A new paper strongly linking chronic kidney disease and lowered creatine disposal rate with hypothyroidism & TPOAb

[diogenes]

This paper just out in Thyroid shows a strong link between chronic kidney disease and hypothyroidism and TPOAb, leading to a poorer action of disposal of creatine by lowered excretion.

ThyroidVol. 30, No. 3

Hypothyroidism and Kidney Function: A Mendelian Randomization Study

Christina Ellervik, Samia Mora, Paul M. Ridker, Daniel I. Chasman, and on behalf of the CKDGen Consortium

Published Online:11 Mar 2020 doi.org/10.1089/thy.2019.0167

Abstract

Background: Uncertainty in the mechanism and directionality of observational associations between thyroid function and kidney function may be addressed by genetic analysis with an instrumental variable method termed bidirectional Mendelian randomization (MR).("a superior statistical method-Diogenes insertion")

Methods: In the Women's Genome Health Study (WGHS), observational associations between thyroid measures and kidney function were evaluated. Genetic instruments for MR were from recent genome-wide association studies (GWAS) of hypothyroidism, thyrotropin (TSH), and free thyroxine (fT4) concentrations within the reference range, thyroid peroxidase antibodies (TPOAb), estimated glomerular filtration rate from creatinine (eGFRcrea), eGFR from cystatin C (eGFRcys), and chronic kidney disease (CKD). In WGHS individual-level data, these instruments were used for bidirectional MR between thyroid (N = 3336) and kidney (N = 23,186) functions. To increase power, MR was also performed using GWAS summary statistics from the Chronic Kidney Disease Genetics Consortium (CKDGen) for eGFRcrea (N = 567,460), eGFRcys (N = 24,063), CKD [N(total) = 480,698, N(cases) = 41,395], and urinary albumin/creatinine ratio (UACR/N = 54,450).

Conclusions: Bidirectional MR supports a directional association from hypothyroidism, increased TSH, and TPOAb, but not fT4, to decreased eGFRcrea and increased CKD.

[Musicmonkey]

Thank you diogenes

[humanbean]

Link to abstract :

liebertpub.com/doi/10.1089/...

Link to full paper :

sci-hub.se/https://www.lieb...

[helvella Administrator]

diogenes

Would lowered creatine disposal rate affect any blood or urine tests?

[diogenes Remembering in reply to helvella]

The creatine test simply measures what is called "the glomerular filtration rate" or the rate at which the kidney glomerulus cells can work forming urine. It's a form of kidney failure which hasn't been completed yet. A test for this is high blood creatinine (a product from creatine) which signals kidney problems. As for T4/3 excretions which normally go through the kidney and excreted as the sulphates or glucuronides, if the kidney cannot handle this completely then I think they would be excreted faecally rather. We should regard CKD from such a cause a nonthyroidal illness, which has implications for the TSH/FT4/FT3 relationship (i.e. FT4 not much altered, FT3 low and TSH perhaps slightly altered upward). The problem with studies like this is that they assume the elevation in TSH is of thyroidal HPT origin, whereas it could rather be simply a manifestation of an NTI for which the thyroid (HPT axis) is not principally involved but is simply responding to an outside trauma..

[Nanaedake in reply to diogenes]

Trying to follow this, what is NTI? Could hypothyroid causal CKD be relevant even without TPOabs?

[helvella Administrator in reply to Nanaedake]

Non-Thyroidal Illness.

[crimple]

Thanks for posting Diogenes. when on 100mcg levo only my GFR was around 58 and pulse rate about the same. Since taking 15mcg T3 in addition to levo my last GFR result was 64 and heart rate is about 62!! Anecdotal evidence?!

[Adam10]

Thank you for posting Diogenes. Is there anything we can do to prevent chronic kidney disease, or help recovery, and protect the kidney in the future?

[diogenes Remembering in reply to Adam10]

A useful start would be to use whatever is required to restore the patient to "euthyroid" rather than using discredited decision trees based on faulty ideas eg TSH-is-all, FT3 not measured. Hypothyroid patients not properly treated may well be more prone to nonthyroidal illness that worsens things even more.

[lidoplace]

Since changing to NDT my e-GFR has gone from 49 to 73 .

[Marvin8 in reply to lidoplace]

What is NDT?

[helvella Administrator in reply to Marvin8]

NDT - Natural Desiccated Thyroid

You will find that and many more (relevant) abbreviations and acronyms here:

dropbox.com/s/2423slilh0or6...

[Marvin8 in reply to helvella]

Thanks!

[lidoplace]

It would be really interesting to see a study with those with impaired conversion of T4 to T3 compared with euthryoid and Hashimoto's (and non- Hashimotos ) . Are their kidneys dis-proportianately affected ?

[Miffie]

Thanks for sharing, I think it is actually Hashimoto’s which is being identified not hypothyroidism. For those of us with no antibodies and who may never have had a raised TSH?

Going to assume it does not apply to me, got enough with kidney problems due to diabetes.

[Murphysmum]

This is interesting, and timely.

I have been having some flank pain on and off for many months but recently have more acute, sharp pain around the kidney area.

A random chat with my husband who has been treated for kidney stones made me realise that this random pain is coming from my kidney.

I had a series of recurrent kidney infections many years ago which were poorly treated at the time and took a long time to get over.

I hadn’t realised until recently either that there was such a link between thyroid and kidney disease.

I intend to take this up with my gp and have this checked out once the current lockdown is over. Hopefully no damage will be done in the meantime.

[KayS68]

This caught my eye as I've only started to have thyroid issues in Feb - started with thyrotoxicosis then went into hypothyroid. Started thyroxine today. But - my renal profile was tested all this time, but nobody ever explained the anomalies in it. My GFR this week went from 55 to 41. And my creatinine is higher. My CRP is 10 (range 0 - 5). And my WBC counts are high - have been since this started.

Tbh - not sure why I'm posting, apart from wondering if there's a link, and should I be asking for any input? The GFR is concerning me, despite me knowing nothing about renal testing.

If anyone has any insight, I'd love to hear it.

[diogenes Remembering in reply to KayS68]

Best to get a paper copy to send to whoever is treating you. And to take one with you to any future appointment so that you can bring it to the doctor's attention then if they hadn't read it before.

[KayS68 in reply to diogenes]

Thank you. That’s a great idea.