILL EVENTUALLY OCCUR IN 20 TO 25
PERCENT OF THESE PATIENTS.
• LESS THAN 10 PERCENT PRESENT WITH EITHER NEPHROTIC SYNDROME
OR ACUTE RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS PICTURE
CHARACTERIZED BY EDEMA, HYPERTENSION, AND RENAL
INSUFFICIENCY AS WELL AS HEMATURIA. RARELY, IGA NEPHROPATHY
MAY PRESENT WITH MALIGNANT HYPERTENSION

9. • CIRRHOSIS, CELIAC DISEASE, AND HIV
INFECTION ARE ALL ASSOCIATED WITH A
HIGH FREQUENCY OF GLOMERULAR IGA
DEPOSITION

10. • NEPHROTIC SYNDROME IN IGA NEPHROPATHY -
USUALLY INDICATIVE OF ADVANCED DISEASE.
SOME PATIENTS HAVE AN ACUTE ONSET OF
THE NEPHROTIC SYNDROME IN WHICH THERE
IS ONLY MILD MESANGIAL PROLIFERATION ON
RENAL BIOPSY AND THE MOST PROMINENT
FINDING IS DIFFUSE FUSION OF THE FOOT
PROCESSES, SIMILAR TO THAT SEEN IN
MINIMAL CHANGE DISEASE . FURTHERMORE,
MANY OF THESE PATIENTS BEHAVE AS IF THEY
HAVE MINIMAL CHANGE DISEASE, WITH
REMISSION OF PROTEINURIA BEING INDUCED
BY GLUCOCORTICOID THERAPY.

11. INDICATIONS FOR RENAL BIOPSY
• A KIDNEY BIOPSY IS USUALLY
PERFORMED FOR THE EVALUATION OF
SUSPECTED IGA NEPHROPATHY ONLY IF
THERE ARE SIGNS SUGGESTIVE OF
MORE SEVERE OR PROGRESSIVE
DISEASE SUCH AS PROTEIN EXCRETION
ABOVE 0.5 TO 1 G/DAY, ELEVATED SERUM
CREATININE CONCENTRATION, OR
HYPERTENSION

12. • PATIENTS WHO HAVE RECURRENT EPISODES OF
GROSS HEMATURIA WITHOUT PROTEINURIA ARE
AT LOW RISK FOR PROGRESSIVE KIDNEY
DISEASE COMPARED WITH PATIENTS WHO HAVE
PERSISTENT MICROSCOPIC HEMATURIA AND
PROTEINURIA. IN ADDITION, ISOLATED
PERSISTENT HEMATURIA (IE, WITH LITTLE OR NO
PROTEINURIA) AT PRESENTATION MAY BE
ASSOCIATED WITH PROGRESSIVE DISEASE
OVER TIME

13. • ISOLATED HEMATURIA, NO OR MINIMAL PROTEINURIA (LESS THAN 500 TO 1000
MG/DAY), AND A NORMAL GLOMERULAR FILTRATION RATE (GFR) ARE TYPICALLY NOT
TREATED AND OFTEN NOT BIOPSIED AND THEREFORE NOT IDENTIFIED AS HAVING
IGA NEPHROPATHY. NEEDS PERIODIC MONITORING AT 6- TO 12-MONTH INTERVALS
SINCE THERE IS AN APPRECIABLE RATE OF PROGRESSIVE DISEASE AS
MANIFESTED BY INCREASES IN PROTEINURIA, BLOOD PRESSURE, AND/OR SERUM
CREATININE.
• ●PATIENTS WITH PERSISTENT PROTEINURIA (ABOVE 1 G/DAY OR PERHAPS ABOVE
500 MG/DAY), A NORMAL OR ONLY SLIGHTLY REDUCED GFR THAT IS NOT DECLINING
RAPIDLY, AND ONLY MILD TO MODERATE HISTOLOGIC FINDINGS ON RENAL BIOPSY
ARE INITIALLY MANAGED WITH NONIMMUNOSUPPRESSIVE THERAPIES TO SLOW
PROGRESSION.
• •ANGIOTENSIN INHIBITION WITH EITHER AN ACE INHIBITOR OR ARB. THE GOALS OF
THERAPY WITH AN ACE INHIBITOR OR ARB ARE A URINARY PROTEIN EXCRETION
BELOW 500 MG/DAY OR 1 G/DAY AND A BLOOD PRESSURE LESS THAN 130/80 MMHG.
• •FISH OIL (3.3 GRAMS/DAY OR MORE) CAN BE TRIED IN PATIENTS WITH PROTEIN
EXCRETION ABOVE 1 G/DAY DESPITE THREE TO SIX MONTHS OF THERAPY WITH AN
ACE INHIBITOR OR ARB.

14. THE INDICATIONS FOR THE USE OF
GLUCOCORTICOIDS ALONE OR IN
COMBINATION WITH OTHER
IMMUNOSUPPRESSIVE DRUGS• NOT WELL DEFINED
• MOST NEPHROLOGISTS DO NOT TREAT MILD, STABLE, OR VERY SLOWLY PROGRESSIVE IGA
NEPHROPATHY WITH GLUCOCORTICOIDS OR OTHER IMMUNOSUPPRESSIVE THERAPIES
• IN GENERAL, ANTI-INFLAMMATORY THERAPY WITH GLUCOCORTICOIDS IN PATIENTS WITH
CLINICAL FEATURES SUPPORTING ACTIVE DISEASE AND PROGRESSION, WHICH INCLUDE
HEMATURIA IN ADDITION TO ONE OR MORE OF THE FOLLOWING:
• ●A PROGRESSIVELY DECLINING GLOMERULAR FILTRATION RATE
• ●PERSISTENT PROTEINURIA ABOVE 1 G/DAY AFTER MAXIMAL ANTIPROTEINURIC THERAPY WITH
ACE INHIBITORS OR ARBS FOR THREE TO SIX MONTHS
• ●MORPHOLOGIC EVIDENCE OF ACTIVE DISEASE BASED ON KIDNEY BIOPSY (EG,
PROLIFERATIVE OR NECROTIZING GLOMERULAR CHANGES)

15. THANK YOU