First signs Proteinuria Renal insufficiency ESRD occurs - PowerPoint PPT Presentation

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First signs Proteinuria Renal insufficiency ESRD occurs

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... First signs Proteinuria Renal insufficiency ESRD occurs in up to 50% Multiple Myeloma Treatment Resolution of underlying disorder Systemic chemotherapy Stem ... – PowerPoint PPT presentation

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Title: First signs Proteinuria Renal insufficiency ESRD occurs


1
DOM Morning ReportNephrotic Syndrome
  • Week of December 1, 2008

2
Objectives
  • To know the main characteristics
  • To understand the clinical sequelae
  • To be able to differentiate and treat the
    underlying disorders

3
Definition
  • Proteinuria
  • Hypoalbuminemia
  • Edema
  • Hyperlipidemia
  • Lipiduria

4
Proteinuria
  • Typically asx until gt 2g/24hrs
  • Severe or nephrotic range gt 3g/24hrs

5
Hypoalbuminemia
  • Decreased plasma oncotic pressure
  • Transudation of fluid into interstitium

6
Edema
  • Perceived ? in effective arterial volume
  • Salt and water retention
  • Activation of RAAS
  • Distal tubular mechanisms
  • Usually prompts patient presentation

7
Hypercholesterolemia
  • Increased hepatic synthesis
  • Hypoalbuminemia
  • Decreased oncotic pressure
  • Cholesteryl ester transfer protein
  • Converts cholesterol to LDL
  • Significantly increased
  • Severe (300-400mg/dL)

8
Sequelae
  • Proteinuria
  • Coagulation abnormalities ? ? VTE risk
  • Urinary loss of fibrinolytic factors
  • Urinary loss of antithrombin III
  • Increased platelet aggregation
  • Increased serum fibrinogen levels

9
Sequelae
  • Hypothyroidism
  • Urinary losses of thyroid-binding globulin
  • Urinary losses of thyroxine
  • Hypocalcemia
  • Hypoalbuminemia
  • Urinary losses of vitamin D binding protein
  • Low levels of 25-hydroxyvitamin D
  • Low levels of 1,25-dihydroxyvitamin D

10
Sequelae
  • Anemia
  • Urinary losses of transferrin
  • Urinary losses of erythropoietin
  • Hypercholesterolemia
  • Accelerated atherosclerosis
  • Exacerbation of CKD

11
Disorders
  • Minimal change disease
  • Focal segmental glomerulosclerosis
  • Membranous nephropathy
  • Membranoproliferative GN

12
Epidemiology
  • Age is major factor
  • Throughout adulthood
  • Minimal change disease ?
  • FSGS and membranous nephropathy ?
  • FSGS most common in black patients
  • Membranous nephropathy most common in white
    patients

13
Treatment
  • BP control
  • Goal 125/75 mmHg
  • ACEI or ARB is standard of care
  • Decreases proteinuria
  • Ameliorates nephrotic syndrome

14
Treatment
  • Hypercholesterolemia
  • TLC only marginally effective
  • Statins ? LDL goal of 100-129mg/dL
  • Fibrates for hypertriglyceridemia

15
Minimal Change Disease
  • Clinical Presentation
  • Proteinuria develops suddenly
  • Relapsing and remitting disease
  • 1/3 have only one episode
  • First relapse typically within six months
  • 10 become corticosteroid dependent

16
Minimal Change Disease
  • Acute renal failure
  • Occurs in adult patients
  • Baseline atherosclerosis
  • Rapid development of proteinuria or edema
  • Resolves with control of proteinuria

17
Minimal Change Disease
  • Treatment
  • Prednisone 60mg daily or QOD x 4 weeks
  • Then 40mg/m2 QOD x 4 weeks
  • Resistance lack of full response

18
Focal Segmental Glomerulosclerosis
  • Clinical presentation
  • Indolent
  • Wide range of proteinuria

19
Focal Segmental Glomerulosclerosis
  • Treatment
  • 16 weeks of daily or QOD prednisone
  • Cyclosporine
  • Remission in 70 of steroid-resistant patients
  • Relapse in 40 after discontinuation
  • Mycophenolate mofetil

20
Membranous Nephropathy
  • Clinical Presentation
  • 1/3 have spontaneous remission
  • 1/3 have persistent proteinuria
  • 1/3 have rapidly progressive course

21
Membranous Nephropathy
  • Treatment
  • Corticosteroid therapy alone ineffective
  • Combination for persistent nephrosis
  • Pulse corticosteroids
  • Cytotoxic therapy
  • Cyclosporine appropriate alternative monotherapy
  • Process returns when discontinued

22
Membranoproliferative Glomerulonephritis
  • Clinical presentation
  • Frequent glomerular hematuria
  • Activated alternative complement pathway
  • Low or depressed C3
  • Normal C4

23
Membranoproliferative Glomerulonephritis
  • Treatment
  • Varies based on signs and symptoms
  • Usually improves with associated disease

24
Secondary Causes
  • Diabetic nephropathy
  • Amyloidosis
  • Multiple myeloma
  • HIV-associated nephropathy

25
Diabetic Nephropathy
  • Clinical presentation
  • Longstanding DM
  • Proteinuria
  • Microalbuminuria ? macroalbuminuria
  • HTN
  • Decline in glomerular filtration rate

26
Diabetic Nephropathy
  • Epidemiology
  • Less prevalent in white patients than
  • Native Americans
  • Mexican Americans
  • African Americans
  • Predictors
  • Family h/o kidney disease
  • Family h/o HTN

27
Diabetic Nephropathy
  • Treatment
  • Glycemic control
  • Blocking RAAS and ? blood pressure
  • Goal 125/75
  • ACEI or ARB
  • Slows rate of GFR decline
  • Equal renoprotective effect

28
Diabetic Nephropathy
  • TLC
  • Protein restriction
  • Treatment of hypercholesterolemia
  • Smoking cessation
  • Renal transplant for ESRD

29
Amyloidosis
  • Clinical presentation
  • Occurs in 30 of pts with AL disease
  • Massive edema
  • Hypotension
  • Mean survival 16 months

30
Amyloidosis
  • Treatment
  • Prednisone
  • Melphalan
  • Cyclophosphamide
  • With or without colchicine

31
Multiple Myeloma
  • Clinical presentation
  • Kidney disorders (men gt women)
  • LCDD (?)
  • Secondary amyloidosis (?)
  • First signs
  • Proteinuria
  • Renal insufficiency
  • ESRD occurs in up to 50

32
Multiple Myeloma
  • Treatment
  • Resolution of underlying disorder
  • Systemic chemotherapy
  • Stem cell transplantation
  • Decrease risk for intratubular casts
  • Fix hypercalcemia
  • Alkalinize urine to pH gt 6

33
HIV-Associated Nephropathy
  • Clinical presentation
  • Primarily effects black patients
  • Heavy proteinuria
  • Renal insufficiency
  • Rapid progression to ESRD

34
HIV-Associated Nephropathy
  • Treatment
  • HAART
  • ACEI
  • Immunosuppression

35
Objectives Revisited
  • Characteristics
  • Proteinuria
  • Hypoalbuminemia
  • Edema
  • Hypercholesterolemia
  • Lipiduria

36
Objectives Revisited
  • Clinical sequelae
  • Coagulation abnormalities ? ? VTE risk
  • Hypothyroidism
  • Hypocalcemia
  • Anemia
  • Accelerated atherosclerosis
  • Exacerbation of chronic kidney disease

37
Objectives Revisited
  • Underlying disorders
  • Minimal change disease
  • Rapid onset, relapsing/remitting
  • Steroids
  • FSGS
  • Variable presentation, most common in blacks
  • Steroids ? cyclosporine

38
Objectives Revisited
  • Membranous nephropathy
  • 1/3, 1/3, 1/3
  • Steroids ? combination therapy
  • Membranoproliferative GN
  • Glomerular hematuria, low C3
  • Manage associated disease

39
Objectives Revisited
  • Diabetic nephropathy
  • Long standing DM, HTN
  • Glycemic control, RAAS blockade, TLC
  • Aymloidosis
  • Multisystem disease
  • TBD

40
Objectives Revisited
  • Multiple myeloma
  • LCDD, renal insufficiency
  • Chemo, stem cell transplant
  • HIV-associated nephropathy
  • Black, HIV, renal insufficiency
  • HAART
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