Case Presentation

Staci Smith DO

GVH Nephrology

Case Presentation 44-year-old white right-handed

male that presented to GVH with complaints of hematuria

had associated abdominal pain and took a Zantac for it

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

recent upper respiratory infection 2 weeks ago with fevers and chills

foamy urine denies any recent known UTI, over-the-

counter NSAIDs, history of nephrolithiasis, contrasted procedure, physical exercise

Case Presentation

PAST MEDICAL HISTORY: OA Tobacco abuse URI 2 weeks ago

PAST SURGICAL HISTORY: Right knee scope

ALLERGIES: None

FAMILY HISTORY: Htn No medical renal dz

MEDS: None

SOCIAL HISTORY: Cleans gutters / construction

work Positive tobacco 1-2 ppd x 20 yrs Social EtOh only

Case Presentation

Positive ROS : Recent URI two weeks ago 10 pound weight gain with LE edema Hematuria Foamy urine Abdominal pain - Zantac

Case Presentation : Physical Exam VS:126/87- 97.9 F (T-max 99.2)- HR 84- RR 20- 96%sat GEN-Awake, alert and oriented x3. Family is at bedside and updated. No

acute distress. HEENT: Poor dentition. Atraumatic, normocephalic. Extraocular muscles

intact. Sclerae are anicteric. Mucous membranes are now moist CHEST: Respirations clear to auscultation bilaterally. No wheezing, rhonchi

or crackles ABDOMEN: Soft, nontender, nondistended. Positive bowel sounds. No

perotoneal signs or Foley EXTREMITIES: No clubbing, cyanosis. Plus 2 pitting edema. There

is no asterixis SKIN: There is no rash or cellulitis NEUROLOGIC: Cranial nerves II-XII grossly intact.

Case Presentation : Labs 133 109 13 122 CCa 9.6 Alb 1.6

5 22 2.0 No Phos or Mg

UA is cloudy with positive nitrite, large blood, 300 protein, too numerous to count red cells, trace bacteria, 1-5 white cells

Case Presentation : Labs CT of the abdomen and pelvis was negative

for any stone, multiple loops of fluid-filled nondilated small bowel without obstruction or contracted GB

Urine Pr/ Cr ratio- 10 CPK was negative at 148. LFTs normal. Amylase and lipase are normal. TSH is 3.03 Total cholesterol 277

total triglycerides 264, HDL 26, LDL 198 7.8 11.3 165 S 79-L 11-M 8 – E 2

33.6

Case Presentation : Labs All negative

Complements ANA, dsDNA Hepatitis profile SPEP/ UPEP with IFE Rheumatoid factor/ Anti CCP Anti GBM P and C ANCA’s HIV ASO

Differential Diagnosis

Back to our case 44 yo with hematura, proteinuria, and lower

extremity edema two weeks after an URI No previous know CKD or AKI Cr now 2.0 10 grams proteinuria Hyperlipidemia

Differential Diagnosis

hematuria proteinuria glomerulonephritis red blood cell casts

Red Blood Cell Casts

Glomerular hematuria Dysmorphic rbc’s

glomerular damage rule out urologic causes

Nephritic syndrome HTN RBC casts Proteinuria Edema

Differential Diagnosis: Glomerulonephritis Postinfectious GN IgA nephropathy Thin basement membrane Henoch-Schönlein purpura Mesangial proliferative GN SLE Goodpasture’s dz Vasculitis

Wegener’s, Churg-Strauss Cryoglobulinemia HIV

Membranoproliferative glomerulonephritis

Rapidly progressive GN Fibrillary glomerulonephritis Focal glomerulosclerosis Membranous nephropathy Amyloidosis Multiple Myeloma DM HUS

Differential Diagnosis: Glomerulonephritis UA with C and S Cbc with differential Renal panel Urine Pr/Cr Renal US Renal Duplex Cystography Urine eosinophils SPEP / UPEP with IFE

Differential Diagnosis: Glomerulonephritis ANA, dsDNA

SLE Cryoglobulins, RF

Cryoglobulinemia, HCV Anti-GBM

Anti-GBM dz Goodpasture’s

ANCA’s c-ANCA: Wegener’s p-ANCA: PAN, Churg

Strauss, MPA

Complements C3, C4, CH50

ASO Post Strept GN

Hepatitis profile MPGN

HIV HIV, FSGS

Renal Biopsy

Renal Biopsy : Ig A Nephropathy Light microscopy - Mesangial hypercellularity

IgA is predominantly polymeric IgA1 mainly derived from the mucosal

immune system

IgA Nephropathy : Berger’s Disease 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

relatively rare in blacks

IgA Nephropathy

large undiagnosed "latent" IgA nephropathy in the general population

the process of mesangial IgA deposition is likely to be separate from the induction of glomerular injury IgA deposition does not necessarily need to be

followed by nephritis

IgA Deposition is Common

IgA deposition in other forms of glomerulonephritis thin basement membrane nephropathy lupus nephritis minimal change disease diabetic nephropathy

IgA Nephropathy

Many patients are detected on routine urine screening asymptomatic hematuria and/or proteinuria higher prevalence

active urine testing program low threshold for renal biopsy

IgA Nephropathy

IgA nephropathy is established only by kidney biopsy

Immunofluorescence microscopy demonstrating large, globular

mesangial IgA deposits also seen with HSP IgA often accompanied by C3

and IgG in the mesangium

IgA Nephropathy

EM electron dense deposits that are limited to the

mesangial regions

IgA Nephropathy

mesangial glomerulonephritis showing segmental areas of increased mesangial matrix and cellularity

Conditions associated with IgA nephropathy

Idiopathic (most cases) Hepatic cirrhosis Gluten enteropathy HIV infection Minimal change

disease Membranous GN

Wegener’s granulomatosis

Dermatitis herpetiformis Seronegative arthritis -

eg, ankylosing spondylitis

Small cell carcinoma Disseminated

tuberculosis Mycosis fungoides

IgA Nephropathy Initiating event in the pathogenesis is the

mesangial deposition of IgA Codeposits of IgG and complement

commonly seen may contribute to disease severity

Between episodes of gross hematuria persistent microhematuria, proteinuria, or both.

Gross hematuria has also followed tonsillectomy, vaccinations, strenuous physical

exercise, and trauma.

Increased Plasma IgA Levels Not alone is not sufficient to produce

mesangial IgA deposits Found in 50% of cases IgA is probably accumulated and deposited

because of a systemic abnormality rather than a defect intrinsic to the kidney

IgA Nephropathy

Two common presentations episodic gross hematuria

40-50% upper respiratory tract infection, or, less often,

gastroenteritis persistent microscopic hematuria

30-40% asymptomatic, with erythrocytes (RBCs), RBC casts,

and proteinuria discovered on urinalysis

IgA Nephropathy

Nephrotic range proteinuria is uncommon occurring in only 5% of patients Indicates more advanced disease

Approximately 1-2% of all patients with IgA nephropathy develop ESRD each year

Hypertension seldom occurs at the time of initial presentation

Ig A Pathophysiology

Platelet Derived Growth Factors Made by mesangial cells Increased PDGG

receceptors in glomerular dz

Infusion of glomerular transfection with PDGF leads to mesangial proliferation

TGF- beta Made by mesangial cells Pro fibrotic Antiinflammatory and

immunosuppresive

Morbidity and Mortality

follow a benign course in most cases at risk for slow progression to ESRD

approximately 15% of patients by 10 years 20% by 20 years

Ig A Nephropathy Outcomes

20-30% progress to ESRD over 20 years 1-2% per year

Clinical predictors of poor renal outcome Absence of gross hematuria Male Older onset age HTN Heavy proteinuria Elevated Cr >2-2.5

Ig A Nephropathy Outcomes

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

Ig A Nephropathy Outcomes

Ace inhibitors Effectively reduce proteinuria in glomerular dz ACE-I better than other anti – HTN meds to

preserve GFR in Ig A Questionable addititive effect with ARBS

Ig A Nephropathy Outcomes

Fish Oil Meta analysis concluded there may be a minor

benefit in heavy proteinuria Dillon 1997 JASN

Low does omega 3 fatty acids as effective as high dose

Cellcept Inhibits de novo guanosine nucleotide synthesis Established use for transplant Not that much improvement for Ig A

Ig A Treatment Summary

If Uprot <0.5 g/d and CrCl >70 Observe and consider ACEI or ARB

If Uprot > 0.5 g/d and Cr Cl > 70 ACEI/ARB for target bp 125/75

If Uprot 1-3 g/d with Cr Cl >70 Maximal ACEI/ ARB Consider 6 months of high dose steroids and taper for 6 mo

If Uprot >3 g/d and CrCl <70 or declining Steroids plus Cytotoxics Possible maintenance with AZA or MMF

Transplant Recipients

high recurrence rate in renal transplant recipients who have IgA nephropathy 25-60%

Increased risk of allograft loss in living related donor

disappearance of the deposits from donor kidneys with IgA nephropathy when transplanted into donors without the disease

Patient Progression

Cr continued to worsen with disease progression March Cr: 2.0 April Cr: 3.09 – 4.2

Initiation of Cytoxan and Steroids ( 2 cycles) ACEI caused hyperkalemia Fish Oil, BB, Lasix , Zaroxolyn, Statin, PPI, Oscal

May Cr :5.2 June 18th: 8.76

ESRD with hemodialysis initiation Uncontrollable edema and pulmonary edema despite

diuretics

Question 1

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

Question 1

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

Question 2

You are seeing a 30yr Asian woman with bx proven Ig A. Her Uprotein is 3.5g/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? A- Add ARB B- Add MMF C- Add steroids D- Add fish oils E-Tonsillectomy

Question 2

You are seeing a 30yr Asian woman with bx proven Ig A. Her Uprotein is 3.5g/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? A- Add ARB B- Add MMF C- Add steroids D- Add fish oils E-Tonsillectomy