1. Morning Report
Jieli Li
03/28/05

2. Chief Complaint
Generalized edema x 1 week

3. HPI
46 y/o AAM with hx of htn, Hep C, syphillis presented to Urgent Care with generalized edema x 1 week
Pt noticed progressive lower extremity edema, then scrotal edema, as well as tightness in abdomen. + facial edema as well
Pt was seen by PMD and started on HCTZ last week without any relief

4. HPI cont. + 2 pillow orthopnea
+ 1 episode of PND and wheezing recently
+ occasional wheezes x 1 yr
+ SOB with exertion
+ occasional cough with yellow phlegm
Baseline exercise capacy excellent
No CP, f/c/s, no diarrhea/constipation
No dysuria, no hemauria

5. PMH Htn – dx’d 1 yr ago Hep C – never treated
Syphillis – treated in 1989
Depression
Hyperlipidemia
Bilateral leg fractures in the past

6. Meds & Allergies Meds: Allergy: Atenolol 50 qd HCTZ 12.5 qd
Simvastatin 10 qhs
Ascorbic acid 500 qd
Alleve prn (OTC)
Allergy:
NKDA

7. Social and Family History
SH:
Single, lives at Midnight Mission
Hx of incarceration x 37 months until Nov 2004, HIV neg in 2000
Hx of cocaine, MJ, no IVDU
Hx of heavy etoh use, quit 40 months ago
Hx of tobacco (1/2 pk per day x 20 yrs), quit 2 yrs ago
FH:
Mother: DM & htn
Father: CAD with triple bypass

8. Physical Exam
VS: 96.8, 73, 20, 178/99, 0/10
Gen: obese AAM with anasarca, NAD, AAO x 4
HEENT: PERRLA, EOMI, op moist and intact, no lesions
Heart: distant heart sounds, no murmurs appreciated
Lungs: cta bilaterally, no crackles/wheezes
Abd: obese, mildly distended, NT, na bs, no hsm

9. PE cont.
GU: + large scrotal edema, non-tender, testes palpable and intact, no masses
Ext: 2-3+ pitting edema bilateral legs, generalized anasarca, + patchy flesh-colored papular lesions bilateral shins, faint pulses bilaterally

10. Lab Studies UA Spot protein/Cr: 2967/396 = 7.5
Spec grav 1.04
PH 6.5
Protein > 600
Glucose neg
Ketones neg
Bilirubin neg
Small occult blood
Urobilinogen 0.2
Spot protein/Cr: 2967/396 = 7.5
24 hr urine protein: 12.1g
Nitrite neg
LE neg
RBC 4
WBC 8
Hyaline casts 40

11. Lab Studies cont.
15.2
44.8 93
Alk Phos 66
ALT 14
Total bili 0.7
Alb 1.1
Total cholesterol 411
Trig 157
HDL 121
LDL 259

12. Glomerulonephritis Panel
RPR 1:1
MHA-TP: 4+
ESR: 89
HIV neg
C3 and C4: nl
RF: neg
ASO: nl
SPEP: hypogammaglobulinemia
Cryoglobulin neg
Hep A ab R, IgM NR
Hep B surface Ag NR
Hep B core Ab NR
HCV RNA 1,010,000
HIV neg

13. Renal u/s Right kidney 14.6 cm, left kidney 13 cm
No definitive abnormalities although there is very mild increased cortical echogenicity
Mildly enlarged prostate without bladder outlet obstruction

14. Hospital Course
Pt was admitted to GMED for workup of his nephrotic syndrome
Hep C induced MPGN vs FSGS vs membranous GN was high on the differential
Pt was started on lasix, titrated up to 40 po bid eventually for his anasarca
He was placed on low salt diet
ACEI was held during diuresis, Cr improved to baseline (1.1)

15. Hospital Course cont.
GI was consulted for possible Hep C treatment after HCV RNA came back > 1 million
Pt’s proteinuria was followed by serial protein/Cr ratio and 24 hr urine protein
Renal biopsy showed minimal change disease confirmed by EM
This was believed to be 2/2 hx of NSAIDS
By the time of discharge, pt has only trace protein on UA, he did not receive any further tx

16. 1 week follow up
At the renal clinic f/u one week after discharge, pt’s proteinuria has dropped from 12 g/day to 0.3 g/day. He has lost nearly 100 lbs on diuresis (back to baseline wt). He is no longer taking NSAIDs.

17. Nephrotic Syndrome Defined by presence of:
heavy proteinuria (> 3g/24hrs)
Hypoalbuminemia (< 3.0 g/dL)
Peripheral edema
Isolated heavy proteinuria is more likely to be due to secondary focal glomerulosclerosis
Urinary sediment:
few cells or casts
Lipiduria (oval fat bodies)

18. Oval Fat Bodies

19. Etiology In children In adults In elderly
Minimal change disease is predominant
In adults
Systemic disease related: 30%
Primary renal disorders: 70%
Membranous nephropathy
Focal glomerulosclerosis
Minimal change disease
Amyloidosis
In elderly
Increased incidence of amyloidosis and decreased incidence of SLE

20. Etiology cont.
Although nephrotic syndrome can develop in patients with postinfectious GN, membranoproliferative GN, and IgA nephropathy, most commonly these disorders present with a “nephritic” picture, i.e., RBC and cellular casts in UA

21. Minimal Change Disease
90% of nephroitic syndrome in children under the age of 10
50% of cases in older children
In adults, can occur as an ideopathic condition or be associated with:
NSAIDs
Cancers as a paraneoplastic phenomenon, most often Hodgekin’s Disease

22. Minimal Change Disease
Light Microscopy
Either normal or reveals only mild mesangial cell proliferation EM
Diffuse fusion of the epithealial cell foot processes

23. Minimal Change Disease

24. Focal Glomerulosclerosis (FGS)
35% of all cases of nephrotic syndrome in the U.S.
> 50% of cases among African Americans
Can occur as an ideopathic condition or be associated with:
HIV disease
reflux nephropathy
Healed previous glomerular injury
NSAIDs
Massive obesity

25. Diagnostic Considerations for FGS
Sampling error in renal biopsy may lead to misclassification of FGS as minimal change disease
Steroid-resistance in minimal change disease pts should raise suspicion for FGS
Primary FGS usually presents with acute onset nephrotic syndrome, tx is corticosteroids.
Secondary FGS usually presents with slowly increasing proteinuria, nephrotic syndrome is rare. Tx is ACEI.

26. Focal Glomerulosclerosis

27. Collapsing FGS
A histologic variant usually associated with HIV infection
Tendency to collapse and sclerosis of the entire glomerular tuft, rather than segmental injury
Often severe tubular injury with proliferative microcyst formation and tubular degeneration
Often with rapidly progressive renal failure
Optimal therapy is uncertain

28. Collapsing FGS

29. Membranous Nephropathy
Basement membrane thickening with little or no cellular proliferation or infiltration
Presence of electron dense deposits across the glomerular basement membrane
Can occur as ideopathic condition or be associated with:
Hep B
Autoimmune diseases
Thyroiditis
Carcinoma
Certain drugs (e.g., gold, penicillamine, captopril and NSAIDs)

30. Membranous Nephropathy

31. Amyloidosis 4-17% of nephrotic syndrome
Increased frequency among elderly
Two major types:
Primary amyloid (AL)
A light chain dyscracia
Fragments of monoclonal light chains form the amyloid fibrils
Secondary amyloid (AA)
Acute phase reactant serum amyloid A forms the amyloid fibrils
Assoc with chronic inflmmatory diseases such as RA or osteomyelitis

32. Amyloidosis

33. Pathophysiology Proteinuria
Increased filtration of macromolecules across the glomerular capillary wall
Commonly due to abnormalities in podocytes
Increased loss of:
Albumin
Clotting inhibitors
Transferrin
Hormone binding proteins (e.g., Vit D binding protein)

34. Pathophysiology Hypoalbuminemia Edema Presumably 2/2 proteinuria
Unclear why hepatic synthesis can not compensate sufficiently
Edema
Marked hypoalbuminemia leading to movement of fluid into the interstitial space by decreasing plasma oncotic pressure
Primary renal sodium retention in collecting tubules

35. Pathophysiology Hyperlipidemia and lipiduria
Decreased plasma oncotic pressure stimulates hepatic lipoprotein synthesis
Diminished clearance may also play a role
Impaired metabolism is primarily responsible for nephrotic hypertriglyceridemia
Oval fat bodies are thought to be degenerated renal tubular epithelial cells containing cholesterol esters

36. Complications of Nephrotic Syndrome
Protein malnutrition
Hypovolemia
Acute renal failure
Urinary loss of hormones
Hyperlipidemia and the potential for accelerated atherosclerosis
Thrombosis
Increased susceptibility to infection

37. Protein malnutrition Loss in lean body mass due to proteinuria
May be masked by concurrent edema
May be compounded by GI symptoms of anorexia and vomiting 2/2 bowel edema

38. Hypovolemia
Often as a result of overdiuresis in those with a serum albumin < 1.5 g/dL
Occurs more often in children

39. Acute Renal Failure Can be seen in: Mechanism not well understood
Minimal Change Disease
Collapsing FGS
Crescentic glomerulonephritis superimposed upon membranous nephropathy
Mechanism not well understood
Hypovolemia
Interstitial edema
Ischemic tubular injury
NSAIDs

40. Thromboembolism
Increased incidence of arterial and venous thromboemboli, particularly DVT and renal vein thrombosis
Mechanism not well understood
Renal vein thrombosis is most often found with membranous nephropathy
Can present acutely with flank pain, gross hematuria and ARF or
Indolent disease without symptoms, suspected only when PE occurs

41. Infection
Before abx became available, this used to be the leading cause of death in children with nephrotic syndrome
Pneumococcal infections, esp peritonitis were most common
Mechanism is not well understood
Low levels of IgG may play a role

42. Proximal tubular dysfunction
Often associated with advanced disease
Can result in:
Glucosuria
Aminoaciduria
Phosphaturia
renal tubular acidosis
Vitamin D deficiency
Thyroid dysfunction – due to loss of thyroxine-binding globulins

43. Diagnosis 24 hour urine collection
> 3 g/day
Total protein to creatinine ratio on spot urine specimen
Correlates with daily protein excretion in g/1.73 m2 of body surface area
In history, should look for hx of DM, SLE, HIV, drugs such as NSAIDs, gold, penicillamine

44. Serologic Studies
Certain serologic tests may preclude the need for renal biopsy:
SPEP/UPEP
Presence of a paraprotein should be followed by fat pad or rectal biopsy to look for amyloidosis
ASO
poststreptococcal glomerulonephritis
Cryoglobulins
Mixed cryoglobulinemia, commonly 2/2 Hep C

45. Renal Biopsy
In adults, renal biopsy is usually required to determine diagnosis
Contraindications:
Uncorrectable bleeding diathesis
Uncontrolled hypertension
Small kidneys generally indicative of chronic irreversible disease
Multiple bilateral cysts or renal tumor
Hydronephrosis
Active renal or perirenal infection
Uncooperative patient

46. Management Proteinuria ACEI / ARB
To lower intraglomerular pressure, which may reduce protein excretion and slow the rate of disease progression
Potential adverse effects include ARF and hyperkalemia
Evidence is unclear on protein restriction

47. Management Edema Dietary sodium restriction Diuretics
Edema is due to primary renal sodium retention in most cases
Diuretics
Proceed slowly to prevent acute hypovolemia
Generally there is lesser natriuresis than in normal patients because of hypoalbuminemia and albuminuria
Serial body weight is important in guiding the titration of diuretics

48. Management Hyperlipidemia Hypercoagulability
Usually reverse with resolution of the renal disease
In case of persistent nephrosis, dietary modification is usually of little value and a statin is usually required
Hypercoagulability
Some have suggested prophylactic anticoagulation in membranous nephropathy due tot high incidence of thromboemboli
In others, if unexplained thrombosis occurs, they should be put on heparin followed by warfarin for as long as the nephrotic syndrome persists