Skinner et al developed a grading system for nephrotoxicity following ifosfamide therapy in children. Serious nephrotoxicity can result in renal failure or the Fanconi syndrome, and may limit the use of the agent in patients with malignancy. The authors are from Newcastle upon Tyne in England.
Parameters for grading system:
(1) glomerular filtrate rate (GFR) in mL/min per 1.73 square meters BSA
(2) renal threshold for phosphate in mmol/L
(3) plasma bicarbonate concentration in mmol/L
(4) early morning urine osmolality in mOsm/kg•H2O
|
GFR in mL/min per 1.73 square meter BSA |
Grade |
|
>= 90 |
0 |
|
60 – 89 |
1 |
|
40 – 59 |
2 |
|
20 – 39 |
3 |
|
<= 19 |
4 |
|
Renal Threshold for Phosphate in mmol/L |
|
Symptoms |
Grade |
|
age < 12 months: >= 1.10 age >= 1 year: >= 1.00 |
AND |
none |
0 |
|
age < 12 months: 0.90 – 1.09 age >= 1 year: 0.80 – 0.99 |
AND |
none |
1 |
|
age < 12 months: 0.70 – 0.89 age >= 1 year: 0.60 – 0.79 |
AND |
none |
2 |
|
age < 12 months: 0.60 – 0.69 age >= 1 year: 0.50 – 0.59 |
AND |
none |
3 |
|
age < 12 months: < 0.60 age >= 1 year: < 0.50 |
OR |
hypophosphatemic rickets or myopathy |
4 |
Hypophosphatemic rickets:
(1) moderate or severe hypophosphatemia (serum phosphate < 0.90 mmol/L if < 0.8 months; < 17.0 if >= 1 year old)
(2) clinical signs: genu valgum, bow legs, rachitic rosary, cranial tabes, swollen wrists and ankles, abnormal gait, painful limp
(3) radiologic findings: widened epiphyseal plate, expanded metaphysis, reduced bone density, secondary hyperparathyroidism with subperiosteal erosions
|
Plasma Bicarbonate in mmol/L |
|
Symptoms |
Grade |
|
age < 12 months: >= 18.0 age >= 1 year: >= 20.0 |
AND |
none |
0 |
|
age < 12 months: 15.0 – 17.9 age >= 1 year: 17.0 – 19.9 |
AND |
none |
1 |
|
age < 12 months: 12.0 – 14.9 age >= 1 year: 14.0 – 16.9 |
AND |
none |
2 |
|
age < 12 months: 10.0 – 11.9 age >= 1 year: 12.0 – 13.9 |
AND |
none |
3 |
|
age < 12 months: < 10.0 age >= 1 year: < 12.0 |
OR |
hyperchloremic metabolic acidosis |
4 |
If a patient is receiving bicarbonate or citrate supplements for acidosis, the bicarbonate grading should be based on the last plasma bicarbonate measurement prior to starting the supplementation. If the supplements are stopped temporarily or permanently then the bicarbonate score can be regarded as appropriate (I think this means that you can grade the patient based on a current plasma bicarbonate value).
Hyperchloremic metabolic acidosis shows:
(1) moderate or severe metabolic acidosis (serum bicarbonate < 15.0 mmol/L if < 12 months; < 17.0 if >= 1 year old)
(2) moderate or severe hyperchloremia (>= 112 mmol/L)
(3) Kussmaul respirations
|
Early Morning Urine Osmolality in mOsm/kg•H2O |
|
Response to DDAVP |
Grade |
|
>= 600 |
OR |
normal response to DDAVP |
0 |
|
500 - 599 |
|
|
1 |
|
400 - 499 |
|
|
2 |
|
300 - 399 |
AND |
no symptoms AND no response to DDAVP |
3 |
|
< 300 |
OR |
nephrogenic diabetes insipidus AND no response to DDAVP |
4 |
Measurement of the early urine osmolality can be used to evaluate the ability of the distal tubule to concentrate urine without the need for a formal water deprivation test or desmopressin test. Testing should be done on 2 separate days if possible.
Response to DDAVP (desmopressin): urine osmolality >= 800 mOsm/kg•H2O (an infant < 12 months old may show a lower urinary concentrating capacity).
Nephrogenic diabetes insipidus:
(1) polyuria and polydipsia
(2) dehydration
(3) may show moderate or severe hypernatremia (serum sodium > 150 mmol/L)
(4) no response to desmopressin
total score =
= SUM(grades for all 4 items)
Interpretation:
• minimum total score: 0
• maximum total score: 16
• The higher the individual grade for each parameter, the more severe the toxicity.
• The higher the total score, the greater the toxicity.
|
Total Score |
Nephrotoxicity |
|
0 |
none |
|
1 to 3 |
mild |
|
4 to 7 |
moderate |
|
>= 8 |
severe |
Purpose: To evaluate a child receiving ifosfamide for nephrotoxicity using the grading system of Skinner et al.
Specialty: Hematology Oncology, Nephrology
Objective: severity, prognosis, stage, adverse effects
ICD-10: T45.1,
