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Transcript
Kidney
Disease
in
Pregnancy
CKD and pregnancy



Fertility is markedly reduced in
patients with CRF
For women with pre-existing renal
disease, pregnancy is associated
with an increased rate of fetal
complications and a considerable
risk of renal disease progression.
Due to substantial improvements in
antenatal and neonatal care, fetal
outcome has improved considerably
in the last two decades
Journal of Medical Case Reports 2008,2:10, Nephrol Dial Transplant 2007: 1 - 5
Pregnancy and CKD


Recent publications report
pregnancy in 1–7% in women
on chronic dialysis
Pregnancy in contemporary
women on dialysis is more
likely to be successful, with
30–50% of pregnancies
resulting in delivery of a
surviving infant
Journal of Medical Case Reports 2008, 2:10,
CKD and pregnancy

It is generally accepted that
pregnancy in women with CKD
and mild renal function
impairment, ie, CKD stages 1 to
2, corresponding to an
estimated GFR of 60
mL/min/1.73 m2 or greater (_1
mL/s/1.73 m2),1 is successful
and does not alter the course of
renal disease
Am J Kidney Dis 2007;49:753-762.
Frequency of Conception in
Women Undergoing Dialysis
World Congress of Nephrology, 2003
World Congress of Nephrology, 2003
Infant survival rate


Since the 1980s, the infant
survival rate has improved
from 20–30% up to 50% in
2003
This is due to the care
provided by a multidisciplinary
management team,
characterized by close
collaboration between patients,
nephrologists, dialysis staff,
obstetricians and
neonatologists. Journal of Medical Case Reports 2008, 2:10,
CKD and pregnancy - Historical Aspects


Historically (before 1975) pregnancy
discouraged for women with CKD and early
termination advised
Confortini et al reported the first successful
pregnancy in a woman on chronic HD
(Proc Eur Dial Transplant Assoc 1971:74-80).
“ children of women with renal disease
used to be born dangerously or not at all
– not at all if their doctors had their
way…...nature takes a helping hand by
blunting fertility as renal function falls”
Lancet ii, 1975, 801-2
CKD and pregnancy

Considerations
 Effect of renal disease on
pregnancy outcomes
 Effect of pregnancy on renal
disease
CKD and pregnancy




Preserved/mildly reduced renal function, Cr < 1.4
– good outcome for pregnancy and renal disease
Moderately impaired renal function, Cr 1.4 – 2.8
– risk progression of renal failure, increased fetal risk
Severe renal insufficiency, Cr > 2.8
– high fetal/maternal morbidity/mortality, low
likelihood of successful outcome, pregnancy
discouraged
High grade proteinuria and severe hypertension
– also important risk factors for progression of renal
disease in pregnancy, worse outcomes
Pregnancy: Effect on Renal function


Progressive deterioration in renal function,
apparently related to pregnancy, estimated
to occur in a considerable proportion of
women with moderate to severe CKD,
ranging from 23% to 43%
Such estimates are a matter of major
concern for women with CKD who wish to
give birth, although these estimates are
not supported by long-term follow-up or by
comparison of rates of progression before
and after pregnancy.
Am J Kidney Dis 2007;49:753-762.
Rates of Maternal Renal Function Decrease
Am J Kidney Dis 2007;49:753-762.
Mean Rate of Renal Function Decrease Before
Conception and After Delivery by Levels of GFR
and Daily Proteinuria at Baseline and Rate
Differences by Combination of the Same Baseline
Factors
Am J Kidney Dis 2007;49:753-762.
Pregnancy and Newborn outcomes by
levels of renal function & Proteinuria
Am J Kidney Dis 2007;49:753-762.
Factors influencing Fetal and
maternal outcomes



Fetal and maternal outcomes may vary not only as a
function of baseline GFR, but also by the presence of
other factors, such as proteinuria, hypertension, and
required therapies.
Angiotensin-converting enzyme (ACE) inhibitors and
angiotensin receptor blockers (ARBs) are avoided
because of their fetotoxicity and potential teratogenic
effect.
It is possible that changes in treatment schedules
and/or worsening of proteinuria and hypertension
control may negatively influence the course of renal
disease
Am J Kidney Dis 2007;49:753-762.
Clin Exp Nephrol. 2008 Apr;12(2):102-9.
Changes in Blood Pressure, Proteinuria,
and Other Complications
Am J Kidney Dis 2007;49:753-762.
Hypertension and CKD-Pregnancy




Hypertension is the most frequently reported
maternal complication in this population,
occurring in 42–80% of these women
Antihypertensive medications are often required
to maintain maternal diastolic blood pressure in
the 80–90 mmHg range
The mainstays of treatment are
 Methyldopa, B-blockers, and hydralazine.
In severe hypertension: clonidine and calcium
channel blockers.
Journal of Medical Case Reports 2008, 2:10 , Nephrol
Dial Transplant 1998:3266-3272. Nephrol Dial
Transplant 1998:3005-3007.,
CKD and pregnancy – diabetic nephropathy




6% of pregnant women with type I DM have overt
diabetic nephropathy (<20/40: Uprot>300mg/d,
macroalbuminuria >300mg/d, alb/creat. ratio
>0.3mg/mg)
Microalbuminuria also associated with an increased
risk of adverse fetal-maternal outcomes
Effect of nephropathy on pregnancy:
prematurity(22%), IUGR (15%), pre-eclampsia
Effect of pregnancy on nephropathy: exacerbation of
proteinuria and hypertension. Return to baseline
post-partum with well preserved renal function.
Kidney. March , 2008
J Coll Physicians Surg Pak. 2004 Feb;14(2):75-8.
World Congress of Nephrology, 2003
World Congress of Nephrology, 2003
CKD and pregnancy – diabetic nephropathy



Pre-eclampsia is the most frequent complication of
pregnancy in women with diabetic nephropathy
Perinatal survival 95% in pregnancy with overt
nephropathy (cf 99% general obstetric population)
Pre-conceptual management:
 Staging of disease; 24 hr Uprot. /Cr Cl, eye exam
(SCr >2.0 and Uprot >2g/24hr relative
contraindications)
 Counseling re: risks to mother and fetus
 Good glycemic/BP control, for at least 6mths preconception
 ACE inhibitors pre-conception – protective benefit
carries over into pregnancy. Substitute for CCB (?)
during pregnancy.
Kidney. March , 2008
J Coll Physicians Surg Pak. 2004 Feb;14(2):75-8.
CKD and pregnancy - ADPKD





Exacerbation of HTN, increased risk of pre-eclampsia
Genetic counselling re: risk to offspring, screening of
offspring (PKD 1 disease: >20, but negative US does
not exclude disease until pt >30-35, negative CT at
25 excludes clinically significant disease)
Prenatal genetic testing for PKD1 disease (C16) available
No increased incidence of simple UTI during
pregnancy
Association between women who have had ³3
pregnancies and worse renal function (Gabow et al)
CKD and pregnancy - Lupus







Rate of relapse not different between pregnant
women and concurrent controls (9-60%).
Major factor determining a pregnancy related
exacerbation is the stability of the disease before
conception.
If in remission for >6mths pre-conception, low
incidence of clinical flare during pregnancy.
In a prospective study of planned pregnancy in
women with inactive SLE, live birth rate was 96%.
Prematurity common.
Irreversible decline in renal function uncommon.
Assess for disease activity once each trimester, more
frequently if active disease in 6mths pre-conception
Lupus. 2006;15(3):148-55
CKD and pregnancy - Scleroderma





Before 1971; 12 case reports of pregnancy in
scleroderma –35% maternal mortality –
renal/pulmonary disease
Incidence of pregnancy in scleroderma increasing
with increasing maternal age (peak onset of this
disease 30-50)
Fertility? – no data. Increased incidence of
spontaneous abortion? – probably. Pregnancy
outcome? – no data
Scleroderma renal crisis vs pre-eclampsia vs TTP etc
High morbidity in women who develop renal crisis
during pregnancy. Women with active renal disease
or early diffuse disease counseled against
pregnancy.
Clin Exp Rheumatol. 2006 Jan-Feb;24(1):87-8.
Pregnancy and BUN values


Despite the fact that no randomized
prospective trials of pregnant women on
dialysis exist, retrospective data suggest
maintaining predialysis BUN values – beyond
16 to 20 weeks – at ≤ 50 mg/dl is an
appropriate goal
Pregnant women on dialysis will generally
require 16–24 hours of HD each week
Journal of Medical Case Reports 2008, 2:10,
Pregnancy with Chronic Kidney
Disease: Outcome in Indian
Women
Journal of Women's Health.
December 1, 2003, 12(10): 1019-1025.
Methods

Retrospective analysis of 51 pregnancies was
conducted at a tertiary care center in India to
estimate the risk of obstetrical complications,
perinatal morbidity and mortality, and the
effect of pregnancy on renal function in
women with different types and severity of
renal disease.
Journal of Women's Health.December 1, 2003, 12(10): 1019-1025.
Results:





The type of renal disease and the degree of renal
insufficiency did not have a significant effect on the
chances of successful pregnancy outcome once the
pregnancy had progressed beyond the first trimester.
The risk of prematurity was significantly increased when
the diastolic blood pressure was ≥ 90 mm Hg at
conception (OR 8.3, CI 1.6-41.5).
All patients with a diastolic blood pressure > 100 mm Hg
delivered preterm.
Hypertension worsened in 16 (35.5%) women during
pregnancy, of which 13 had to be terminated preterm
because of uncontrolled blood pressure.
Serum creatinine deteriorated during pregnancy in 32.5%,
the percentage increase showing a significant inverse
correlation to the baseline creatinine clearance.
Journal of Women's Health.December 1, 2003, 12(10): 1019-1025.
Study Conclusion

Hypertension at conception was a significant
independent factor influencing the gestational
age at delivery. The baseline renal function
did not correlate with the risk of acceleration
of hypertension during pregnancy. However,
the deterioration of renal function during
pregnancy had a significant inverse
correlation to basal creatinine clearance.
Journal of Women's Health.December 1, 2003, 12(10): 1019-1025.
Nutritional management of
pregnant with CKD


The nutritional management of pregnant
adults with chronic kidney disease (CKD)
presents the challenge of combining
necessary modifications in nutrient
requirements for both pregnancy and kidney
impairment.
The dietitian must follow these women
closely to ensure adequate intakes of
kilocalories, protein, and specific vitamins
and minerals.
Advances in Chronic Kidney Disease 2007: April 14 (2): 212-214
Nutritional management of pregnant with
CKD


Combining the suggested energy and protein needs
for CKD recommended by the Kidney Disease
Outcomes Quality Initiative (K/DOQI) guidelines with
those for the general population seems feasible
during pregnancy.
Vitamin and mineral requirements are also a
combination of those for CKD and pregnancy.
Although diets may need to be restricted because of
CKD, goals are to have good communication among
members of the health-care team to allow the patient
optimal nutrition combined with quality medical care.
Advances in Chronic Kidney Disease 2007: April 14 (2): 212-214
Nutrition and CKD-Pregnancy
1 g/kg/day protein intake plus an
additional 20 g/day for fetal
development have been suggested
 Folate supplementation is required,
particularly early in fetal development
 Replacement of water-soluble vitamins
should be continued during pregnancy

Journal of Medical Case Reports 2008
Pregnancy and Serum Calcium


Dialysate adjustment may be needed to
maintain appropriate levels of serum calcium
and to avoid hypocalcemia and/or posttreatment hypercalcemia.
Since the placenta converts some 25hydroxyvitamin D3 to 1, 25-dihydroxyvitamin
D3, adjustment of vitamin D may be required
during pregnancy and should be guided by
measurement of levels of vitamin D,
parathyroid hormone, calcium and
phosphorus
Journal of Medical Case Reports 2008, 2:10 , Edntna-Erca J 2002, 28(2):91-94.
Anemia and CKD-Pregnancy




Anemia occurs during pregnancy and pregnant
dialysis patients require intensive anemia
management.
Erythropoietin has been given safely to pregnant
dialysis patients
Erythropoietin doses need to be increased by
approximately 50% in order to maintain target
hemoglobin levels of 10–11 g/dl
Higher erythropoietin doses is required due to
 increased vascular volume with subsequent
hemodilution and
 possibly erythropoietin resistance (due to
enhanced cytokine production) during pregnancy
may contribute
Journal of Medical Case Reports 2008, 2:10 , Edntna-Erca J 2002, 28(2):91-94.
Intravenous iron and heparin
Both intravenous iron and heparin
appear to be safe during pregnancy
 However frequent monitoring of iron
stores is required and minimizing
heparin dose is recommended

Journal of Medical Case Reports 2008, 2:10 , Edntna-Erca J 2002, 28(2):91-94.
Etiology of renal disease and
outcomes in pregnancy
Best outcomes; chronic
interstitial disease (eg:reflux)
 Worse outcomes (for any
given degree of renal
impairment); lupus (?) and
MPGN
 Women with scleroderma
and polyarteritis nodosa
discouraged in past from
attempting pregnancy but
case reports of successful
outcomes with quiescent
e-medicine
disease

May 17, 2006
May26, 2008
Improving Infant Survival



Multiple causes of premature
delivery exist, including
polyhydramnios,maternal
hypertension and premature
rupture of the membranes
Since increasing dialysis frequency lowers predialysis
BUN levels, adequate dialysis may reduce the
occurrence of polyhydramnios and thus lower the risk of
premature labor
Increasing the dialysis dose prolongs gestation,
resulting in a higher infant birth weight and thus an
infant with better chance of survival
Journal of Medical Case Reports 2008, 2:10, Nephrol Dial Transplant
Dialysis and fetal outcome


In the largest study to date, the Registry for Pregnancy
in Dialysis Patients reported a significant correlation
between hours spent on dialysis therapy and improved
fetal outcome.
The increase in dialysis time seems to improve the
pregnancy outcome and offer several advantages:
 It ensures less uremic environment to the fetus and
allows the mother more liberal diet (Potassium and
protein),
 it may help to control hypertension and fluid intake
and may also reduce the amplitude of blood voulme
and electrolyte shifts
Okundaye I, Abrinko P, Hou S: Registry of pregnancy in dialysis
patients. Am J Kidney Dis 1998:766-773.
Effect of low GFR and Proteinuria
on Pregnancy




The association of low GFR and proteinuria with
protein greater than 1 g/d has a greater effect on
pregnancy-related GFR decrease than either factor
alone.
Effect of this association is greater than other
commonly considered factors impacting on the
decrease in renal function, such as arterial
hypertension or underlying renal disease.
Proteinuria is a well-recognized predictor of rate of
progression of diabetic and nondiabetic CKD.
Therefore, women with a lower GFR and greater
proteinuria may be more susceptible to the potentially
harmful effects of hemodynamic adaptation to
pregnancy, which, in turn, may impact on both
maternal and fetal outcomes.
Am J Kidney Dis 2007;49:753-762.
Fetal outcomes in CKD Pregnancy





Women with renal function impairment were shown
to be at risk of adverse fetal outcomes.
A high rate of fetal loss was reported in the past for
women in this condition.
Advances in perinatal care achieved in the last
decades made possible an improvement in rate of
live births that accounted for 93% of the series
published in 1996.
Recent data shows that perinatal mortality limited
to 4% of patients. This rate represents an
additional improvement.
However, it remains nearly 3-fold greater than that
in the general population
Am J Kidney Dis 2007;49:753-762.
Fetal Complications in CKD Pregnancy






Number of preterm deliveries are very high, and most
newborns are low birth weight or SGA.
Prematurity occurs in most cases and growth retardation,
increase in hypertension, or decrease in renal function noted
An anticipated delivery may be reasonable because most lowbirth-weight infants have a good prognosis provided that
delivery occurs in a setting with adequate perinatal care.
However, complications in premature infants have not been
completely eliminated by advances in neonatology, especially
for very-lowbirth-weight babies (1,500 g).
These infants are at greater risk of neonatal mortality and
such late consequences as low intelligence quotient and
neurosensory impairment.
These risks should be considered when the time of delivery is
planned and should be included in the information offered to
women with CKD who contemplate a pregnancy.
Am J Kidney Dis 2007;49:753-762.
Summary…



Women with moderately decreased GFR (60 to 40
mL/min/1.73 m2 [1.0 to 0.067 mL/s/1.73 m2]) may
have a successful pregnancy without substantial risk
of accelerated progression of their renal disease.
A more severe renal function impairment combined
with urinary protein excretion exceeding 1 g/d
predicts a deleterious effect on the course of renal
disease after pregnancy.
Fetal outcome also is strongly related to the
combined presence of these factors.
Am J Kidney Dis 2007;49:753-762
…Summary



Women of childbearing age with CKD should have an
early referral to a nephrologist to assess the risks of a
possible pregnancy.
In the event they become pregnant, they should have
adequate monitoring of obstetric and renal
parameters.
To minimize risks associated with pregnancy, they
should be referred to centers in which strict
cooperation between nephrologist and obstetrician is
feasible and an intensive care neonatal unit is
available.
Am J Kidney Dis 2007;49:753-762.
Conclusion



All aspects of dialysis, including duration,
adequacy, nutrition, anemia, calcium and
phosphate metabolism and BP control needs to be
closely followed throughout the course of
pregnancy.
Furthermore, a successful pregnancy in woman on
dialysis requires collaboration among
nephrologists, dialysis unit staff and obstetricians.
Finally, since pregnancy can occur in woman on
dialysis, health care providers should discuss
fertility and contraception with their premenopausal
dialysis patients.