Women and Kidney Diseases: Questions Unanswered and Answers Unquestioned

Chronic kidney disease (CKD) affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide,1GBD 2015 Disease and Injury Incidence and Prevalence CollaboratorsGlobal, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.Lancet. 2016 08; 388: 1545-1602Abstract Full Text Full Text PDF PubMed Scopus (2118) Google Scholar and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community, and the next generations; as well as to strive to be more curious about the unique aspects of kidney disease in women, so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Besides childbearing, women are essential in childrearing and contribute to sustaining family and community health. Women in the 21st century continue to strive for equity in business, commerce, and professional endeavors, while recognizing that in many situations, equality does not exist. In various locations around the world, access to education and medical care is not equitable among men and women; women remain underrepresented in many clinical research studies, thus limiting the evidence base on which to make recommendations to ensure the best outcomes (Figure 1). In this editorial, we focus on what we do and do not know about women's kidney health and kidney disease, and what we might learn in the future to improve outcomes for all. Pregnancy is a unique challenge and is a major cause of acute kidney injury (AKI) in women of childbearing age; AKI and preeclampsia (PE) may lead to subsequent CKD, but the entity of the risk is not completely known.2von Dadelszen P. Payne B. Li J. et al.Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model.Lancet. 2011; 377: 219-227Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar, 3Mol B.W.J. Roberts C.T. Thangaratinam S. et al.Pre-eclampsia.Lancet. 2016; 387: 999-1011Abstract Full Text Full Text PDF PubMed Scopus (455) Google Scholar, 4Vikse B.E. Irgens L.M. Leivestad T. et al.Preeclampsia and the risk of end-stage renal disease.N Engl J Med. 2008; 359: 800-809Crossref PubMed Scopus (401) Google Scholar, 5Theilen L.H. Fraser A. Hollingshaus M.S. et al.All-cause and cause-specific mortality after hypertensive disease of pregnancy.Obstet Gynecol. 2016; 128: 238-244Crossref PubMed Scopus (63) Google Scholar CKD has a negative effect on pregnancy even at very early stages.6Piccoli G.B. Cabiddu G. Attini R. et al.Risk of adverse pregnancy outcomes in women with CKD.J Am Soc Nephrol. 2015; 26: 2011-2022Crossref PubMed Scopus (117) Google Scholar, 7Zhang J.-J. Ma X.-X. Hao L. Liu L.-J. et al.A systematic review and meta-analysis of outcomes of pregnancy in CKD and CKD outcomes in pregnancy.Clin J Am Soc Nephrol. 2015; 10: 1964-1978Crossref PubMed Scopus (87) Google Scholar The risks increase with CKD progression, thus posing potentially challenging ethical issues around conception and maintaining of pregnancies.6Piccoli G.B. Cabiddu G. Attini R. et al.Risk of adverse pregnancy outcomes in women with CKD.J Am Soc Nephrol. 2015; 26: 2011-2022Crossref PubMed Scopus (117) Google Scholar, 7Zhang J.-J. Ma X.-X. Hao L. Liu L.-J. et al.A systematic review and meta-analysis of outcomes of pregnancy in CKD and CKD outcomes in pregnancy.Clin J Am Soc Nephrol. 2015; 10: 1964-1978Crossref PubMed Scopus (87) Google Scholar, 8Alkhunaizi A. Melamed N. Hladunewich M.A. Pregnancy in advanced chronic kidney disease and end-stage renal disease.Curr Opin Nephrol Hypertens. 2015; 24: 252-259Crossref PubMed Scopus (52) Google Scholar We do know that PE increases the probability of hypertension and CKD in later years, but we have not evaluated a surveillance or reno-protective strategy to determine whether progressive loss of kidney function can be attenuated.9Piccoli G.B. Cabiddu G. Castellino S. et al.A best practice position statement on the role of the nephrologist in the prevention and follow-up of preeclampsia: the Italian Study Group on Kidney and Pregnancy.J Nephrol. 2017; 30: 307-317Crossref PubMed Scopus (35) Google Scholar, 10Liu Y. Ma X. Zheng J. et al.Pregnancy outcomes in patients with acute kidney injury during pregnancy: a systematic review and meta-analysis.BMC Pregnancy Childbirth. 2017; 17: 235Crossref PubMed Scopus (44) Google Scholar, 11Jim B. Garovic V.D. Acute kidney injury in pregnancy.Semin Nephrol. 2017; 37: 378-385Abstract Full Text Full Text PDF PubMed Google Scholar, 12Acharya A. Management of acute kidney injury in pregnancy for the obstetrician.Obstet Gynecol Clin North Am. 2016; 43: 747-765Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Specific systemic conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic scleroderma (SS) are more likely to affect women than men. We do not know the relative contribution of these acute and chronic conditions on progression to end-stage renal disease (ESRD) in women. In CKD cohorts, the prevalence in women is always less than in men, and they have slower progression to ESRD.13Iseki K. Gender differences in chronic kidney disease.Kidney Int. 2008; 74: 415-417Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 14Nitsch D. Grams M. Sang Y. et al.Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis.BMJ. 2013; 346: 324Crossref PubMed Scopus (187) Google Scholar, 15Levin A. Djurdjev O. Beaulieu M. Er L. Variability and risk factors for kidney disease progression and death following attainment of stage 4 CKD in a referred cohort.Am J Kidney Dis. 2008; 52: 661-671Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar We do not know why and how much of this is due to differences in identification of kidney impairment, different access to care, or true difference in disease severity and prevalence. Women with CKD have a higher cardiovascular risk than women without CKD,16Weiner D.E. Tighiouart H. Elsayed E.F. et al.The Framingham predictive instrument in chronic kidney disease.J Am Coll Cardiol. 2007; 50: 217-224Crossref PubMed Scopus (187) Google Scholar but their risk is still lower than that of men with similar degrees of kidney impairment. In hemodialysis cohorts, there are differences in vascular access types in women versus men, which may be due to biological or systemic factors. In some locations, there is differential use of peritoneal and hemodialysis in women and men. Women are more likely to donate kidneys for transplantation than to receive them. We do not know whether this is because of the differential incidence of CKD in men versus women, cultural factors, or other reasons. There remain gender differences in access to care in different regions of the world, and we do not have data to directly evaluate the extent of these differences, in the poorest parts of the world in particular. PE is the principal cause of AKI and maternal death, particularly in developing countries.2von Dadelszen P. Payne B. Li J. et al.Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model.Lancet. 2011; 377: 219-227Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar, 17Oladapo O.T. Adetoro O.O. Ekele B.A. et al.When getting there is not enough: a nationwide cross-sectional study of 998 maternal deaths and 1451 near-misses in public tertiary hospitals in a low-income country.Br J Obstet Gynaecol. 2016; 123: 928-938Crossref Scopus (82) Google Scholar Pregnancy is the most common cause of AKI in women of childbearing age.10Liu Y. Ma X. Zheng J. et al.Pregnancy outcomes in patients with acute kidney injury during pregnancy: a systematic review and meta-analysis.BMC Pregnancy Childbirth. 2017; 17: 235Crossref PubMed Scopus (44) Google Scholar, 18Tranquilli A.L. Dekker G. Magee L. et al.The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP.Pregnancy Hypertens. 2014; 4: 97-104Crossref PubMed Scopus (628) Google Scholar, 19Liu Y. Bao H. Jiang Z. et al.Pregnancy-related acute kidney injury and a review of the literature in China.Intern Med. 2015; 54: 1695-1703Crossref PubMed Scopus (39) Google Scholar Several diseases and conditions, besides PE, hypertensive disorders of pregnancy, and CKD, can lead to pregnancy-related AKI. Causes vary in different regions. Septic abortion after an illegal procedure is the leading cause of early AKI in countries where legal abortions are not available, whereas PE after assisted fertilization is becoming a leading cause in developed countries.12Acharya A. Management of acute kidney injury in pregnancy for the obstetrician.Obstet Gynecol Clin North Am. 2016; 43: 747-765Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 20Prakash J. Pant P. Prakash S. Sivasankar M. et al.Changing picture of acute kidney injury in pregnancy: study of 259 cases over a period of 33 years.Indian J Nephrol. 2016; 26: 262-267Crossref PubMed Scopus (34) Google Scholar, 21Ibarra-Hernández M. Orozco-Guillén O.A. de la Alcantar-Vallín M.L. et al.Acute kidney injury in pregnancy and the role of underlying CKD: a point of view from México.J Nephrol. 2017; 30: 773-780https://doi.org/10.1007/s40620-017-0444-4Crossref PubMed Scopus (29) Google Scholar, 22Blázquez A. García D. Rodríguez A. et al.Is oocyte donation a risk factor for preeclampsia? A systematic review and meta-analysis.J Assist Reprod Genet. 2016; 33: 855-863Crossref PubMed Scopus (57) Google Scholar PE and hypertensive disorders of pregnancy occur in 3% to 10% of all pregnancies2von Dadelszen P. Payne B. Li J. et al.Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model.Lancet. 2011; 377: 219-227Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar, 3Mol B.W.J. Roberts C.T. Thangaratinam S. et al.Pre-eclampsia.Lancet. 2016; 387: 999-1011Abstract Full Text Full Text PDF PubMed Scopus (455) Google Scholar, 18Tranquilli A.L. Dekker G. Magee L. et al.The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP.Pregnancy Hypertens. 2014; 4: 97-104Crossref PubMed Scopus (628) Google Scholar; in these disorders, the kidney is the main target of an unbalanced pro-angiogenic and anti-angiogenic derangement, leading to hypertension, proteinuria, and widespread endothelial damage. The incidence of PE, higher in low-to-middle−income countries (possibly reflecting undiagnosed predisposing diseases), peaks at the extremes of reproductive age for reasons mentioned above.12Acharya A. Management of acute kidney injury in pregnancy for the obstetrician.Obstet Gynecol Clin North Am. 2016; 43: 747-765Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 20Prakash J. Pant P. Prakash S. Sivasankar M. et al.Changing picture of acute kidney injury in pregnancy: study of 259 cases over a period of 33 years.Indian J Nephrol. 2016; 26: 262-267Crossref PubMed Scopus (34) Google Scholar, 21Ibarra-Hernández M. Orozco-Guillén O.A. de la Alcantar-Vallín M.L. et al.Acute kidney injury in pregnancy and the role of underlying CKD: a point of view from México.J Nephrol. 2017; 30: 773-780https://doi.org/10.1007/s40620-017-0444-4Crossref PubMed Scopus (29) Google Scholar, 22Blázquez A. García D. Rodríguez A. et al.Is oocyte donation a risk factor for preeclampsia? A systematic review and meta-analysis.J Assist Reprod Genet. 2016; 33: 855-863Crossref PubMed Scopus (57) Google Scholar The relationship between the kidney and placenta is biunivocal, and the presence of CKD is a risk factor for PE and hypertensive disorders of pregnancy (Figure 2). Besides CKD, other conditions cited as risk factors for PE (diabetes, immunologic diseases, baseline hypertension, obesity, and metabolic syndrome), are also risk factors for CKD. Given that even minor alterations of kidney function are present in many of these disorders, the importance of kidney function is indirectly recognized in the development of PE. Newer definitions of PE recognize differences between "placental" and "maternal" causes of PE, based on novel angiogenic-antiangiogenic markers,23O'Gorman N. Wright D. Poon L.C. et al.Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations.Ultrasound Obstet Gynecol. 2017; 49: 756-760Crossref PubMed Scopus (98) Google Scholar, 24Zeisler H. Llurba E. Chantraine F. et al.Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia.N Engl J Med. 2016; 374: 13-22Crossref PubMed Scopus (444) Google Scholar which may be important for management during and after pregnancy. There are long-term effects of PE on both maternal and fetal health, but this remains an area of active research with many unknowns. PE is a risk factor for the future development of CKD and ESRD in the mother.3Mol B.W.J. Roberts C.T. Thangaratinam S. et al.Pre-eclampsia.Lancet. 2016; 387: 999-1011Abstract Full Text Full Text PDF PubMed Scopus (455) Google Scholar, 4Vikse B.E. Irgens L.M. Leivestad T. et al.Preeclampsia and the risk of end-stage renal disease.N Engl J Med. 2008; 359: 800-809Crossref PubMed Scopus (401) Google Scholar, 5Theilen L.H. Fraser A. Hollingshaus M.S. et al.All-cause and cause-specific mortality after hypertensive disease of pregnancy.Obstet Gynecol. 2016; 128: 238-244Crossref PubMed Scopus (63) Google Scholar The reasons are not fully understood; podocyte loss is a hallmark of PE, suggesting permanent glomerular damage.25Garovic V.D. The role of the podocyte in preeclampsia.Clin J Am Soc Nephrol. 2014; 9: 1337-1340Crossref PubMed Scopus (33) Google Scholar Endotheliosis, associated with PE but also found in normal pregnancies, may herald glomerulosclerosis; tubular and vascular damage may also be present, and all these alterations may coexist.26Wide-Swensson D. Strevens H. Willner J. Antepartum percutaneous renal biopsy.Int J Gynaecol Obstet. 2007; 98: 88-92Crossref PubMed Scopus (34) Google Scholar, 27Shiiki H. Dohi K. Hanatani M. et al.Focal and segmental glomerulosclerosis in preeclamptic patients with nephrotic syndrome.Am J Nephrol. 1990; 10: 205-212Crossref PubMed Google Scholar Besides maternal risks, PE is associated with intrauterine and perinatal death, preterm delivery, and restricted intrauterine growth; the latter 2 are linked to "small babies."2von Dadelszen P. Payne B. Li J. et al.Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model.Lancet. 2011; 377: 219-227Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar, 3Mol B.W.J. Roberts C.T. Thangaratinam S. et al.Pre-eclampsia.Lancet. 2016; 387: 999-1011Abstract Full Text Full Text PDF PubMed Scopus (455) Google Scholar, 5Theilen L.H. Fraser A. Hollingshaus M.S. et al.All-cause and cause-specific mortality after hypertensive disease of pregnancy.Obstet Gynecol. 2016; 128: 238-244Crossref PubMed Scopus (63) Google Scholar Small babies and preterm babies have highly increased risks of neurological deficits and postnatal complications, especially sepsis.28Linsell L. Malouf R. Morris J. et al.Risk factor models for neurodevelopmental outcomes in children born very preterm or with very low birth weight: a systematic review of methodology and reporting.Am J Epidemiol. 2017; 185: 601-612Crossref PubMed Scopus (31) Google Scholar, 29Guellec I. Lapillonne A. Marret S. et al.Effect of intra- and extrauterine growth on long-term neurologic outcomes of very preterm infants.J Pediatr. 2016; 175: 93-99Abstract Full Text Full Text PDF PubMed Google Scholar, 30Moore T. Hennessy E.M. Myles J. et al.Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies.BMJ. 2012; 345: e7961Crossref PubMed Scopus (412) Google Scholar, 31Guillén Ú. DeMauro S. Ma L. Zupancic J. et al.Relationship between attrition and neurodevelopmental impairment rates in extremely preterm infants at 18 to 24 months: a systematic review.Arch Pediatr Adolesc Med. 2012; 166: 178-184Crossref PubMed Scopus (65) Google Scholar, 32Ranke M.B. Schweizer R. Rodemann S.M. et al.Schoolchildren born VLBW or VLGA show height-related changes in body composition and muscle function but no evidence of metabolic syndrome risk factors. Results from the NEOLONG study.J Pediatr Endocrinol Metab. 2015; 29: 163-172Google Scholar The risks may be higher in low-income countries, as survival and deficit-free survival depend on the provision of postnatal intensive care.20Prakash J. Pant P. Prakash S. Sivasankar M. et al.Changing picture of acute kidney injury in pregnancy: study of 259 cases over a period of 33 years.Indian J Nephrol. 2016; 26: 262-267Crossref PubMed Scopus (34) Google Scholar, 21Ibarra-Hernández M. Orozco-Guillén O.A. de la Alcantar-Vallín M.L. et al.Acute kidney injury in pregnancy and the role of underlying CKD: a point of view from México.J Nephrol. 2017; 30: 773-780https://doi.org/10.1007/s40620-017-0444-4Crossref PubMed Scopus (29) Google Scholar In the long term, small babies are at risk for the development of diabetes, metabolic syndrome, cardiovascular disease (CVD), and CKD in adulthood.33Castanys-Muñoz E. Kennedy K. Castañeda-Gutiérrez E. et al.Systematic review indicates postnatal growth in term infants born small-for-gestational-age being associated with later neurocognitive and metabolic outcomes.Acta Paediatr. 2017; 106: 1230-1238Crossref PubMed Scopus (46) Google Scholar, 34Ong K.K. Kennedy K. Castañeda-Gutiérrez E. et al.Postnatal growth in preterm infants and later health outcomes: a systematic review.Acta Paediatr. 2015; 104: 974-986Crossref PubMed Scopus (110) Google Scholar, 35Low Birth Weight and Nephron Number Working GroupThe impact of kidney development on the life course: a consensus document for action.Nephron. 2017; 136: 3-49Crossref PubMed Scopus (54) Google Scholar, 36Luyckx V.A. Bertram J.F. Brenner B.M. et al.Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease.Lancet. 2013; 382: 273-283Abstract Full Text Full Text PDF PubMed Scopus (265) Google Scholar, 37Luyckx V.A. Brenner B.M. Birth weight, malnutrition and kidney-associated outcomes—a global concern.Nat Rev Nephrol. 2015; 11: 135-149Crossref PubMed Scopus (119) Google Scholar Because kidney development is completed in the last phases of pregnancy, delayed, insufficient kidney growth, resulting in low nephron number, is probably the basis of the increased risk of CKD and hypertension in small-for−gestational age and preterm babies.33Castanys-Muñoz E. Kennedy K. Castañeda-Gutiérrez E. et al.Systematic review indicates postnatal growth in term infants born small-for-gestational-age being associated with later neurocognitive and metabolic outcomes.Acta Paediatr. 2017; 106: 1230-1238Crossref PubMed Scopus (46) Google Scholar, 34Ong K.K. Kennedy K. Castañeda-Gutiérrez E. et al.Postnatal growth in preterm infants and later health outcomes: a systematic review.Acta Paediatr. 2015; 104: 974-986Crossref PubMed Scopus (110) Google Scholar, 35Low Birth Weight and Nephron Number Working GroupThe impact of kidney development on the life course: a consensus document for action.Nephron. 2017; 136: 3-49Crossref PubMed Scopus (54) Google Scholar, 36Luyckx V.A. Bertram J.F. Brenner B.M. et al.Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease.Lancet. 2013; 382: 273-283Abstract Full Text Full Text PDF PubMed Scopus (265) Google Scholar, 37Luyckx V.A. Brenner B.M. Birth weight, malnutrition and kidney-associated outcomes—a global concern.Nat Rev Nephrol. 2015; 11: 135-149Crossref PubMed Scopus (119) Google Scholar CKD is a risk factor for adverse pregnancy outcomes from its early stages6Piccoli G.B. Cabiddu G. Attini R. et al.Risk of adverse pregnancy outcomes in women with CKD.J Am Soc Nephrol. 2015; 26: 2011-2022Crossref PubMed Scopus (117) Google Scholar, 38Davison J.M. Lindheimer M.D. Pregnancy and chronic kidney disease.Semin Nephrol. 2011; 31: 86-99Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 39Hall M. Pregnancy in women with CKD: a success story.Am J Kidney Dis. 2016; 68: 633-639Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar (Table 1). The risks increase from CKD stage 1 to CKD stage 5, and may be higher in glomerular nephropathies, autoimmune diseases, and diabetic nephropathy.6Piccoli G.B. Cabiddu G. Attini R. et al.Risk of adverse pregnancy outcomes in women with CKD.J Am Soc Nephrol. 2015; 26: 2011-2022Crossref PubMed Scopus (117) Google Scholar, 7Zhang J.-J. Ma X.-X. Hao L. Liu L.-J. et al.A systematic review and meta-analysis of outcomes of pregnancy in CKD and CKD outcomes in pregnancy.Clin J Am Soc Nephrol. 2015; 10: 1964-1978Crossref PubMed Scopus (87) Google Scholar, 38Davison J.M. Lindheimer M.D. Pregnancy and chronic kidney disease.Semin Nephrol. 2011; 31: 86-99Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 39Hall M. Pregnancy in women with CKD: a success story.Am J Kidney Dis. 2016; 68: 633-639Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 40Nevis I.F. Reitsma A. Dominic A. et al.Pregnancy outcomes in women with chronic kidney disease: a systematic review.Clin J Am Soc Nephrol. 2011; 6: 2587-2598Crossref PubMed Scopus (137) Google Scholar, 41Cabiddu G. Castellino S. Gernone G. et al.A best practice position statement on pregnancy in chronic kidney disease: the Italian Study Group on Kidney and Pregnancy.J Nephrol. 2016; 29: 277-303Crossref PubMed Scopus (54) Google Scholar Results of pregnancy after kidney donation suggest that reduction of kidney parenchyma may be associated with a higher risk of PE and hypertensive disorders of pregnancy.42Garg A.X. Nevis I.F. McArthur E. et al.Gestational hypertension and preeclampsia in living kidney donors.N Engl J Med. 2015; 372: 124-133Crossref PubMed Scopus (100) Google Scholar, 43Josephson M.A. Transplantation: pregnancy after kidney donation: more questions than answers.Nat Rev Nephrol. 2009; 5: 495-497Crossref PubMed Scopus (29) Google ScholarTable 1Adverse pregnancy outcomes in patients with chronic kidney disease and in their offspringTermDefinitionMain issuesMaternal deathDeath in pregnancy or within 1 wk to 1 mo postpartumToo rare to be quantified, at least in highly resourced settings, where cases are in the setting of severe flares of immunologic diseases (SLE in premature infants). Still an in AKI and in low resourced not in countries, where it with in in to a higher CKD and may be linked to in the of of the kidney between and in advanced CKD. not increased in early CKD flares and of immunologic diseases in to be increased in pregnancy, in in probably a risk in patients who pregnancy with an active disease, or with a of a is not in diseases, do not to be increased with to in to are not increased with to may be an in pregnancies, in be increased in CKD, but data are in immunologic diseases but not linked to the presence of and in diabetic of a after not increased in early may be an in not linked to may specifically linked to immunologic diseases and diabetic deathDeath within 1 wk to 1 mo after a of which a risk of very small at to be with to early extremely or completed in risk of preterm and early preterm CKD extremely preterm may be an important in undiagnosed or referred CKD and or for and to preterm and are probably to risk for hypertension, metabolic syndrome, and CKD in of are not increased in CKD patients not by diabetic to diseases, such as may be at kidney of of CKD recognize a or besides and disease, kidney tubular disorders and diseases have a in and not always risk of hypertension and CKD in of in a lower nephron in preterm the risks are probably higher in than in preterm infants for long-term due to or are not to CKD, but are a in all preterm acute kidney of the kidney and CKD, chronic kidney glomerular filtration intrauterine growth target of preeclampsia acute kidney kidney small for age; systemic lupus in a acute kidney of the kidney and CKD, chronic kidney glomerular filtration intrauterine growth target of preeclampsia acute kidney kidney small for age; systemic lupus and at baseline are important of pregnancy-related the risks, we know that are not increased with to the of the of diseases, such as kidney disease, or of the kidney and death is in highly resourced countries, whereas the incidence of preterm and of small-for−gestational age is increased in stage 1 CKD and with the of kidney the effect of pregnancy on CKD progression is not fully because of different study and of and long-term in kidney function is in early CKD, but the risk increases as CKD severity G.B. Cabiddu G. Attini R. et al.Risk of adverse pregnancy outcomes in women with CKD.J Am Soc Nephrol. 2015; 26: 2011-2022Crossref PubMed Scopus (117) Google Scholar, 7Zhang J.-J. Ma X.-X. Hao L. Liu L.-J. et al.A systematic review and meta-analysis of outcomes of pregnancy in CKD and CKD outcomes in pregnancy.Clin J Am Soc Nephrol. 2015; 10: 1964-1978Crossref PubMed Scopus (87) Google Scholar, 38Davison J.M. Lindheimer M.D. Pregnancy and chronic kidney disease.Semin Nephrol. 2011; 31: 86-99Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 39Hall M. Pregnancy in women with CKD: a success story.Am J Kidney Dis. 2016; 68: 633-639Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 40Nevis I.F. Reitsma A. Dominic A. et al.Pregnancy outcomes in women with chronic kidney disease: a systematic review.Clin J Am Soc Nephrol. 2011; 6: 2587-2598Crossref PubMed Scopus (137) Google Scholar, 41Cabiddu G. Castellino S. Gernone G. et al.A best practice position statement on pregnancy in chronic kidney disease: the Italian Study Group on Kidney and Pregnancy.J Nephrol. 2016; 29: 277-303Crossref PubMed Scopus (54) Google Scholar, D. S. G. et pregnancy have impact on long term damage and on the outcome of lupus 2017; PubMed Scopus Google Scholar, K. A. K. Hladunewich M.A. Pregnancy and glomerular disease: a

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