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Late Effects

Renal and Genito-Urinary



Chemotherapy-induced renal damage can cause:

  • Acute irreversible renal failure
  • Slowly progressive chronic renal failure
  • Specific defects in renal tubule cell function

Patients may have:

  • Hypertension
  • Proteinuria
  • Variable renal insufficiency

Chemotherapy drugs associated with renal damage:



Can damage renal tissue even if mesna is used concurrently.

Causes proximal tubular dysfunction and less frequently decreased GFR.

During therapy, acute renal tubular dysfunction often resolves before the next course but permanent and potentially progressive kidney damage can also occur.

Risk of renal damage increased with:

  • High cumulative drug dose (>60 to 100 g/m2)
    • Most important factor
  • age <3 to 5 years
  • concurrent or previous platinum therapy
  • renal RT
  • unilateral nephrectomy
  • Hydronephrosis

One third of ifosfamide-treated children develop a persistent tubulopathy and 5% have clinically significant Fanconi syndrome.

Fanconi syndrome:

  • Caused by generalized dysfunction of renal proximal tubule cells.
  • Defined by excessive urinary excretion of glucose, amino acids, phosphate, bicarbonate, and other solutes handled by this nephron segment.
  • In many cases, tubular dysfunction is asymptomatic.
  • Growth failure and rickets occur if untreated.
  • Some children with ifosfamide-induced Fanconi syndrome recover sufficient renal
    tubular function one-third continue to have clinically significant renal tubular damage.

Significant hypertension may occur.

Both tubular and glomerular function may deteriorate further even after completion
of therapy.

Subclinical magnesium wasting may occur.


Cisplatin and Carboplatin

Renal damage is the major dose-limiting side effect of cisplatin

  • Treatment protocols may reduce or omit this medication when pre-treatment GFR is less than 60 ml/min/1.73 m2
  • Most children receiving cisplatin have some acute loss of renal function - but severity varies.
  • Womer et al. found a mean 8% decrease in GFR rate per 100 mg/m2 dose received.
  • Magnitude of GFR decline directly correlates with peak serum or urine platinum concentrations and cisplatin infusion rates.
  • Usually there is recovery or stability of renal function after this drug (though data is limited).
    • Mean GFR generally increases from immediately post-treatment compared to one year later
  • Magnesium-wasting tubulopathy
    • Occurs in most patients treated with cisplatin
    • Can be severe enough to require magnesium supplementation and cause hypocalcemia and/or hypokalemia.
    • This side effect tends to be long-lasting. one third to two thirds of children with cisplatin-induced hypomagnesemia remain hypomagnesemic.

Cisplatin used concurrently with other nephrotoxic agents (especially ifosfamide) increases the risk of renal injury.


  • Cisplatin analogue with a spectrum of activity similar to cisplatin
  • Less nephrotoxic than cisplatin
  • Myelosuppression is its major dose-limiting side effect
  • Not as nephrotoxic a cisplatin (not transformed into toxic metabolites by renal tubule cells).
  • Clinically important reductions in GFR and hypomagnesemia rare following carboplatin
  • The risk of renal insufficiency and tubulopathies is higher with carboplatin/ ifosfamide than with cisplatin/ifosfamide combination therapy

Methotrexate (MTX)

High-dose MTX (HDMTX) (doses in the range of 1,000–33,000 mg/m2)
used in combination with leucovorin can cause acute renal dysfunction in some patients (between 0–12 %of patients. Overall incidence rate of 1.8%) .

MTX-induced renal dysfunction results in delayed elimination of the drug and its metabolites.

Mechanism for MTX nephrotoxicity is most likely precipitation of MTX and metabolites within the renal tubular lumen.

MTX related nephrotoxicity appears to be completely reversible, with a median time to recovery of renal function of 16 days (range 4–48 days).

Subsequent HDMTX has been successfully given to patients who previously experienced renal dysfunction without recurrence of acute renal failure.



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