Rethinking Cardiac and Metabolic Risk in Kidney Transplant Candidates
Reevaluating Standard Cardiac Testing in Renal Transplant Candidates
Author’s Note
Although published here in my blog, this article was originally written in the style of a medical journal by Dr. John Sciales and is intended for both healthcare professionals caring for transplant patients and the patients themselves. Transplant recipients represent a unique group of people with unique responsibilities and unique illnesses. This piece is directed to those entrusted with their care, with the goal of supporting wise, evidence-based, and life-saving decisions.
Acknowledgment
I would like to express my deep gratitude to Dr. Paul Ridker for his pioneering research identifying inflammation as a central driver of cardiovascular disease. I had the privilege of meeting Dr. Ridker at the national Cardiometabolic Health Congress, and beyond being a visionary scientist and humanitarian, he is a true gentleman; an individual who practices what he preaches. He embodies the principles he teaches, not only through his work but also through his own personal health and athletic lifestyle. His life and leadership are a living testament to the principles of prevention and resilience, setting an example for all of us in medicine to follow.
I would also like to extend a special thank you to Dr. Matthew Budoff, a true champion of cardiac imaging and preventive care. I have also had the privilege of meeting him, and much of his groundbreaking work has guided my own. He is not only an exceptional physician and an extraordinary intellect, but also a man of deep humanity — his dedication to caring for others is an example to us all.
Case Study
Patient: Thomas L.
Age: 64
Condition: Cystinuria, congenital solitary functioning kidney, end-stage renal disease (ESRD), on dialysis for over six months. He is on eliquis for Factor V Leiden deficiency.
Transplant Plan: Scheduled for renal transplantation with his son as the donor.
Medical Background:
Athletic, BMI 28.46, nonsmoker, follows a healthy diet.
Hypertension and hyperlipidemia in the past, with a family history of myocardial infarction (father died in his 50s).
Not on any cardiometabolic medications.
Current imaging & lipid profile:
HgbA1c: 5.4
Low HDL: 40
Elevated TG: 166
TG/HDL Ratio: 4.15 (previously >7)
Imaging shows abdominal aortic atherosclerosis.
Nuclear stress test: Normal, and he was cleared for surgery.
Medical clearance: Acknowledged his cardiovascular (CV) risk factors.
Intervention:
As a cardiometabolic specialist and friend, I was concerned about the validity of the normal stress test in ruling out CV atherosclerotic disease. Given his history of chronic kidney disease (CKD), which is a strong driver of atherosclerosis, I suspected the stress test might not reflect his true CV risk. His strong family history, lipid profile and TG/HDL ratio indicated insulin resistance and elevated CV risk.
To better assess his coronary status, I ordered a coronary calcium score, which came back as 538, showing heavy calcification in the proximal LAD and diffuse disease in the RCA. This raised red flags.
Symptoms: While he denied chest pain, he reported declining exercise tolerance, fatigue, and dyspnea since starting dialysis. These symptoms, combined with his test results, prompted an urgent cardiology referral.
Further Testing & Findings:
Catheterization was Recommended, but given his Factor V Leiden deficiency and chronic anticoagulation, I advocated for a CT coronary angiography (CCTA) with FFR. FFR has a high negative predictive value and could avoid invasive testing.
CCTA results:
Calcium score: 575
Severe stenosis in the small OM-1 branch
Mild stenosis in multiple coronary vessels (left main, LAD, Circumflex, RCA)
Mild concentric left ventricular hypertrophy (LVH)
FFR was Never Sent/Requested by his Management Team
Cardiac Catheterization: Confirmed multivessel 30-40% stenosis: LM patent with minimal disease, Moderate proximal Circumflex (DFR0.98), mild diffuse 40% LAD disease, mild Proximal and diffuse 30-40% mild mid RCA, high moderate stenosis in small OM-1, 80% which is a small vessel
Final Diagnosis: Diffuse non-obstructive coronary artery disease was identified. There was no intervention performed and no revascularization required. Notably, there was an approximately 80% stenosis in a very small distal vessel, which was not suitable for percutaneous intervention or surgical revascularization.
OGTT showed normal glucose values (fasting 81 mg/dL, 1-hour 127, 2-hour 98), but a disproportionately high insulin response (fasting 15.4 μIU/mL, 1-hour 85, 2-hour 59)
Despite initially clearing him for surgery, the physicians managing this case missed a serious cardiac and metabolic issue that was undetected by the stress test. The additional testing allowed for proper diagnosis and safe surgical clearance although the lack of FFRct analysis may have contributed to an unnecessary invasive catheterization.
Discussion
Chronic kidney disease (CKD) is not simply a renal disorder — it is one of the most potent accelerators of cardiovascular disease. From stage 3 onward, CKD creates a chronic pro-inflammatory and insulin-resistant state that drives diffuse atherosclerosis, vascular calcification, and microvascular dysfunction. (5,6) A GFR below 60 doubles the risk of cardiovascular events, a GFR between 30–44 triples it, and a GFR <15 increases cardiovascular risk more than seventeen-fold while raising mortality twenty-fold (1).
Even when patients receive a successful transplant, they do not return to “normal.” With a single kidney, GFR remains below 60 by definition, despite a normalization in the serum creatinine, and cardiovascular risk persists — magnified further by the metabolic and vascular toxicity of anti-rejection medications.(2,3,6) It is no surprise that cardiovascular disease is the leading cause of death in renal transplant recipients, responsible for 30–40% of mortality (2,3).
Cardiovascular deaths in this population occur both early and late. In the first 1–2 years after transplantation, events are often related to perioperative stress and previously unrecognized coronary disease (4). Silent ischemia, triple-vessel balanced disease, and left main lesions — commonly missed by functional stress testing — account for a substantial portion of sudden cardiac deaths in this window. The case patient above indeed as predicted had triple vessel disease. (8-10) Beyond five to ten years, the risk remains high, now fueled by the long-term metabolic consequences of immunosuppression: hypertension, diabetes, dyslipidemia, vascular calcification, and chronic inflammation (5,6). By ten years, up to one in three transplant patients will have died from cardiovascular causes, making CVD the dominant threat to survival across the entire post-transplant course (3).
In patients that are going for a kidney transplant, the vast majority are on dialysis and have been suffering from progressive renal insufficiency for many years. Renal transplant has offered many of these hope for the future and transplant greatly improves survival compared to dialysis. However, this staggering CardioMetabolic burden greatly influences life expectancy.(2,3,5,6) Pre-existing morbidities drive adverse outcomes but in addition, the immunosuppressive(anti-rejection) medications used after the transplant increase the risk of atherosclerosis and cardiometabolic disease. (12,13)
Calcineurin inhibitors (CNIs) can cause vasoconstriction, leading to increased blood pressure and affecting kidney function by decreasing renal blood flow and increasing renal vascular resistance. CNIs, particularly cyclosporine, can also raise lipid levels by increasing triglycerides and cholesterol. This combination of hypertension, dyslipidemia, and potential nephrotoxicity can accelerate vascular damage and increase cardiovascular risk.(12,13) The corticosteroids induce insulin resistance and possible weight gain, can also promote hypertension and dyslipidemia, especially the atherogenic dyslipidemia (13). Lastly, the mTOR inhibitors are associated with the atherogenic Lipid, endothelial repair and progression of vascular disease. (12,13)
Immunosuppressive drugs used in transplant patients not only prevent rejection but also increase the risk of cardiovascular disease by inducing a pro-atherogenic state characterized by metabolic syndrome, dyslipidemia, and diabetes. This, combined with pre-existing vascular damage from chronic kidney disease or end-stage renal disease, puts transplant recipients at a significantly higher risk of long-term cardiovascular complications compared to the general population.(5,6,12,13) Essentially, these therapies can add fuel to any pre-existing vascular issues, making this population extremely high-risk for cardiovascular events.
CTA Coronary Arteries: Looking under the hood, not just going for a Test Drive
Stress testing is like taking a car for a quick spin around the block — it might seem fine on the surface, but you never actually look under the hood. For renal transplant candidates, that approach is not enough. The cardiac CT angiogram (CCTA) with fractional flow reserve (FFRct) allows us to look directly under the hood, revealing the true condition of the coronary arteries. CCTA identifies the presence of coronary artery disease, quantifies plaque burden, evaluates the degree of stenosis, and determines how many vessels are involved. This information provides powerful risk stratification and guides future treatment in a proactive, meaningful way. Importantly, a normal CCTA carries a negative predictive value of nearly 99%, meaning that if no significant stenosis is found, we can be confident this is accurate (7,17,18,20).
By contrast, nuclear stress testing is well known to be faulty when it comes to balanced ischemia. In patients with triple-vessel disease — the very highest-risk group — up to 15% (1 in 6) will have a normal test (8–10). These patients are then told, “Good news, your heart is fine,” when in fact they carry the gravest risk. Left main and triple-vessel disease simply cannot be missed — and yet stress testing does exactly that. The tragic case of journalist Tim Russert, who died of an acute heart attack just six weeks after a “normal” stress test and with an LDL <70, underscores how misleading this approach can be (10,11). Transplant candidates cannot afford this margin of error.
Identifying atherosclerosis, especially in such a high-risk population, is crucial. The purpose of transplant surgery is not just to restore independence and quality of life in the short term, but to extend life in the long term. That requires the ability to identify and address cardiovascular risk proactively, not reactively. Because CCTA requires IV contrast, it is imperative that this evaluation be performed before transplantation, not after (7,16–18,20). Functional stress testing, long entrenched in cardiology, can identify myocardial ischemia, but it is not sufficient for the long-term management of patients with advanced cardiovascular risk (7,18–20).
For transplant candidates, the choice is clear: we must look under the hood, not just take a test drive.
Why Functional Testing Fails CTA Coronary Arteries
Despite these CardioMetabolic risks, the standard pre-transplant cardiac workup continues to rely on functional testing — treadmill stress, stress echo, nuclear SPECT, or stress MRI — designed only to detect ischemia from stenoses >70%. (7,10) There is a fundamental limitation. Pathology and angiographic studies confirm that ~65–70% of myocardial infarctions arise from lesions <50% stenosed, while only 15–20% arise from lesions >70% (8,9). Vulnerable plaques with high inflammatory activity and thin fibrous caps rupture silently and unpredictably. These are the very lesions that functional tests cannot detect. (8,9) And these are the very lesions found in renal patients, fueled by the proinflammatory state and insulin resistance. This is not my opinion, this is medical and scientific fact.
When looking at nuclear stress testing, 59% of the time when the test is positive, there was no coronary artery disease on angiogram , but conversely, a negative stress test still had a 28% risk of coronary artery disease. (7,10,11,18-20) When comparing the Functional testing to the findings on invasive coronary angiography for the presence of >50% stenosis based on a positive test result, SPECT=45%, Stress echo =44%, Exercise Stress Test =45% and with Cardiac MRI=45%.
With CCTA and FFR, the specificity and sensitivity of obstructive coronary disease and full limiting disease is higher, >90%, than all of the others. Regarding risk stratification long term, In the major studies, if no plaque was present, there were no CV events in a follow up of 10 years. A higher plaque burden on CCTA imaging is associated with an exponentially increased risk. Getting it right and predicting future risks should not be an afterthought.
The problem is also cultural. Cardiologists are trained, credentialed, and reimbursed to perform functional testing and invasive catheterization. Moving diagnosis to radiology, with CCTA and FFRct, challenges both prestige and financial incentives. This entrenched system perpetuates outdated testing even as evidence demonstrates the inferiority of functional testing and invasive functional testing and invasive angiography, whereas CCTA/FFRct shifts diagnosis toward anatomic/physiologic imaging with high rule‑out value (11,18–20).
Effective long-term management is crucial for renal transplant patients, who, despite improved kidney function, still have chronic kidney disease (CKD) and face increased cardiovascular risks due to anti-rejection medications' atherogenic effects. It's essential for transplant teams to assess and stratify individual cardiovascular risks, as primary care providers may not adequately address these complexities. Notably, patients with known coronary artery disease typically have cardiology follow-up, whereas those with “negative” functional tests do not.
In this case, however, there was a lack of discussion regarding cardiac risk stratification, the heightened cardiovascular risk associated with CKD, and the potential effects of anti-rejection medications. It was always someone else’s job to do that. Triple vessel CAD, considering its severity and ominous prognosis, is not an afterthought or something that can't be missed...especially by one of the most prestigious Medical Centers in New York, if not in the entire United States.(22)
Metabolic Burden of Transplantation
The September 9, 2025 Annals of Internal Medicine has a full discussion about Chronic Kidney Disease. It states very clearly:
“Although CKD is commonly attributed to diabetes or hypertension, there is growing awareness of the interplay among cardiovascular, kidney and metabolic health. Progression of CKD can result in metabolic abnormalities and end stage kidney disease, but cardiovascular events are even more common. The main goals of CKD treatment include slowing the decline in kidney function, preventing cardiovascular disease, and treating metabolic complications.” (21)
As we saw with this patient, none of this happened. In fact, he was given the reassurance that his heart was fine. Why is nobody paying attention when the stakes are so high? The data is there and it’s not new — yet leading medical institutions continue to ignore it, clinging to outdated protocols and superficial evaluations. They wait for the catastrophe to declare the diagnosis, rather than acting on the evidence staring them in the face.
Due to multiple metabolic insults, eventually 20–50% of transplant recipients without pre-existing diabetes develop post-transplant diabetes or impaired glucose tolerance, and the majority show insulin resistance (14). Within the first year, 30–60% gain significant weight due to increased appetite, steroid use, improved overall health, and reduced activity (15). Restriction of protein intake often drives increased carbohydrate consumption, which elevates insulin, promotes fat storage, and slows metabolism — worsening the cycle of metabolic dysfunction. These are not theoretical risks; they directly translate into myocardial infarction, heart failure, stroke, and sudden cardiac death.(2,3,5,6,14,15)
HbA1c is falsely lowered in CKD due to shortened red blood cell lifespan, erythropoietin use, and dialysis circuit blood loss, making it an unreliable marker of glycemia. Fasting glucose, meanwhile, often remains normal until late disease, whereas the Oral Glucose Tolerance Test (OGTT) with a fasting, 1 & 2 hour insulin response can unmask early insulin resistance and impaired glucose handling long before overt diabetes develops. Identifying diabetes/insulin resistance — even in its earliest stages — opens the door to additional, meaningful risk reduction through targeted therapy, lifestyle intervention, and closer cardiometabolic surveillance. (5,6,14,15).
In fact, in this patient’s case, the OGTT showed normal glucose values (fasting 81 mg/dL, 1-hour 127, 2-hour 98), but a disproportionately high insulin response (fasting 15.4 μIU/mL, 1-hour 85, 2-hour 59), clearly demonstrating insulin resistance despite normal glycemia. This pattern underscores why OGTT with insulin should be a mandatory pre-transplant evaluation, as it reveals hidden metabolic dysfunction that drives post-transplant diabetes, vascular injury, and cardiovascular events.
Identifying insulin resistance is not merely academic — it opens the door to actionable interventions: targeted nutrition, lifestyle strategies, and evidence-based therapies such as SGLT2 inhibitors, GLP-1 agonists, and even pioglitazone (shown to reduce mortality by ~51% in diabetic dialysis patients). By addressing insulin resistance upfront, we can meaningfully reduce cardiometabolic risk, improve transplant outcomes, and extend survival. (5,6,14,15)
Glucose values are normal at all time points.
Insulin levels are excessively elevated, indicating insulin resistance despite normal glycemia.
This hidden metabolic dysfunction would have been missed if only HbA1c or fasting glucose were measured.
Clinical Significance:
Insulin resistance drives post-transplant diabetes, vascular calcification, and accelerated atherosclerosis.
Early identification creates opportunities for targeted therapies, lifestyle intervention, and closer surveillance — interventions that may extend survival and reduce cardiovascular events.
Why the Identification of Atherosclerosis vs Ischemia is Imperative
The goal of cardiac imaging is three fold:(7,18-20)
1. Identify pre-existing coronary artery disease.
2. Risk stratification, including how many vessels are involved and degree of stenosis.
3. Guiding treatment decisions in the future.
Traditionally, patients without a diagnosis of coronary artery disease are sent for Functional testing. They are sent for either treadmill stress testing, stress echocardiogram, stress MRI, or SPECT nuclear testing. All these tests look for evidence of myocardial ischemia indicating a stenosis of 70% or more. They do not help diagnose coronary disease, they do not assist with risk stratification, and they do not help guide future treatment decisions. In fact, they can give a false sense of security and reassurance. (7,10,11,18-20) The post-transplant period is a critical time when decision making needs to be precise, individualized and guided by science, not a false sense of security . (2,3,5,6) A patient’s hopes and dreams … and lives … are literally in our hands and when most view the actual transplant as the end of a long journey, in reality it’s just the beginning.
As an internist and a CardioMetabolic Specialist, I study the root cause of disease and try to identify and modify risk in a logical and proactive manner. In that way I can prevent or modify disease progression rather than just being reactive and treating illness. Identifying atherosclerosis especially in this high risk population is crucial. This is not something that can be ignored or overlooked. Risk is risk and disease is disease… our thorough evaluations are so crucial for life and death and this is more so in these high risk populations.
Evidence for CCTA with FFRct
CCTA meets the criteria for identifying coronary disease, excels in risk stratification and is crucial for guiding future treatment decisions. (7,17,18-20)
NEJM 2018 reported a ~41% reduction in death/MI at five years with CCTA vs. standard care (18). PROMISE (N Engl J Med 2015) demonstrated superior discrimination and reclassification with an anatomic strategy in ~10,000 patients, with particularly strong signals in higher‑risk groups such as diabetes (7,19). PRECISE (JACC 2021) showed a ~70% reduction in death/MI/unnecessary catheterization at 12 months using a CCTA + selective FFRct strategy vs. functional testing (20).
Because ESRD and diabetes feature diffuse atherosclerosis and microvascular dysfunction—often with silent ischemia and higher false‑negative rates on stress testing—an anatomic/physiologic strategy is especially compelling (5,6,8–11,17–20).
Analysis showed that the majority of late adverse cardiovascular events — 57% — occurred in patients with completely normal functional testing (17–20). These were the very individuals reassured with, “Good news, Mr. Smith, your cardiac stress test is normal,” only to be left with a false sense of security. By contrast, only 5% of events occurred in those with a normal CCTA, which demonstrated superior discrimination, risk reclassification, and more robust event prediction — detectable as early as 42 months. This raises the most important question about a negative test: “Does this mean I have no heart disease, or only that I don’t currently need revascularization?”
Given the high cardiovascular risk and mortality rates in post-transplant patients, it is logical to assume that this population would derive significant benefit, even if it has not been specifically studied in renal transplant cohorts. In both diabetes and end-stage renal disease, cardiovascular disease typically manifests as diffuse atherosclerosis and microvascular dysfunction rather than isolated blockages (5,6,8–11). Patients in both groups frequently have silent ischemia and higher false-negative rates on stress testing because the disease is widespread and involves the small vessels. The fundamental driver in each condition is a chronic proinflammatory state with insulin resistance, which accelerates plaque formation, vascular calcification, and endothelial injury.
CCTA provides direct visualization of plaque burden, number of vessels involved, and stenosis severity. Adding FFRct delivers physiologic significance with near-invasively accurate precision. (7,18-20)
Together they offer:
Presence of disease — early detection of CAD.
Risk stratification — plaque burden and distribution.
Guidance for treatment — tailoring prevention and interventions.
Performance metrics are unmatched:
Negative predictive value ~99% (7).
Radiation exposure: Average exposure from sun/TV/airline travel (3mSv/yr) vs CCTA (1–3 mSv) vs. nuclear stress (9–12 mSv) vs. angiography (5–30 mSv depending on stenting) (16).
Diagnostic accuracy: FFRct at 94%, compared with ~70% for SPECT (17).
Recommendations for New Standards of Care
Based on the overwhelming evidence and the unique risk profile of this population, my recommendations are:
1. All pre‑transplant patients without known CAD should undergo CCTA with FFRct, regardless of functional testing results, unless specifically contraindicated (7,17–20).
2.All pre-transplant patients without diagnosed diabetes should undergo a 2-hour OGTT with insulin response (fasting, 1-hour, 2-hour) to detect insulin resistance and early dysglycemia — key drivers of post-transplant diabetes and cardiovascular risk (5,6,14,15). Notably, pioglitazone has been associated with ~51% lower mortality in diabetic patients on hemodialysis, according to supportive data from the broader dialysis literature, and therefore merits individualized consideration in collaboration with nephrology and cardiology (contextualized with 5,6,14). More broadly, any intervention that targets insulin resistance has the potential to improve both renal and cardiovascular outcomes.
3. Cardiometabolic evaluation should be proactive and continuous, recognizing that CKD and post‑transplant therapies accelerate atherosclerosis and metabolic disease (2,3,5,6,12–15).
Transplant surgery aims to enhance patients' quality of life in both the short and long term. Effective long-term management involves proactive risk identification and mitigation. Considering many cardiac tests require I.V. contrast dye, it's crucial to complete these assessments before transplantation. Our current decisions impact future outcomes. A strategic approach, like planning several moves ahead in chess, allows for early intervention and a more positive long-term prognosis. Establishing baseline cardiometabolic status in a meaningful, sophisticated and efficient manner– including cardiovascular and metabolic health – empowers us to make informed decisions and take control of the health trajectory.(2,3,5-7,12-15,18-20)
Conclusion
The goal of renal transplantation is not only to restore kidney function but to improve overall health and survival. A death is a death, regardless of GFR at the time, and outcomes must be measured in lives extended and lives improved. To achieve this, blinders must be removed: risk factor identification and modification — pharmacologic, nutritional, and behavioral — must be implemented in a pragmatic, individualized way.
Pre-transplant risk assessment is central to long-term success. CCTA with FFRct should be the standard of care, not an optional add-on for select patients (5,6,8–11). Seeing plaque on a screen changes behavior in ways numbers cannot. Confusing “no ischemia” on a stress test with “no disease” is unacceptable. A normal stress test is not a normal heart, and in transplant candidates this false reassurance endangers both immediate surgical safety and long-term prognosis. Ischemia may determine perioperative risk, but undiscovered disease dictates long-term survival.
Metabolic assessment must also be mandatory in all non-diabetic transplant candidates. This case illustrates the danger of relying on static glucose or HbA1c, which in ESRD is both misleading and unpredictable. Although glucose values on the OGTT appeared normal, the insulin response revealed clear resistance — elevated fasting levels, an exaggerated one-hour peak, and incomplete recovery at two hours. This hidden dysfunction fuels atherogenic dyslipidemia, systemic inflammation, vascular calcification, and progression of CKD and CVD. We have been focusing on the wrong target for too long — glucose alone — while ignoring insulin resistance, the true driver of post-transplant diabetes and cardiovascular risk.
Insulin resistance in the transplant setting magnifies the toxicity of immunosuppressive drugs, accelerating atherosclerosis and driving morbidity and mortality. Early identification opens the door to meaningful interventions: nutrition, lifestyle modification, targeted supplementation such as high-dose omega-3 EPA, and pharmacologic agents like pioglitazone when appropriate. These strategies extend not only renal graft survival but overall survival.
Renal transplantation is meant to extend life, not shorten it. Yet when one in three transplant recipients ultimately dies of cardiovascular disease, it is clear that current practices are failing. Functional stress testing reassures when it should alarm. A normal stress test does not mean a normal heart; it means an incomplete evaluation. By contrast, a normal CCTA with FFRct carries the weight of true prognostic reassurance. Continuing to rely on functional stress testing in this population is both medically inadequate and ethically indefensible (2,3,5,6,18–20). Equally unacceptable is the absence of dynamic metabolic testing — an omission unsupported by modern standards of care. The myopic focus must widen: transplant teams must evolve from protecting kidneys to preserving life, adopting cardiometabolic principles that have been established for years but remain underutilized.
The very centers that pride themselves on performing miracles of transplantation fail to recognize a simple truth: cardiovascular disease remains the leading cause of death after kidney transplantation. Without proactive cardiometabolic care, transplantation simply exchanges one form of failure for another.
And beyond this, transplant teams often fail to use available tools that could prevent long-term adverse outcomes, staying narrowly focused on short-term accomplishments. This systemic passivity echoes the moral failure of the Tuskegee Syphilis Study. Then, physicians observed the predictable, devastating consequences of untreated disease. Today, we see the same inertia in transplant medicine — documenting risk but refusing to act, observing decline but not intervening. The disease is different; the ethical breach is the same. To know the outcome and still choose to “watch and see” is not practicing medicine — it is abandoning it.
As Arthur Schopenhauer, the German philosopher, observed:
“All truth passes through three stages.
First, it is ridiculed;
second, it is violently opposed; and
third, it is accepted as being self-evident.”
The truth here is already self-evident: in renal transplant candidates, functional testing is obsolete. CCTA with FFRct along with metabolic assessment must become the standard of care. Anything less is failure. Let us not forget our mission, for in this population the stakes are nothing less than life and death.
Follow up post transplant surgery with Commentary : a sad state of affairs.
The patient in question underwent a successful renal transplant with his son as the living donor. His postoperative course was largely uneventful, aside from a persistent drain left in place for monitoring x 7 days. He was ultimately discharged home in stable condition. His medication list was extensive, as is typical for transplant recipients, including pantoprazole, aspirin, carvedilol, Bicitra, Eliquis, MiraLAX, phosphate and potassium supplementation, calcitriol, tacrolimus, prednisone, mycophenolate, valganciclovir, Bactrim, and nystatin suspension. From an immunosuppressive standpoint, the regimen adhered to conventional post-transplant protocols.
What is most striking—and frankly indefensible—is not what was prescribed, but what was completely omitted. This is a patient with advanced, well-documented cardiometabolic disease at every level: triple-vessel nonobstructive coronary artery disease confirmed on catheterization, a coronary calcium score of 575, and a profoundly atherogenic lipid profile (LDL 114 mg/dL, HDL 30 mg/dL, triglycerides 208 mg/dL) yielding a TG/HDL ratio of 7—an unmistakable metabolic signature of advanced insulin resistance (23). Insulin resistance was confirmed by oral glucose tolerance testing with insulin response. He also has mild concentric left ventricular hypertrophy, established aortic atherosclerosis, and is in the vulnerable post-transplant period with a solitary kidney and an eGFR under 60, consistent with CKD stage 3 (24). And yet—despite this perfect storm of cardiometabolic risk—he was discharged without a single therapy directed toward cardiovascular or metabolic protection. Not one.
There was no statin. No GLP-1 receptor agonist. No SGLT2 inhibitor. No pioglitazone. No icosapent ethyl. But perhaps even more shocking than the omissions in therapy is the absence of the most basic patient education. This patient was started on high-dose prednisone—well known to induce hyperglycemia and exacerbate insulin resistance (25) —and no one even warned him of this risk. No instructions on monitoring glucose. No finger-stick guidance. No nutritional or lifestyle counseling. It is difficult to avoid the conclusion that they simply didn’t think about it. These are not small oversights—they are foundational failures of metabolic and cardiovascular risk management. This is precisely the kind of patient for whom these therapies and anticipatory strategies exist, supported by evidence and embedded in every major cardiometabolic guideline (26-29).
Worse still, the medications he was prescribed amplify the inflammatory and metabolic milieu driving his disease. High-dose prednisone and tacrolimus promote insulin resistance, visceral adiposity, endothelial dysfunction, and beta-cell injury (30-32) —superimposed on an already high-risk state. Beyond metabolic disruption, this is an inherently pro-inflammatory state, and inflammation is not a side note here—it is a primary engine of disease progression.
As Paul Ridker and others have shown, vascular inflammation is a central driver of atherosclerotic cardiovascular disease, often more predictive than cholesterol levels alone (33,34). The absence of an integrated strategy to address inflammation and insulin resistance in this context is particularly egregious. Even his antihypertensive plan reflects reflexive, not strategic thinking: carvedilol was prescribed without clear indication, while truly disease-modifying options were ignored. A patient like this should have had insulin-sensitizing and anti-inflammatory therapies front and center. To overlook these interventions is not a subtle gap in care—it is a profound failure of clinical reasoning and preventive cardiometabolic medicine.
From a nephrology perspective, the lapses are equally profound. The contemporary standard of care for patients with CKD includes a multi-pronged strategy to reduce cardiorenal risk: renin-angiotensin-aldosterone system (RAAS) blockade with ACE inhibitors or ARBs, SGLT2 inhibition, mineralocorticoid receptor antagonism when appropriate, and GLP-1 receptor agonists for additional glycemic and cardiovascular benefit (35-38). Not a single one of these therapies was addressed. Despite clear evidence and robust guidelines, they were simply ignored.
Perhaps the most baffling omission is icosapent ethyl. The REDUCE-IT trial demonstrated a dramatic reduction in cardiovascular events among high-risk patients, including those with residual triglyceride elevation despite statin therapy (39). The EVAPORATE trial went further, showing regression of coronary plaque (40). This patient, with a CAC score of 575 and diffuse non-obstructive disease, is an ideal candidate. To not consider this therapy borders on negligence.
What makes this case especially unsettling is where it took place: NYU Langone Medical Center, ranked number one in the nation for Cardiology and Heart Surgery by U.S. News & World Report for 2025–2026. This is not a story of care in a rural or underfunded hospital. This is not a critique of a busy outpatient office overwhelmed by paperwork. This is an indictment of elite academic medicine and its persistent failure to integrate prevention, metabolism, and whole-person care.
We know the statistics. The majority of kidney transplant recipients will die within five to ten years—not from graft failure, but from cardiovascular disease (41). We know that nearly half will develop prediabetes or frank diabetes in the post-transplant period, a complication often triggered or accelerated by immunosuppressive therapy (42-43). And yet—these realities were ignored. What makes this even more striking is that every patient who undergoes renal transplantation is required to undergo extensive pre-transplant cardiac testing, often more rigorously than the general population (44).
Many of these patients, at the time of surgery, have negative stress tests, normal or near-normal ejection fractions, and no flow-limiting stenoses. And yet, when compared with matched control groups who also have negative cardiac testing, the long-term outcomes are dramatically different (45-46). Ten years later, the death rates in the transplant population are exponentially higher.
This is not because their cholesterol is higher. It is because they live in a chronic pro-inflammatory, pro-insulin resistant state—driven by immunosuppression, visceral adiposity, endothelial dysfunction, and metabolic injury (47). As Paul Ridker and others have demonstrated, inflammation—not cholesterol alone—is a fundamental driver of atherosclerosis and cardiovascular events (48).
These are predictable, measurable risks, and yet they were not even addressed. There was no glycemic monitoring, no nutritional guidance, no plan for preventing steroid-induced hyperglycemia. There was no pioglitazone, no GLP-1 receptor agonist, no individualized strategy to protect the terrain. The myopic focus remained on the graft—the kidney—while the smoldering fire of cardiovascular and metabolic disease was left to burn.
This case is more than a missed opportunity. It is a vivid illustration of a deeply fragmented system. Each specialty acted in isolation. Cardiology focused on anatomy. Nephrology focused on clearance. Transplant focused on immunosuppression. And no one focused on the person. The consequences of this approach are not theoretical. They are deadly. The patient will follow up proudly with his transplant team and may feel grateful for his new kidney—but unless the rest of his physiology is addressed, his future is not secure.
Einstein famously warned that insanity is doing the same thing over and over and expecting different results (49). This is precisely what we are doing in modern medicine. We allow a parade of comorbidities to emerge post-transplant—diabetes, heart failure, myocardial infarction—and then scramble to treat them with expensive interventions that could have been prevented (50-51). We praise short-term surgical outcomes while turning a blind eye to the long-term risks we failed to mitigate. And we do this again and again, even in the most advanced institutions in the world.
What happened here is not just disappointing—it is emblematic of a dangerous status quo. The prestige of the institution cannot excuse the absence of personalized, system-wide prevention. The patient’s chart is full of documentation, prescriptions, and procedure notes—but empty of coordinated strategy. This is why I wrote this commentary. Not to assign blame, but to illuminate a blind spot that continues to cost lives. Until we shift from reactive to proactive, from protocols to people, from silos to systems—we will continue to manage grafts, but lose patients.
The saddest part is that the patient was grateful. He believed he had a full team of experts surrounding him—physicians collaborating to secure his future. But what he really had were technicians. Not doctors in the truest sense, but specialists focused on numbers, on organs, on isolated domains. No one saw the whole. No one cared to. As long as the transplanted kidney was functioning, the mission was considered a success. Whether he developed a heart attack, diabetes, or dropped dead from a preventable vascular event—none of that mattered. Because in this fragmented system, a patient dying with a working kidney still gets counted as a win. That’s not medicine. That’s mechanical maintenance. And we are done pretending otherwise.
This is exactly why cardiometabolic medicine must take center stage. The heart and kidneys are Siamese twins—but so are the liver, the pancreas, the brain, the gut, and the vascular system. You cannot treat one organ without affecting the others. Nothing in the body exists in isolation. And yet medicine continues to behave as if it does. Until we have physicians trained to see through a cardiometabolic lens—doctors who understand the underlying terrain, the interconnected systems beneath the symptoms—patients will continue to die unnecessarily. This is not a philosophical difference. This is life and death.
Cardiologists who wish to step into the field of cardio-oncology must first understand the principles of cardiometabolic medicine. They must understand that inflammation is not a footnote—it is the engine. It is the driver of atherosclerosis, the accelerant of endothelial injury, and the silent partner in almost every major cardiovascular event (52-54).
As Paul Ridker and others have shown, vascular inflammation—not LDL alone—is the critical determinant of risk (55). If cardio-oncologists ignore the pro-inflammatory state induced by cancer therapies, immunosuppression, metabolic dysfunction, and visceral adiposity, they will be standing at the wrong battlefield, fighting the wrong war.
The time for metabolic indifference is over. The time for checking boxes while patients walk toward predictable outcomes is over. We need a new kind of clinician—one who recognizes that these diseases are systemic, terrain-based, and inflammatorily driven. One who refuses to let patients fall through the cracks of a fragmented model of care. Because the next patient isn’t just a “case.” It’s someone’s mother. Father. Brother. Or your own.
Author: Dr John Sciales
Director, CardioCore Metabolic Wellness Center
"Getting to the Core- where being Healthy is Not an Accident"
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