Rapidly progressive renal failure Dr.

Overview Introduction Etiology Conclusions Pathology Clinical features Management Conclusions

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

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

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

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

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

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

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

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

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

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

RPGN: Classification Immunological classification: based on the + or - of ANCAs The disorders are also classified based on their clinical presentation

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

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

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+

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+

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

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

RPGN: Tests & diagnosis Anti-glomerular basement membrane antibody tests Antineutrophil cytoplasmic antibodies BUN and creatinine Complement levels Creatinine clearance & Urinalysis

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

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

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

RPGN: Prevention The prompt treatment of disorders that can cause RPGN may prevent the development of this disease

RPGN:Complications *Congestive heart failure *Pulmonary edema *Hyperkalemia *Acute renal failure *Chronic renal failure *End-stage renal disease

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

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

HRS: Aggravating factors

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

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

HRS: Pathophysiology (Contd)

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

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

HRS: Treatment (Contd) Spcific measures Renal vasodilators Systemic vasoconstrictors TIPS Renal replacement therapy Liver/renal replacement therapy Liver transplantation TIPS: Transjugular intrahepatic portosystemic shunt

RPRF: Other causes Multiple Myeloma

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

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

Meyloma Kidney: Causes of renal failure in MM Cast Nephropathy

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

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

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

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

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

RPRF: Other causes (Contd) Causes of acute-on-chronic renal failure Dehydration Drugs Disease relapse/acceleration Infection Obstruction Hypercalcemia Hypertension Heart failure Interstitial nephritis

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

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