Table 2.

Main immunosuppressive drugs in pregnant CKD patients

Drug	Main features	FDA
Usually considered as relatively safe, when absolutely needed [341–349]
Azathioprine	This is the most widely used immunosuppressive drug. It is teratogenic in animal models, but not in humans, possibly because the foetal liver is not able to activate the drug. K-DIGO and European Best Practice Guidelines suggest switching from Mycophenolate to Azathioprine before pregnancy [341–343]	D
Cyclosporine A	This Calcineurin inhibitor has not been associated with increased teratogenicity; however, small for gestational age babies and preterm delivery have been reported, possibly due to the maternal disease and not specifically to the drug; levels may vary in pregnancy and the hypertensive, hyperglycaemic and nephrotoxic effects should be mentioned [344]	C
Tacrolimus	The drug has similar effects and side effects as Cyclosporine A; since it is a relatively new drug, experience is more limited than with the previous drug [345]	C
Steroids	Together with azathioprine these are the most often employed and best known drugs. The most frequently used short-acting corticosteroids include prednisone, methylprednisolone and prednisolone, while betamethasone and dexamethasone are among the long-acting drugs. No major malformations have been reported, and the issue of labio-palatoschisis is debated. A higher risk of premature rupture of membranes has been reported. Other relevant side effects include infectious risk, and the increased risk of gestational diabetes [346]	C
Hydroxy-chloroquine	This synthetic anti-malaric agent crosses the placenta but was not found to be associated with foetal toxicity [217–219]	B
To be avoided [341 – 349]
Cyclo-phosphamide	This alkylating agent is contraindicated in pregnancy; a few reports suggest that pregnancy termination is common in the case of inadvertent use or need for life saving therapy. A few positive reports, mainly in women with SLE are also available [68]	D
Mycophenolate	Severe foetal malformations are reported, mainly involving cardiovascular and cranial malformations. Discontinuation for at least 6 months, to stabilize kidney function, is usually indicted after kidney transplantation [347, 348]	D
Rituximab	There are no data on whether rituximab can cause foetal harm. Rituximab was detected postnatally in the serum of infants exposed in utero: B-cell lymphocytopenia generally lasting less than 6 months can occur in infants. The manufacturer recommends contraception for up to 12 months following therapy [369, 370]	C
m-Tor inhibitors	Very few studies have considered their use in pregnancy. They are teratogenic in animals and discontinuation in humans is a matter of debate; KDIGO guidelines suggest discontinuation in anticipation of pregnancy [347, 349]	C

FDA site of the Food and Drug Administration [340]; FDA rating: A, controlled human studies show no risk; B, no evidence of risk in studies; C, risk cannot be ruled out; D, positive evidence of risk; X, contraindicated in pregnancy