Does an AKI episode Impact Subsequent Pregnancy?

#NephJC chat

Tuesday March 14th 9 pm Eastern

Wednesday March 15th 8 pm GMT, 12 noon Pacific

J Am Soc Nephrol. 2016 Dec 22. pii: ASN.2016070806. doi: 10.1681/ASN.2016070806. [Epub ahead of print]

Pregnancy Outcomes after Clinical Recovery from AKI.

Tangren JSPowe CEAnkers EEcker JBramham KHladunewich MAKarumanchi SAThadhani R.

PMID: 28008002

Free full text link (thanks to JASN!) 

Supplemental Data PDF link


Pregnancy is always a challenging time, not least for the kidneys. As a pregnancy progresses, the kidneys and placenta must work to meet the homeostatic demands of a developing human. For instance, GFR increases during pregnancy up to 50% above baseline levels to help meet these demands. What are the consequences for pregnancy if the kidneys have previously sustained an injury? We know that even early stage CKD leads to significantly worse outcomes in pregnancy. Furthermore, donor nephrectomy also increases the risk of preeclampsia. The link between past AKI and risk of development of CKD is well established.  So the authors of this study reasoned that the subclinical renal dysfunction present after AKI, even with full clinical recovery, might increase the risk of poor outcomes in pregnancy.

Study design:

  • Retrospective single centre study over 9 years.
  • AKI defined solely on creatinine (rise ≥ 1.5x baseline)
  • Compared maternal outcomes including preeclampsia, gestational hypertension gestational age, and Cesarean section.
  • Compared fetal outcomes including birth weight, perinatal death, NICU admission, and small for gestational age.

Inclusion criteria

  • Women with an episode of AKI with subsequent recovery of renal function (eGFR >90) prior to pregnancy
  • Exclusion criteria
  • Women with CKD (I-IV) or eGFR<90 prior to conception without a CKD diagnosis
  • Multiple pregnancies
  • 2+ proteinuria at the initial prenatal visit
  • Presentation after 20 weeks gestation


    Figure 1 from Tangren et al JASN 2017

    Figure 1 from Tangren et al JASN 2017

    Participant characteristics

    Overall, the groups were well matched with the exceptions that:

    Controls were more likely to be of self-reported nonwhite race

    Women with recovered AKI were more likely to be diabetic

    Women with AKI prior to pregnancy experienced AKI with a range of etiologies. Most were either pre-renal injury or acute tubular necrosis (40%). Thereafter drug-induced renal injury (12%) and AKI as a result of a previous pregnancy (12%) vied for the next most common.

    AKI resulting from a previous pregnancy, incorporated a range of pathologies:

    • Hyperemesis gravidarum
    • Pre-eclampsia or HELLP syndrome
    • Obstetric haemorrhage  

    Women with recovered AKI were significantly more likely to have a lower gestational age at delivery and need a cesarean section. Their rates of preeclampsia were also significantly higher. Offspring of women with recovered AKI were more likely to require NICU admission, highlighting the apparent high risk nature of these pregnancies.

    The authors used three analysis strategies to avoid confounding effects:

    Multivariate logistic regression

    After multivariate analysis, the association of recovered AKI with preeclampsia and adverse fetal outcomes persisted

    Matched analysis

    Matching each woman with recovered AKI to two without, by age, race, BMI, parity, diabetes status, and diastolic BP in the first trimester.

    The results of this were much the same, however, the frequency of small for gestational age was not significant.

    Figure 2 from Tangren et al JASN 2017

    Figure 2 from Tangren et al JASN 2017

    Subgroup analysIs

    Past preeclampsia increases the risk of having preeclampsia with subsequent pregnancies. 12% women with recovered AKI experienced AKI as a result of pregnancy, so the authors went on to perform a subgroup analysis excluding these women. As they did not have past preeclampsia data history on all women, they also performed a subgroup analysis in nulliparous women.

    They also performed subgroup analyses excluding various populations to try and dissociate the effect from other risk factors for adverse outcomes:

    • Diabetes Mellitus
    • Hypertension
    • Obesity (BMI >30)
    Figure 3 from Tangren et al JASN 2017

    Figure 3 from Tangren et al JASN 2017

    In all these analyses, the association with adverse pregnancy outcomes, particularly pre-eclampsia, was maintained.


    Women who previously experienced a creatinine rise of over 0.3 mg/dl over 48 hours (meeting KDIGO criteria) were not assigned a diagnosis of AKI. These cases of mild AKI will have been included in the control group.

    Relatively small number of patients with previously recovered AKI

    31% of recovered AKI was of unknown cause

    Despite a disparity in the racial profile between groups, there was no subgroup or matched control approach to avoid the potentially confounding effects of race.


    Overall, a previous episode of AKI even when followed by clinical recovery of renal function acts as a risk factor for adverse maternal and fetal outcomes in pregnancy, independently of other risk factors.

    It is possible that the increased risk of preeclampsia observed here after recovered AKI might explain global variations in the incidence of preeclampsia. Both preeclampsia and early life episodes of AKI are more common in low income countries.

    The pathophysiological mechanisms behind the increased risk observed here isn’t clear. The authors speculate that the underlying process might converge on endothelial injury. Perhaps there is a shared risk factor for both AKI and pre-eclampsia which might explain this association.

    This study raises interesting questions concerning risk stratification in pregnancy. Based on these results, it appears that women with a history of any renal injury should be counselled carefully about the risk of adverse pregnancy outcomes.

    Summary by Ben Stewart and Anna Burgner

    #NephJC chat

    Tuesday March 14th 9 pm Eastern

    Wednesday March 15th 8 pm GMT, 12 noon Pacific

    Dialysis for the Undocumented Immigrant

    #NephJC Chat

    Tuesday Feb 28th 9 pm Eastern

    Wednesday March 1st 8 pm GMT, 12 noon Pacific

    JAMA Intern Med. 2017 Feb 6. doi: 10.1001/jamainternmed.2016.8865. [Epub ahead of print]

    The Illness Experience of Undocumented Immigrants With End-stage Renal Disease.

    Cervantes LFischer SBerlinger NZabalaga MCamacho CLinas SOrtega D.

    PMID: 28166331

    Free Access (courtesy JAMA Int Med):  Link (expires March 3rd 2017)

    Commentary in JAMA Int Med 

    Related article on Hospice Access for undocumented immigrants in same issue

    Commentary from @MethodsmanMD, Perry Wilson:

    Post on the RFN from Nate Hellman 

    A New  York Times article on this issue (from 2010)


    Francisco is an undocumented immigrant who works as a landscaper and has been living in the U.S. for the last 35 years. He regularly sees a physician and pays in cash for his clinics visits and medications; he was diagnosed with CKD 8 years ago, but now is approaching ESRD. His extended family (some of them living legally in the US) are potential living kidney donors and are willing to undergo testing. Francisco does not want to give up and he wants to continue being productive and provide for his family. His clients have offered him monetary assistance . What are his options? Should we wait until he needs urgent hemodialysis? Should we provide a referral for dialysis, education, AVF or kidney transplant evaluation? Should Francisco return to his country of origin? Should he move to a more “undocumented people-friendly state”? Can he buy health insurance?

    The Emergency Medical Treatment & Labor Act (EMTALA) was enacted in 1986 to “ensure public access to emergency services, regardless of ability to pay…”; however, the Patient Protection and Affordable Care Act (ACA, iaka Obamacare) does not include access to healthcare for undocumented immigrants.

    A survey in 2009 among Nephrologists reported that 642 nephrologists (out of 990 who responded), have provided dialysis services to undocumented patients and 67% of those nephrologists did it as outpatient and 59% provided emergency dialysis care. The majority felt that reimbursement was inadequate. Furthermore, there is a misconception that undocumented patients come to the U.S for health benefits; the latest literature reveals that in fact, undocumented immigrants contribute less to health care costs and use fewer medical services. Surprisingly, in a small survey in 2012 among AJKDblog readers, close to 58% of respondents, did not support kidney transplantation.  

    Currently, in the United States there are approximately 6,500 undocumented immigrants needing a form of renal replacement therapy, mainly hemodialysis. I am unaware of any data of patients undergoing peritoneal dialysis, which would be far more cost effective.  These patients, depending on the state in which they live, have to either have insurance coverage to undergo scheduled hemodialysis or must wait to develop fluid overload symptoms in order to meet criteria to be admitted for emergent hemodialysis. The cost for receiving emergent hemodialysis ranges from $285,00 to 400,000 across the U.S. This present qualitative study of 20 undocumented hemodialysis patients from Latin America, living in the US for at least 4.2 years, for the first time explored the feelings of undocumented patients undergoing urgent hemodialysis. According to this previous report, there are approximately 6,500 undocumented immigrants on hemodialysis.  This issue is not exclusive to the United States, but also to first world countries that receive large numbers of immigrants.

    Study Design:

    • Single center study in Denver, Colorado, from July 1 to December 2015
    • 20 semistructured interviews with undocumented Hispanic patients requiring hemodialysis
    • Patients signed informed consent and received financial compensation.
    • Professional Interpreters were used at the time of interview.
    Box from Cervantes et al, JAMA IM 2017

    Box from Cervantes et al, JAMA IM 2017

    Inclusion Criteria

    • Patient needing urgent hemodialysis (with no access to schedule HD)
    • Arteriovenous fistula
    • Admission criteria for urgent hemodialysis: potassium >5.2 mEq/L, bicarbonate less than 15, hypoxia (<90%), uremic symptoms (confusion, dyspnea, nausea, vomiting, altered mental status)
    • Patients were admitted for two nights; received hemodialysis two days in a row (When available).

    Exclusion Criteria

    • Patients lacking decisional capacity


    Table 1 from Cervantes et al, JAMA IM 2017

    Table 1 from Cervantes et al, JAMA IM 2017

    After the questionnaire was performed, answers were split in themes:

    1. Distressing Symptom Burden and Unpredictable Access to Emergent-Only Hemodialysis
    2. Death Anxiety Associated With Weekly Episodes of Life-Threatening Illness
    3. Family and Social Consequences of Accommodating Emergent-Only Hemodialysis
    4. Perceptions of the Health Care System
    Table 2 from Cervantes et al, JAMA IM 2017

    Table 2 from Cervantes et al, JAMA IM 2017


    As the authors suggest, this is one of the first studies that focus on the psychological and physical challenges, including near-death experiences that undocumented immigrants endure during their hemodialysis journey.  I have taken care of many undocumented patients (not only Hispanics), and as a health care provider, I feel a great deal of empathy after reading the comments of the patients included in the study. As a physician, I just want to deliver the best standard of care for my patients. The best option is not always the most expensive, but the more cost effective, which sometimes happens to be the one with the best outcomes. Although this article included only 20 patients, it sheds light about the problems these patients face on a daily basis which varies according to the state in which patients reside.  Even though they received substandard health care, they are still grateful with healthcare personnel.

    The following States provide scheduled maintenance hemodialysis and is important for every Nephrologist to know: Arizona, Delaware, Florida, Illinois, Massachusetts, Minnesota, New York, North Carolina, Virginia, Washington and District of Columbia. Some states, like Illinois, have begun to cover (PDF link) undocumented immigrants in need of a kidney transplant as well, clearly decreasing the costs of dialysis. New York State has a similar program with certain limitations. In other states, there are safety net hospitals, which provide dialysis, amongst other services, for undocumented immigrants. Furthermore, many of these patients have a donor, but because their lack of access to health care (even if they are good transplant candidates), they are not eligible, unless they pay out-of-pocket. In fact, it has been shown that undocumented immigrants tend to have better outcomes than their U.S. counterparts.

    So what would be the ideal health insurance plan for an undocumented patient? An off-exchange policy, but the ACA prohibits undocumented patients from using such a plan so changes in the Federal and State law (like California) would have to be implemented.  

    I found minimal limitations in the study other than those acknowledged by the authors including the use of a single center and the small sample size.  I wonder if some patients declined to be in the study for fear of immigration repercussions. It would be interesting to know the experience of undocumented immigrants on scheduled hemodialysis as well. .

    As the editorial suggested, small changes in local and state laws to the health care system have been enacted to include undocumented immigrants; some non-profit organizations have also stepped in, but the Medical and Nephrology Societies and Federal Government need to address the issue of undocumented immigrants living in the U.S. needing hemodialysis (or experiencing some of the catastrophic diseases) so we, as physicians, would not have to deliver substandard care or have an ethical dilemma, regardless of costs or immigrations status. The fact the these patients have to wait to develop near-death symptoms to be dialyzed, is alarming to me and should be a concern for Nephrologists and Lawmakers.

    The Renal Physicians Association states: ” care professionals have an ethical obligation to treat the sick (including the ESRD population), and the Federal Government has an ethical responsibility to provide life-sustaining care for anyone within the U.S. borders….”

    Summary written by Hector Madariaga, Nephrologist, Boston


    #NephJC Chat

    Tuesday Feb 28th 9 pm Eastern

    Wednesday March 1st 8 pm GMT, 12 noon Pacific

    Some thoughts on Table 2 for tonight's #JHMChat

    Last week my summary of Cost of Acute Kidney Injury in Hospitalized Patients included a bubble chart of Table 2.

    Where is CHF and COPD? These are two of the most common reasons for hospital admission.

    Where is CHF and COPD? These are two of the most common reasons for hospital admission.

    This made clear one of the points of the study that is hard to accept, the fact that an myocardial infarction adds only $14. Does this indicate that the model flawed in some way? Or does this represent a medical system that has developed detailed and efficient pathways for the diagnosis of acute MI such that these patients do not represent meaningful increase in cost of care?

    I do not suppose there is anything to learn if the model is merely broken. But if we suppose the model is accurate what can that teach us about how we should take care of AKI?

    Hospitals are tuned for the inpatient management of acute MI. Chest pain units that quickly and efficiently guide patients through risk stratification, then intervention versus medical management leading to brisk outpatient follow-up are all components that allow efficient quality care for acute MI. The proof is in the outcomes.

    Differential Time Trends of Outcomes and Costs of Care for Acute Myocardial Infarction Hospitalizations by ST Elevation and Type of Intervention in the United States, 2001–2011

    Differential Time Trends of Outcomes and Costs of Care for Acute Myocardial Infarction Hospitalizations by ST Elevation and Type of Intervention in the United States, 2001–2011

    What would an AKI pathway look like? Can we systemitize the management of these patients to shorten admissions?

    Over and over again I see decisions made by nephrologists that prolong hospitalizations while not providing advantages to the patient.

    Can we agree that if the creatinine is falling for a day or two we do not need to watch the creatinine fall all the way to baseline before they are ready for discharge? I have seen that done.

    In rhabdomyolysis, if the patient didn't develop AKI when the CPK peaked at 20,00 do we need to keep the patient admitted on IV fluids until the CPK is normal? I have seen that done.

    If the patient has AKI and the creatinine is stable and the electrolytes are good, we do not need to keep the patient admitted until renal recovery. We should not emphasize creatinine voyeurism as an end to itself.

    AKI is so expensive because we have not researched or developed validated pathways for dealing with these patients quickly, efficiently and personally.

    Wash U Episode 14: Immune complex GN

    • Lupus nephritis
    • Poststreptococcal GN
    • Membranous nephropathy
    • IgA nephropathy
    • MPGN

    Other than giving headaches to medical students, what do all of these disorders have in common?  They all fall under the umbrella of "immune complex mediated" glomerulonephritis.  Of course, there are others as well - immunotactoid, fibrillary, C3 glomerulopathy, the list goes on and on.  But sometimes a biopsy and a case don't fall into the simple bucket that we expect, and oftentimes clinicians are left feeling a bit unsure of themselves because the lines between these diseases blur together.  The February video from the Wash U Nephrology Web Series left us scratching our heads a bit, but real life cases aren't always quite like the textbook.  Check it out.

    Next NephJC, The Cost of AKI

    Hot on the heals of our chat with #RheumJC we will be teaming up with the editors of the Journal of Hospital Medicine to discuss Cost of Acute Kidney Injury in Hospitalized Patients. Open access to the article is available here. You will also be able to get CME for participating in this chat. Information on that here.

    Two items of note:

    1. We will be doing this February 6th, which is a Monday
    2. We will be using the hashtag #JHMChat

    We are still discussing if we will have a EU/GB chat for this article. If you would participate in an EU discussion of this article tweet us.

    Expect a full background post on this article once we get a chance to read it ;-)

    PRECISION Trial wrap up

    We had a great discussion the The PRECISION Trial with the #RheumJC. Participation was bonkers!

    New dad, Hector Madariaga continues to crush it with the Storify.

    American Chat

    The EU plus Great Britain Chat

    Archive of all the tweets:

    NSAID Part 1

    NSAID Part 2

    NSAID Part 3

    PRECISION Trial: The Visual Abstract

    Here is our second attempt to putting together a visual abstract. Went horizontal instead of vertical this time. Still feeling out this new medium.

    And here is the animated GIF

    I think GIFCreator is the best online GIF creator. Tried a few of them. This was the best and gave me the most control.

    When looking for the NEJM logo in google image search I came across this page. Breaks my heart. We miss you Alex.