February 2014 E-Journal Club


February came in and went out like a lion this year.  Charlottesville has seen more snow in 2014 than we have in a long time.  Weather and other assorted responsibilities resulted in postponement of our February journal club until the waning days of the month.  Our February article is not brand new, but since we have recently been engaged in active negotiations about protein and uremia, we have been re-scouring the literature for anything we may have previously missed.

February Citation:

Gunst J, Vanhorebeek I, Casaer MP, et al.  Impact of early parenteral nutrition on metabolism and kidney injury.  J Am Soc Nephrol. 2013;24(6):995-1005.


This study was a planned re-analysis of data from the EPaNIC trial to investigate the effects of early supplemental PN on the incidence of, and recovery from acute kidney injury(AKI). The EPaNIC study involved 4640 mixed medical-surgical adult patients from 7 ICU’s, with 2312 patients receiving PN within 48 hours after ICU admission (early-initiation group) and 2328 patients who received PN delayed until day 8 (late-initiation group).  If you have not committed the methods and results of the original EPaNIC study to memory, see our July 2011 ejournal club for full details.

The current study analyzed the 1133 patients that developed AKI (≥ 2X baseline creatinine) based on their pre-illness creatinine (843 patients based on initial hospital pre-randomization creatinine).  Patients were analyzed by the overall incidence of AKI, as well as subgroups of the various stages of AKI, time receiving renal replacement therapy (RRT), lab and urine markers, urine output, as well as nitrogen balance.  Calorie needs were calculated based on corrected ideal body weight (see online supplemental tables) with 24 kcals/kg for females > 60 years, 30 kcals/kg for females < 60 years, 30 kcals/kg for males > 60 years and 36 kcals/kg for males < 60 years.

Inclusion and Exclusion Criteria:

Inclusion criteria:

Admission to a participating ICU, a nutritional risk screening (NRS) score of 3 or more (on a scale of 1 to 7 with a score ≥3 indicating that the patient was nutritionally at risk), AKI, and those not meeting any of the exclusion criteria.

Exclusion criteria:

Patients with a “do not resuscitate” code at the time of ICU admission, expected to die within 12 hours, readmitted to the ICU after randomization to the EPaNIC trial, enrolled in another trial, transferred from another ICU after a stay of > 7 days, suffering from ketoacidotic or hyperosmolar coma on admission, BMI <17 (kg/m2), short bowel syndrome treated with home-PN, on home mechanical ventilation, pregnant or lactating women, no clinical indication, or with a contra-indication, for a central venous catheter placement, able to take oral nutrition on ICU admission or with an NRS score lower than 3.

Major Results:

In the total AKI population and stage 1 AKI, the duration of AKI in the ICU, LOS in the ICU and hospital, renal recovery at ICU and hospital discharge, and the ICU, hospital, and 90-day mortality were unaffected by early PN.

In just those patients with stage 2 AKI, the duration of AKI in the ICU and the time to alive hospital discharge were significantly longer in the early PN group. However, there was no significant difference in the number of patients who were alive and AKI-free at hospital discharge.  In patients with stage 3 AKI, ICU LOS was longer in the early PN group without a difference in renal recovery parameters or mortality.  In patients with new RRT (n=359, 7.7%), the number of patients who were deceased or still RRT-dependent at hospital discharge was not affected by early PN.

Plasma urea was significantly higher with early PN from day 5 to day 10.  The plasma urea/creatinine ratio was slightly higher in the late PN group at day 2, but substantially increased in the early PN group from day 4 on, and it was higher than in the late PN group from day 4 to 11.

In both groups, nitrogen loss increased with time in ICU, and from day 4 to 11, nitrogen loss was significantly higher with early PN.  The calculated nitrogen balance was numerically less negative with early PN from day 2 to 7, whereas from day 8 to 12, the calculated nitrogen balance was less negative with late PN.  After 1 week, ∼30% of the “extra” (difference between early and late PN) administered nitrogen by early PN was net broken down to urea.  At day 14, 63% of the extra nitrogen intake went to ureagenesis.

Author’s Conclusions:

“Early PN had no impact on the AKI incidence or the time course of renal function parameters.  In patients with established AKI, there was no major impact on renal recovery, although early PN may have delayed recovery in patients with stage 2 AKI. The extra amino acid supply by early PN seemed inefficient to reverse the negative nitrogen balance…..The substantial catabolism of the extra amino acids, leading to pronounced urea generation, may have prolonged the RRT duration observed with early PN.”


EPaNIC was a large multicenter study, but the “n” is much smaller once you begin to look at subgroups of patients.  Also, once multiple subgroups and many factors are investigated, there is an increased likelihood that something will be significantly different by chance.  It is hard to single out anything profound regarding stage 2 AKI when the overall incidence of AKI was not significantly different.  The authors suggest that the “extra” protein in the early PN group may have contributed to the trend of longer renal replacement therapy, but the amounts of protein provided were quite modest.  The graphs reveal that total protein in the early PN group was less than 1 gram/kg.  Additionally, after 8 days the groups were receiving near identical nutrition, so it is hard to blame protein provision for any difference after that point.  It is also important to remember that early PN resulted in significantly more infectious complications, which explains the trend for more AKI, and longer RRT.  Increased infections in the early PN group would compromise nitrogen balance and explain some of the increased urea generation.

Our Take Home Message (s)

Early PN:

  • Results in increased infectious complications
  • Appears to increase the duration of RRT in the ICU.
  • May compromise nitrogen utilization.


Other News on the UVAHS GI Nutrition Website: (www.ginutrition.virginia.edu):

Upcoming Webinars 2012/2013:

–April 29:  Micronutrient Issues in Gastric Bypass

–May 20:  Peri-op Nutrition, CHO Loading Prior, and Earlier Post-op Feeding

–June 24:  Managing Absorption in the Adult Short Bowel Patient

Check out What’s New:

Resources for the Nutrition Support Clinician

Latest Practical Gastroenterology article:–Fisher C, Bethany Blalock B. Best Practice for Clearing Clogged Feeding Tubes.  Practical Gastroenterology 2014;XXXVIII(3):16.


Joe Krenitsky MS, RD

Carol Rees Parrish MS, RD

PS – Please feel free to forward on to friends and colleagues