IG A NEPHROPATHY

GAYATHRI THAMPATTY

PGY2

• 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

• 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-

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

LIGHT MICROSCOPY

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

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

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

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

• 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.

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

• 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

• 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.

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)

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