Thread by @Dilushiwijay

1/ When bubbles settle on the surface of the urine it indicates disease of the kidneys-Hippocrates

In the day, urinary exam was so crucial, the urine flask was as much a symbol of a physician as today's white🥼!

🧵Is proteinuria a worthy rival to GFR?
#Nephmadness #primarycare

2/
*⃣Normal urinary protein excretion is <150mg/d and comprises mainly Tamm-Horsfall proteins, with very little albumin (5-10mg/d)

*⃣ We don't understand what happens to albumin in the kidney 💯

*⃣ But overall the degree of albuminuria is a ⚖️of filtration + reabsorption 👇

3/Albuminuria is common in injury to the GBM (GLOMERULAR proteinuria)

But non-albumin proteins sometimes dominate the filtrate.
The classic case is OVERFLOW proteinuria in paraproteinemia
CLUE: Neg dipstick, with⬆️Urine PCR

💡Urine dip +=Albuminuria #renalrules

4/ TUBULAR proteinuria occurs in tubulointerstitial disease due to⬇️uptake of filtered LMW proteins by tubules
Eg Beta 2 microglobulin

Shown👇:How absence of urinary beta 2 microglobulin in the presence of albuminuria helped localize pathology to gloms in HTN
More on that later!

5/ So should we be measuring albuminuria or proteinuria?🤔

✅Albuminuria is preferred because proteinuria measurement hasn't been standardized
✅Also ELISA used for albumin is more specific than the (Bradford) chemical assay for proteins

The down side?
Cost and availability💰

6/ It's not just a marker. Albuminuria is toxic ☠️

⬆️PCT albumin reabsorption and/or misdirected filtering of albumin into the interstitium 👉inflammation +fibrosis 👉CKD progression🙁

THE FLIP SIDE!

Drugs that⬇️albuminuria (RAAS blockers) can slow progression👏

7/ Back to Parving et al!

They used immunoassays (IA) to detect TINY amounts of albuminuria (30-300mg/d) in patients with HTN- they called this MICROALBUMINURIA (MA)

Morgen et al used the same IA in a 9-year follow up of patients with T2DM
👉MA predicted proteinuria, DN & 🪦!

8/ The results were groundbreaking!

✅Here was albuminuria, an non-invasive, cheap test that could be used to screen for kidney disease at population level!

✅Previously undetectable amounts of albuminuria were predicting dire outcomes

9/ Enter the PREVEND study

A wonderfully ambitious study calling for all 80000 residents of Groningen, 🇳🇱 to provide a urine sample!

Half obliged, leading to wealth of data on follow up!

✔️Even ⬇️⬇️degrees of urinary albumin (<30 mg/d) were associated with risk of 🪦

10) PREVEND had more news..

✔️Albuminuria (not GFR) is a CV risk factor independent of traditional factors used in Framingham risk scoring👇

11) How could this be explained?

What did albuminuria have to do with CV risk?

*⃣ Was albuminuria itself increasing the risk❓
*⃣ Was a common disease process causing both albuminuria and CVD❓
*⃣ Or was CVD causing albuminuria secondarily❓

12/ It is likely that albuminuria is a manifestation of generalized endothelial dysfunction.

Endothelial dysfunction may

a) ⬆️intraglomerular pressure and ⬇️the charge selectivity of the GBM leading to albuminuria.

b) cause poor CV outcomes

#Pisseprophet indeed!🔮

13/ So can the prophecy be reversed?
Thankfully, yes!

*⃣The LIFE trial showed that falling albuminuria during treatment with losartan was linked to BETTER CV outcomes

acc.org/latest-in-card…

*⃣Many studies have shown that RAASi and SGLT2i slow progression of proteinuric CKD

14/ One focus of #primarycare in CKD is screening & monitoring to improve outcomes

*⃣In risk groups (e.g. DM, HTN) screening for proteinuria detects those in danger of adverse outcomes before GFR ⬇️

*⃣ This provides a chance to intervene before irrecoverable damage occurs🤞

15/ So is your 🗳️for GFR or proteinuria in #primarycare #NephMadness ?

View my🧵on GFR for a quick recap!

https://twitter.com/Dilushiwijay/status/1374341211922731010

And check out the blog at ajkdblog.org/2021/03/01/nep…

Thanks to @NSMCInternship @Nephro_Sparks @RacquelbelleMD @cjdiamantidis @drM_sudha @docanjuyadav