Kidney News January 2017 9#1 : Page 1

January 2017 | Vol. 9, Number 1 Prior Acute Kidney Injury May Contribute to Adverse Pregnancy Outcomes lished in the Journal of the American Soci-ety of Nephrology , point to a newly defined group of high-risk women. Previous research has shown that AKI can increase the risk of later developing chronic kidney disease (CKD) and dy-ing prematurely, but the consequence of an episode of AKI on health out-comes relevant to young women— especially those who may become pregnant—has not been addressed fully. Several studies have report-ed adverse pregnancy outcomes in women with early stages of CKD, and even subclinical kidney dysfunction may jeopardize healthy pregnancies. Therefore, recovered AKI (r-AKI) may represent an under-recognized threat to women who wish to bear children. To study whether a history of r-AKI increases a woman’s risk of later prob-lems during pregnancy, Jessica Sheehan Tangren, MD, a Research Fellow in the Division of Nephrology at Massachusetts General Hospital, and her colleagues ret-rospectively studied all women who de-livered infants between 1998 and 2007 at her institution: 105 women with r-AKI and 24,640 women without a history of kidney disease. Women with r-AKI had an increased rate of preeclampsia compared with controls (23% vs. 4%). Also, infants of women with r-AKI were born earlier than infants of controls (average 37.6 vs. 39.2 weeks), with increased rates of small-for-gestational-age births (15% vs. 8%) and newborns admitted to the neonatal inten-sive care unit (26% vs. 8%). There were 189 perinatal deaths in the cohort, with significantly more deaths in the offspring of mothers with recovered AKI (3.0% vs. 0.8%); however, this association became non-significant in a multivariate logistic regression analysis. Recovered AKI was linked with a 5.9-times increased risk of preeclampsia and a 2.4-times increased risk of adverse fetal outcomes, after adjustments were made for various patient factors includ-ing maternal age, body mass index, race, parity, history of diabetes, and diastolic blood pressure at first prenatal visit. When women with r-AKI and controls were matched 1:2 by age, race, body mass Continued on page 3 Inside State of Kidney Care Dialysis Organization Chief Medical Officers and ASN President Eleanor Lederer look at the state of kidney care as we closed out 2016 and move into 2017 Kidney Watch 2017 Changes in the health care landscape top our list of what to watch in 2017. We also look at what fellows really want and whose role it is to educate the evolving nephrology care team A cute kidney injury (AKI) is most often considered a concern for elderly and critically ill popula-tions, but a new study indicates that it may also pose risks for pregnant women and their babies, even when women have recovered their kidney function before pregnancy. The findings, which are pub-Fellows Corner A look at shared decision-making in discussions about starting or stopping dialysis Policy Update Can 21st Century Cures cure what ails health care? Older Age Should Not Rule Out Organ Donation after Death, According to New Research By Tracy Hampton Findings Kidney disease markers reflect heart failure risk in African Americans N Practice Pointers Nephrology study. “Nowadays, in many countries, about 30% to 60% of deceased kidney grafts are included in the so-called ‘extended criteria.’ However, as witnessed by the heterogeneity of organ discard rate across the transplant community, the limits of this policy are not well defined despite the development of several scoring systems,” the study authors wrote. They noted that donor age in particular represents a major reason for organ discard, but data on the reliability of organs from elderly donors are currently limited and relevant studies have generated conflicting results. The donor organ shortage has led to recent efforts to find ways to expand kid-ney recovery criteria, however, including the consideration of older deceased donor kidneys. Strategies incorporating such kid-neys include old for old protocols that aim to match the estimated graft survival to Continued on page 3 ew research indicates that age cut-offs for deceased organ do-nors prevent quality kidneys from being available to patients in need of life-saving transplants. Even kidneys from donors ≥80 years of age functioned for years after transplantation in a recent Clinical Journal of the American Society of IgA nephropathy

Prior Acute Kidney Injury May Contribute To Adverse Pregnancy Outcomes

Acute kidney injury (AKI) is most often considered a concern for elderly and critically ill populations, but a new study indicates that it may also pose risks for pregnant women and their babies, even when women have recovered their kidney function before pregnancy. The findings, which are published in the Journal of the American Society of Nephrology, point to a newly defined group of high-risk women.

Previous research has shown that AKI can increase the risk of later developing chronic kidney disease (CKD) and dying prematurely, but the consequence of an episode of AKI on health outcomes relevant to young women— especially those who may become pregnant—has not been addressed fully. Several studies have reported adverse pregnancy outcomes in women with early stages of CKD, and even subclinical kidney dysfunction may jeopardize healthy pregnancies. Therefore, recovered AKI (r-AKI) may represent an under-recognized threat to women who wish to bear children.

To study whether a history of r-AKI increases a woman’s risk of later problems during pregnancy, Jessica Sheehan Tangren, MD, a Research Fellow in the Division of Nephrology at Massachusetts General Hospital, and her colleagues retrospectively studied all women who delivered infants between 1998 and 2007 at her institution: 105 women with r-AKI and 24,640 women without a history of kidney disease.

Women with r-AKI had an increased rate of preeclampsia compared with controls (23% vs. 4%). Also, infants of women with r-AKI were born earlier than infants of controls (average 37.6 vs. 39.2 weeks), with increased rates of small-for-gestational- age births (15% vs. 8%) and newborns admitted to the neonatal intensive care unit (26% vs. 8%). There were 189 perinatal deaths in the cohort, with significantly more deaths in the offspring of mothers with recovered AKI (3.0% vs. 0. 8%); however, this association became non-significant in a multivariate logistic regression analysis.

Recovered AKI was linked with a 5. 9-times increased risk of preeclampsia and a 2.4-times increased risk of adverse fetal outcomes, after adjustments were made for various patient factors including maternal age, body mass index, race, parity, history of diabetes, and diastolic blood pressure at first prenatal visit. When women with r-AKI and controls were matched 1:2 by age, race, body mass index, diastolic blood pressure, parity, and diabetes status, r-AKI was associated with a 4.7-times increased risk of preeclampsia and a 2.1-times increased risk of adverse fetal outcomes. A similar association between r-AKI and adverse pregnancy outcomes was observed in analyses excluding all women with diabetes, obesity, and hypertension.

“We believe that this study highlights an important finding that will be useful for medical providers caring for reproductive- age women,” Tangren said. In particular, health care providers should consider the study’s findings when counseling women with previous AKI—not just those with advanced preexisting kidney disease—about the risk of adverse outcomes in pregnancy.

The investigators stressed that the interaction between diseased kidneys and the feto-placental unit during gestation remains unknown and requires additional research. They hypothesize that in women with prior AKI, subclinical vascular endothelial injury may sensitize the vasculature to the toxic effects of circulating antiangiogenic factors that rise prior to term in all pregnancies. Additional animal and human studies are needed to test this potential explanation, however. “Our goal in future studies is to address why women with a history of AKI are at higher risk for pregnancy complications and to identify strategies to lower their risk,” Tangren said. They also would like to know if AKI severity is associated with future preeclampsia risk. In this study, because there were a small number of events in each AKI stage, the investigators did not have the power to address this relationship.

The varying rates of preeclampsia reported worldwide may be explained, at least partially, by the study’s findings, Tangren noted. Preeclampsia rates range from 1% to 15%, with higher rates reported in low-income countries. Also, rates of AKI are higher among young women in low-income countries.

Giorgina Piccoli, MD, who was not involved with the study and is the Chair of the Division of Nephrology at the University of Torino in Italy, noted that the cross-talk between the kidney and the placenta is important. “[It is] no wonder perhaps if all types of kidney damage are reflected and amplified in pregnancy, a situation in which the kidney is under functional stress,” she said. “The study’s findings are in line with previous studies of our group and others that suggest an effect of even minor renal damage in the development of adverse pregnancy-related outcomes. I’m concerned about how many patients we do not follow as highrisk pregnancies, and about how much we have to do to offer the best treatment to all of our patients.”

The article, entitled “Pregnancy Outcomes Following Clinical Recovery from Acute Kidney Injury,” appeared online at jasn.asnjournals.org/ on December 22, 2016, doi: 10.1681/ASN.2016070806.

Read the full article at http://onlinedigeditions.com/article/Prior+Acute+Kidney+Injury+May+Contribute+To+Adverse+Pregnancy+Outcomes/2679938/373726/article.html.

Older Age Should Not Rule Out Organ Donation After Death, According To New Research

Tracy Hampton

New research indicates that age cut-offs for deceased organ donors prevent quality kidneys from being available to patients in need of life-saving transplants. Even kidneys from donors =80 years of age functioned for years after transplantation in a recent Clinical Journal of the American Society of Nephrology study.

“Nowadays, in many countries, about 30% to 60% of deceased kidney grafts are included in the so-called ‘extended criteria.’ However, as witnessed by the heterogeneity of organ discard rate across the transplant community, the limits of this policy are not well defined despite the development of several scoring systems,” the study authors wrote. They noted that donor age in particular represents a major reason for organ discard, but data on the reliability of organs from elderly donors are currently limited and relevant studies have generated conflicting results.

The donor organ shortage has led to recent efforts to find ways to expand kidney recovery criteria, however, including the consideration of older deceased donor kidneys. Strategies incorporating such kidneys include old for old protocols that aim to match the estimated graft survival to recipient life expectancy and dual kidney transplantation that is intended to compensate for the limited nephron mass of older donor kidneys.

To see how donor age affects the longterm functioning of transplanted kidneys, Luigi Biancone, MD, of the University of Torino, in Italy, and his colleagues retrospectively analyzed information on all deceased donor kidney transplants performed at the Turin University Renal Transplant Center over an 11-year period from 2003 through 2013, with kidney transplants from extended criteria donors classified according to donor age classes. In the first study specifically focusing on donors =80 years old and dividing extended criteria donor cohort into decades, the team assessed the most relevant long-term outcomes together with associated risk factors.

The investigators excluded multi-organ grafts from 1199 consecutive transplants. Of the remaining 1124, there were 647 kidney transplants from extended criteria donors, which were defined as all donors 60 years and those aged 50 to 59 years with =2 of the following characteristics: serum creatinine at procurement >1.5 mg/ dL, cerebrovascular cause of death, and history of hypertension.

After a median follow-up of 4.9 years, patient and kidney survival rates were comparable among the 4 age groups considered (50–59 years, 60–69 years, 70–79 years, and =80 years). The 5-year patient survival rates ranged from 87.8% to 90. 1% in these age groups, and the 5-year kidney survival rates ranged from 65.9% to 75.2%. Patient and graft survival rates were comparable between dual and single kidney transplants, except for the =80 year age group, which had better graft survival with dual kidney transplantation.

Donor age classes did not correlate with most adverse events, including vascular and urological complications, new onset diabetes, and malignancies. Acute rejection rates were also comparable in the 4 groups, whereas infection rates appeared to be lower in the =80 year age group, particularly for cytomegalovirus infection (11.1% vs. 26. 4% of group 1, 31.8% of group 2, and 28. 3% of group 3).

“The results of this study support the use of extended criteria donors, even donors older than 80 years, but they have to be accurately selected and managed with dedicated protocols,” Biancone said.

Rates of kidney discard before transplantation were similar for kidneys from donors in the 3 younger age groups (15. 4%, 17.7%, and 20.1% respectively), but the discard rate was strikingly higher (48. 2%) among kidneys from octogenarian donors. Most of the reasons for discard were age-related; in particular, macroscopic flaws and Karpinski score >6 were found in 20% and 11.8% of organs harvested from donors =80 years vs. 4.8% and 3.7% of those from the youngest extended criteria donors.

“Kidneys from octogenarian donors, which currently represent a significant proportion of the donor pool, are discarded in almost 100% of the cases by many transplant centers,” said Umberto Maggiore, MD, who was not involved with the study and is a transplant nephrologist at the University Hospital of Parma, in Italy.

“This study provides findings that might help transplant physicians for decision- making purposes,” Maggiore said. “I would summarize this with a simple rule of thumb, called the ‘half rule,’ as follows: using histological parameters (in this study a dedicated renal pathologist evaluated a formalin-fixed needle biopsy using the Karpinski score), half of the kidneys will be discarded; of those recovered, almost half of the donors will be eventually used for dual transplantation, the 5-year cumulative incidence of graft failure of those allocated to dual transplantation being half compared with single transplantation.”

Other evaluation tools—such as those that analyze vascular resistances and perfusate biomarkers during kidney machine reconditioning or donor urinary biomarkers for ischemia-reperfusion injury—may allow for an accurate allocation of organs from elderly donors.

The article, entitled “Long-term Outcomes and Discard Rate of Kidneys by Decade of Extended Criteria Donor Age,” appeared online at cjasn.asnjournals.org/ on December 15, 2016, doi: 10.2215/ CJN.05990616.

Read the full article at http://onlinedigeditions.com/article/Older+Age+Should+Not+Rule+Out+Organ+Donation+After+Death%2C+According+To+New+Research/2679947/373726/article.html.

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