- Email: [email protected]
The importance of increased dialysis and anemia management for infant survival in pregnant women on hemodialysis
co m m e nta r y
inequities that leave populations vulnerable and exposed. We must continue to equip individuals and institutions with the skills and resources needed to survive and recover from a disaster. We must continue to examine our successes and failures and establish best practices to deliver optimal care to patients in a catastrophe. The activities of the RDRTF and KCERC are excellent steps along this path. With proper effort and resources, we can avert disaster experiences similar to Hurricane Katrina in the future. DISCLOSURE All the authors declared no competing interests.
ACKNOWLEDGMENTS This work was supported by Ruth L Kirschstein National Research Service Award Institutional Research Training Grant T32-DK061296 (to Khaled Abdel-Kader).
see original article on page 1217
The importance of increased dialysis and anemia management for infant survival in pregnant women on hemodialysis Sai Subhodhini Reddy1 and Jean L. Holley2 Despite advances in recent decades, infant survival in pregnant women on hemodialysis remains suboptimal. Asamiya et al. found that higher maternal hemoglobin was associated with successful pregnancy and maternal blood urea nitrogen (BUN) was negatively correlated with infant birth weight and gestational age. Their study suggests that increased or intensive dialysis to achieve predialysis maternal BUN levels < 48 mg/dl along with increased doses of erythropoietin to ensure maternal hemoglobin levels ≥ 9.6 ± 0.9 g/dl, should be the standard for pregnant women on hemodialysis. Kidney International (2009) 75, 1133–1134. doi:10.1038/ki.2009.14
REFERENCES 1.
Solez K, Bihari D, Collins AJ et al. International dialysis aid in earthquakes and other disasters. Kidney Int 1993; 44: 479–483. 2. Sever MS, Vanholder R, Lameire N. Management of crush-related injuries after disasters. N Engl J Med 2006; 354: 1052–1063. 3. EM-DAT: The Office of U.S. Foreign Disaster Assistance/Center for Research on the Epidemiology of Disasters international disaster database. Université Catholique de Louvain, Brussels, Belgium. Accessed 15 October 2008. (http://www.emdat.be). 4. Brodie M, Weltzien E, Altman D et al. Experiences of hurricane Katrina evacuees in Houston shelters: implications for future planning. Am J Public Health 2006; 96: 1402–1408. 5. Anderson AH, Cohen AJ, Kutner N et al. Missed dialysis sessions and hospitalization in hemodialysis patients after Hurricane Katrina. Kidney Int 2009; 75: 1202–1208. 6. Kopp JB, Ball LK, Cohen A et al. Kidney patient care in disasters: lessons from the hurricanes and earthquake of 2005. Clin J Am Soc Nephrol 2007; 2: 814–824. 7. Masozera M, Bailey M, Kerchner C. Distribution of impacts of natural disasters across income groups: a case study of New Orleans. Ecol Econ 2007; 63: 299–306. 8. Elder K, Xirasagar S, Miller N et al. African Americans’ decisions not to evacuate New Orleans before Hurricane Katrina: a qualitative study. Am J Public Health 2007; 97(Suppl 1): S124–S129. 9. Eisenman DP, Cordasco KM, Asch S et al. Disaster planning and risk communication with vulnerable communities: lessons from Hurricane Katrina. Am J Public Health 2007; 97(Suppl 1): S109–S115. 10. Leon GR. Overview of the psychosocial impact of disasters. Prehosp Disaster Med 2004; 19: 4–9. Kidney International (2009) 75
Since Confortini et al.,1 first reported a successful pregnancy in a woman on chronic hemodialysis in 1971, the incidence of pregnancy in hemodialysis patients has risen from 1 to 7%.2 Recently, Barua and colleagues reported a pregnancy incidence of 15.6% in women on nocturnal hemodialysis.2 Moreover, during the past 37 years the survival of infants born to women on chronic hemodialysis has improved from 20% to as high as 85%.3–5 The improved infant survival is a result of changing medical practices involving maternal dialysis care, obstetrical care, and neonatal care (Figure 1). Pregnant hemodialysis patients are now generally dialyzed six times a week for 3–4 h each session; optimal blood pressure management and
1 Nephrology Unit, University of Rochester
Medical Center, Rochester, New York, USA; 2Nephrology Division, Department of Medicine,
University of Illinois at Urbana-Champaign, Urbana, Illinois, USA Correspondence: Sai Subhodhini Reddy, Nephrology Unit, University of Rochester Medical Center, Box 675, 601 Elmwood Avenue, Rochester, New York 14642, USA. E-mail: [email protected]
improved nutritional and anemia management are also stressed.3,4,6 Obstetrical care includes close monitoring of the mother and fetus, with more frequent visits, biophysical profiles, nonstress testing, and fetal ultrasounds.4 Over the past three decades there have also been advancements in neonatal care, particularly in technological monitoring and interventions. Yet despite these improvements in medical care, present-day infant survival for women on hemodialysis remains suboptimal. Prematurity is associated with neonatal death and other permanent organ damage and is seen in 80% of infants born to pregnant women on hemodialysis.3,4,6 Additionally, as birth weight corresponds to gestational age, infants born to women on chronic dialysis typically weigh less than 2000 g and have an average gestational age of 32 weeks or less.6 Asamiya et al.7 (this issue) conducted a retrospective study analyzing maternal data in relation to fetal gestational age and birth weight, as these factors impact infant survival. A negative correlation between gestational age and birth weight and maternal blood urea nitrogen (BUN) level, and a positive correlation between these variables and successful pregnancy were 1133
com m enta r y
Obstetric care • Biophysical profile • Nonstress test • Ultrasound
Maternal factors • Urea • Hemoglobin • Blood pressure • Nutrition
Dialysis Erythropoietin Ultrafiltration
Fetal survival
Infant factors • Preterm delivery • Gestational age • Birth weight
Neonatal care • Technological advancements
Figure 1 | Factors affecting infant survival in women on chronic hemodialysis.
observed, suggesting that maternal BUN level is a marker for fetal survival.7 Over the past three decades many case reports and retrospective studies have documented increased infant survival in women with BUN levels lower than 50 mg/100 ml,2,3,6 but Asamiya et al.7 are the first to analyze the associations between maternal BUN and fetal gestational age and birth weight. A negative correlation of maternal BUN and each of these fetal factors was shown: a birth weight of 1500 g corresponded to a BUN of 49.0 mg/dl, and a gestational age of 32 weeks corresponded to a BUN of 48.0 mg/100 ml, lending credence to the suggested maternal BUN goal of ⭐ 50 mg/100 ml in a pregnant woman on hemodialysis. The pathophysiologic process responsible for improved fetal survival in women with lower predialysis BUN is unclear. However, polyhydramnios is associated with a higher incidence of preterm delivery. Increased maternal urea is thought to cause a fetal solute diuresis, consequently resulting in polyhydramnios. Furthermore, rapid urea clearance during hemodialysis may result in decreased oncotic pressure and movement of water into the amniotic space.5 Thus, dialysis and ultrafiltration are thought to reduce the occurrence of polyhydramnios.3,5 Additionally, daily dialysis allows for better fluid management and optimal blood pressure control.2,3 In the recent article by Barua et al.,2 six of seven pregnancies were successful; the mean gestational age was 36.2 ± 3 weeks, and the mean birth weight was 2417.5 ± 657 g. All these women received nocturnal hemodialysis for 7–8 h, 5–7 nights per week.2 1134
It has previously been documented that anemia in pregnancy is associated with a higher incidence of preterm delivery, which in turn is known to result in higher infant mortality.8 Anemia worsens in pregnancy because of the 3- to 4-l increase in plasma volume that occurs without a concomitant increase in red blood cell mass.3,9 Erythropoietin production increases in the normal pregnant woman during the first trimester.9 In order to achieve target hemoglobin levels of 10–11 g/100 ml in pregnant women on chronic hemodialysis, erythropoietin dosage must be increased by 50–100%.3 Although the reasons are not completely understood, it is thought that increased red cell mass and decreased erythropoietin responsiveness in the first trimester may be due to increased cytokine production.10 Additional studies are needed to confirm this hypothesis. The analysis by Asamiya and colleagues7 of 24 pregnant hemodialysis patients showed a positive correlation between maternal hemoglobin and successful fetal outcome. The average hemoglobin was significantly higher in the successful pregnancies compared with the unsuccessful group (9.6 ± 0.9 versus 8.3 ± 1.9 g / 100 ml, P = 0.036). The importance of this finding is limited because the study was a singlecenter retrospective study of a small number of women. Moreover, although there was a significant difference in maternal hemoglobin and fetal outcome, there was no correlation between maternal hemoglobin and gestational age and birth weight.7 Additional study is required to determine the upper limit of optimal hemoglobin in pregnant women on chronic hemodialysis.
Since the first reported case of a successful pregnancy in a woman on chronic hemodialysis, a marked improvement in infant survival in women on dialysis has been observed. A better understanding of pregnancy in women on chronic hemodialysis and the dialysis factors that affect pregnancy outcomes will probably lead to further improvement in infant survival. Increased dialysis leads to lower maternal BUN. Lower BUN is associated with higher birth weight and gestational age at delivery.7 Likewise, higher maternal hemoglobin seems to be associated with a lower rate of preterm delivery.7 Nephrologists should strive for predialysis BUN levels ⭐ 48 mg/100 ml and optimal anemia management in pregnant woman on hemodialysis, with the goal of increasing fetal survival by reducing preterm deliveries and achieving higher fetal birth weights. DISCLOSURE The authors declared no competing interests. REFERENCES 1.
Confortini P, Galant G, Ancona G et al. Full-term pregnancy and successful delivery in a patient on chronic hemodialysis. Proc Eur Dial Transplant Assoc 1971; 8: 74–78. 2. Barua M, Hladunewich M, Keunen J et al. Successful pregnancies on nocturnal home hemodialysis. Clin J Am Soc Nephrol 2008; 3: 392–396. 3. Reddy SS, Holley JL. Management of the pregnant chronic dialysis patient. Adv Chronic Kidney Dis 2007; 14: 146–155. 4. Chou CY, Ting IW, Lin TH et al. Pregnancy in patients on chronic dialysis: a single center experience and combined analysis of reported results. Eur J Obstet Gynecol Reprod Biol 2008; 136: 165–170. 5. Haase M, Morgera S, Bamberg C et al. A systematic approach to managing pregnant dialysis patients – the importance of an intensified haemodiafiltration protocol. Nephrol Dial Transplant 2005; 20: 2537–2542. 6. Holley JL, Reddy SS. Pregnancy in dialysis patients: a review of outcomes, complications, and management. Semin Dial 2003; 16: 398–402. 7. Asamiya Y, Otsubo S, Matsuda Y et al. The importance of low blood urea nitrogen levels in pregnant patients undergoing hemodialysis to optimize birth weight and gestational age. Kidney Int 2009; 75: 1217–1222. 8. Levy A, Fraser D, Katz M et al. Maternal anemia during pregnancy is an independent risk factor for low birthweight and preterm delivery. Eur J Obstet Gynecol Reprod Biol 2005; 122: 182–186. 9. Cavill I. Iron and erythropoiesis in normal subjects and in pregnancy. J Perinat Med 1995; 23: 47–50. 10. Bagon JA, Vernaeve H, De Muylder X et al. Pregnancy and dialysis. Am J Kidney Dis 1998; 31: 756–765. Kidney International (2009) 75
inequities that leave populations vulnerable and exposed. We must continue to equip individuals and institutions with the skills and resources needed to survive and recover from a disaster. We must continue to examine our successes and failures and establish best practices to deliver optimal care to patients in a catastrophe. The activities of the RDRTF and KCERC are excellent steps along this path. With proper effort and resources, we can avert disaster experiences similar to Hurricane Katrina in the future. DISCLOSURE All the authors declared no competing interests.
ACKNOWLEDGMENTS This work was supported by Ruth L Kirschstein National Research Service Award Institutional Research Training Grant T32-DK061296 (to Khaled Abdel-Kader).
see original article on page 1217
The importance of increased dialysis and anemia management for infant survival in pregnant women on hemodialysis Sai Subhodhini Reddy1 and Jean L. Holley2 Despite advances in recent decades, infant survival in pregnant women on hemodialysis remains suboptimal. Asamiya et al. found that higher maternal hemoglobin was associated with successful pregnancy and maternal blood urea nitrogen (BUN) was negatively correlated with infant birth weight and gestational age. Their study suggests that increased or intensive dialysis to achieve predialysis maternal BUN levels < 48 mg/dl along with increased doses of erythropoietin to ensure maternal hemoglobin levels ≥ 9.6 ± 0.9 g/dl, should be the standard for pregnant women on hemodialysis. Kidney International (2009) 75, 1133–1134. doi:10.1038/ki.2009.14
REFERENCES 1.
Solez K, Bihari D, Collins AJ et al. International dialysis aid in earthquakes and other disasters. Kidney Int 1993; 44: 479–483. 2. Sever MS, Vanholder R, Lameire N. Management of crush-related injuries after disasters. N Engl J Med 2006; 354: 1052–1063. 3. EM-DAT: The Office of U.S. Foreign Disaster Assistance/Center for Research on the Epidemiology of Disasters international disaster database. Université Catholique de Louvain, Brussels, Belgium. Accessed 15 October 2008. (http://www.emdat.be). 4. Brodie M, Weltzien E, Altman D et al. Experiences of hurricane Katrina evacuees in Houston shelters: implications for future planning. Am J Public Health 2006; 96: 1402–1408. 5. Anderson AH, Cohen AJ, Kutner N et al. Missed dialysis sessions and hospitalization in hemodialysis patients after Hurricane Katrina. Kidney Int 2009; 75: 1202–1208. 6. Kopp JB, Ball LK, Cohen A et al. Kidney patient care in disasters: lessons from the hurricanes and earthquake of 2005. Clin J Am Soc Nephrol 2007; 2: 814–824. 7. Masozera M, Bailey M, Kerchner C. Distribution of impacts of natural disasters across income groups: a case study of New Orleans. Ecol Econ 2007; 63: 299–306. 8. Elder K, Xirasagar S, Miller N et al. African Americans’ decisions not to evacuate New Orleans before Hurricane Katrina: a qualitative study. Am J Public Health 2007; 97(Suppl 1): S124–S129. 9. Eisenman DP, Cordasco KM, Asch S et al. Disaster planning and risk communication with vulnerable communities: lessons from Hurricane Katrina. Am J Public Health 2007; 97(Suppl 1): S109–S115. 10. Leon GR. Overview of the psychosocial impact of disasters. Prehosp Disaster Med 2004; 19: 4–9. Kidney International (2009) 75
Since Confortini et al.,1 first reported a successful pregnancy in a woman on chronic hemodialysis in 1971, the incidence of pregnancy in hemodialysis patients has risen from 1 to 7%.2 Recently, Barua and colleagues reported a pregnancy incidence of 15.6% in women on nocturnal hemodialysis.2 Moreover, during the past 37 years the survival of infants born to women on chronic hemodialysis has improved from 20% to as high as 85%.3–5 The improved infant survival is a result of changing medical practices involving maternal dialysis care, obstetrical care, and neonatal care (Figure 1). Pregnant hemodialysis patients are now generally dialyzed six times a week for 3–4 h each session; optimal blood pressure management and
1 Nephrology Unit, University of Rochester
Medical Center, Rochester, New York, USA; 2Nephrology Division, Department of Medicine,
University of Illinois at Urbana-Champaign, Urbana, Illinois, USA Correspondence: Sai Subhodhini Reddy, Nephrology Unit, University of Rochester Medical Center, Box 675, 601 Elmwood Avenue, Rochester, New York 14642, USA. E-mail: [email protected]
improved nutritional and anemia management are also stressed.3,4,6 Obstetrical care includes close monitoring of the mother and fetus, with more frequent visits, biophysical profiles, nonstress testing, and fetal ultrasounds.4 Over the past three decades there have also been advancements in neonatal care, particularly in technological monitoring and interventions. Yet despite these improvements in medical care, present-day infant survival for women on hemodialysis remains suboptimal. Prematurity is associated with neonatal death and other permanent organ damage and is seen in 80% of infants born to pregnant women on hemodialysis.3,4,6 Additionally, as birth weight corresponds to gestational age, infants born to women on chronic dialysis typically weigh less than 2000 g and have an average gestational age of 32 weeks or less.6 Asamiya et al.7 (this issue) conducted a retrospective study analyzing maternal data in relation to fetal gestational age and birth weight, as these factors impact infant survival. A negative correlation between gestational age and birth weight and maternal blood urea nitrogen (BUN) level, and a positive correlation between these variables and successful pregnancy were 1133
com m enta r y
Obstetric care • Biophysical profile • Nonstress test • Ultrasound
Maternal factors • Urea • Hemoglobin • Blood pressure • Nutrition
Dialysis Erythropoietin Ultrafiltration
Fetal survival
Infant factors • Preterm delivery • Gestational age • Birth weight
Neonatal care • Technological advancements
Figure 1 | Factors affecting infant survival in women on chronic hemodialysis.
observed, suggesting that maternal BUN level is a marker for fetal survival.7 Over the past three decades many case reports and retrospective studies have documented increased infant survival in women with BUN levels lower than 50 mg/100 ml,2,3,6 but Asamiya et al.7 are the first to analyze the associations between maternal BUN and fetal gestational age and birth weight. A negative correlation of maternal BUN and each of these fetal factors was shown: a birth weight of 1500 g corresponded to a BUN of 49.0 mg/dl, and a gestational age of 32 weeks corresponded to a BUN of 48.0 mg/100 ml, lending credence to the suggested maternal BUN goal of ⭐ 50 mg/100 ml in a pregnant woman on hemodialysis. The pathophysiologic process responsible for improved fetal survival in women with lower predialysis BUN is unclear. However, polyhydramnios is associated with a higher incidence of preterm delivery. Increased maternal urea is thought to cause a fetal solute diuresis, consequently resulting in polyhydramnios. Furthermore, rapid urea clearance during hemodialysis may result in decreased oncotic pressure and movement of water into the amniotic space.5 Thus, dialysis and ultrafiltration are thought to reduce the occurrence of polyhydramnios.3,5 Additionally, daily dialysis allows for better fluid management and optimal blood pressure control.2,3 In the recent article by Barua et al.,2 six of seven pregnancies were successful; the mean gestational age was 36.2 ± 3 weeks, and the mean birth weight was 2417.5 ± 657 g. All these women received nocturnal hemodialysis for 7–8 h, 5–7 nights per week.2 1134
It has previously been documented that anemia in pregnancy is associated with a higher incidence of preterm delivery, which in turn is known to result in higher infant mortality.8 Anemia worsens in pregnancy because of the 3- to 4-l increase in plasma volume that occurs without a concomitant increase in red blood cell mass.3,9 Erythropoietin production increases in the normal pregnant woman during the first trimester.9 In order to achieve target hemoglobin levels of 10–11 g/100 ml in pregnant women on chronic hemodialysis, erythropoietin dosage must be increased by 50–100%.3 Although the reasons are not completely understood, it is thought that increased red cell mass and decreased erythropoietin responsiveness in the first trimester may be due to increased cytokine production.10 Additional studies are needed to confirm this hypothesis. The analysis by Asamiya and colleagues7 of 24 pregnant hemodialysis patients showed a positive correlation between maternal hemoglobin and successful fetal outcome. The average hemoglobin was significantly higher in the successful pregnancies compared with the unsuccessful group (9.6 ± 0.9 versus 8.3 ± 1.9 g / 100 ml, P = 0.036). The importance of this finding is limited because the study was a singlecenter retrospective study of a small number of women. Moreover, although there was a significant difference in maternal hemoglobin and fetal outcome, there was no correlation between maternal hemoglobin and gestational age and birth weight.7 Additional study is required to determine the upper limit of optimal hemoglobin in pregnant women on chronic hemodialysis.
Since the first reported case of a successful pregnancy in a woman on chronic hemodialysis, a marked improvement in infant survival in women on dialysis has been observed. A better understanding of pregnancy in women on chronic hemodialysis and the dialysis factors that affect pregnancy outcomes will probably lead to further improvement in infant survival. Increased dialysis leads to lower maternal BUN. Lower BUN is associated with higher birth weight and gestational age at delivery.7 Likewise, higher maternal hemoglobin seems to be associated with a lower rate of preterm delivery.7 Nephrologists should strive for predialysis BUN levels ⭐ 48 mg/100 ml and optimal anemia management in pregnant woman on hemodialysis, with the goal of increasing fetal survival by reducing preterm deliveries and achieving higher fetal birth weights. DISCLOSURE The authors declared no competing interests. REFERENCES 1.
Confortini P, Galant G, Ancona G et al. Full-term pregnancy and successful delivery in a patient on chronic hemodialysis. Proc Eur Dial Transplant Assoc 1971; 8: 74–78. 2. Barua M, Hladunewich M, Keunen J et al. Successful pregnancies on nocturnal home hemodialysis. Clin J Am Soc Nephrol 2008; 3: 392–396. 3. Reddy SS, Holley JL. Management of the pregnant chronic dialysis patient. Adv Chronic Kidney Dis 2007; 14: 146–155. 4. Chou CY, Ting IW, Lin TH et al. Pregnancy in patients on chronic dialysis: a single center experience and combined analysis of reported results. Eur J Obstet Gynecol Reprod Biol 2008; 136: 165–170. 5. Haase M, Morgera S, Bamberg C et al. A systematic approach to managing pregnant dialysis patients – the importance of an intensified haemodiafiltration protocol. Nephrol Dial Transplant 2005; 20: 2537–2542. 6. Holley JL, Reddy SS. Pregnancy in dialysis patients: a review of outcomes, complications, and management. Semin Dial 2003; 16: 398–402. 7. Asamiya Y, Otsubo S, Matsuda Y et al. The importance of low blood urea nitrogen levels in pregnant patients undergoing hemodialysis to optimize birth weight and gestational age. Kidney Int 2009; 75: 1217–1222. 8. Levy A, Fraser D, Katz M et al. Maternal anemia during pregnancy is an independent risk factor for low birthweight and preterm delivery. Eur J Obstet Gynecol Reprod Biol 2005; 122: 182–186. 9. Cavill I. Iron and erythropoiesis in normal subjects and in pregnancy. J Perinat Med 1995; 23: 47–50. 10. Bagon JA, Vernaeve H, De Muylder X et al. Pregnancy and dialysis. Am J Kidney Dis 1998; 31: 756–765. Kidney International (2009) 75