R P Pelletier

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Researchers compared blood sugar control in the first month after simultaneous pancreas-kidney transplantation between patients with type 1 and type 2 diabetes. Glucose levels, insulin use, and complications were nearly identical between the two groups despite their different disease histories. A single standard care protocol works equally well for both diabetes types after this transplant.

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This study asked whether kidney transplants from incompatible live donors carry additional risk for patients over age 60 compared to younger patients. Older recipients had higher mortality and lower rates of acute rejection, but the impact of being in an incompatible transplant versus a compatible one was similar at all ages. Age alone should not be used to deny patients access to incompatible living donor transplantation.

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Researchers quantified how having pre-existing donor-specific antibody affects early complications after incompatible living donor kidney transplantation. Stronger antibody mismatches were associated with higher rates of delayed graft function and acute rejection, but the downstream impact of these complications on long-term survival was not worse than in compatible transplants. These risks should inform preoperative counseling but need not preclude transplantation.

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This multicenter study examined how much transplant center practices drive differences in outcomes after incompatible living donor kidney transplantation. After adjusting for patient factors, less than 5% of variation in mortality and graft loss was attributable to which center performed the transplant. Unlike most areas of transplant surgery, outcome differences after incompatible transplantation cannot be explained by center volume or practice patterns.

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Using both mouse models and a small patient series, researchers tested whether combining bortezomib (which kills antibody-producing plasma cells) with belatacept (which blocks new plasma cell generation) could reverse active antibody-mediated rejection. In mice the combination selectively depleted donor-specific antibodies, and all six treated patients resolved their acute rejection episodes with sustained antibody clearance for up to 30 months. The approach provides a proof-of-principle for a mechanistically rational treatment for a complication that has no consistently effective therapy.

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Researchers analyzed hospital readmission patterns over 12 years for kidney transplant recipients at a single large center. Readmission rates were 31% within 30 days and 53% within a year, with early readmission and Black race strongly linked to graft failure and frequent readmissions linked to patient death. Despite these high readmission rates, overall 1-year graft and patient survival remained excellent.

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This study investigated whether a specific type of CD8 T cell (CXCR5+IFN-γ+) in blood is associated with antibody development after kidney transplant. Recipients who developed donor-specific antibodies in the first year had significantly fewer of these cells than those who remained antibody-free. This T-cell subset may identify patients at high risk for antibody development before it occurs, potentially allowing earlier intervention.

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Researchers tested whether post-transplant donor-specific antibodies that bind complement (C3d) are more harmful than those that do not. Recipients with C3d-binding antibodies had significantly higher rates of antibody-mediated rejection and lower kidney survival, with the worst outcomes in those with complement-binding antibodies to both HLA class I and class II. Complement-binding capacity meaningfully refines which antibodies pose the greatest clinical risk.

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This multicenter study compared hospital readmission rates between incompatible living donor transplant recipients and two matched control groups. Incompatible recipients had a 28% higher readmission risk than compatible transplant controls in the first month, peaking to 67% higher risk at 6-12 months. However, after the first year, incompatible recipients had lower readmission risk than patients still waiting on dialysis, reflecting the overall survival benefit of the transplant.

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Three patients with renal artery aneurysms unsuitable for endovascular repair were treated with laparoscopic kidney removal, bench aneurysm repair, and reimplantation. All three procedures succeeded with good kidney function preserved. This approach should be considered for complex aneurysms, and donor kidneys with reparable aneurysms should not be discarded.

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This study calculated the additional cost of performing kidney transplantation across HLA antibody barriers using national cost accounting data. Incompatible transplants cost 20-39% more than comparable compatible transplants, with the most antibody-mismatched cases costing 39% more and carrying longer hospital stays and higher Medicare payments. Payers and regulators should account for this cost differential when evaluating transplant program performance.

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Researchers reviewed outcomes of kidney transplants from high-quality-risk (KDPI >=85%) deceased donors to identify which recipients fare worst. Diabetic recipients who also had pre-existing coronary artery disease had a dramatically higher risk of death when receiving a high-KDPI kidney, with a hazard ratio of 4.33 compared to low-KDPI recipients. Avoiding high-KDPI kidneys in diabetic patients with established coronary disease may improve patient survival.

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A 22-center study confirmed that patients receiving kidney transplants from HLA-incompatible live donors live longer than patients who remain on the waiting list, regardless of antibody strength. At 8 years, incompatible recipients had survival rates of 71-89% compared to 43-65% for matched waitlist controls, with the benefit holding even after excluding the highest-volume center. This multicenter validation established incompatible living donor transplantation as a clearly life-extending option.

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This study linked the type of immunosuppression patients received in the first year post-transplant to their risk of later developing donor-specific antibodies. Recipients on rapamycin plus mycophenolic acid without a calcineurin inhibitor had the highest antibody rates (30.7% by last follow-up), while calcineurin inhibitor plus rapamycin combinations had the lowest (18.6%). Early immunosuppression choices have lasting consequences for immune sensitization and graft survival.

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This report summarized outcomes from 1,500 consecutive hand-assisted laparoscopic donor nephrectomies performed over 14 years at a single center. The procedure was completed successfully in all cases with a 0.27% open conversion rate and a mean hospital stay of 2.1 days, with only 0.9% early graft loss among recipients. The data confirm the procedure is safe and effective for living kidney donors at high volume.

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Researchers investigated whether specific HLA types predispose transplant recipients to post-transplant lymphoproliferative disorder (PTLD). HLA-B40 significantly increased PTLD risk in EBV-seronegative patients and HLA-B8 increased risk in EBV-seropositive patients, while African American recipients had reduced risk. These HLA associations are novel susceptibility markers that could guide pre-transplant surveillance strategies.

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This 22-center multicenter study quantified the increased graft loss and mortality risks associated with transplanting kidneys incompatible by different levels of donor-specific antibody. Positive cytotoxic crossmatch recipients had over 5-fold higher graft loss and nearly 5-fold higher mortality compared to compatible controls. The study showed that ignoring these risks in regulatory performance reports places centers offering this life-saving treatment in jeopardy of unfair regulatory action.

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Researchers examined whether adding pre-transplant cardiovascular disease data to the standard SRTR risk model improves predictions used to evaluate transplant center performance. Including cardiovascular covariates improved model discrimination by 8-13% for living donor cases and substantially changed expected graft loss calculations. Incorporating cardiovascular comorbidities into regulatory models would meaningfully alter which centers appear to be over- or under-performing.

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Using mouse models of antibody-mediated rejection, researchers found that CD4 T cells are the critical drivers of graft damage even when CD8 T cells are more abundant in the graft. Depleting CD4 cells prevented acute graft loss and eliminated donor-specific antibodies, while CD8 depletion had no effect. This work identifies CD4 T cells as a key therapeutic target in mixed antibody-mediated rejection.

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This study tracked the sequence of tissue changes leading to graft dysfunction in desensitized kidney recipients who developed antibody-mediated rejection. Complement deposition (C4d) appeared first, followed by tubular injury, and finally cellular infiltration, with functional deterioration coinciding with cellular inflammation rather than with initial antibody deposition. This detailed timeline clarifies when during rejection targeted therapies might be most effective.

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This randomized trial tested whether stopping prednisone one year after kidney transplant improves bone density. Recipients who discontinued steroids gained significantly more bone mass at the lumbar spine and hip over the following year compared to those who continued. Steroid withdrawal after renal transplantation safely and meaningfully improves bone health.

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This report describes a chain of 10 kidney transplantations initiated by a single altruistic donor and coordinated across six centers in five states over eight months. Five of the transplants were performed simultaneously while five used bridge donors who continued the chain months after their paired recipients had already received kidneys. The case demonstrates the power of nonsimultaneous extended altruistic donor chains to dramatically expand the pool of patients who can receive a living donor kidney.

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Researchers compared outcomes after late acute rejection (occurring more than a year post-transplant) in biopsies with and without complement deposition (C4d). Unlike early rejection, the presence of C4d in late acute rejection did not predict worse graft survival or function at 20-month follow-up. C4d positivity during late rejection may not carry the same prognostic weight it does in the early post-transplant period.

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A steroid-free maintenance protocol using sirolimus and reduced-dose cyclosporine was tested in 97 pancreas transplant recipients and compared to a historical steroid-based cohort. The steroid-free group had a significantly lower acute rejection rate (9.3% vs 28.3%) and no graft losses from rejection, compared to seven in the comparison group. Eliminating steroids from pancreas transplant immunosuppression substantially reduces rejection without sacrificing graft survival.

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This study compared tolerability of two formulations of mycophenolic acid (MMF vs enteric-coated MPA) in kidney recipients on a steroid-free rapamycin and cyclosporine protocol. Significantly more patients on MMF required dose changes or discontinued the drug, and dose changes were strongly linked to acute rejection and graft loss. The enteric-coated formulation was better tolerated with fewer dose modifications in this regimen.

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Researchers tested a delayed-type hypersensitivity assay designed to detect anti-inflammatory regulatory T-cell responses to donor antigens in 420 kidney and kidney-pancreas recipients. An unexpectedly high 22% of patients showed these responses, but they did not correlate with better graft outcomes or with HLA matching degree. Detecting anti-inflammatory T-cell responses to donor antigens does not reliably identify recipients who have achieved graft-protective tolerance.

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This study evaluated outcomes in 301 primary kidney transplant recipients maintained on a steroid-free sirolimus-cyclosporine protocol compared to 502 historical controls on steroids. One-year patient and graft survival were equivalent between groups, while biopsy-proven rejection was cut nearly in half (4.9% vs 9.4%) in the steroid-free group. Eliminating steroids from kidney transplant maintenance is safe and reduces rejection without compromising survival.

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A prospective randomized trial in 120 low-risk kidney recipients on triple immunosuppression tested whether stopping prednisone between 6 and 36 months post-transplant was safe. At both 1-year and mean 3.7-year follow-up, rejection rates, graft survival, and kidney function were identical between the withdrawal and continuation groups, while cholesterol and bone density improved with steroid discontinuation. Steroid withdrawal is safe in low-risk kidney recipients and delivers meaningful metabolic benefits.

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This report traced immunosuppression evolution across 22 years and 3,211 primary kidney transplants at Ohio State University, identifying five distinct protocol eras with progressively improving outcomes. Each era brought new drug combinations that incrementally reduced acute rejection and improved graft and patient survival. The longitudinal data illustrate how systematic protocol evolution drives long-term outcome improvements in kidney transplantation.

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Researchers prospectively compared hand-assisted laparoscopic donor nephrectomy with traditional open nephrectomy in 80 sequential cases. Operative time was longer with the laparoscopic approach, but blood loss was lower, donor recovery was faster, and three months after surgery donors reported less incisional pain. The laparoscopic approach offers a better recovery experience for living kidney donors.

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Using mice injected with human immune cells, researchers found that a specific variant in the interferon-gamma gene (A/A genotype at position +874) was overrepresented in donors whose cells rapidly developed EBV-associated lymphoproliferative disease. TGF-beta appeared to suppress anti-EBV immune responses in these donors, and blocking TGF-beta reduced tumor development. This gene variant may help identify transplant candidates at highest risk for post-transplant lymphoproliferative disorder.

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Three liver transplant patients with abdominal pain after T-tube removal were evaluated using contrast-enhanced MRI cholangiography instead of CT or nuclear imaging. The MRI technique successfully identified the presence, location, and extent of bile leaks in all three cases. This noninvasive approach offers a reliable first-line method for diagnosing bile leaks after liver transplantation.

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Researchers evaluated whether MRI angiography could replace conventional angiography for assessing kidney donors' vascular anatomy before donation. MRA correctly identified the vascular anatomy in 91.5% of 189 donors, with inaccuracies in the remaining 8.5% that did not adversely affect recipient outcomes. Noninvasive MRA is an acceptable substitute for conventional angiography in living donor evaluation.

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This review article introduces microdialysis as a technique for directly measuring drug concentrations in brain tumor tissue rather than relying on blood or cerebrospinal fluid levels. Microdialysis samples extracellular fluid via a probe implanted in the tumor and surrounding brain, enabling real-time pharmacokinetic monitoring. A National Cancer Institute consortium proposed using this technology in phase 1 trials to assess whether drugs actually reach their intended brain targets.

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Researchers found that EBV DNA was detectable in 65% of kidney allograft biopsies from recipients with PTLD compared to 26% in those without PTLD. EBV infection in the allograft, localizing to proximal tubular cells, was present in all patients with PTLD near the graft and could precede PTLD diagnosis by up to 42 months. Graft EBV infection may represent an early warning sign and possible local driver of PTLD development.

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This single-center review of simultaneous pancreas-kidney transplantation outcomes emphasized careful patient selection as the key to maintaining excellent results with this complex procedure. Patient death remained the primary cause of graft loss, highlighting the importance of thorough pretransplant cardiovascular evaluation in this high-risk population. The program's long-term results supported continued use of SPKT as the procedure of choice for appropriate candidates with type 1 diabetes and kidney failure.

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This report summarized outcomes from over 4,000 abdominal solid organ transplants performed at Ohio State University over 20 years, organized into five immunosuppressive eras. Each new drug protocol brought incremental reductions in acute rejection and improvements in graft and patient survival. The data provide a compelling record of how immunosuppression advances have transformed transplant outcomes over two decades.

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Researchers examined the impact of mycophenolate mofetil dose reductions in 721 kidney transplant recipients in the first year after transplant. Seventy percent of patients required at least one dose change, and this correlated with a 6-fold higher rejection rate and significantly worse 3-year graft survival (76% vs 88%). Maintaining full MMF dosing in the first year post-transplant is critical to preventing rejection and preserving graft longevity.

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Using a delayed-type hypersensitivity assay, researchers found that 52% of kidney transplant recipients had detectable cellular sensitization to donor antigens, far exceeding the 20% with circulating antibodies. Importantly, donor-reactive cellular responses did not predict worse clinical outcomes, and they did not correlate with antibody presence. Current immunosuppression effectively blocks the consequences of T-cell sensitization even when it cannot prevent sensitization itself.

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Eleven consecutive kidney transplant recipients with EBV-positive PTLD were treated uniformly with immunosuppression reduction and acyclovir. Ten of eleven achieved durable complete remission, though nearly half lost their allografts, particularly those with PTLD involving the transplanted kidney. Sustained expansion of CD8 T cells and a cellular immune response to EBV lytic antigens appeared to be the key mechanism driving tumor clearance.

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This study of 1,574 kidney transplant recipients found that statin use was associated with 24% better patient survival after adjusting for age, transplant year, and cholesterol levels. The protective association was only apparent after statistical adjustment, since statin users had inherently higher cholesterol levels. Statins may reduce the high cardiovascular mortality burden that kidney transplant recipients face.

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This review traced parallel lines of evidence showing that both humans and mice can generate either pro-inflammatory (rejection) or anti-inflammatory (tolerogenic) immune responses to transplanted organs. Donor-reactive delayed-type hypersensitivity assays developed in mice were adapted for human use and confirmed that human transplant recipients make the same spectrum of immune response types. The parallels strengthen the case for using mouse models to guide human transplant immunology.

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This mouse study demonstrated that the type of organ transplanted determines whether the immune response leads to rejection or acceptance, even when donor-recipient genetic differences are identical. Cardiac grafts provoked rejection with pro-inflammatory immunity, while kidney grafts in the same strain combination were spontaneously accepted with regulatory TGF-beta responses. The allograft itself actively shapes the immune response it induces.

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Researchers tracked alloantibody production in 277 kidney and kidney-pancreas recipients and found that post-transplant antibodies to HLA class II, but not class I, were an independent risk factor for chronic rejection. Eighteen percent of recipients developed new antibodies after transplant, most directed at class II antigens, with incidence rising with prior acute rejection episodes. Preventing acute rejection and monitoring for post-transplant class II antibodies may reduce chronic allograft loss.

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A prospective randomized trial in the current era of mycophenolate and cyclosporine immunosuppression tested whether adding OKT3 induction therapy still provides benefit. OKT3 induction cut the rejection rate from 27% to 11% without increasing infectious complications or significantly raising costs. Even with modern baseline immunosuppression, peri-transplant antibody induction with OKT3 meaningfully reduced early rejection.

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Researchers confirmed that DBA/2 kidneys transplanted into fully MHC-mismatched C57BL/6 mice are spontaneously accepted without immunosuppression, unlike cardiac or skin grafts in the same combination. The accepted kidneys had lymphocytic infiltrates and were associated with TGF-beta-mediated counter-regulation of donor-reactive immune responses in the recipients. TGF-beta-driven immune regulation is associated with spontaneous renal allograft acceptance in mice.