Kidney Health and Rapamycin

Do you have thoughts on rapamycin use and kidney health?

Here’s a concerning study:
“Acute rapamycin nephrotoxicity in native kidneys of patients with chronic glomerulopathies”

"In four patients, discontinuation of the drug resulted in improvement of renal
function close to baseline levels. One patient required
haemodialysis and had no subsequent recovery of renal
function. In another patient, renal function recovered
after discontinuation of the drug and then rapamycin
was resumed at a lower dose when creatinine returned
to baseline. This resulted in a second acute increase in
serum creatinine that failed to return to baseline when
the medication was discontinued. "

The study focuses on a specific population, but I’m curious about the risk for elderly people who may have undiagnosed mild chronic glomerulopathies.

Do you check kidney biomarkers (e.g., urine albumin-creatinine ratio, serum creatinine, or cystatin C)? Have you observed any changes?

Just supplement with empagliflozin 10mg. It’s the best kidney health medication on the market right now.

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@justaguest

Glomerulonephritis is one of at least 15 different types of kidney disease. My CKD has never been specified, but I think it resulted from an acute kidney injury, triggered by high BP. In any case, after more than a year of using rapamycin, I have detected no difference, good or bad, on my kidney function. I do a monthly check of creatinine, which continues to decline, along with a corresponding rise in GFR. These markers have been slowly improving for years. The gods have been good to me.

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The study quoted has ZERO implications on otherwise healthy subjects based on the studies’ subject selection and rapamycin 35 mg/week high dosing… in other words its results are non-applicable to general population without renal disease and using much lower rapamycin doses.
I can tell you from my experience that any patient with CRF has to be very careful with any drug administration and dosing.

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Yes, but the study mentions proteinuria as a key factor. Elderly people often have proteinuria, which can be a side effect of diabetes as I understand.

We conducted a study to examine the efficacy and safety of rapamycin in patients with progressive chronic renal failure.

Virtually all people with CRF have proteinuria.
Not all people with proteinuria have CRF.

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I have been taking moderately high doses of Rapamycin (10-14 mg eq.) on a weekly schedule for roughly 2 years and my creatinine and eGFR numbers are close to perfection. I have noticed only minor changes in my kidney function numbers which amount to statistical noise IMHO. N=1

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This makes sense. Do we have good data on rapamycin’s effects on people with proteinuria but without chronic renal failure?

not that I know of, but check Rapamune PI

TABLE 1: ADVERSE REACTIONS OCCURRING AT A FREQUENCY OF ≥20% IN AT LEAST ONE OF THE RAPAMUNE TREATMENT GROUPS IN A STUDY OF PROPHYLAXIS OF ORGAN REJECTION FOLLOWING RENAL TRANSPLANTATION (%) AT ≥ 12 MONTHS POST-TRANSPLANTATION (STUDY 2)*|Adverse Reaction|–––Rapamune Oral Solution–––||
|2 mg/day
(n = 218)|5 mg/day
(n = 208)|Placebo
(n = 124)|
|*
Patients received cyclosporine and corticosteroids.|
|Peripheral edema|54|58|48|
|Hypertriglyceridemia|45|57|23|
|Hypertension|45|49|48|
|Hypercholesterolemia|43|46|23|
|Creatinine increased|39|40|38|
|Constipation|36|38|31|
|Abdominal pain|29|36|30|
|Diarrhea|25|35|27|
|Headache|34|34|31|
|Fever|23|34|35|
|Urinary tract infection|26|33|26|
|Anemia|23|33|21|
|Nausea|25|31|29|
|Arthralgia|25|31|18|
|Thrombocytopenia|14|30|9|
|Pain|33|29|25|
|Acne|22|22|19|
|Rash|10|20|6|
|Edema|20|18|15|

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Interestingly, this study found significant benefit with a lower dosage twice a day:

“Therapy consisted of 16 mg/d of methylprednisolone and 1
mg twice daily of rapamycin.

“Rapamycin blood levels were kept between 5 and 15 ng/mL.”

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