"The Road Not Taken..."
The patient is a 28 year old woman who is carrying her first pregnancy. In 2000, she was developed kidney failure and was found to have a condition called Goodpasteur’s syndrome. This is a disease wherein the individual develops autoantibodies against the glomerular basement membrane. Both her kidneys were removed and after awhile on dialysis, she became a candidate for a kidney transplant. A donor was found and she had this procedure performed at a university medical center. With immunosuppressive therapy, the transplant held and remained in excellent functioning condition, and other than periodic checks with the transplant team, her routine care was assumed by a group of nephrologists who practiced at her local hospital.
After consultation with her transplant doctors, she and her husband decided to risk a pregnancy. Her immunosuppressive therapy was reduced to "maintenance levels to minimize risks to the baby” and she conceived earlier this year without difficulty. Other than for the mild hypertension with which she entered the pregnancy, probably the consequence of her immunosuppressive drugs, and modest therapy for the same, the pregnancy had progressed without significant complications until recently. Baseline studies early in pregnancy revealed good renal function, a normal serum creatinine and creatinine clearance, and a 24 hour urine protein of only about 100 mg.
At 24 2/7 weeks, she presented to her physicians with a severe headache, the acute onset of swelling (diffuse edema) and weight gain, and “4+ proteinuria.” Her blood pressure was elevated over what it had been. She was admitted to the hospital with the presumptive diagnosis of severe preeclampsia. A 24 hour urine collection revealed that she now was spilling1600 mg of protein. Her liver function tests, LDH, and coagulation studies were all normal. Her serum albumin had drifted down to 2.4 mg/dL reflecting the loss in her urine and possibly reduced production by her liver.
Assuming that an extremely premature delivery was going to be necessary soon, her physicians gave her betamethasone to help accelerate fetal lung maturation and arranged for consultation with her local nephrologists and the neonatal intensive care unit. To help assess fetal status in this equation, she was sent to our office for an ultrasound. This showed normal fetal growth, normal amniotic fluid, and normal Doppler flow studies. In other words, the baby was well-grown, was having no trouble pushing blood through the placenta ,and did not appear to be starving as the result of poor placental function. Indeed, the fetal heart rate tracing was even very reassuring for this early gestational age. Her nephrologist came to see her and his only terrifying comment to her was that “your pregnancy is going to have to be terminated early for severe preeclampsia.” No other management plan was offered.
Less than satisfied with the nephrologist’s input, and even more chagrined by the comments made directly to the patient, her obstetrician corralled me in the hall for my “curbside consult.” He filled me in on her past medical history, pregnancy course, the events leading to her hospitalization, and results of her evaluation to date in the hospital. The patient certainly was at high risk for preeclampsia because of her history of an autoimmune kidney disease, renal transplant, and baseline hypertension and for all intents and purposes, she met the criteria for this diagnosis. But, two plus two did not entirely equal four at this point in her case. Usually severe preeclampsia at this early gestational age is accompanied by poor placentation resulting in fetal growth restriction, abnormal Doppler flow studies (increased resistance to fetal placental perfusion and fetal blood flow redistribution, otherwise known as “cranial sparing”), and decreased amniotic fluid as a consequence of the former. The baby had none of these problems. It appeared that her “preeclampsia” was being driven from the maternal side, not as the result of fetal compromise as is typically the case. In my past experience with renal transplant patients, I had seen similar consequences as the result of transplant rejection during the pregnancy.
It was at this point that we went to talk with the patient. She was as advertised. She complained of a headache but had no visual disturbances. She had no epigastric or right upper quadrant pain. She had diffuse edema of the face, hands, and especially the lower extremities, but reflexes were completely normal. When questioned about her immunosuppressive therapy, she confirmed that this was still at the maintenance levels of cyclosporin and prednisone at which she started the pregnancy. We suspected that between her pregnancy weight gain, normal plasma volume expansion, and the normal increases in metabolic rate during pregnancy, her cyclosporin levels were now subtherapeutic and she probably was undergoing renal allograft rejection.
While waiting for the cyclosporin levels to return from the lab, a quick phone call to her transplant doctors resulted in permission to raise the dose in the interim. The levels came back within 24 hours and were found to be undetectable despite the fact she had conscientiously been taking the prescribed amount of the drug. Within days after raising the dose of cyclosporin, her swelling began to resolve, her weight dropped, her blood pressure improved, and her serum albumin started to rise. Indeed, now two weeks later, she appears stable, the baby remains ’happy’, and more importantly, is now at a gestational age where morbidity and mortality related to prematurity improve with every passing day of gestation.
Is she out of the woods? Probably not. As I told her at the outset, I will be very surprised if she gets past 30 weeks in the pregnancy. But, miracles happen and we are now hopeful that she might. She is still at high risk for developing preeclampsia and differentiating that from transplant rejection remains a challenge. Indeed, she might succeed in the pregnancy, but still lose her kidney as a result of complications. However, I often wonder at times such as these if more than chance is at play because it was another one of those situations when the right person just happened to be in the right place at the right time and “the road not taken” might make “all of the difference.”