Combination therapy with ACE-Is and ARBs may be used for additive anti- proteinuric and renoprotective effects, but this approach has rarely been studied in children. Small randomized trials of combinations of ACE-Is and ARBs in children with CKD demonstrate significant reductions in urine protein levels as compared to the use of only one of the drug classes.335,352 However, further study of long-term outcomes and safety data are necessary. Use of ACE-Is and ARBs should be individualized on the basis of susceptibility to hypotension and of the risk of pregnancy in young women of child-bearing age. ACE-Is and ARBs are labelled by the US FDA as pregnancy category C for the first 3 months of pregnancy and category D for the last 6 months (the second and third trimesters). Pregnancy category C means that a risk may exist but its magnitude is unknown because of a lack of trustworthy studies in pregnant women, and animal studies either have shown risk in pregnancy or have not been performed. Pregnancy category D means that there have been studies in pregnant women showing that the drug is associated with some risk for the fetus, but the benefit of the drug may still outweigh that risk for some patients.84,85 Monitoring for hyperkalemia may be considered in high- risk children as kidney function declines. In the ESCAPE individuals with CKD receiving a high-dose ACE-I had an increase in mean ( standard deviation [SD]) serum potassium levels from 4.31 0.52 mmol/l to 4.71 0.57 mmol/l. The upper limit of the normal range for children (5.6 mmol/l) was exceeded in 3.3% of tests. 