Topic Discussion: ECMO and the Kidney

Extracorporeal membrane oxygenation (ECMO) is an effective therapy for patients with reversible cardiac and/or respiratory failure. AKI  often occurs in patients supported with ECMO; it frequently evolves into chronic kidney damage or end-stage renal disease and is associated with a reported 4-fold increase in mortality rate. What are the mechanisms of injury of AKI with ECMO?

This table below summarizes what might be the potential causes.

Here is a nice reference

Patient-related variables
Pretreatment factors	Hypoperfusion, loss of autoregulation Hypoxia
	Nephrotoxic drugs Systemic inflammation
ECMO-related variables
Hemodynamic factors	Blood flow alterations
Hormonal factors	Renin-angiotensin-aldosterone dysregulation ANP downregulation
ECMO-related	Blood shear stress
Systemic inflammation	Exposure to a non-self membrane Blood/air interface
Organ crosstalk	Cardio-renal syndrome
Circuit-related factors	Hypermyoglobinemia
	Embolism
	Hemolysis

Hemolysis is an interesting cause. This is an image of a patient getting CRRT on ECMO.  CRRT was on a zero K bath and high clearance rates. Within hours of starting CRRT, effluent bags of the CRRT turn red. Despite being on max CRRT,  patient’s potassium rose to 9mmol/L. This is hemolysis and can be reported in 18% of cases with ECMO.  Rhabdomyolysis can also be noted in some cases. Checking a free Hgb and effluent myoglobin can aid diagnosis for both entities. In addition, classic markers for hemolysis such as LDH, haptoglobin, anemia and so forth should be checked regularly. 

 https://www.ncbi.nlm.nih.gov/pubmed/26606144

 https://www.ncbi.nlm.nih.gov/pubmed/28470926

Topic Discussion: Non-nephrogenic calciphylaxis

Calciphylaxis in Patients With Normal Renal Function is usually unusual as most of the cases we encounter as nephrologists are in ESRD and or CKD patients

A recent review and literature update by the MGH researchers defined concomitant risk factors, treatment, and outcomes for patients with nonnephrogenic calciphylaxis.

116 patients today were reviewed.  Vitamin K antagonism and obesity were the most common concomitant factors. In the literature review, lower age and higher body mass index  were associated with the central location of lesions, whereas vitamin K antagonism was associated with the peripheral locations.  None of the treatments were associated with lesion improvement or survival.

As summarized by the authors: the risk factors are the 4Ws:- Warfarin, White race, Women and overWeight in patients with normal renal function. Interesting that warfarin is a risk factor in both renal and non renal calciphylaxis. It’s perhaps about time the renal community embrace apixaban over warfarin

A larger set of risk factors exists that were mentioned in the recent NEJM review in 2018 that also add: ESRD( what we see), hypercalcemia( probably in setting of CKD as pure – not really evident), DMII, hyperparathyroidism( we have seen this), Vitamin K deficiency, Autoimmune disorders, metastatic cancers, rapid weight loss, skin trauma to name a few.

Check out this interesting tweetorial from ISN education on this topic

Consult Rounds: Toxic alcohol ingestions

A summary of all potential alcohol toxicities ( Renal perspective)

Name	Metabolic Acidosis	Osmolar Gap	Anion Gap	Ketones	Ca Oxolate Stones	Reduced Vision
Alcohol	Yes	Yes	Yes( lactate also)	Yes	No	No
Methanol	Yes	Yes( earlier on and then disappears)	Yes	No	No	Yes
Ethylene Glycol	Yes	Yes	Yes	No	Yes	No
Isopropyl Alcohol	No	Yes	No	Yes	No	Yes
Propylene Glycol	Yes	Yes(initially)	Yes(converted to lactate)	No	No	No

Topic Discussion: Interesting HTN, hypokalemia and Met Alk syndromes: a summary

There are certain syndromes that lead to HTN, hypokalemia and metabolic alkalosis that are very rare but often confusing. Here is a breakdown of the 3 ones that often can get confusing.

Syndrome	Defect	Pathophysiology	Treatment	Comments
Liddle Syndrome	Missense mutation in ENaC channel	Constitutive activation of the ENaC channel	Triamterene or Amiloride	Low renin and low aldosterone level, no response to spironolactone
Congenital Adrenal hyperplasia	11-B hydroxylase deficiency	Leading to excessive mineralocorticoid production	Life-long steroids to help shut off ACTH	Diagnosis is confirmed by elevations of 11-deoxycortisol and 11-deoxycorticosterone
Glucocorticoid remediable Aldosteronism	Chimeric gene crossover of ACTH and Angio-11 genes	Normal ACTH controls cortisol and AngII controls Aldo. In this gene mutation, ACTH starts controlling Aldo and hence causing HTN and ongoing changes Leading to excessive aldosterone production.	Life-long steroids to help shut off ACTH	Low renin but high Aldo in these cases.
Syndrome of Apparent mineralocorticoid excess	11-B hydroxysteroid dehydrogenase type 2 mutation or inhibition	Normally, 11-B hydroxysteroid dehydrogenase in-actives cortisol via making to cortisone. This avoids cortisol mediated mineralocorticoid activity to maintain it’s specificity to aldosterone. If this is blocked, then cortisol activates mineralocorticoid activity	Amiloride or spironolactone	Diagnosis made via free urinary cortisol to cortisone ratio Renin and Aldo levels are low Licorice that has glycyrrhic acid that can also inhibit 11-B hydroxysteroid dehydrogenase.