| PREGNANCY IN CHRONIC RENAL INSUFFICIENCY AND END-STAGE RENAL DISEASE |
| S.
Hou, Maywood, USA |
| Chair:
B. Broumand, Tehran, Iran |
| A.M.
Davison, Ancrum, United Kingdom |
|
|
Chairman: The next presentation is by Dr Hou from the United States: pregnancy in chronic renal insufficiency and end-stage renal disease, which has been partly covered really.
Slide 1
Dr Hou: I want to thank the organisers of the conference for inviting me. I am going to speak only briefly about chronic renal insufficiency because Professor Davison has covered some of that.
Slide 2
One of the questions he addressed was whether you have chronic renal insufficiency when you become pregnant will that lead to renal failure?
Slide 3
I think you have seen the data from John Hayslett’s study and from Professor
Junger’s study in Paris. This is a very small study we did in women
with diabetic nephropathy and renal insufficiency. The reason we did that
is because shortly before that, there had been several studies that had come
out that said that pregnancy did not have any adverse effects on nephropathy.
Our thought was really how bad is the creatinine that makes the difference.
Slide 4
We had 11 women and 14 pregnancies, at this time we sort of mixed women with
moderate and severe renal insufficiencies. They also had other manifestations
of diabetes. Serum creatinine ranged from 1.4 to 4.1, most of them were not
nephritic, but most were hypertensive and many were already anaemic.
Slide 5
The
initial serum creatinine was 1.8, and the mean final creatinine was 2.5. Most
of the patients - 8 out of the 11- became nephritic during the course of the
pregnancy.
Slide 6
Most importantly, 7 had deterioration in renal function, which did not reverse after pregnancy. The majority of these were moderate rather than severe renal insufficiencies. Nonetheless, 7 of these patients progressed to dialysis within the year or two after pregnancy.
Slide 7
73% had hypertension and more than half had permanent worsening of their renal function.
Slide 8
Remarkably,
all the babies survived. I think this just pinpoints the dilemma that Professor
Davison had brought up: you have a situation where you have a very strong
chance of worsening renal function, but we have now arrived where you have
a very good chance of having a baby that survives. However, some of these
babies were less than (at least 1 of these babies) 540 grams at less than
28 weeks gestation.
One of the things we tried to make a guess at was how big an effect does it
have if you say, ”You will be on dialysis 3-4 months sooner, if you
become pregnant.” That’s not as important as more serious rapidity
of decline.
Slide 9
What we did (there are obviously some reservations about the method) was to take the slope of creatinine in these women prior to pregnancy (only the women who had a decline during pregnancy) and we projected it out to where they would have needed dialysis had they followed that same course. Then we compared it to the time of course where they actually ended up on dialysis. The difference was about 4 or 5 years. For the women who had an acceleration of renal dysfunction during pregnancy, it was a very big difference as to when they ended up on dialysis. We should bear in mind that this was at a time before where really realised that ACE inhibitors would prevent the progression of renal disease in patients with diabetes. Now, I think all of us have had the experience of someone with diabetic nephropathy sit at a creatinine of 2 or sometimes even 3 for many years. The impact of pregnancy might be even greater now.
Slide 10
Slide 11
I am going to go ahead and talk about dialysis. When I first became interested
in looking at women with end stage renal disease and the issue of birth control
and contraception, I spoke to one of my colleagues who responded: “Show
me a birth control method that is more effective than end stage renal disease.”
Slide 12
This here is one of a number of surveys that had been done throughout the world that we tried to contact every dialysis unit in the USA. We got about half of them to respond, or at least the dialysis units caring for half of the women aged 14 to 44 responded. I believe the only complete survey has been from Belgium where they somehow got all the units to respond. At this time, there was some thought that people on peritoneal dialysis were more likely to have normal hormonal function than women on hemodialysis.
Slide 13
Again, my same colleague said: “You know even if they ovulate, then CAPD doesn’t just float away!”
Slide 14
Both of his predictions have turned out to be true. Indeed, when looking for
our denominator, we used as a numerator only the pregnancy while we were doing
the survey, so it was over a 4-year period and those 6000 women were a decent
denominator for the people who became pregnant. It was about 0.5% per year,
so 1 out of 200 women of childbearing age becomes pregnant every year. Indeed,
the frequency is significantly higher on hemodialysis than on peritoneal dialysis.
Although some of the peritoneal dialysis patients told us that it wasn’t
that the egg floated away, it’s just they spent so much of their time
doing dialysis that they didn’t have time to have sex. That wasn’t
accounted for difference.
I think in the study from Belgium, which was more inclusive, the frequency
was only 0.3% per year. In Saudi Arabia, there have been surveys where the
frequency is slightly higher. This probably underestimates the ability of
a woman who is on dialysis to become pregnant since when you are doing a survey
you are lucky to get someone to answer 2 questions! So, we only know how many
women of childbearing age and how many pregnancies. We don’t know how
many women were sexually active, how many women were using birth control,
how many women got cytoxan for their lupus and were infertile for that reason.
So, for a woman who is trying to become pregnant, the likelihood of pregnancy
may be higher, but not so high that you have any effectiveness in trying to
figure out which woman to counsel or to counsel intensively. If you are trying
to counsel all of your patients of childbearing age, there are a lot of them
for whom the message may not have much relevance. It is worth trying anyway.
Slide 15
The 1 group of women who should truly be counselled are women who have been
pregnant once before because they do have a high likelihood of becoming pregnant
again. This looks at the outcome of pregnancy and all the women we saw who
were treated with dialysis. These are women who became pregnant after they
had started on dialysis. As you can see, less than half of these pregnancies
resulted in a surviving infant. I think what is more striking is that even
though, in general, pregnancy loss for the rest of the population is primarily
first trimester loss, many of these women had second trimester losses. I wish
we could get an obstetric answer to this problem because somewhere between
16 weeks on, you have a miscarriage often with very few contractions and almost
painless dilatation of the cervix and loss of the foetus. Some obstetricians
who filled out questionnaires fro the registries have told me that these women
have incompetent cervix, and that is what we were seeing. It is almost a continuum
from 16 weeks onward all the way through the early third trimester, so many
of the neonatal deaths are simply a few weeks later on than the spontaneous
abortions. In my figures, I have taken away all of the therapeutic abortions.
The therapeutic abortions listed here were either for severe hypertension,
or one here was for critical aortic stenosis.
Slide 16
This is just a comparison. When we think about women who become pregnant with
renal insufficiency, the most severe group are those who progress to needing
dialysis while they are pregnant. You can see their foetal outcome is not
that bad, it’s about 75% of those infants survive. You again have the
dilemma of the woman who is likely to get worse during pregnancy still has
the chance of having a successful pregnancy. Unless you can promise her a
transplant, it may be her last chance to have a successful pregnancy.
Slide 17
For a brief period during the 1980s, we thought maybe peritoneal dialysis
was more effective and had a higher rate of surviving infants, but I think
the problem was two-fold: one was we were comparing the outcomes we were seeing
with the outcomes from the 1970s that the European Dialysis and Transplant
Registry reported, and we were also mixing together a group of women who started
dialysis after conception and the women who became pregnant while on dialysis.
If you look at the 2 groups of women who were on dialysis when they became
pregnant, there is not a statistically significant difference in the outcome
for hemodialysis or peritoneal dialysis. However, this is not a comparison
of hemodialysis with intensified dialysis.
One of the things that has long been advocated for pregnant women on dialysis
is to do more dialysis, although it has been hard to figure out exactly how
much more we should do.
Slide 18
The rationale was that women with residual renal function had better outcome, you could remove less fluid with each treatment, and therefore, have less hypertension. You could also liberalize the person’s diet. We know that the babies when they are born have a tremendous osmotic dialysis, and women on dialysis often have polyhydramnios. We thought perhaps this is because the high osmotic load in the foetus, from the high urea levels.
Slide 19
These are some of the problems you are going to encounter when you start intensifying
dialysis, and I think we don’t actually do much intensive daily dialysis
in patients in the US, but we talk about it a lot and fantasize that someday
we will have the resources to do daily dialysis. I think, probably, Seattle
is the only place that’s really achieved this. But, at least we have
become familiar with some of the problems that go along with it. One is alkalosis;
most dialysis machines are designed to take care of acid that is produced
every 2 days, and the normal bicarbonate in a pregnant woman is around 18
or 19. Most of your dialysis regiments aren’t designed to get it there.
So, you may have to add some hemodiafiltration or some adjustments if you
have someone particularly or if the pregnancy is complicated by hyperemesis.
Hypercalcemia can be overcome by adjusting the bath, the same with hypokalemia.
Hyperphosphatemia is something we really see in our non-pregnant dialysis
patients, and we haven’t met with a lot of objections to having to lower
the dose of phosphate binders. In some cases it’s been marked enough
that you have to actually add phosphate to the dialysis bath. We markedly
increased - tripled or quadrupled - the dose of water-soluble vitamins because
your requirements increase with pregnancy and your losses increase with intensive
dialysis. One question that’s been asked whether progesterone decreases
and if this precipitates labour during dialysis. What’s happened to
serum progesterone is very variable - anywhere from a 50% decrease to an 8%
increase - that’s been the progesterone levels during dialysis in pregnant
women.
Slide 20
How much do you have to increase the dialysis? We found (this has reached
statistical significance) is that unless you increase it all the way to 20
hours a week, you don’t seem to make any improvement in the outcome.
The outcome actually gets up to 70% successful in women you can dialyse 20
hours a week. That is not as easy as it sounds. I think I run into now much
less patient fatigue than I used to than more patient willingness to go for
20 hours. You still have the problem if the access works every time especially
if it is someone new to dialysis who doesn’t yet have a permanent access.
In Chicago, the problem is whether or not you can actually get to the dialysis
unit during a snowstorm so that it becomes very difficult to achieve this
since it requires dialysis almost every day. Sometimes we aim for 24 hours
per week with the idea that we are not going to be able to keep it going that
long.
Slide 21
In addition to survival, we look at pre-maturity. The number of babies born
beyond 32 weeks gestation is much higher in the women dialysed more than 20
hours a week. I would add that the ones who were less than 28 weeks is higher
in the intensively dialysed group, in part because there was a set of twins
born at 27 week, and that mother was dialysed 22 hours a week. There’s
another contributing factor to pre-maturity in at least 2 of those babies.
Slide 22
Severe hypertension is one of the biggest problems we run into, and hypertensive crisis. When you get up to 20 hours a week, you have a much lower incidence of very severe hypertension. Again, increasing the dialysis frequency just a little bit doesn’t seem to help.
Slide 23
You wonder how can any normal adaptations take place in someone with no kidneys.
I think the plasma volume does expand and you do get vaso-dilatation. One
of the ways you figure out someone is pregnant is you can’t remove fluid
anymore. Somehow, that increased plasma volume takes place because there’s
vaso-dilatation preventing fluid removal. But, there’s no increase in
red cell production, which is probably already at the point completely determined
by whatever erythropoietin dose. This is 1 patient’s EPO requirements.
I picked her because her iron saturation was 95% throughout the pregnancy,
so that I don’t think iron deficiency played a role, although that is
another confounding factor in a lot of women. If you notice, we had been decreasing
her dose because she was hematocritic well over 35 all the way until she conceived.
As soon as she conceived, the hematocrit dropped dramatically. We spent the
rest of the pregnancy chasing the hemotocrate to keep up, but only when we
had 4 times the original dose did we manage to get back to out target hematocrit
level.
Slide 24
Peritoneal dialysis, again, much less common in pregnancy, but you should
remember that peritonitis can infect the baby or uterus, and similarly any
obstetric infection can infect and cause peritonitis. In the registries, there
are 6 babies who had peritonitis and 5 of them had live births. We didn’t
actually have a lot of pre-mature labour. What’s really remarkable is
how few people have peritonitis and how careful these patients must have been.
Slide 25
We have had peritoneal catheter problems with leaking/failure to drain, particularly if the catheter is put in during pregnancy. In fact, we had 1 women who couldn’t drain depending on what position the baby was in. One of the most dramatic complications is laceration of one of the uterine veins by the peritoneal catheter.
Slide 26
If you see bloody peritoneal fluid in a pregnant woman you have to take it very seriously, usually hospitalise the patient until you know what’s is going on.
Slide 27
The gestational age of infants born to dialysis patients remains very low,
and probably the increase in survival is due in large part to our ability
to take care of babies even less than 28 weeks of gestation. It is really
disconcerting to see a distribution of gestational ages where there are more
babies born earlier than 28 weeks than born at term. This is an ongoing problem
even as we try to increase the success rate, which still has very pre-mature
babies.
Slide 28
These are some of the things that have been used for pre-mature labour: my
experience is that beta antagonists don’t work very well, that if you
put someone on magnesium, the one thing to be very careful of if your obstetrician
put someone on magnesium is that the patient does not get a 2-gram per hour
of magnesium which gives her a respiratory arrest before the next dialysis.
Slide 29
We don’t have follow-up on very many of the children, but about 10 of them had some development delays, and 11 had congenital anomalies, but most of these were minor.
Slide 30
I want to thank my colleagues and John Davison, who said that we know a lot
more about pregnancy now than we did before because of research, but we also
know a lot more because we have a host of patients who have ignored our advice
for many years and gone ahead and taken the chance of getting pregnant anyway.
Thank you!
Chairman: Thank you very much, Dr Hou! I guess she answered a lot of questions, but if there are any further questions, we have time for a few. Go ahead.
Question: I had a question about pregnancy and SLE. We have seen 9 patients of pregnancy on dialysis, and out of them 2 on SLE had a disastrous outcome. Though we followed instructions as you put in the journals and books, keeping less than 50 and managing as you put in the guidelines, but we have seen this disastrous outcome. Probably it depends also on the underlying disease as well. What would become the outcome on dialysis in these patients?
Dr Hou: I think that patients with SLE are among the most nerve-wracking patients to take care of in any circumstances. In the registry, I don’t think the outcome has been much worse with patients with SLE, but 1 of the maternal deaths was a result of SLE. I think taking care of some other dialysis patient is much easier than taking care of someone with SLE. There are only a few things that happen to the dialysis patient, and they don’t get renal failure because they already have it, but the patient with SLE can have cerebritis, pericarditis, and I don’t know how to make it easier. I think it is just a matter of vigilance, but nothing makes me more nervous than taking care of someone with lupus.
Chairman:
Thank you! I feel we must move forward because of the shortage of time. If
we have time at the end we will try to cover more questions. Thank you very
much!
