Rapidly progressive renal failure

1
Rapidly progressive renal failure
Dr.
2
Overview

• Introduction
• Etiology
• Pathology
• Clinical features
• Management
• Conclusions

3
Introduction

• Rapidly progressive renal failure (RPRF)
• Deterioration of the GFR, associated with the
  accumulation of wastes such as urea and
  creatinine (azotemia) within weeks to months
• Note Acute renal failure (ARF) duration is
  hours to weeks

GFR Glomerular Filtration Rate
4
Etiology

• RPRF may be due to various causes
• Pre-renal
• Renal
• Post-renal

5
Etiology

• Acute Nephritis
• Rapidly progressive glomerulonephritis (RPGN)
• Acute on chronic renal failure

6
RPGN

• Characterized clinically by
• A rapid decrease in the GFR of at least 50 over
  a short period, from a few days to 3 months

7
RPGN History

• The term RPGN was first used to describe a
• Group of patients who had an unusually fulminant
  poststreptococcal glomerulonephritis and a poor
  clinical outcome
• Several years later,
• The anti-GBM antibody was discovered to produce a
  crescentic glomerulonephritis in sheep, and,
  following this discovery,
• The role of anti-GBM antibody in Goodpasture
  syndrome was elucidated

Anti GBM antiglomerular basement membrane
8
RPGN History (Contd)

• Soon afterward,
• The role of the anti-GBM antibody in RPGN
  associated with Goodpasture disease was
  established
• In the mid 1970s,
• A group of patients was described who fit the
  clinical criteria for RPGN but in whom no cause
  could be established

9
RPGN History (Contd)

• Many of these cases were
• Associated with systemic signs of vascular
  inflammation (systemic vasculitis), but some
  cases were characterized only by renal disease
• A distinct feature of these cases was
• The virtual absence of antibody deposition after
  immunofluorescence staining of the biopsy
  specimens, which led to the label pauci-immune
  RPGN

10
RPGN History (Contd)

• More than 80 of patients with pauci-immune RPGN
  were subsequently found to have
• Circulating antineutrophil cytoplasmic antibodies
  (ANCAs), and,
• Thus, this form of RPGN is now termed
  ANCA-associated vasculitis

11
RPGN Causes

• Abscess of any internal organ
• Anti- GBM antibody disease
• Blood vessel diseases such as
• Vasculitis or polyarteritis
• Collagen vascular disease such as
• Lupus nephritis and Henoch-Schonlein purpura
• Goodpasture syndrome
• IgA nephropathy History of cancer
• Membranoproliferative GN
• Blood or lymphatic system disorders
• Exposure to hydrocarbon solvents

12
RPGN Pathology

• The main pathologic finding is
• Extensive glomerular crescent formation
• Focal rupture of glomerular capillary walls that
  can be seen by light microscopy and electron
  microscopy

13
RPGN Classification

• Immunological classification based on the or
  - of ANCAs
• The disorders are also classified based on their
  clinical presentation

14
RPGN Classification (Contd)

• Anti-GBM antibody (Approx. 3 of cases)
• Goodpasture syndrome (lung and kidney
  involvement)
• Anti-GBM disease (only kidney involvement)
• Note 10-40 of patients may be ANCA positive

15
RPGN Classification (Contd)

• Immune complex
• Postinfectious (staphylococci/streptococci)
• Collagen-vascular disease
• Lupus nephritis
• Henoch-Schönlein purpura (immunoglobulin A and
  systemic vasculitis)
• Immunoglobulin A nephropathy (no vasculitis)
• Mixed cryoglobulinemia

16
RPGN Classification (Contd)

• Immune complex contd.
• Primary renal disease
• Membranoproliferative glomerulonephritis
• Fibrillary glomerulonephritis
• Idiopathic
• Note Of all patients with crescentic immune
  complex glomerulonephritis, 25 are ANCA lt 5
  of patients with noncrescentic immune complex
  glomerulonephritis are ANCA

17
RPGN Classification (Contd)

• Pauci-immune
• Wegener granulomatosis (WG)
• Microscopic polyangiitis (MPA)
• Renal-limited necrotizing crescentic
  glomerulonephritis (NCGN)
• Churg-Strauss syndrome
• Note 80-90 of patients are ANCA

18
RPGN Symptoms
Edema (swelling) of the face, eyes, ankles,
feet, legs, or abdomen Blood in the
urine Dark or smoke-colored urine Decreased
urine volume Abdominal pain Cough
Diarrhea General ill feeling Fever Joint
aches Muscle aches Loss of appetite
Shortness of breath
19
RPGN Signs

• A physical examination reveals edema (swelling)
• Abnormal heart and lung sounds may be present
• Blood pressure may be high

20
RPGN Tests diagnosis

• Anti-glomerular basement membrane antibody tests
• Antineutrophil cytoplasmic antibodies
• BUN and creatinine
• Complement levels
• Creatinine clearance Urinalysis

21
RPGN Treatment

• Depends on the underlying cause
• Corticosteroids may relieve symptoms in some
  cases
• Medications that suppress the immune system may
  also be prescribed, depending on the cause
• Plasmapheresis may relieve the symptoms in some
  cases

22
RPGN Treatment

• Persons should be closely watched for signs of
  progression to kidney failure
• Dialysis or a kidney transplant may ultimately be
  necessary

23
RPGN Prognosis
Without treatment, RPGN often worsens rapidly to
kidney failure and end-stage kidney disease in
6 months, although a few cases may just go away
on their own Those who receive treatment may
recover some or rarely all of their original
kidney function The extent of recovery is related
to the degree of kidney function at diagnosis and
degree of crescent formation The disorder may
recur If the disease occurs in childhood, it is
likely that kidney failure will eventually develop
24
RPGN Prevention
The prompt treatment of disorders that can cause
RPGN may prevent the development of this disease
25
RPGNComplications
Congestive heart failure Pulmonary
edema Hyperkalemia Acute renal
failure Chronic renal failure End-stage renal
disease
26
RPRF Other causes

• Hepatorenal syndrome (HRS)
• Frerichs (1861) and Flint (1863) first noted
  association of liver disease and oliguria without
  renal histologic changes

27
HRS Types

• Type 1
• Rapidly progressive renal failure
• Doubling of creatinine
• Precipitating factor frequently identified
• Type 2
• Moderate, steady renal failure
• Milder elevation of creatinine
• May arise spontaneously

28
HRS Aggravating factors
29
HRS Pathologphysiology

• Hallmark Intense renal vasoconstriction
• Starts at an early time point and progresses with
  worsening liver disease

30
HRS Pathophysiology (Contd)

• Peripheral (splanchnic) arterial vasodilation
  subsequent renal vasoconstriction
• Stimulation of renal sympathetic nervous system
• Cardiac dysfunction circulatory derangements and
  renal hypoperfusion
• Cytokine/mediator action on renal circulation

31
HRS Pathophysiology (Contd)
32
HRS Prognosis

• Type 1 RPRF
• 80 2 week mortality,
• 90 3 month
• Prognosis worse if precipitating factor exists
• Severity of liver disease a determinant of
  survival

33
HRS Treatment

• General measures
• Central venous access
• Monitor fluid status
• Volume albumin/furosemide to titrate CVP
• Nutrition critical avoid high protein low salt,
  free water restriction

34
HRS Treatment (Contd)

• Spcific measures
• Renal vasodilators
• Systemic vasoconstrictors
• TIPS
• Renal replacement therapy
• Liver/renal replacement therapy
• Liver transplantation

TIPS Transjugular intrahepatic portosystemic
shunt
35
RPRF Other causes

• Multiple Myeloma

36
Myeloma KidneyEpidemiology

• In two large multiple myeloma studies, 43 (of
  998 pts) had a creatinine gt 1.5 and 22 (of 423
  pts) had a Cr gt 2.0
• The one-year survival was 80 in pts with Cr lt
  1.5 compared to 50 in pts with a Cr gt 2.3
• Prognosis is especially poor in pts who require
  dialysis

37
Meyloma Kidney Causes of renal failure in MM

• Cast nephropathy
• Light chain deposition disease
• Primary amyloidosis
• Hypercalcemia
• Renal tubular dysfunction
• Volume depletion
• IV contrast dye, nephrotoxic meds

38
Meyloma Kidney Causes of renal failure in MM
Cast Nephropathy
39
Myeloma Kidney Treatment of renal failure in MM

• Hydration with IV fluids
• Treatment of hypercalcemia
• Loop diuretics
• Caution with bisphosphonates
• Treatment of myeloma
• Pulse steroids /- thalidomide
• VAD chemotherapy
• Possible role for plasmapheresis
• Dialysis, as necessary

40
Myeloma Kindey Prevention of renal failure in MM

• IVF hydration
• Discontinuation of nephrotoxic drugs (i.e.
  NSAIDs, etc.)
• Chemotherapy/steroids treatment of multiple
  myeloma to decrease the filtered light chain load

41
RPRF Other causes

• Drug induced, e.g.
• Acyclovir
• Orlistat
• The increased intraluminal free fatty acids
  complex with intraluminal calcium ions,
  competitively inhibiting the precipitation of
  oxalate with calcium
• The increase in soluble uncomplexed oxalate
  facilitates oxalate absorption, resulting in
  hyperoxaluria and oxalate stone

42
RPRF Other causes

• Type 2 Diabetes with renal failure, Factors
  Affecting Progression of
• hypoalbuminemia, anemia, higher mean blood
  pressure, and lack of use of insulin predict
  rapid progression of renal failure, but HbA1c
  does not, and insulin therapy may be possibly an
  indicator of the delay in progression of renal
  failure

Diabetes Care, May 200326(5)1530
43
RPRF Other causes (Contd)

• Diabetes Dietary acid load and rapid progression
  to end-stage renal disease
• High ingestion of nonvolatile acids with food
  increases susceptibility for progression to
  end-stage renal failure
• These high dietary acid loads lead to
  compensatory increases in renal acid excretion
  and ammoniagenesis.
• The price paid for maintenance of acid-base
  homeostasis is renal tubulointerstitial injury,
  with subsequent decline in renal function and
  induction of hypertension

J Nephrol. 2010 Sep 24
44
RPRF Other causes (Contd)

• Causes of acute-on-chronic renal failure
• Dehydration
• Drugs
• Disease relapse/acceleration
• Infection
• Obstruction
• Hypercalcemia
• Hypertension
• Heart failure
• Interstitial nephritis

45
Conclusions

• RPRF is defined based on duration of decline in
  renal function (weeks to months) with various
  etiologies
• Patient should be evaluated for the cause and
  treated accordingly
• RPGN is common group for RPRF
• Diabetes, HRS, Multiple myeloma may also be the
  reasons for RPRF

46
THANK YOU !