2CKD 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 decadesJournal of Medical Case Reports 2008,2:10, Nephrol Dial Transplant 2007: 1 - 5
3Pregnancy and CKDRecent publications report pregnancy in 1–7% in women on chronic dialysisPregnancy in contemporary women on dialysis is more likely to be successful, with 30–50% of pregnancies resulting in delivery of a surviving infantJournal of Medical Case Reports 2008, 2:10,
4CKD and pregnancyIt 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 diseaseAm J Kidney Dis 2007;49:
5Frequency of Conception in Women Undergoing Dialysis World Congress of Nephrology, 2003
7Infant survival rateSince the 1980s, the infant survival rate has improved from 20–30% up to 50% in 2003This 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,
8CKD and pregnancy - Historical Aspects Historically (before 1975) pregnancy discouraged for women with CKD and early termination advisedConfortini 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
9CKD and pregnancy Considerations Effect of renal disease on pregnancy outcomesEffect of pregnancy on renal disease
10CKD and pregnancy Preserved/mildly reduced renal function, Cr < 1.4 – good outcome for pregnancy and renal diseaseModerately impaired renal function, Cr 1.4 – 2.8– risk progression of renal failure, increased fetal riskSevere renal insufficiency, Cr > 2.8– high fetal/maternal morbidity/mortality, low likelihood of successful outcome, pregnancy discouragedHigh grade proteinuria and severe hypertension– also important risk factors for progression of renal disease in pregnancy, worse outcomes
11Pregnancy: 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:
12Rates of Maternal Renal Function Decrease Am J Kidney Dis 2007;49:
13Mean 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 FactorsAm J Kidney Dis 2007;49:
14Pregnancy and Newborn outcomes by levels of renal function & Proteinuria Am J Kidney Dis 2007;49:
15Factors 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 diseaseAm J Kidney Dis 2007;49:Clin Exp Nephrol Apr;12(2):102-9.
16Changes in Blood Pressure, Proteinuria, and Other Complications Am J Kidney Dis 2007;49:
17Hypertension and CKD-Pregnancy Hypertension is the most frequently reported maternal complication in this population, occurring in 42–80% of these womenAntihypertensive medications are often required to maintain maternal diastolic blood pressure in the 80–90 mmHg rangeThe mainstays of treatment areMethyldopa, B-blockers, and hydralazine.In severe hypertension: clonidine and calcium channel blockers.Journal of Medical Case Reports 2008, 2:10 , Nephrol Dial Transplant 1998: Nephrol Dial Transplant 1998: ,
18CKD 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 outcomesEffect of nephropathy on pregnancy: prematurity(22%), IUGR (15%), pre-eclampsiaEffect of pregnancy on nephropathy: exacerbation of proteinuria and hypertension. Return to baseline post-partum with well preserved renal function.Kidney. March , 2008J Coll Physicians Surg Pak Feb;14(2):75-8.
21CKD and pregnancy – diabetic nephropathy Pre-eclampsia is the most frequent complication of pregnancy in women with diabetic nephropathyPerinatal 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 fetusGood glycemic/BP control, for at least 6mths pre-conceptionACE inhibitors pre-conception – protective benefit carries over into pregnancy. Substitute for CCB (?) during pregnancy.Kidney. March , 2008J Coll Physicians Surg Pak Feb;14(2):75-8.
22CKD and pregnancy - ADPKD Exacerbation of HTN, increased risk of pre-eclampsiaGenetic 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) - availableNo increased incidence of simple UTI during pregnancyAssociation between women who have had ³3 pregnancies and worse renal function (Gabow et al)
23CKD 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-conceptionLupus. 2006;15(3):148-55
24CKD and pregnancy - Scleroderma Before 1971; 12 case reports of pregnancy in scleroderma –35% maternal mortality – renal/pulmonary diseaseIncidence 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 dataScleroderma renal crisis vs pre-eclampsia vs TTP etcHigh morbidity in women who develop renal crisis during pregnancy. Women with active renal disease or early diffuse disease counseled against pregnancy.Clin Exp Rheumatol Jan-Feb;24(1):87-8.
25Pregnancy 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 goalPregnant women on dialysis will generally require 16–24 hours of HD each weekJournal of Medical Case Reports 2008, 2:10,
26Pregnancy with Chronic Kidney Disease: Outcome in Indian Women Journal of Women's Health.December 1, 2003, 12(10):
27MethodsRetrospective 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):
28Results: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 ).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):
29Study ConclusionHypertension 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):
30Nutritional 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):
31Nutritional 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):
32Nutrition and CKD-Pregnancy 1 g/kg/day protein intake plus an additional 20 g/day for fetal development have been suggestedFolate supplementation is required, particularly early in fetal developmentReplacement of water-soluble vitamins should be continued during pregnancyJournal of Medical Case Reports 2008
33Pregnancy and Serum Calcium Dialysate adjustment may be needed to maintain appropriate levels of serum calcium and to avoid hypocalcemia and/or post-treatment hypercalcemia.Since the placenta converts some 25-hydroxyvitamin 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 phosphorusJournal of Medical Case Reports 2008, 2:10 , Edntna-Erca J 2002, 28(2):91-94.
34Anemia and CKD-Pregnancy Anemia occurs during pregnancy and pregnant dialysis patients require intensive anemia management.Erythropoietin has been given safely to pregnant dialysis patientsErythropoietin doses need to be increased by approximately 50% in order to maintain target hemoglobin levels of 10–11 g/dlHigher erythropoietin doses is required due toincreased vascular volume with subsequent hemodilution andpossibly erythropoietin resistance (due to enhanced cytokine production) during pregnancy may contributeJournal of Medical Case Reports 2008, 2:10 , Edntna-Erca J 2002, 28(2):91-94.
35Intravenous iron and heparin Both intravenous iron and heparin appear to be safe during pregnancyHowever frequent monitoring of iron stores is required and minimizing heparin dose is recommendedJournal of Medical Case Reports 2008, 2:10 , Edntna-Erca J 2002, 28(2):91-94.
36Etiology 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 MPGNWomen with scleroderma and polyarteritis nodosa discouraged in past from attempting pregnancy but case reports of successful outcomes with quiescent diseaseMay 17, 2006May 17, 2006May 17, 2006e-medicine May26, 2008
37Improving Infant Survival Multiple causes of premature delivery exist, including polyhydramnios,maternal hypertension and premature rupture of the membranesSince increasing dialysis frequency lowers predialysis BUN levels, adequate dialysis may reduce the occurrence of polyhydramnios and thus lower the risk of premature laborIncreasing the dialysis dose prolongs gestation, resulting in a higher infant birth weight and thus an infant with better chance of survivalJournal of Medical Case Reports 2008, 2:10, Nephrol Dial Transplant 1998:
38Dialysis 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 shiftsOkundaye I, Abrinko P, Hou S: Registry of pregnancy in dialysis patients. Am J Kidney Dis 1998:
39Effect 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:
40Fetal 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 populationAm J Kidney Dis 2007;49:
41Fetal 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 notedAn anticipated delivery may be reasonable because most low-birth-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:
42Summary…Women with moderately decreased GFR (60 to 40 mL/min/1.73 m2 [1.0 to 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:
43…SummaryWomen 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:
44ConclusionAll 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.