Kevin J. Fowler Principal The Voice of the Patient

Alex Kula @Kidney_Kula · Oct 22, 2019

Reading the most recent issue of @CJASN and I was struck by this figure from Joseph Bonventre’s editorial. I hope findings like these can help our health system appreciate the need for and value of nephrologists and their research! #medtwitter #pedneph

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Vatican News Verified account @VaticanNews · Oct 13

Pope Leo XIV underwent thoracic surgery at Gemelli Hospital on Tuesday afternoon, as planned, according to a statement from Dr. Luigi Carbone and Professor Stefano Margaritora released by the Holy See Press Office.

The surgeons removed the lower lobe of the Pope’s right lung, and tissue examined during the operation confirmed the diagnosis of “lung adenocarcinoma,” as suspected from tests conducted beforehand.

The Pope was in the operating room approximately three hours, while the operation itself lasted about 90 minutes. The doctors said it was successful and there were no complications.

Pope Leo awoke normally after surgery and, following a brief period of observation, returned to his room on the hospital’s 10th floor, according to the statement.
vaticannews.va/en/pope/news/2…

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Kevin J. Fowler Principal The Voice of the Patient Verified account @gratefull080504 · Sep 4, 2020

On #PKDAwarenessDay I would like to recognize my Aunt. As she was dying my sister + I encouraged her to make a decision about her estate Her donation of almost $1.7 million to the @PKDFoundation was the largest gift ever. Her decision keeps research funded in perpetuity #ADPKD

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ERA - European Renal Association Verified account @ERAkidney · Jun 5

Are We Still Using 'Too Much' CNI? Yes | #ERA26

90-95 percent of kidney transplant patients get calcineurin inhibitor at discharge. 80-90 percent stay on it long term. But Luuk Hilbrands at #ERA26 says fear of rejection is driving overuse, threatening long-term graft survival.

Why CNIs Are Overused: Status Quo Bias
Success became habit: CNIs drastically reduced acute rejection when introduced and became the default backbone of immunosuppression. Clinicians continue using them out of habit even when alternatives exist
Fear-driven prescription: Acute rejection is visible and immediate, so clinicians increase CNI. Chronic kidney disease and cancer from CNI are delayed and multifactorial, so less attributed. This "fear nudges" doctors to continue CNI when alternatives may be better
Nephrotoxicity is the Achilles heel: CNI causes acute kidney injury, thrombotic microangiopathy, and interstitial fibrosis with tubular atrophy leading to progressive chronic kidney disease

The Cost of CNI Overuse
Metabolic + other toxicity: Hypertension more with cyclosporine than tacrolimus. Diabetes mellitus more with tacrolimus than cyclosporine. Plus hyperlipidemia, neurotoxicity-tremor, diarrhea, infections, malignancies
Long-term graft loss: Indisputable nephrotoxic effects of CNIs threaten long-term graft survival despite good early outcomes

Alternatives Exist - Data Supports Conversion
Belatacept conversion trial: Budde et al J Am Soc Nephrol 2021. 446 patients 6-60 months posttransplant converted to belatacept vs continued CNI. At 24 months: patient and graft survival 98 percent vs 97 percent. Renal function 55.5 vs 48.5 milliliters per minute per 1.73 square meters favoring belatacept. Biopsy proven acute rejection 8 percent vs 4 percent. De novo donor specific antibodies 1 percent vs 7 percent
Less new-onset diabetes: Pooled BENEFIT data shows 5 percent new-onset diabetes with belatacept intensive or less intensive vs 10 percent with cyclosporine. Vanrenterghem et al Transplantation 2011
Long-term graft survival: Vincenti et al NEJM 2016. 7-year data shows belatacept vs cyclosporine hazard ratio for death or graft loss 0.57, p equals 0.02. Beneficial long-term graft survival with belatacept
mTOR substitution: CNI substitution by belatacept or mammalian target of rapamycin inhibitor is viable. CNI minimization or withdrawal from triple to double therapy: mycophenolate mofetil or azathioprine plus prednisone, mycophenolate mofetil or azathioprine plus mammalian target of rapamycin inhibitor, mammalian target of rapamycin inhibitor plus prednisone

The Trade-off: More Early Rejection, Better Long-term
Higher early acute rejection: BENEFIT trial shows acute rejection less than 1 year: belatacept more intensive 22 percent, belatacept less intensive 17 percent, cyclosporine 7 percent. Kaufman et al shows more biopsy proven acute rejection with alemtuzumab or rATG plus belatacept vs rATG plus tacrolimus
But grafts last longer: Despite higher early rejection, long-term graft survival is better with belatacept. 2-year conversion data shows improved estimated glomerular filtration rate with no graft survival penalty

Takeaway: Yes, we still use too much CNI. Status quo bias keeps 90 percent of patients on nephrotoxic drugs long term. Conversion to belatacept 6-60 months posttransplant improves renal function, reduces diabetes and donor specific antibodies, and improves 7-year graft survival despite higher early acute rejection. CNI substitution or minimization is possible. Time to move beyond "fear-driven prescription".

Presentation: Luuk Hilbrands | Tweet: @eroldemir83 on behalf of SoMe Team

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Rep. Vern Buchanan Verified account @VernBuchanan · Apr 7

More than 37 million Americans are living with kidney disease.

I’m working with @RepLloydDoggett to urge @HHSGov to explore establishing a Kidney Health Officer to strengthen prevention, improve outcomes and support millions of Americans. buchanan.house.gov/2026/4/buchana…

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