GIM lunchtime teaching 20th May

Literally quite interesting

Created with xaringan.

Meta-analysis of 123 trials with 600,000 participants.

WRF = permissive hypercreatininaemia

Ellison & Felker (NEJM 2019) and Braunwald (EHJ 2014):

• down-shift in CCF due to RAS + / SNS + / DCT hypertrophy
• right-shift in curve due to renal insufficiency (reduced secretion)
• ...NB log scale - hence why we double doses in resistance
• gut oedema doesn't affect total amount absorbed but does slow absorption and so blunt the peak
• NaCl intake should be low to allow excretion to exceed intake (periods of anti-natriuresis)

n = 300: factorial low (IV dose = N oral) vs. high (2.5x oral) and bolus vs. IVI
Co-primary end-points of symptom score and SCr at 72 hrs (= 3 days).

Not powered to detect hard clinical endpoints.

No difference between bolus or infusion.
Higher dose had better symptom control, greater diuresis, more transient SCr rises (not reaching p < 0.05).

Cr went up a tiny bit (0.05 mg/dL = 5 mcM) in all but no difference between groups.

Association of linear change from baseline over 72 hrs with outcomes over 60 days.

n = 188. More serious adverse events in the UF group (72% vs 57%) - mainly renal failure / bleeding / line-related.

Variants protective against trypanosomiasis in heterozygote state. 15% AAs hom / compound het.

Spectrum of ApoL1 disease from arterionephrosclerosis (case above!) > collapsing GN.
Viral trigger for collapsing GN > IFN response > TRIs. (HIV)

Clinical notes

Pseudohyponatraemia caused because serum is diluted prior to analysis - so still seen with contemporary ISE methods (although was even worse in era of flame photometry). Can detect this by running a sample through ABG machine (as this uses an undiluted sample, so Na will be normal if pseudohypoNa) - see European guidelines.

Glycine encountered in gynaecological / urological irrigation fluids - e.g. TURP syndrome.

The risk of cerebral oedema is not elevated in i) and ii). The risk of cerebral oedema is high in iii) because serum tonicity is LOW - even when osmolality is high.

Basic concepts

See European guidelines, KI quiz and JAMA review.

Remember basic definitions:

• osmolality (or better "osmotic concentration") = number of solute particles per unit volume
• tonicity = osmotic pressure between two compartments (a function of the effective osmoles - i.e. the osmolar concentration and the properties of the semi-permeable membrane)
• reflection coefficient = a measure of how well a solute passes through a membrane (1 = impermeable; 0 = completely permeable)
• effective osmole = unable to penetrate the membrane
• ineffective osmole = able to freely cross the membrane

Na, K etc. are effective osmoles.

EtOH is an ineffective osmole (reflection coefficient for EtOH ~ 0).

Urea is intermediate. Is hydrophobic and so doesn't cross lipid bilayers; reflection coefficient depends on expression of urea transporters. Reflection coefficient for urea ~ 0 for skeletal muscle and ~0.5 for the cerebral capillaries. Therefore rapid changes in urea can cause cerebral oedema (e.g. in dialysis equilibrium) - but for the purposes of evaluating hypoNa, can consider urea as an ineffective osmole (as will have equilibrated when not changing rapidly). See Sterns and Halperin reviews. NB Urea is an effective osmole in the distal nephron - hence its utility in treating SiADH.

At one point, was thought that the contribution of EtOH to Osm may be higher than its molar concentration - so conversion factors of 3.7 -- 4.0 used. However, this was based on flawed reasoning, so it is in fact correct to convert based on its molar concentration (i.e. divide by 4.6 as MW is 46 g/mol). In practice, easiest to remember by dividing by 4 to approximate.

See UpToDate.

Figures from small Greek case-series.