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

   Patients with the neoplastic diseases are exposed
    to continuous antigenemia, which stimulates
    antibody production and forms circulating
    immune complexes.
              Semin Nephrol 1993,13:258–272.

   Membranous nephropathy appears to be the most
    common glomerular lesion in patients with solid
    tumors.
Paraneoplastic Glomerulopathy


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

   Occurs in malignancies that are highly
    proliferative and have high tumor burdens, such as
    lymphomas and leukemias.

   Metabolic abnormalities—including
    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.
   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.
     TUMOR LYSIS SYNDROME
   2. Maintain adequate hydration and urine
    output (>3 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 >7.0 (hypotonic
    NaHCO3 infusion; Diamox if necessary)
     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.
     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.
     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
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.
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.
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 Feb;7(2):233-9.
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.
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.
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, 8:1348–1354.
Renal involvement in lymphoma
   The incidence was higher in patients with
    lymphosarcoma or histiocytic lymphoma than in
    those having Hodgkin’s 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
    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 .
    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.
   (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.
    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).
            Radiation Nephritis
   Acute form within 1 year

   Chronic form within a decade.

   Pathologically : interstitial fibrosis

   Prevention: fractionate the dose,shielding and
    avoid nephrotoxic drugs.
     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.
      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.
            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.
            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
    MYELOMA KIDNEY

            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).
            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).
            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,.
               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.
                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.
Thank You For Your
    Attention

				
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