1. Rapidly progressive renal failure
Dr.

2. Overview Introduction Etiology Conclusions 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 Acute – on – chronic renal failure
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, In the mid 1970s,
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+; < 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. RPGN:Complications *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 Type 2 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 Kidney:Epidemiology
In two large multiple myeloma studies, 43% (of 998 pts) had a creatinine > 1.5 and 22% (of 423 pts) had a Cr > 2.0
The one-year survival was 80% in pts with Cr < 1.5 compared to 50% in pts with a Cr > 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 2003;26(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 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 !