Tag Archives: renal dysfunction

Renal Disease Associated With Fatty Liver Disease & Dexamethasone-COVID-19 Data

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Looking for and managing hypertension has been an important component of care in children and adults with nonalcoholic fatty liver disease (NAFLD)/metabolic syndrome.  In addition, hypertension is frequently associated with renal impairment.

As such, it is perhaps not surprising that in both adults and children, there is a high rate of renal impairment.   The data in children is much more sparse than in adults.  A recent retrospective pediatric cohort study (T Yodoshi et al. J Pediatr 2020; 222: 127-33) adds more information to this problem.

More background information:

  • Chronic kidney disease is highly prevalent in adults with NAFLD: 20-55% (J Hepatol 2020; 72: 785-801; Am J Kidney Dis 2014; 64: 638-52)
  • NAFLD is currently the leading indication for concurrent liver and kidney transplantation
  • In adults, the severity of NAFLD histology is associated with renal impairment
  • The first stage of renal impairment is glomerular hyperfiltration. This is hypothesized to be a precursor of intraglomerular hypertension which leads to albuminuria and glomerular filtration rate (GFR) decline/progressive renal dysfunction
  • Early intervention in high risk patients with angiotensin receptor inhibitors may prevent or delay progressive renal disease

Key findings in 179 patients with biopsy-confirmed NAFLD:

  • 82% non-Hispanic, median age 14 yrs
  • 36 (20%) had glomerular hyperfiltration and 26 (15%) had low GFR (w/in 3 months of liver biopsy) based on Schwartz equation
  • Hyperfiltration was independently associated with higher NAFLD activity score (aOR 2.96)

Discussion:

  • Mechanism: The authors speculate that “it is possible that they [renal and liver disease] are both the end result of the same ‘hit.’ The renin-angiotensin system may play a key role….Notably, there is an ongoing…clinical trial investigating an ATI receptor blocker, losartan, for the treatment of NAFLD in children.” Other potential contributors include fructose and insulin resistance.
  • Limitations: This single center biopsy-confirmed population may not be representative of most children with NAFLD.  Also, as this was a retrospective study, more precise measures of renal function were not available.

My take: This study confirms a high rate of renal dysfunction (35%) in children with NAFLD. As such:

  • Children with NAFLD need to have their blood pressure monitored
  • Clinicians should have a low threshold for nephrology referral if suspected renal impairment.

NEJM Recovery Collaborative Group: July 17, 2020
DOI: 10.1056/NEJMoa2021436: Full Link: Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

Form NEJM Journal blog:

In the open-label RECOVERY trial, some 2100 U.K. patients hospitalized with COVID-19 were randomized to usual care plus oral or intravenous dexamethasone (6 mg once daily for up to 10 days), and 4300 were randomized to usual care alone.

Among patients on invasive mechanical support at the time of randomization, the mortality rate within 28 days was significantly lower with dexamethasone than with usual care alone (29% vs. 41%). A benefit was also seen among those on oxygen without invasive ventilation (23% vs. 26%). However, among patients not receiving respiratory support, mortality rates did not differ significantly between treatment groups.

Alive and well? 10 years after liver transplantation

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As survival has improved with liver transplantation (LT), long-term health outcomes have become more important.  Reported 5-year survival rate after pediatric LT in North America is >85%.  More data on long-term health consequences are provided in a review of 167 10-year survivors from a North American Database (Studies of Pediatric Liver Transplantation –SPLIT) (J Pediatr 2012; 160: 820-6).

Ng VL et al report on frequency of comorbidities as well as quality of life.  Of the 10-year survivors who were included in this study: 85 (50.9%) were transplanted in the first year of life; 69 (41.3%) received transplants between 1-7.9 years.  Biliary atresia accounted for 55.1% of the transplanted cohort; the remainder were due to the following: metabolic liver disease 23 (13.8%), acute liver failure 18 (10.8%), other cholestatic conditions 17 (10.2%), tumor 6 (3.6%), and other 11 (6.6%).

First allograft survival rates were 94% at 1 year and 88% at 10 years.   Health-related quality of life (HRQOL) as assessed by the PedsQL 4.0 Generic Core Scales revealed lower patient self-reported total scale scores for LT survivors compared with healthy children (77.2 vs 84.9, P<.001).  14% had HRQOL >2 SDs below that of a matched healthy population.  Other specific post-LT morbidities included the following:

  • Impaired linear growth (23% <10th percentile); ongoing steroid therapy was associated with increased risk of poor linear growth.
  • Renal dysfunction (9%) –defined as calculated glomerular filtration rate <90 mL/min/1.73 m2.
  • Hyperlipidemia: 20% with hypercholesterolemia, and 26% with hypertriglyciridemia
  • Lymphoproliferative disease (5%).  EBV seroconversion occurred in 46 (47%) of 97 who had been EBV-negative prior to LT.  25 (15%) developed symptomatic EBV infection.
  • School performance: 32 (23%) had repeated a grade or were held back at least 1 school year.
  • Liver fibrosis: at 10 years, elevated aminotransferases were noted in 11% and increased gamma gluatmyl transpeptidase in 15%.  Previous studies from SPLIT indicate fibrosis is common in long-term survivors even with good clinical outcomes.

Alive and well?  While survival has improved remarkably, better outcomes are still needed.

Related posts:

Picking winners and losers with liver transplantation allocation

Good care 24/7

Big gift, how much risk

Additional references:


  • -Pediatrics 2008; 122: 1128-35.  Outcomes of 461 pediatric LT.
  • -Am J Transplant 2008; 8: 2506-13.  Improving long-term outcomes of LT.
  • -Hepatolog 2009; 49: 880-6.  LT-Liver fibrosis at 10 year followup.
  • -JPGN 2008; 47: 165. ~50% below 1.3 SD of adult height. Many show partial catch up growth.
  • -Liver Transplant 2006; 12: 1310. Review article on nutrition for OLTx patient.