Case Presentation
Staci Smith DO
GVH Nephrology
Case Presentation
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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
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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
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PAST MEDICAL HISTORY:
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OA
Tobacco abuse
URI 2 weeks ago
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MEDS:
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SOCIAL HISTORY:
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PAST SURGICAL HISTORY:
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ALLERGIES:
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Right knee scope
None
FAMILY HISTORY:
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Htn
No medical renal dz
None
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Cleans gutters / construction
work
Positive tobacco 1-2 ppd x 20 yrs
Social EtOh only
Case Presentation
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Positive ROS :
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Recent URI two weeks ago
10 pound weight gain with LE edema
Hematuria
Foamy urine
Abdominal pain - Zantac
Case Presentation : Physical Exam
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VS:126/87- 97.9 F (T-max 99.2)- HR 84- RR 20- 96%sat
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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
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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
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133 109 13
5
22 2.0
122
CCa 9.6 Alb 1.6
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
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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
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All negative
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Complements
ANA, dsDNA
Hepatitis profile
SPEP/ UPEP with IFE
Rheumatoid factor/ Anti CCP
Anti GBM
P and C ANCA’s
HIV
ASO
Differential Diagnosis
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Back to our case
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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
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hematuria
proteinuria
red blood cell casts
glomerulonephritis
Red Blood Cell Casts
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Glomerular hematuria
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Dysmorphic rbc’s
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glomerular damage
rule out urologic causes
Nephritic syndrome
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HTN
RBC casts
Proteinuria
Edema
Differential Diagnosis: Glomerulonephritis
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Postinfectious GN
IgA nephropathy
Thin basement membrane
Henoch-Schönlein purpura
Mesangial proliferative GN
SLE
Goodpasture’s dz
Vasculitis
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Wegener’s, Churg-Strauss
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Cryoglobulinemia
HIV
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Membranoproliferative
glomerulonephritis
Rapidly progressive GN
Fibrillary glomerulonephritis
Focal glomerulosclerosis
Membranous nephropathy
Amyloidosis
Multiple Myeloma
DM
HUS
Differential Diagnosis: Glomerulonephritis
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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
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ANA, dsDNA
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Anti-GBM dz
Goodpasture’s
ANCA’s
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c-ANCA: Wegener’s
p-ANCA: PAN, Churg
Strauss, MPA
Complements
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Cryoglobulinemia, HCV
Anti-GBM
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SLE
Cryoglobulins, RF
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ASO
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MPGN
HIV
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Post Strept GN
Hepatitis profile
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C3, C4, CH50
HIV, FSGS
Renal Biopsy
Renal Biopsy : Ig A Nephropathy
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Light microscopy - Mesangial
hypercellularity
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IgA is predominantly polymeric IgA1
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mainly derived from the mucosal
immune system
IgA Nephropathy : Berger’s Disease
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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
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relatively rare in blacks
IgA Nephropathy
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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
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IgA deposition does not necessarily need to be
followed by nephritis
IgA Deposition is Common
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IgA deposition in other forms of
glomerulonephritis
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thin basement membrane nephropathy
lupus nephritis
minimal change disease
diabetic nephropathy
IgA Nephropathy
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Many patients are detected on routine urine
screening
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asymptomatic hematuria and/or proteinuria
higher prevalence
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active urine testing program
low threshold for renal biopsy
IgA Nephropathy
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IgA nephropathy is established only
by kidney biopsy
Immunofluorescence microscopy
 demonstrating large, globular
mesangial IgA deposits
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also seen with HSP
IgA often accompanied by C3
and IgG in the mesangium
IgA Nephropathy
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EM
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electron dense deposits that are limited to the
mesangial regions
IgA Nephropathy
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mesangial glomerulonephritis showing segmental areas of
increased mesangial matrix and cellularity
Conditions associated with IgA nephropathy
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Idiopathic (most cases)
Hepatic cirrhosis
Gluten enteropathy
HIV infection
Minimal change
disease
Membranous GN
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Wegener’s
granulomatosis
Dermatitis herpetiformis
Seronegative arthritis eg, ankylosing
spondylitis
Small cell carcinoma
Disseminated
tuberculosis
Mycosis fungoides
IgA Nephropathy
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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
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persistent microhematuria, proteinuria, or both.
Gross hematuria has also followed
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tonsillectomy, vaccinations, strenuous physical
exercise, and trauma.
Increased Plasma IgA Levels
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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
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Two common presentations
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episodic gross hematuria
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40-50%
upper respiratory tract infection, or, less often,
gastroenteritis
persistent microscopic hematuria
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30-40%
asymptomatic, with erythrocytes (RBCs), RBC casts,
and proteinuria discovered on urinalysis
IgA Nephropathy
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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
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Platelet Derived Growth
Factors
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Made by mesangial cells
Increased PDGG
receceptors in glomerular
dz
Infusion of glomerular
transfection with PDGF
leads to mesangial
proliferation
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TGF- beta
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Made by mesangial cells
Pro fibrotic
Antiinflammatory and
immunosuppresive
Morbidity and Mortality
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follow a benign course in most cases
at risk for slow progression to ESRD
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approximately 15% of patients by 10 years
20% by 20 years
Ig A Nephropathy Outcomes
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20-30% progress to ESRD over 20 years
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1-2% per year
Clinical predictors of poor renal outcome
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Absence of gross hematuria
Male
Older onset age
HTN
Heavy proteinuria
Elevated Cr >2-2.5
Ig A Nephropathy Outcomes
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Therapy remains to be defined
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Antibiotics
Tonsillectomy
Cyclophosphamide, dipyridamole
High dose immunoglobulin therapy
Statins
Fish Oils
Ace inhibition
Cellcept (mycophenolate mofetil)
Ig A Nephropathy Outcomes
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Ace inhibitors
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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
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Fish Oil
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Meta analysis concluded there may be a minor
benefit in heavy proteinuria
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Dillon 1997 JASN
Low does omega 3 fatty acids as effective as high
dose
Cellcept
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Inhibits de novo guanosine nucleotide synthesis
Established use for transplant
Not that much improvement for Ig A
Ig A Treatment Summary
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If Uprot <0.5 g/d and CrCl >70
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If Uprot > 0.5 g/d and Cr Cl > 70
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ACEI/ARB for target bp 125/75
If Uprot 1-3 g/d with Cr Cl >70
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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 CrCl <70 or declining
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Steroids plus Cytotoxics
Possible maintenance with AZA or MMF
Transplant Recipients
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high recurrence rate in renal transplant
recipients who have IgA nephropathy
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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
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Cr continued to worsen with disease progression
 March Cr: 2.0
 April Cr: 3.09 – 4.2
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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
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ESRD with hemodialysis initiation
Uncontrollable edema and pulmonary edema despite
diuretics
Question 1
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Which of the following is the most predictive
for progression of Ig A
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A- elevated levels of IgA
B- elevated Cr at baseline diagnosis
C- male gender
D- absence of gross hematuria
Question 1
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Which of the following is the most predictive
for progression of Ig A
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A- elevated levels of IgA
B- elevated Cr at baseline diagnosis
C- male gender
D- absence of gross hematuria
Question 2
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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?
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A- Add ARB
B- Add MMF
C- Add steroids
D- Add fish oils
E-Tonsillectomy
Question 2
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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?
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A- Add ARB
B- Add MMF
C- Add steroids
D- Add fish oils
E-Tonsillectomy