Study Details Impact of Pancreas Transplantation on Kidney Function

Ravinder Jeet Kaur, MBBS

Credit: ResearchGate

The risk of adverse kidney outcomes among patients receiving pancreas transplantation alone (PTA) may suggest the need for careful screening based on age, gender, and estimated glomerular filtration rate (eGFR), according to findings from a multicenter retrospective cohort study.

Although most patients had acceptable kidney risk at 2 years post-transplant, 53.5% experienced >50% decline in eGFR, had eGFR < 30 mL/min/1.73 m2, and/or received a kidney transplant 10 years after their initial PTA, with the most significant decline in kidney function observed 6 months post-PTA.¹

“To our knowledge, this is the first multicenter study evaluating kidney outcomes in a large number of PTA recipients and also tracked the progression of CKD stages over 10 years,” wrote Ravinder Jeet Kaur, MBBS, research fellow in the division of endocrinology, diabetes, metabolism, and nutrition at Mayo Clinic Rochester, and colleagues.¹ “This information may help physicians counsel prospective PTA candidates about eGFR change post-PTA based on baseline GFR levels.”

Although it is not a standard treatment for the condition, most pancreas transplants are done to cure type 1 diabetes by restoring insulin production and improving blood sugar control. Often, pancreas and kidney transplants are performed to address kidney failure related to type 1 diabetes, although the procedures can be performed separately. However, many have raised concerns about the potential negative impact of pancreas transplantation on kidney function, pointing to a lack of understanding regarding the incidence and progression of kidney dysfunction following PTA that merits further research.^2,3

To assess the impact of PTA on long-term kidney outcomes, morbidity, and mortality, investigators in the Multicenter Transplant Alliance-Pancreas (MTA-P) group, representing Mayo Clinic Rochester, Indiana University, and University of Wisconsin, collected data for patients ≥18 years of age who received a PTA at their institution between January 1, 1998, and May 31, 2018, with no previous pancreas transplants.¹

The study’s primary endpoint was a combined >50% decline in eGFR, eGFR < 30 mL/min/1.73 m2, and/or receipt of a kidney transplant, assessed at 10 years post-PTA. Secondary endpoints included eGFR in each CKD stage at different study time points over 10 years, CKD stage-to-stage progression based on CKD-EPI eGFR, and overall patient survival, death-censored graft survival, and graft thrombosis by 10 years post-PTA.¹

A total of 1,031 patients underwent PTA between January 1, 1998, and May 31, 2018. After excluding patients younger than 18 years of age (n = 40), pancreas re-transplants (n = 158), and patients with no baseline serum creatinine (n = 11), investigators enrolled the remaining 822 patients in the study.¹

Among the cohort, the mean age was 43.6 (Standard deviation [SD], 10.7) years, 50.1% of participants were male, and the mean BMI was 26.1 (Standard deviation [SD], 4.8) kg/m2. Investigators noted 58% of participants had type 1 diabetes, while the remaining 42% were diagnosed with other conditions including type 2 diabetes, diabetes secondary to chronic pancreatitis or cystic fibrosis without pancreatectomy, or unknown.¹

Out of 183 PTA recipients at 10 years of follow-up, 98 (53.5%) had combined >50% decline in eGFR, eGFR < 30 mL/min/1.73 m2, and/or received a kidney transplant within 10 years of their PTA. The primary outcome incidences were 10.3%, 19.0%, and 29.8% at 6 months, 2 years, and 5 years, respectively. Investigators pointed out 45 patients experienced a >50% decrease in eGFR by 10 years post-transplant, 38 had eGFR < 30 mL/min/1.73 m2, and 49 required a kidney transplant.¹

Further analysis showed median creatinine changed from 1.0 mg/dL at baseline to 1.2 mg/dL at 6 months post-transplant (P < .0001) and further increased to 1.2 mg/dL, 1.3 mg/dL, and 1.4 mg/dL at 2, 5, and 10 years, respectively (P < .0001). Kidney function declined from median eGFR of 76.3 mL/min/1.73 m2 at baseline to 65.5 mL/min/1.73 m2 at 6 months post-transplant (P < .0001) and was 59.5 mL/min/1.73 m2 at 2 years, 54.7 mL/min/1.73 m2 at 5 years, and 51.3 mL/min/1.73 m2 at 10 years (P < .0001).¹

Patient survival was 89%, 81%, and 68% at 2 years, 5 years, and 10 years respectively. The median time to death was 4.0 (1.3–9.8) years. Of patients with baseline eGFR < 60, 34% died within 10 years compared to 19% in the eGFR ≥ 60 groups.¹

Death-censored graft survival was 86% at 2 years, 76% at 5 years, and 68% at 10 years, with a median time to graft failure of 1.8 (.3–4.2) years. Pancreas graft thrombosis-free survival was 94% at 2 years, 93% at 5 years, and 92% at 10 years, with a median time to graft thrombosis of 6.0 (1.0–238.2) days.¹

After adjusting for centers and other variables, investigators noted only older recipient age remained a statistically significant predictor for mortality, graft failure, and thrombosis.¹

“We contend that most of the patients in our cohort did well initially with PTA but there is still considerable risk associated with decline in kidney function and careful selection of patients based on age, gender and eGFR is required. Future studies are required to address the specific causes of kidney dysfunction in this population and new protocols that might ameliorate it including CNI minimization,” investigators concluded.¹

References:

1. Kaur RJ, Mujtahedi SS, Fridell JA, et al. Impact of pancreas transplantation alone on kidney function: A multicenter clinical cohort study. Clinical Transplantation. https://doi.org/10.1111/ctr.15212
2. Mayo Clinic. Pancreas Transplant. Tests & Procedures. May 24, 2022. Accessed December 19, 2023. https://www.mayoclinic.org/tests-procedures/pancreas-transplant/about/pac-20384783
3. National Kidney Foundation. Kidney-Pancreas Transplant. Accessed December 19, 2023. https://www.kidney.org/atoz/content/kidpantx