Ig A nephropathy haiying liu department of nephrology

Ig. A nephropathy haiying liu department of nephrology the second hospital of shandong university

Ig. A Nephropathy : Berger’s Disease n n the most common lesion found to cause primary glomerulonephritis peak incidence in the second and third decades of life 2: 1 male to female greatest frequency in Asians and Caucasians q relatively rare in blacks

Ig. A Nephropathy n n large undiagnosed "latent" Ig. A nephropathy in the general population the process of mesangial Ig. A deposition is likely to be separate from the induction of glomerular injury q Ig. A deposition does not necessarily need to be followed by nephritis

Ig. A Deposition is Common n Ig. A deposition in other forms of glomerulonephritis q q thin basement membrane nephropathy lupus nephritis minimal change disease diabetic nephropathy

Ig. A Nephropathy n Many patients are detected on routine urine screening q q asymptomatic hematuria and/or proteinuria higher prevalence n n active urine testing program low threshold for renal biopsy

Ig. A Nephropathy n n Ig. A nephropathy is established only by kidney biopsy Immunofluorescence microscopy q demonstrating large, globular mesangial Ig. A deposits q Ig. A often accompanied by C 3 and Ig. G in the mesangium

Ig. A Nephropathy n EM q electron dense deposits that are limited to the mesangial regions

Ig. A Nephropathy n mesangial glomerulonephritis showing segmental areas of increased mesangial matrix and cellularity

Conditions associated with Ig. A nephropathy n n n Idiopathic (most cases) Hepatic cirrhosis Gluten enteropathy HIV infection Minimal change disease Membranous GN n n Wegener’s granulomatosis ankylosing spondylitis Small cell carcinoma Disseminated tuberculosis

Ig. A Nephropathy n n n Initiating event in the pathogenesis is the mesangial deposition of Ig. A Codeposits of Ig. G and complement q commonly seen q may contribute to disease severity Between episodes of gross hematuria q n persistent microhematuria, proteinuria, or both. Gross hematuria has also followed q tonsillectomy, vaccinations, strenuous physical exercise, and trauma.

Increased Plasma Ig. A Levels n n n Not alone is sufficient to produce mesangial Ig. A deposits Found in 50% of cases Ig. A is probably accumulated and deposited because of a systemic abnormality rather than a defect intrinsic to the kidney

Ig. A Nephropathy n Two common presentations q episodic gross hematuria n n q 40 -50% upper respiratory tract infection, or, less often, gastroenteritis persistent microscopic hematuria n n 30 -40% asymptomatic, with erythrocytes (RBCs), RBC casts, and proteinuria discovered on urinalysis

Ig. A Nephropathy n n n Nephrotic range proteinuria is uncommon q occurring in only 5% of patients q Indicates more advanced disease Approximately 1 -2% of all patients with Ig. A nephropathy develop ESRD each year Hypertension seldom occurs at the time of initial presentation

Morbidity and Mortality n n follow a benign course in most cases at risk for slow progression to ESRD q q approximately 15% of patients by 10 years 20% by 20 years

Ig A Nephropathy Outcomes n 20 -30% progress to ESRD over 20 years q n 1 -2% per year Clinical predictors of poor renal outcome q q q Absence of gross hematuria Male Older onset age Heavy proteinuria Elevated Cr >2 -2. 5

Ig A Nephropathy Outcomes n Therapy remains to be defined q q q q Antibiotics Tonsillectomy Cyclophosphamide, dipyridamole High dose immunoglobulin therapy Statins Fish Oils Ace inhibition Cellcept (mycophenolate mofetil)

Ig A Nephropathy Outcomes n Ace inhibitors q q q Effectively reduce proteinuria ACE-I preserve GFR in Ig A Questionable addititive effect with ARBS

Ig A Nephropathy Outcomes n Fish Oil q Meta analysis concluded there may be a minor benefit in heavy proteinuria n q n Dillon 1997 JASN Low does omega 3 fatty acids as effective as high dose Cellcept q q Established use for transplant Not that much improvement for Ig A

Ig A Treatment Summary n If Uprot <0. 5 g/d and Cr. Cl >70 q n If Uprot > 0. 5 g/d and Cr Cl > 70 q n ACEI/ARB for target bp 125/75 If Uprot 1 -3 g/d with Cr Cl >70 q q n Observe and consider ACEI or ARB Maximal ACEI/ ARB Consider 6 months of high dose steroids and taper for 6 mo If Uprot >3 g/d and Cr. Cl <70 or declining q q Steroids plus Cytotoxics Possible maintenance with AZA or MMF

Transplant Recipients n high recurrence rate in renal transplant recipients who have Ig. A nephropathy q n 25 -60% disappearance of the deposits from donor kidneys with Ig. A nephropathy when transplanted into donors without the disease

Case Presentation n n n 44 -year-old white male with complaints of hematuria had associated abdominal pain no history of known CKD and has not actually seen a doctor in 25 years no history of other hematuria, prostate trouble, dysuria, nocturia, incontinence not on any outpatient anticoagulation 20 years of tobacco abuse

Case Presentation n recent upper respiratory infection 2 weeks ago with fevers and chills foamy urine denies any recent known UTI, over-thecounter NSAIDs, history of nephrolithiasis, contrasted procedure, physical exercise

Case Presentation n Positive signs : q q q Recent URI two weeks ago 10 pound weight gain with edema Hematuria Foamy urine Abdominal pain

Case Presentation : Labs n 133 109 13 5 22 2. 0 122 CCa 9. 6 Alb 1. 6 No Phos or Mg UA is cloudy with positive nitrite, 10 grams protein, too numerous to count red cells, trace bacteria, 1 -5 white cells

Case Presentation : Labs n CT of the abdomen and pelvis was negative for any stone, multiple loops of fluid-filled nondilated small bowel without obstruction or contracted GB

Case Presentation : Labs n All negative q q q q Complements ANA, ds. DNA Hepatitis profile Anti GBM P and C ANCA’s HIV ASO

Differential Diagnosis n Back to our case q q q 44 yo with hematura, proteinuria, and lower extremity edema two weeks after an URI No previous know CKD or AKI Cr now 2. 0 mg/dl 10 grams proteinuria Hyperlipidemia

Red Blood Cell Casts n Glomerular hematuria q Dysmorphic rbc’s n n glomerular damage rule out urologic causes

Differential Diagnosis: Glomerulonephritis n n n n n Postinfectious GN Ig. A nephropathy Thin basement membrane Mesangial proliferative GN SLE Goodpasture’s syndrome Vasculitis Cryoglobulinemia HIV n n n n Membranoproliferative glomerulonephritis Rapidly progressive GN Focal glomerulosclerosis Membranous nephropathy Amyloidosis Multiple Myeloma DM HUS

Renal Biopsy : Ig A Nephropathy n Light microscopy - Mesangial hypercellularity n Ig. A is predominantly polymeric Ig. A 1 q mainly derived from the mucosal immune system

Patient Progression n Cr continued to worsen with disease progression q March Cr: 2. 0 q April Cr: 3. 09 – 4. 2 n n n q q Initiation of Cytoxan and Steroids ( 2 cycles) ACEI caused hyperkalemia Fish Oil, BB, Lasix , Zaroxolyn, Statin, PPI, Oscal May Cr : 5. 2 June 18 th: 8. 76 n n ESRD with hemodialysis initiation Uncontrollable edema and pulmonary edema despite diuretics

Question 1 n Which of the following is the most predictive for progression of Ig A q q A- elevated levels of Ig. A B- elevated Cr at baseline diagnosis C- male gender D- absence of gross hematuria

Question 1 n Which of the following is the most predictive for progression of Ig A q q A- elevated levels of Ig. A B- elevated Cr at baseline diagnosis C- male gender D- absence of gross hematuria

Question 2 n You are seeing a 30 yr Asian woman with proven Ig A. Her Uprotein is 3. 5 g/d despite maximal ACEI, Bp is 100/70, Cr stable at 1. 6 for the past year. Diffuse foot process effacement is seen on EM. What is the next step for management? q q q A- Add ARB B- Add MMF C- Add steroids D- Add fish oils E-Tonsillectomy

Question 2 n You are seeing a 30 yr Asian woman with bx proven Ig A. Her Uprotein is 3. 5 g/d despite maximal ACEI, Bp is 100/70, Cr stable at 1. 6 for the past year. Diffuse foot process effacement is seen on EM. What is the next step for management? q q q A- Add ARB B- Add MMF C- Add steroids D- Add fish oils E-Tonsillectomy