Spectrum of kidney diseases in malignancy

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Spectrum of kidney diseases in malignancy

• Ayman El-Sebaie, MRCP(UK)
• Head of Nephrology Dept., IMC

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INTRODUCTION

• Patients with malignancy are particularly
  vulnerable to development of renal abnormalities.
• High percentage of cancer patients are candidates
  for aggressive chemotherapy or radiation therapy,
  or both.

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INTRODUCTION

• The administration of NSAIDs for analgesia in
  the cancer patient may lead to ARF by elimination
  of the prostaglandin-mediated intra renal
  vasodilatation.

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INTRODUCTION

• Para proteins generated by multiple myeloma and
  other lymphoid neoplasms may produce renal
  dysfunction .
• Malignancy-induced metabolic abnormalities, such
  as hypercalcemia and hyperuricemia, may impair
  renal function.

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INTRODUCTION

• Extra renal malignancy may involve the kidney by
  producing obstruction of urine flow via extrinsic
  compression of the urinary tract.
• This occurs most often with gynecologic and other
  pelvic neoplasm in women and with prostatic
  cancer in men.

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CLINICAL SYNDROMES

• 1-Acute renal failure
• Pre renal,Intrinsic,Post renal.
• 2-Chronic renal failure.
• 3-Tubular dysfunction with fluid and electrolyte
  disorders.
• 4-Hematuria and/or nephrotic syndrome.

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CAUSES OF HEMATURIA AND/OR NEPHROTIC SYNDROME

• Paraneoplastic glomerulonephritis
• Membranous GN
• Minimal change nephrotic syndrome
• Crescentic GN
• Membranoproliferative GN
• Primary or metastatic renal cancer
• Chemotherapy agents causing nephrotic syndrome
• Mitomycin C
• Gemcitabine

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Paraneoplastic Glomerulopathy

• Patients with the neoplastic diseases are exposed
  to continuous antigenemia, which stimulates
  antibody production and forms circulating immune
  complexes.
• Semin Nephrol 1993,13258272.
• Membranous nephropathy appears to be the most
  common glomerular lesion in patients with solid
  tumors.

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Paraneoplastic Glomerulopathy

• Minimal change glomerulopathy is another major
  form of glomerular disease associated with
  lymphomas, particularly with Hodgkin's disease.

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TUMOR LYSIS SYNDROME

• Occurs in malignancies that are highly
  proliferative and have high tumor burdens, such
  as lymphomas and leukemias.
• Metabolic abnormalitiesincluding
  hyperphosphatemia, hyperkalemia, hyperuricemia
  and/or hypocalcemia, and renal dysfunction.
• Often, hyperuricemia (uric acid level 8 mg/dL)
  is a hallmark finding of tumor lysis syndrome.

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TUMOR LYSIS SYNDROME

• A. Patients presenting (before chemotherapy)
  with evidence of large, rapidly proliferating
  tumor burden and hyperuricemia
• Prophylaxix
• 1. Correct initial electrolyte and fluid
  imbalance, and azotemia, if possible dialysis as
  indicated for established renal failure or
  unresponsive electrolyte or metabolic
  abnormalities.

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TUMOR LYSIS SYNDROME

• 2. Maintain adequate hydration and urine output
  (gt3 L/d). May require 4 to 5 L/24 h of
  intravenous hypotonic saline .
• 3. Give Allopurinol (300 mg/m2) at least 3 days
  before therapy if possible.
• 4. Alkalinize urine to pH gt7.0 (hypotonic NaHCO3
  infusion Diamox if necessary)

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TUMOR LYSIS SYNDROME

• 5. Postpone chemotherapy (if possible) until uric
  acid and electrolytes are reasonably normalized
• 6. Continuous-flow leukapheresis might be
  indicated for patients with a high circulating
  blast count especially CML AML.

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TUMOR LYSIS SYNDROME

• B. Patients presenting (before chemotherapy) with
  normouricemia, but still at risk
• 1. Allopurinol 300 mg/m2 at least 2 days before
  therapy if possible
• 2. 4 to 5 L/d of intravenous fluids.
• 3. Urinary alkalinization.

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TUMOR LYSIS SYNDROME

• C. Patients presenting (usually after
  chemotherapy) with renal failure
• Same as for patients with tumor and
  hyperuricemia if sufficient renal function
  remains.
• If dialysis is necessary,continuous hemodialysis
  or hemofiltration may be preferable if severe
  hyperuricemia or hyperkalemia is present

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TUMOR LYSIS SYNDROME

• Spontaneous or treatment-induced tumor lysis
  syndrome (TLS) can cause significant morbidity
  and potential mortality.
• Vigorous hydration, alkalinization and
  inhibition of uric acid synthesis with
  allopurinol are the most frequently used methods
  for treatment and prevention of TLS.

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TUMOR LYSIS SYNDROME

• However, this approach fails to prevent renal
  insufficiency in up to 25 of high-risk patients.
  
• Unlike allopurinol, urate oxidase promptly
  reduces the existing uric acid pool, prevents
  accumulation of xanthine and hypoxanthine and
  does not require alkalinization, facilitating
  phosphorus excretion.

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TUMOR LYSIS SYNDROME

• A recombinant form of urate oxidase, Rasburicase,
  is now registered for the treatment and
  prevention of TLS.
• Expert Rev Anticancer Ther. 2007
  Feb7(2)233-9.

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HEMOLYTIC UREMIC SYNDROME

• HUS is a thrombotic microangiopathy presenting as
  an acute illness characterized by renal failure,
  thrombocytopenia, and microangiopathic hemolytic
  anemia.
• Vascular and endothelial cell injury leads to
  microvascular thrombosis and ischemic organ
  damage.
• HUS has been reported after chemotherapy for
  cancer.

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HEMOLYTIC UREMIC SYNDROME

• HUS can occur in diverse clinical settings,
  including metastatic carcinoma, particularly of
  the stomach, breast, or lung .
• The initiating factor is presumably tumor emboli.
• These patients have an extremely poor prognosis
  and often die within a few weeks of diagnosis.

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Renal involvement in lymphoma.

• Although primary renal lymphoma is rare, 5 to
  10 of patients with disseminated lymphoma
  exhibit clinically detectable renal involvement.
• At autopsy, the incidence of renal involvement by
  lymphoma has been estimated by several series to
  be more than 30 .
• J Am Soc Nephrol 1997, 813481354.

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Renal involvement in lymphoma

• The incidence was higher in patients with
  lymphosarcoma or histiocytic lymphoma than in
  those having Hodgkins disease, with its
  occurrence in mycosis fungoides being
  intermediate in frequency.
• The majority of patients had involvement of both
  kidneys.
• Lymphoma may involve the kidney by multinodular
  or diffuse infiltration

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Renal involvement In Leukemia

• Renal infiltration occurs in approximately
  50 per cent of patients with leukaemia.
• Infiltration of the kidney is most often
  asymptomatic, only 13.5 of patients may present
  with flank pain hematuria.
• Although all types of leukemia may infiltrate the
  kidney, this most commonly occurs with
  lymphoblastic leukemia (83 in one study), when
  it is usually bilateral and diffuse throughout
  the cortex .

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Renal involvement In Leukemia

• The presence of large kidneys without
  hydronephrosis on U/S in a patient with lymphoma
  or leukemia, is highly suggestive of tumor
  infiltration.
• The renal prognosis is dependent on the
  responsiveness of the tumor to radiation or
  chemotherapy.
• A rapid reduction in renal size and return of
  renal function toward the baseline level may be
  seen within a few days with responsive tumors.

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• (A) Contrast-enhanced CT of the abdomen. Note the
  symmetrical, bilateral renal enlargement. The
  cortex of both kidneys is widened, the bipolar
  diameter of the kidneys amounts to 15 cm.
• (B) CT of the abdomen in the same patient, after
  chemotherapy, 43 days later. A remarkable
  decrease in the size of both kidneys is seen. The
  widening of the cortex has disappeared. Note the
  subcapsular haematoma of the right kidney, caused
  by the renal biopsy.

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Renal involvement In Leukemia

• CLL may cause renal dysfunction in many different
  ways include
• uric-acid nephropathy (Tumor lysis syndrome).
• light-chain nephropathy,
• amyloidosis,
• hypercalcaemia,
• urinary obstruction,
• glomerulonephritis, cryoglobulinaemia ,
• diffuse infiltration of leukaemic cells
  throughout the renal parenchyma (rare).

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Radiation Nephritis

• Acute form within 1 year
• Chronic form within a decade.
• Pathologically interstitial fibrosis
• Prevention fractionate the dose,shielding and
  avoid nephrotoxic drugs.

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Contrast Nephropathy

• It is a relatively common cause of ARF in
  hospitalized patients.
• Patients typically develop a rise in their serum
  Cr within 24 hours after the radio-contrast,
  sometimes with oliguria.
• Renal failure is usually transient, although
  occasionally patients may require dialysis.

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Contrast Nephropathy

• Prevention
• Avoid unnecessary use of contrast studies.
• High risk patients should be given saline Iv at a
  rate of 1 ml/kg/h beginning 12 hs before the
  procedure 12 h afterwards.
• Usage of non-ionic, low osmolality agents.
• Avoid usage of other nephro-toxic drugs
  concomitantly.

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MULTIPLE MYELOMA

• In up to 25 of patients with multiple myeloma,
  ARF may be present at the time of initial
  diagnosis.
• In others, it may occur at any time during the
  disease.
• Renal failure can be due to diverse mechanisms.

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MULTIPLE MYELOMA

• Causes of ARF
• Light-chain cast nephropathy
• AL amyloidosis
• Light-chain deposition disease
• Plasma cell infiltration of the kidney
• Tubular dysfunction
• Hypercalcemic nephropathy
• Acute uric acid nephropathy
• Radiocontrast nephropathy

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MYELOMA KIDNEY

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CISPLATIN

• Cisplatin is the most frequently used
  antineoplastic agent for the treatment of solid
  tumors.
• Cisplatin-induced ARF is dose related,
  nonoliguric, and usually reversible.
• The serum creatinine level may increase
  immediately after administration and often peaks
  in 3 to 10 days dialysis is rarely required.

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CISPLATIN

• Treatment protocols involving prehydration and
  vigorous diuresis with saline and mannitol have
  greatly decreased the incidence of ARF.
• A commonly used protocol involves initiating
  diuresis 12 to 24 hours before cisplatin
  administration.

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BMT Nephropathy

• During the period of conditioning, tumor-lysis
  syndrome and stored marrow-infusion toxicity are
  most common.
• 10 to 28 days after transplantation, the peak
  incidence of ARF is observed, most notably due to
  a hepatorenal-like syndrome associated with
  veno-occlusive disease (VOD).

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BMT Nephropathy

• After 1 month, the hemolytic-uremic syndrome
  (HUS) can be observed.
• The greatest risk for development of ARF occurs
  10 to 21 days after BMT, with the usual cause at
  this time being pre renal acute renal failure due
  to hepatic veno-occlusive disease.
• This causes a syndrome very similar to the
  hepato-renal syndrome (HRS).

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BMT Nephropathy

• clinical similarities between the two syndromes
  
• 1) jaundice and portal hypertension precede
  the onset of ARF.
• 2) a very low fractional excretion of sodium .
• 3) the blood urea nitrogen (BUN)/creatinine
  ratio is very high.
• 4) mild hyponatremia and a decrease in systemic
  arterial blood pressure are usually present,.

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MESSAGES

• Good Collaboration between the Oncologist and
  Niphrologist is paramount.
• Early referral of renal impaired patients is
  crucial.
• Cautious adjustment of drugs especially to old
  patient with malignancy.

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MESSAGES

• Avoid unnecessary use of contrast media and
  follow the protocol for patients at risk.
• Close follow up to high risk cancer patients who
  receiving nephrotoxic drugs by serum Cr,
  electrolytes and fluid chart.

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Thank You For Your Attention