I forgot to add: Fx is the ratio of the change in secretory clearance to the change in GFR. When Fx = 1, tubular secretion declines proportionally to GFR (INH holds); when Fx < 1, secretion declines more than GFR would predict (INH fails).
💊 Authors' recommendation for CKD 4-5:
For anionic drugs (OAT1/3) with high secretory contribution → consider an additional 50% reduction in secretory clearance beyond GFR-based adjustment
📄 doi.org/10.1002/cpt....
📄 doi.org/10.1002/cpt....
📊 OAT1/3 substrates (anionic drugs) in severe CKD:
→ Fx = 0.50 ± 0.29, CV = 58%
→ Penicillins, methotrexate, tenofovir
OCT2/MATE substrates (cationic drugs):
→ Fx ≈ 1.0 (range 0.77–1.13)
→ Metformin, amantadine, trimethoprim
Anions are unpredictable, cations follow GFR 🎯
📄 doi.org/10.1002/cpt....
The Intact Nephron Hypothesis has guided renal drug dosing for 60+ years. The idea: as GFR drops, tubular secretion drops proportionally.
Sounds elegant, right?
But new data shows it's WRONG for many drugs in severe CKD.
Here's what you need to know 🧵👇
#Nephrology #NephSky #Pharmacokinetics
🧵11/11
Source: Joshi A, et al. Sjögren's syndrome and hepatitis C virus infection presenting as hypokalemic quadriparesis: A case report. Journal of International Medical Research 2025;53(12):1-8. DOI: 10.1177/03000605251404767
🧵10/11
KEY LESSONS 🎯:
1. Consider autoimmune diseases (especially Sjögren's) in refractory hypokalemia + distal RTA
2. Sicca symptoms may be subtle - ask specifically about them!
3. HCV can mimic Sjögren's - check viral load
4. Early diagnosis + electrolyte correction = rapid recovery
🧵9/11
TREATMENT:
✅ Sodium bicarbonate 1g BID
✅ Spironolacton 50mg daily
✅ Potassium chloride (oral)
OUTCOME:
Day 5: Patient could WALK! 🎉
At discharge: Normal muscle strength in all limbs, normalized lab parameters. Complete recovery achieved!
🧵8/11
PATHOPHYSIOLOGY of distal RTA in Sjögren's:
Autoimmune attack → absence of H+-ATPase pumps in intercalated cells → can't excrete H+ into urine → H+ retention → metabolic acidosis with normal anion gap.
Increased urinary K+ loss → severe hypokalemia → quadriparesis 💪
🧵7/11
But wait - there's a twist! 😮
HCV antibody: POSITIVE
This created a diagnostic dilemma because chronic HCV infection can mimic primary Sjögren's syndrome with similar clinical & lab features.
Solution: HCV RNA PCR was ordered. It was NEGATIVE ✅ This excluded active viral replication.
🧵6/11
What causes distal RTA in a young woman? 🔍
Autoimmune workup showed:
ANA 97.2 AU/mL ↑
SSA/Ro-52 antibodies +++
Directed history: She'd had DRY EYES for months 👁️
Schirmer's test: positive (severe bilateral dry eyes)
DIAGNOSIS: Primary Sjögren's syndrome with distal RTA!
🧵5/11
Muscle enzymes were dramatically elevated:
CK 36,614 IU/L ↑↑↑
AST 348 U/L ↑↑
LDH 404 U/L ↑↑
Initially suggested inflammatory myopathy, BUT:
❌ Acute onset (not gradual)
❌ No rash
❌ Enzymes normalized WITHOUT immunosuppression
Diagnosis: hypokalemia-induced rhabdomyolysis!
Normal anion gap metabolic acidosis + positive urine anion gap = RENAL TUBULAR ACIDOSIS
But which type? Proximal vs distal?🤔
Key findings that pointed to DISTAL RTA:
✅ Severe hypo-K
✅ Urine pH >5.5 despite systemic acidosis
✅ NO Fanconi syndrome features
www.kireportscommunity.org/post/renal-t...
🧵3/11
Despite adequate K+ and fluid replacement AND no more vomiting after antiemetics, potassium levels REMAINED critically low! 🚨
This refractory hypokalemia suggested something more than just GI losses.
ABG was ordered and revealed:
pH 7.296 ↓
HCO3- 14.4 mmol/L ↓
Normal anion gap: 11
🧵2/11
Initial labs showed SEVERE electrolyte disturbances:
K+ 1.7 mmol/L ↓↓ (critical!)
Na+ 130.1 mmol/L ↓
Mg2+ 1.05 mg/dL ↓
Working diagnosis: quadriparesis secondary to hypokalemia.
Treatment started: IV fluids, potassium supplementation, antiemetics.
But there was a problem...
CASE REPORT: Hypokalemic Quadriparesis for Nephrologist
A woman in her mid-20s presented to the ER with sudden-onset weakness in all limbs, unable to stand from sitting position. She'd had lower abdominal pain, vomiting & leg muscle pain for one week.
What was causing this dramatic presentation? 🧵
Summary #GlomCon
American Society of Nephrology Kidney Week 2025 Original Article | Nov. 7, 2025 | NEJM.org Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis Fig. 1A. A Serious Cardiovascular Events The NEJM identity sits at the bottom.
In the PISCES trial involving participants receiving hemodialysis, fish oil (n−3 fatty acids) was compared with corn-oil placebo. The rate of serious cardiovascular events was lower with daily fish-oil supplementation. Full trial results: nej.md/49zWuqo
@asnkidney.bsky.social | #KidneyWk
The latest empadata dump: @nephroseeker.medsky.social writes up a #NephJC short on the meta analysis
www.nephjc.com/news/2025/10...
Seeking collaboration with #MedLibs for scoping review on predictive models in peritoneal dialysis!
Protocol nearly finalized. Looking for expertise in search strategy peer-review (PRESS checklist) + optional database searches/deduplication.
DM if interested in co-authorship for this project!
Lots of different ways to do observational causal inference—IV, proximal inference, etc. What if you could compare those strategies more directly?
New preprint w/ @melodyyhuang.bsky.social tries to do just that. Here's one cool figure—we're able to visualize bias of 3 estimators on the same plot
"It remains important to consider bromism in patients presenting with new neurologic, psychiatric, and/or dermatologic symptoms, as well as hyperchloremia
with a negative anion gap." (...) Elevated levels of halides such as bromide falsely increase chloride reading.
Urine sodium (Urine Na) levels post-saline infusion in differentiating non-edematous hyponatremia ca. 2025
#Nephpearls #NephSky
👉🏼 pubmed.ncbi.nlm.nih.gov/40775013/
#statstab #390 modelbased: An R package to make the most out of
your statistical models through marginal means,
marginal effects, and model predictions
Thoughts: Great package for getting predicted probabilities for your models.
#rstats #r #easystats
doi.org/10.21105/jos...
The Double-Icodextrin Dose Randomized Controlled Trial of a Double #Icodextrin Dose for #Older Patients on Incremental Continuous Ambulatory Peritoneal Dialysis #CAPD
#VisualAbstract by @md_abdulqader83
www.kireports.org/ar...
@lobbedezt.bsky.social @clemencebechade.bsky.social
The "reproducibility crisis" in science constantly makes headlines. Repro efforts are often limited. What if you could assess reproducibility of an entire field?
That's what @brunolemaitre.bsky.social et al. have done. Fly immunity is highly replicable & offers lessons for #metascience
A 🧵 1/n
[Skim] KI-Tools für die wissenschaftliche Literaturrecherche: Potenziale, Problematiken, Didaktik und Zukunftsperspektiven www.degruyterbrill.com/document/doi... - or AI Tools for Academic Literature Search: Possibilities, Problems, Didactics, and Future Prospects insanely comprehensive! (1)
Next level of cherry-picking. Lack of significance in Student's t-test? Report then F-test and interpret it as a t-test 🫣🫣🫣
(F-test compares variances, not means🤡)
Source: doi.org/10.3390/cell...
#Statistics thought of the day: Need power calculations for a 2-group comparison on an ordinal or continuous response variable Y with/without clumping at a specific value (e.g., 0) of Y, with a possibly bimodal, heavy tailed, or skewed distribution? See www.fharrell.com/post/pop/ #RStats #StatsSky
