1/
Nephrology:
“We will forever argue about validity of equations to convert serum creatinine to eGFR using age, sex etc”

Also nephrology:
“We will make no adjustment for muscle mass when using urinary creatinine within urine ACR”

A #tweetorial on two albuminuria paradoxes 👇
2/
Recap: why use early morning urine ACR?

✅Correlates well with ‘gold standard’ 24hr urine collection (pain to perform)

✅Creatinine in denominator corrects for urine dilution - works when creat excretion constant (but, note some daily variation)

ncbi.nlm.nih.gov/pmc/articles/P…
3/
Albuminuria quantification is useful prognostically (as well as clear diagnostic utility!):
❗️Independent risk factor for CV mortality
❗️ RENAAL showed higher uACR = higher risk of CKD progression in patients with type 2 diabetes

pubmed.ncbi.nlm.nih.gov/15302780/
4/
But enter PARADOX 1️⃣…

Urinary creatinine excretion is proportional to muscle mass, just like serum creatinine is.

So why does the uACR value not undergo extensive adjustment like eGFR does, based on studies looking to adjust for patient body surface area, age, sex, etc?
5/
(It’s worth noting that the heavy-lifting of converting serum creatinine to eGFR is done by indexing to body surface area (BSA), with age & sex (rather imperfectly) doing fine-tuning.
ajkd.org/article/S0272-…

But we don’t even standardise uACR to BSA, let alone age or sex.)
6/
Does this matter? Sometimes!

e.g. in males (so therefore ⬆️muscle mass & ⬆️urinary creatinine denominator) with diabetes, spot uACR gave much lower results than when albuminuria measured by timed urine collection.

ncbi.nlm.nih.gov/pmc/articles/P…
7/
On flip side, raised uACR can mark low muscle mass rather than large albumin excretion, due to a lower urinary creatinine denominator.

Therefore therapies by uACR threshold (RAASi, SGLT2i, etc) are targeted more at those with lower muscle mass (on average older, female pts).
8/
This graph shows that heavier & younger patients need higher actual 24 hour albuminuria to reach the old KDOQI threshold for uACR “microalbuminuria” - so they’d miss out on earlier treatment with RAASi.

karger.com/Article/Fullte…
9/
However, is there any advantage to this sloppy approach?

Well - spot uACR performs BETTER than 24hr urine albumin collection in predicting CKD progression!

ncbi.nlm.nih.gov/pmc/articles/P…
10/
It’s because uACR is a bipolar tool – it captures ⬆️protein leak AND ​​⬇️muscle mass, & both are negative prognostic factors.

This is an occasion when ‘surrogate test' performs BETTER than ‘gold standard’ test. Can anyone think of other examples of this in medicine? I can’t
11/
These principles also apply to urine Protein-Creatinine ratio (uPCR) but we’ll stick with discussing uACR for now.

If you want to recap the evidence for converting between these measures see the great #NephJC blogpost from @sophia_kidney

nephjc.com/news/acrpcr
12/
Now let’s also think about uACR PARADOX 2️⃣!

Patient 1 – GFR 120, weight 50kg, loses 1g albuminuria per 24 hours, uACR 70mg/mmol

Patient 2 – GFR 40, weight 50kg, loses 1g albuminuria per 24 hours, uACR 70mg/mmol

How does their glomerular permeability compare?
13/
They have the same urine ACR & 24hr albumin leak, but (simplistically speaking) patient 2 only has 1/3 the nephrons, so therefore each individual glom is 3 times leakier!

This will have prognostic and therapeutic implications - but this isn’t factored in by using uACR.
14/
At 1g/day albuminuria this may not be treatment altering, but at lower levels and when ‘labelling’ patients as having CKD, it is potentially problematic.

Therefore, logically, when calculating uACR we should factor in the nephron mass across which albumin is lost.
15/
So what could be done differently?

We could all divide uACR by the eGFR, and use that number instead.

This would:
🧩Provide some adjustment for muscle mass, to address Paradox 1
🧩Account for size of functioning nephron mass, to adjust for Paradox 2
16/
Evidence that this approach would do anything to improve patient care is absent - but at least the world would be logical???

Further reading for those interested:
karger.com/Article/Fullte…
17/
So why don’t we bother?
✅ Variability is high between different uACR samples within individuals
✅ Importance of trends > absolute values
✅ Few clinical diagnoses or decisions hinge on small differences
18/
But just in case you had arbitrary cut-offs in mind like:

“I would biopsy this woman as her uACR is 110mg/mmol, but not this man whose uACR is only 80mg/mmol”

bear in mind the latter might just have the greater albumin leak!
Take homes:
👍Spot uACR can often replace 24hr urine collection
👍Be mindful that ANY urine ratio test with creatinine as denominator will underestimate in more muscular & overestimate in sarcopaenia
👍 Having said that - uACR is a great prognostic test, do send it & use it!
Thanks to @amyaimei @Nephro_Sparks @drM_sudha @docanjuyadav for their comments and feedback, and to @EllamTim (sadly not a twitter fan) for lots of teaching on the topic!

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More from @jamiekwillows

30 Apr 20
Do you manage the renal impact of #covid19 on general wards?

My summarised recommendations on;
✅ AKI
✅ Volume status
✅ ACEi
✅ Transplant & dialysis patients

taken from @RenalAssoc, #eraedta, #nephjc & @UpToDate

= lots of relevant info in 8 tweets👇

#medtwitter #covid4mds
AKI 1

✅ Many potential factors;
✔️hypovolaemia due to fever / GI symptoms
✔️sepsis & cytokine release
✔️rhabdo, even without myalgia; check CK!
✔️direct viral tubule invasion?
✅ Low grade proteinuria & haematuria common
✅ Don’t miss ‘usual’ post-renal AKI; bladder scan +- US
Volume status

Assessment not easy at best of times!

Balance of maintaining volume to prevent AKI & avoiding hypervolaemia which impairs oxygenation in ARDS

🟠 UK Renal Assoc - “target euvolaemia”

🟠 Uptodate - “fluid goals conservative as per ARDS criteria” but individualise
Read 10 tweets
1 Mar 20
1/
#medtwitter is fairly comfortable managing “normal” DKA right? But how about in the anuric dialysis patient? The cookbook protocol can be deadly.

Read this #tweetorial to learn about how their DKA pathophysiology is fascinatingly different.

#meded #nephpearls #endotwitter
2/
Quick recap of normal DKA pathophysiology;

🔑 insulin requirement > insulin supply

✅ “stress hormones” rise
✅ blood glucose rises & because glucose is an osmotic diuretic, there is a huge, inappropriate urine output
✅ body makes ketones as alternative fuel, so pH falls
3/
Recap of normal DKA;

✅ patient symptomatic,extracellularly dry, 6 litres down & counting
✅ whole body K low due to osmotic diuresis, but often ⬆️K at first due to hypertonicity/ low insulin/ acidosis
- serum K then rapidly falls as INsulin drives K & glucose INtracellularly
Read 18 tweets
26 Jan 20
1/
Hyperkalaemia treatment

KDIGO have just published their conference conclusions on managing acute #hyperkalaemia so I run through some learning points, some criticisms and the bits I’m not sure about as a renal reg.

#medtwitter #nephpearls #meded
2/
Before we start - why do we care?

Because hyperkalaemia associates with a large increase in risk of death in the next 24 hours.

☠️ mortality not necessarily caused by the hyperkalaemia itself, but can indicate that something bad is happening

ncbi.nlm.nih.gov/m/pubmed/19546…
3/
So, the KDIGO conference paper.

Firstly, no one can even agree on the definition of hyperK. What’s up with the Swiss? 4.5mmol/l as the upper limit of normal? Compare this with some values used in research papers.....!
Read 14 tweets
25 Aug 19
Last week twitter was unexpectedly keen for renal registrar on-call tips, so here’s round 2️⃣ of kidney #tipsfornewdocs covering iv fluids, AKI, “renal screen” bloods, immunosuppression, electrolytes, DKA in ESKD, peritoneal dialysis, proteinuria, meds & ⬆️BP (thread)
#nephpearls
Iv fluids; Renal #tipsfornewdocs 2️⃣ 1/15

✅ 1L 5% dextrose 12 hourly = 50g glucose = 55 skittles. Not same as feeding patient.
✅ “iv fluid for AKI plus furosemide to keep it off their chest” isn’t a thing - commit to goal of wetter or drier.
(specialist use only eg. ⬆️Ca, ⬆️K)
AKI; Renal #tipsfornewdocs 2️⃣ 2/15

✅ In AKI anticipate accumulating meds (eg opiates,insulin) & ⬇️dose before complications
✅ Seeing unobstructed AKI pt, BP/K/pH fine but becoming oligoanuric at 1am despite euvolaemia? It’s OK to watch + wait. Trial by drowning not obligatory.
Read 17 tweets
18 Aug 19
To celebrate 1 yr of taking referrals as the renal registrar on-call, it’s time for some kidney-themed #tipsfornewdocs covering high K, AKI, “nephrotoxins”, medications, iv contrast, hypertension, & caring for kidney transplant & dialysis patients. #nephpearls (thread)
⬆️K - Renal #tipsfornewdocs 1/18

✅ Insulin-dextrose is not benign (⬇️BM risk) & does not get rid of K (only hides it), therefore rather than give round after round do phone us for help!
✅ Repeat ECG, re-bolus calcium gluconate if persistent changes
✅ Salbutamol dose = 10-20mg
⬆️K - Renal #tipsfornewdocs 2/18

✅ Get a bicarb level (correct acidaemia to help ⬇️K)
✅ No one who can’t name 3 side-effects of bicarb should decide to give bicarb (not a bad rule for any drug!)
✅ Review NSAIDs, ACEi, A2RBs, spironactone, beta-blockers, trimethoprim, diet
Read 20 tweets

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