Post-transplant metabolic dysregulation: Insights and implications for kidney graft survival

Abstract

Kidney transplantation is the preferred treatment for end-stage kidney disease, improving survival and quality of life. Yet, metabolic disorders including post-transplant diabetes mellitus, dyslipidemia, hyperuricemia, secondary hyperparathyroidism, and obesity are common in kidney transplant recipients and threaten graft function and patient outcomes. Post-transplant diabetes mellitus affects up to 30% of recipients within the first year, while transient hyperglycemia occurs in 60% of nondiabetic patients post-surgery. Dyslipidemia, obesity, and hyperuricemia exacerbate cardiovascular and metabolic risks, and secondary hyperparathyroidism impairs bone health and graft longevity. Immunosuppressive agents such as corticosteroids, calcineurin inhibitors, and mammalian target of rapamycin inhibitors contribute significantly to these complications, underscoring the need for tailored regimens. Management strategies should be comprehensive, combining lifestyle modification, pharmacological interventions (sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists), and, in selected cases, bariatric surgery. Close monitoring of post-transplant weight gain, particularly visceral fat, is essential to prevent insulin resistance and metabolic syndrome. Despite these advances, significant gaps persist in evidence-based guidelines, and emerging therapies alongside multidisciplinary collaboration hold promise in addressing these complex metabolic challenges. This review underscores the prevalence, pathophysiology, and clinical implications of post-transplant metabolic dysregulation, emphasizing the need for early detection, personalized management, and integrated care to optimize graft survival and long-term patient outcomes.

Key Words: Dyslipidemia; Graft survival; Hyperuricemia; Immunosuppressive therapy; Kidney transplantation; Obesity; Persistent hyperparathyroidism; Post-transplant diabetes mellitus

Core Tip: Kidney transplantation is the preferred treatment for patients progressing to end-stage kidney disease. Several metabolic processes are altered following kidney transplantation, primarily due to the overlap between preexisting risk factors and the side effects of immunosuppressive agents. Among the metabolic alterations, post-transplant diabetes, dyslipidemia, hyperuricemia, secondary hyperparathyroidism, and obesity are the most significant, given their clinical impact and their potential to threaten graft survival and patient outcomes. Lifestyle modification, pharmacological interventions such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, bariatric options, and close monitoring of weight gain are essential strategies, though evidence gaps remain, particularly in the management of hyperparathyroidism.

INTRODUCTION

Kidney transplantation (KT) has revolutionized the management of end-stage kidney disease (ESKD), offering patients improved survival, enhanced quality of life, and freedom from dialysis dependence[1]. It is widely regarded as the optimal therapeutic option for those approaching or living with ESKD, with outcomes that surpass other kidney replacement therapies[2]. Yet, despite these well-documented benefits, kidney transplant recipients (KTRs) continue to face disproportionately high risks of morbidity and mortality compared to the general population[3]. Among these, cardiovascular disease (CVD) remains the leading cause of death in this population, reflecting the persistent vulnerability of patients even after successful transplantation[4]. Beyond cardiovascular complications, the long-term durability of kidney grafts is increasingly challenged by a spectrum of metabolic disorders that arise in the post-transplant period. Post-transplant diabetes mellitus (PTDM), dyslipidemia, hyperuricemia, secondary hyperparathyroidism (HPT), obesity, and metabolic syndrome are particularly prevalent and exert multifaceted effects on both graft function and patient outcomes. These conditions not only accelerate cardiovascular risk but also compromise bone health, metabolic stability, and overall survival. Indeed, metabolic syndrome develops in nearly one-fifth of recipients, significantly increasing the risk of graft loss and cardiovascular events[5]. Importantly, their pathogenesis reflects a complex interplay between immunosuppressive regimens, pre-existing comorbidities, and transplant-related physiological changes, highlighting the delicate balance required to maintain graft function while minimizing systemic complications. The recently introduced cardiovascular-kidney-metabolic (CKM) syndrome concept by the American Heart Association (AHA) highlights the interconnected nature of metabolic risk factors, chronic kidney disease (CKD), and cardiovascular outcomes[6]. This framework emphasizes that excessive or dysfunctional adiposity, together with classical risk factors such as obesity, diabetes, hypertension (HTN), and dyslipidemia, contributes to systemic dysfunction[7]. In transplant recipients, additional risks arise from pre-existing CKD, inflammatory status, anemia, proteinuria, and the secondary effects of immunosuppressive therapy[8]. Calcineurin inhibitors (CNIs), corticosteroids, and mammalian target of rapamycin (mTOR) inhibitors, while essential for graft survival, exacerbate metabolic derangements by promoting insulin resistance, hyperlipidemia, and bone loss[8]. The consequences of post-transplant metabolic dysregulation extend well beyond the immediate recovery period, influencing transplant candidacy, adherence to long-term immunosuppressive therapy, and the sustainability of graft function. Persistent metabolic complications contribute to chronic allograft dysfunction, diminished quality of life, and increased healthcare burden. Therefore, early recognition of risk factors, timely identification of high-risk recipients, and targeted interventions are essential to reduce the incidence of metabolic syndrome after KT[8]. This mini-review consolidates current evidence on the prevalence, pathophysiology, and clinical implications of metabolic disorders in KTRs, underscoring the importance of personalized management, multidisciplinary collaboration, and proactive strategies to enhance survival and long-term outcomes.

LITERATURE SEARCH

This study was conducted as a narrative review. A comprehensive literature search was performed using electronic databases, including PubMed, MEDLINE, Scopus, and Web of Science. The search covered publications from January 1992 to September 2025 to ensure inclusion of both foundational and contemporary studies. A broad set of keywords and Medical Subject Heading terms was applied to identify relevant literature, such as “Kidney transplantation”, “Post-transplant diabetes mellitus”, “Dyslipidemia”, “Post-transplant hypertension”, “Hyperuricemia”, “Secondary hyperparathyroidism”, “Obesity”, “Metabolic complications”, “Immunosuppressive agents”, “SGLT2 inhibitors”, “GLP-1 receptor agonists”, “Bariatric interventions”, “Graft survival”, and “Long-term patient outcomes”. Boolean operators (AND, OR) were used strategically to refine and optimize search results.

Inclusion criteria were: (1) Peer-reviewed original research articles, systematic reviews, or meta-analyses; (2) Studies involving human subjects who underwent KT; (3) Publications addressing metabolic complications, pathophysiology, management strategies, or patient and graft outcomes following transplantation; and (4) Articles published in English. Exclusion criteria were: (1) Conference abstracts without full text, case reports with insufficient detail, editorials, and commentaries; and (2) Studies focusing exclusively on non-metabolic complications or non-renal organ transplantation.

Two reviewers independently screened titles and abstracts to identify potentially relevant studies, followed by full-text review. Any disagreements were resolved through discussion or, when necessary, consultation with a third reviewer. Reference lists of included studies were manually searched to identify additional eligible articles. Data extraction was carried out to synthesize evidence for this descriptive review, focusing on study design, population characteristics, type of metabolic complication, immunosuppressive regimens, interventions, outcomes, and key findings. Given the narrative design, methodological quality was not formally assessed. Instead, guidelines and metaanalyses were prioritized, with key randomized controlled trials highlighted for clinical relevance. A simplified flow diagram (Figure 1) is provided to illustrate the screening process, but its purpose is descriptive rather than systematic.

Figure 1 Flow diagram showing study methodology for selecting the articles.

PTDM

PTDM is a common complication of KT that adversely affects patient quality of life, survival, and graft viability[9,10]. Routine screening for hyperglycemia is recommended after transplantation[11]. The diagnostic criteria for PTDM are similar to those for diabetes in the general population, with the oral glucose tolerance test considered the gold standard[12]. Glycated hemoglobin (HbA1c) may be used as a diagnostic parameter only after 12 months post-transplant, since anemia in the early period can lead to underdiagnosis[12-14]. The term PTDM has replaced new-onset diabetes after transplantation, as it encompasses both patients who develop diabetes after transplantation and those with previously undiagnosed diabetes[15]. Formal diagnosis should be made once the patient is stable on maintenance immunosuppression (typically ≥ 45 days post-transplant) and in the absence of acute infection[15]. PTDM excludes transient post-transplant hyperglycemia and requires persistent hyperglycemia for at least six weeks, meeting American Diabetes Association (ADA) criteria[16]. Importantly, PTDM describes diabetes irrespective of whether it was undetected before transplantation or developed afterward. Differentiating between undiagnosed pre-transplant diabetes (often type 2) and true post-transplant diabetes is clinically relevant, given differences in pathophysiology[17-19]. Unlike type 2 diabetes, PTDM may resolve over time, particularly with early initiation of glucose-lowering therapy and/or adjustment of immunosuppressive regimens. Most studies have reported that transplant patients with PTDM have higher rates of rejection, infection, and re-hospitalization[20,21].

Epidemiology

The incidence of PTDM varies, influenced by definitions, timing, populations, and immunosuppressive regimens used for individual studies. Overall, about 15%-20% of KTRs without a prior history of diabetes develop PTDM within six months[20], rising to 20%-30% with long-term follow-up[10].

Pathophysiology of PTDM

The development of PTDM is driven by a complex interplay of metabolic and cellular mechanisms. Central to its pathogenesis is insulin resistance, which reduces the effectiveness of insulin in peripheral tissues, particularly muscle and adipose tissue. In addition, impaired insulin secretion occurs due to structural and functional injury to pancreatic beta cells. Such injury may be triggered by inflammatory mediators, oxidative stress, mitochondrial dysfunction, and the direct toxic effects of immunosuppressive drugs[22]. Another contributing factor is the dysregulated release of glucagon from pancreatic alpha cells, which further aggravates hyperglycemia by promoting hepatic glucose production. Notably, evidence suggests that pancreatic beta-cell dysfunction may already be present before transplantation. Studies indicate that nearly 80% of KT candidates exhibit elevated proinsulin levels, a marker of defective insulin processing and increased insulin resistance, even prior to surgery. This pre-existing vulnerability predisposes patients to PTDM once additional stressors, such as immunosuppressive therapy and post-transplant metabolic changes, are introduced[23].

Risk factors for PTDM include both pre- and post-transplant contributors. Pre-transplant modifiable risks are obesity, body mass index (BMI) (≥ 30 kg/m²), which is strongly associated with PTDM[24,25], and hepatitis C infection, which increases risk nearly fourfold due to islet cell dysfunction and insulin resistance; treatment prior to transplantation may reduce incidence[26,27]. Non-modifiable risks include older age (≥ 40-45 years)[28,29], history of gestational diabetes or family history of type 2 diabetes, and genetic predisposition, although genetic testing is not routinely recommended[30]. Perioperative hyperglycemia is another strong predictor, with nearly one-third of affected patients developing PTDM within a year[31,32]. Additional peri- and post-transplant risks include human leukocyte antigen mismatching, male sex, deceased-donor grafts, cytomegalovirus infection[33,34], polycystic kidney disease[35], and hypomagnesemia, the latter requiring correction when present[36].

Post-transplant, immunosuppressive therapy is the most important risk factor. Glucocorticoids raise postprandial glucose in a dose-dependent manner, and while steroid-sparing regimens have lowered PTDM rates compared to earlier decades, complete withdrawal is not clearly protective and may increase rejection risk[37,38]. CNIs especially tacrolimus (TAC) are more diabetogenic than cyclosporine (CsA), causing reversible islet toxicity and impaired insulin transcription[39,40]. mTOR inhibitors such as sirolimus also worsen insulin resistance[40,41], while agents like azathioprine (AZA), mycophenolate mofetil (MMF), and belatacept are not independently diabetogenic and may lower risk when combined with reduced steroid use[42].

Thus, PTDM arises from a combination of pre-transplant metabolic abnormalities and post-transplant factors that amplify beta-cell dysfunction and insulin resistance, as summarized in Table 1. These mechanisms, together with the influence of immunosuppressive agents, infections, and genetic predisposition, explain why PTDM remains a frequent and clinically significant complication after KT.

Table 1 Risk factors for post-transplant diabetes mellitus.

Category	Risk factor	Implications
Pre-transplant (modifiable)	Obesity (BMI ≥ 30 kg/m2)	Strong association with PTDM
	HCV infection	4 × higher risk; mechanisms include islet dysfunction and insulin resistance; treatable pre-transplant
Pre-transplant (non-modifiable)	Age ≥ 40-45 years	Increased risk
	History of gestational diabetes/family history of T2DM	Genetic predisposition
	Genetic factors	Inconclusive; not recommended for routine testing
Peri-/early post-transplant	Perioperative hyperglycemia	Strong predictor; 29% incidence within 1 year if present
	Other peri-/early factors	HLA mismatching, male sex, deceased donor, CMV infection
	Potential contributors	Polycystic kidney disease, hypomagnesemia (should be corrected if present)
Post-transplant (immunosuppressive therapy)	Glucocorticoids	Dose-dependent risk; withdrawal not clearly protective; high-dose pulses increase the risk
	CNIs (tacrolimus > cyclosporine)	Tacrolimus is more diabetogenic; reversible islet toxicity
	mTOR inhibitors (sirolimus, everolimus)	Worsens insulin resistance; diabetogenic
	Other agents (AZA, MMF, belatacept)	No independent diabetogenic effect; may lower PTDM risk

BMI: Body mass index; PTDM: Post-transplant diabetes mellitus; HCV: Hepatitis C virus; T2DM: Type 2 diabetes; HLA: Human leukocyte antigen; CMV: Cytomegalovirus; CNIs: Calcineurin inhibitors; mTOR: Mammalian target of rapamycin; AZA: Azathioprine; MMF: Mycophenolate mofetil.

Management of early post-transplant hyperglycemia

Early post-transplant hyperglycemia is common and represents a major risk factor for PTDM, requiring close monitoring and timely management. The strategy for addressing early post-transplant hyperglycemia aligns closely with the recommendations outlined by the 2024 international consensus meeting on PTDM[43]. In critically ill patients, hyperglycemia ≥ 180 mg/dL should be treated with intravenous insulin infusion according to ADA protocols[44-46], with most centers targeting glucose levels between 140-180 mg/dL[47,48]. Once stable, patients are transitioned to subcutaneous insulin, with the regimen individualized based on steroid dose, graft function, infection status, and nutritional needs.

In non-critically ill patients, fasting glucose < 140 mg/dL and random glucose < 180 mg/dL are targeted, as intensive control has not demonstrated benefit and may increase the risk of rejection and hypoglycemia. Sliding-scale insulin may be sufficient for those with minimal insulin requirements[49], but basal insulin is generally more effective and may reduce the risk of PTDM, though it carries a higher risk of hypoglycemia[50,51].

Outpatient management depends on insulin requirements. Patients requiring ≥ 20 units/day should continue insulin after discharge, often with neutral protamine Hagedorn insulin timed to steroid dosing, while those requiring < 20 units/day may transition to oral agents such as meglitinides (e.g., repaglinide) or dipeptidyl peptidase-4 (DPP-4) inhibitors, with linagliptin preferred. Post-discharge, patients on therapy should monitor glucose at home using fingerstick testing or continuous glucose monitoring[52,53], while those not requiring therapy should undergo fasting or afternoon glucose checks alongside immunosuppressive trough levels[54]. Glycemic targets generally follow ADA guidelines, aiming for HbA1c < 7% when safe, or 7%-7.5% in patients at higher risk of hypoglycemia. Therapy should be intensified if targets are not achieved[55]. Table 2 summarizes the management of early post-transplant hyperglycemia.

Table 2 Management of early post-transplant hyperglycemia.

Category	Risk factors	Drug contributions	Potential benefits of newer therapies
Perioperative	Surgical stress, infection, high-dose steroids	Glucocorticoids → insulin resistance; CNIs (especially tacrolimus) → β-cell toxicity	Early basal insulin; CGM for tighter monitoring
Early outpatient	Weight gain, impaired graft function, pre-existing diabetes	Steroids → hyperglycemia; CNIs → impaired insulin secretion	DPP-4 inhibitors (linagliptin); GLP-1 receptor agonists
Monitoring	Obesity, family history	Steroids sustain hyperglycemia	Individualized HbA1c targets. Safer oral agents (meglitinides, sulfonylureas with low renal clearance)

CNIs: Calcineurin inhibitors; CGM: Continuous glucose monitoring; DPP-4: Dipeptidyl peptidase-4; GLP-1: Glucagon-like peptide-1; HbA1c: Hemoglobin A1c.

Management of PTDMs

PTDM or prediabetes in KTRs requires a tailored approach that balances glycemic control with graft stability and comorbidities. A stepwise approach to managing chronic hyperglycemia[43] begins with lifestyle modification, including dietary changes, weight reduction, and increased physical activity, followed by pharmacologic therapy. Limited data are available on the effects of lifestyle interventions in the transplant population[56], and no beneficial effects on insulin secretion or insulin sensitivity have been demonstrated after six months of follow-up[56].

Management of PTDM depends on allograft stability and the severity of hyperglycemia. In patients with unstable graft function, HbA1c is often unreliable; therefore, glucose monitoring with fingerstick testing or continuous glucose monitoring is preferred. Severe hyperglycemia is best managed with insulin, which can be rapidly titrated as graft function and steroid doses fluctuate. In cases of corticosteroid-induced insulin resistance, a combination of rapid-acting and slow-acting insulin is recommended.

For mild cases, linagliptin is the preferred DPP-4 inhibitor due to minimal renal clearance[57], while meglitinide (repaglinide) may be used for postprandial hyperglycemia. Repaglinide can be effective in some patients but has unpredictable glucose-lowering efficacy and requires multiple daily dosing[58]. In patients with stable graft function, sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists are recommended as first-line therapies because of their cardiovascular, renal, and weight benefits[59-61].

Alternative options include metformin, other DPP-4 inhibitors, sulfonylureas (glipizide or glimepiride), or meglitinides when preferred agents are contraindicated or unavailable. Metformin use is controversial due to risks of acute kidney injury and lactic acidosis, and it is restricted to patients with an estimated glomerular filtration rate (eGFR) above 30 mL/minute/1.73 m²[62]. Sulfonylureas carry a high risk of hypoglycemia, particularly when combined with CsA or azole antifungals, though glipizide and glimepiride are preferred if needed[63]. Thiazolidinediones are not recommended in KRs due to the increased risk of edema and heart failure[64]. Alpha-glucosidase inhibitors can be used as second- or third-line therapy to minimize hypoglycemia risk, but their glucose-lowering effect is modest and gastrointestinal side effects often limit use. Insulin remains the treatment of choice for severe or persistent hyperglycemia despite oral or injectable therapy.

Agent selection should also consider comorbidities: SGLT2 inhibitors are preferred for patients with heart failure, GLP-1 receptor agonists for those with atherosclerotic CVD (ASCVD) or obesity, and kidney-protective agents in cases of reduced graft function. Other drugs such as finerenone, tirzepatide, glucokinase activators, dorzagliatin, imeglimin, amycretin, and pramlintide may improve and change the management of PTDM; however, further studies are required to validate their use in the transplant population. Table 3 summarizes the management of PTDM, including risk factors, drug-related contributions, and the potential benefits of newer therapies.

Table 3 Management of post-transplant diabetes mellitus.

Clinical context	Risk factors	Drug contributions	Newer/preferred therapies
Unstable graft	High steroid dose, fluctuating renal function	Steroids → insulin resistance; CNIs → β-cell toxicity	Insulin for glycemia well above target (rapid titration). DPP-4 inhibitor (linagliptin preferred vs vildagliptin/sitagliptin) for mild hyperglycemia (safe in renal dysfunction). Meglitinides (repaglinide) for postprandial hyperglycemia
Stable graft	Obesity, pre-existing diabetes	CNIs, steroids	SGLT2 inhibitors (CV/renal protection). GLP-1 receptor agonists (weight loss, CV benefit)
Severe hyperglycemia	HbA1c > 9%, fasting glucose > 250	Steroids, CNIs	Insulin therapy (short-term stabilization)
Comorbidities	ASCVD, HF, obesity	Steroids worsen CV risk	GLP-1 receptor agonists for ASCVD/obesity. SGLT2i for HF/renal protection

CNIs: Calcineurin inhibitors; DPP-4: Dipeptidyl peptidase 4; SGLT2: Sodium-glucose cotransporter 2; CV: Cardiovascular; GLP-1: Glucagon-like peptide-1; HbA1c: Glycated hemoglobin; ASCVD: Atherosclerotic cardiovascular disease; HF: Heart failure.

DYSLIPIDEMIA IN KIDNEY TRANSPLANT

Dyslipidemia remains one of the most frequent metabolic complications both before and after KT, even when allograft function is preserved. Its high prevalence underscores its clinical importance, as lipid abnormalities contribute to atherosclerosis, CVD, and graft dysfunction, making routine lipid assessment and management a critical component of post-transplant care. Dyslipidemia is defined by one or more of the following: Elevated plasma total cholesterol (> 200 mg/dL), elevated low-density lipoprotein cholesterol (LDL-C) (> 100 mg/dL), elevated triglycerides (TGs) (> 150 mg/dL), low high-density lipoprotein cholesterol (HDL-C) (< 40 mg/dL in men or < 45 mg/dL in women), or non-high-density lipoprotein cholesterol > 130 mg/dL[65]. These lipid abnormalities contribute to atherosclerosis and increase the risk of CVD, the leading cause of morbidity and mortality in this population[66]. Dyslipidemia can also promote thrombotic disturbances through increased platelet reactivity and is associated with reduced graft function due to excess visceral or subcutaneous adipose tissue. Elevated total cholesterol and TGs may cause podocyte injury and proteinuria in the kidney graft, while hypertriglyceridemia is a recognized cause of severe pancreatitis in transplant recipients[66]. Although a direct causal association between dyslipidemia and cardiovascular risk has not been definitively proven in KTRs, the high incidence of atherosclerotic events in this population has led several national groups to consider KT a coronary heart disease equivalent. Therefore, the assessment and treatment of dyslipidemia should be an integral part of routine post-transplant care.

Prevalence of dyslipidemia

Dyslipidemia is highly prevalent among KTRs, affecting the majority of patients within the first year post-transplantation. Historically, single- and multicenter studies reported that 80%-90% of adult KT recipients develop total cholesterol levels above 200 mg/dL, while 90%-97% show LDL-C levels exceeding 100 mg/dL within one year of transplantation. Mean TGs levels in these cohorts ranged between 160-200 mg/dL[67,68]. More recent data suggest somewhat lower rates, likely reflecting changes in immunosuppressive regimens and the widespread use of statins. For example, a multicenter prospective cohort study of 935 KT recipients found that 45% had LDL-C levels above 100 mg/dL, with mean TGs levels of 142 mg/dL at six months post-transplantation, and 41% of patients were receiving statin therapy[69].

Causes of dyslipidemia

Dyslipidemia in KT recipients is commonly caused by immunosuppressive agents, particularly glucocorticoids, CNIs, and mTOR inhibitors, each exerting dose-related effects on serum lipid levels. Glucocorticoids alter lipoprotein metabolism and raise cholesterol levels through mechanisms such as hyperinsulinemia-induced stimulation of hepatic very-low-density lipoprotein synthesis and downregulation of LDL-C receptors, possibly via adrenocorticotropic hormone suppression[70,71]. While glucocorticoid withdrawal may lower total cholesterol and TGs levels, this benefit is offset by increased risks of acute rejection, graft loss, and recurrent glomerulonephritis, and may also reduce protective HDL-C, leaving the HDL-C to total cholesterol ratio unchanged.

CNIs also contribute, with CsA directly causing post-transplant hypercholesterolemia in a dose-dependent manner, elevating total and LDL-C while reducing HDL-C[72]. TAC, in contrast, is associated with a more favorable lipid profile, and conversion from CsA to TACs has been shown to significantly reduce LDL-C and TG levels in clinical trials[72].

mTOR inhibitors such as sirolimus and everolimus are frequently linked to post-transplant dyslipidemia, particularly hypertriglyceridemia, by blocking insulin-stimulated lipoprotein lipase and reducing the catabolism of apoB100-containing lipoproteins[73]. This effect is dose-dependent and improves when the dose is reduced or drug levels are lowered. Although no studies have directly compared the dyslipidemic effects of sirolimus and everolimus, clinical data show that patients on sirolimus have higher TG, LDL-C, and total cholesterol levels compared to those on CNIs, especially in the early post-transplant period. These differences tend to diminish over time, though many patients still require lipid-lowering therapy.

On the other hand, MMF, mycophenolic acid, AZA, and induction agents such as polyclonal anti-lymphocyte antibodies and monoclonal antibodies (anti-CD25, rituximab) do not alter lipid levels. Belatacept also does not modify lipid levels. Beyond immunosuppressive drugs, other secondary causes of dyslipidemia in this population include nephrotic syndrome, hypothyroidism, diabetes mellitus, excessive alcohol intake, obesity, and chronic liver disease, while genetic predisposition and low physical activity further contribute to abnormal lipid profiles. Table 4 outlines the causes of dyslipidemia in KTRs, highlighting risk factors, drug-related contributions, and the potential benefits of newer therapies.

Table 4 Causes of dyslipidemia in kidney transplant recipients: Risk factors, drug contributions, and potential benefits of newer therapies.

Cause	Risk factors	Drug contributions	Potential benefits of newer therapies
Glucocorticoids	Obesity, diabetes	Cholesterol increase, VLDL increase, LDL receptor activity decrease	Statins, PCSK9 inhibitors for resistant dyslipidemia
CNIs	CsA > TAC	CsA → LDL increase, HDL decrease; TAC → better lipid profile	Switching CsA → TAC improves LDL/TG
mTOR inhibitors	Sirolimus, everolimus	TGs increase, LDL increase, lipoprotein lipase activity decrease	Early statin therapy. Ezetimibe adjunct
Other causes	Diabetes, hypothyroidism, obesity, alcohol	Lifestyle + comorbidities	Lifestyle modification + statins

VLDL: Very-low-density lipoprotein; LDL: Low-density lipoprotein; PCSK9: Proprotein convertase subtilisin-kexin type 9; CNIs: Calcineurin inhibitors; CsA: Cyclosporine; TAC: Tacrolimus; HDL: High-density; TGs: Triglycerides; mTOR: Mammalian target of rapamycin.

Management of dyslipidemia in KTRs

The management of dyslipidemia to reduce cardiovascular risk in KTRs is similar to that in non-transplant patients with CKD, but requires special consideration due to immunosuppressive therapy, drug-drug interactions, and risks of nephrotoxicity.

Management of LDL-C

Statins are the cornerstone of dyslipidemia treatment as they have been shown to lower LDL-C levels and reduce cardiovascular events. Statin therapy not only improves lipid profiles but also reduces the risk of cardiovascular mortality and graft failure[71]. The approach to LDL-C reduction depends on whether patients have established ASCVD or not. For secondary prevention (established ASCVD), KTRs with prior coronary, cerebrovascular, or peripheral arterial disease should receive maximally tolerated statin therapy, as in the general population. For primary prevention (no ASCVD), statins are recommended in adults > 40 years with a 10-year ASCVD risk > 10%. In those aged 30-40 years, statins are generally advised, while treatment in younger patients (18-29 years) should be individualized, weighing modest benefit against the risks of polypharmacy.

Target doses for patients not on CsA include fluvastatin 80 mg, atorvastatin 20 mg, rosuvastatin 10 mg, pravastatin 40 mg, or simvastatin 40 mg daily. CsA users require lower doses due to drug interactions. Careful monitoring is essential given potential adverse effects such as hepatotoxicity and rhabdomyolysis, particularly with statins metabolized via CYP3A4. Hydrophilic statins such as pravastatin and rosuvastatin offer safer profiles due to fewer interactions[70].

Ezetimibe, which inhibits intestinal cholesterol absorption, is recommended for statin-intolerant patients or in combination with statins when target doses are not tolerated. Evidence for proprotein convertase subtilisin-kexin type 9 inhibitors (evolocumab, alirocumab) or bempedoic acid in KTRs remains limited, though they may be considered in select cases such as familial hypercholesterolemia or statin intolerance[73].

No specific LDL-C target is mandated; instead, therapy intensity is assessed by LDL-C reduction (> 50% for high-intensity, 30%-50% for moderate, < 30% for low). Annual lipid monitoring is advised to ensure adherence and therapeutic response. Guidelines from the ACC/AHA, Kidney Disease: Improving Global Outcomes, and the Italian Society of Nephrology endorse statins as the foundation of therapy, despite limited transplant-specific evidence. The Assessment of LEscol in Renal Transplantation trial demonstrated a trend toward ASCVD reduction, though statistical significance was not achieved, reinforcing the need for ongoing vigilance[74]. Despite this, statins remain recommended due to the high cardiovascular risk in KTRs.

Management of hypertriglyceridemia

Hypertriglyceridemia in KTRs is often driven by immunosuppressive agents and requires a cautious, multifaceted approach. Lifestyle interventions are first-line, including dietary modification, weight reduction, increased physical activity, and reduced alcohol intake, ideally under the guidance of a transplant dietitian. A low-fat, high-fiber diet enriched with omega-3 fatty acids can further improve lipid profiles[73]. Medications known to worsen lipid levels should be avoided or replaced when possible.

When pharmacologic therapy is necessary, ezetimibe, omega-3 fatty acids, and niacin may be used, though supporting evidence in transplant recipients is limited. Fibrates (such as gemfibrozil), are generally avoided due to risks of myositis, rhabdomyolysis, nephrotoxicity, and reversible elevations in serum creatinine, which complicate graft function assessment. Adjustments to immunosuppressive regimens may also be considered, such as switching CsA to TACs, discontinuing sirolimus if dyslipidemia develops, and maintaining low-dose prednisone[75].

HTN IN KT

HTN is a key component of metabolic syndrome[76] and one of the most common yet modifiable risk factors for CVD[77]. It is nearly universal, spanning from advanced stages of CKD through the post-transplant period. In KTRs, HTN is defined as persistently elevated blood pressure (BP) or normotension sustained with antihypertensive therapy. Although the definition remains debated and outcome data are limited, the 2017 American College of Cardiology/AHA guidelines and emerging evidence suggest that a threshold of ≥ 130/80 mmHg may be appropriate in this population[78,79].

Epidemiology of post-transplant HTN

The reported prevalence of post-transplant HTN varies widely, ranging from 24% to 90%, depending largely on the criteria used and the methods of BP assessment[80]. Overall, rates have shown an upward trend over time, which may be linked to the introduction of CsA[81]. Consequently, patients transplanted in later years required a greater number of antihypertensive agents compared to those transplanted earlier.

Pathogenesis

HTN in KTRs results from a complex interplay of traditional cardiovascular risk factors, CKD-related mechanisms, and transplant-specific influences. In ESKD, factors such as volume overload, activation of the renin-angiotensin-aldosterone system, increased sympathetic nervous activity, arterial stiffness, endothelial dysfunction, obstructive sleep apnea (OSA), and the use of erythropoiesis-stimulating agents play a major role[82].

After transplantation, both residual non-immunological factors from the ESKD stage and immunological influences associated with immunosuppressive therapy contribute to post-transplant HTN. The prevalence and causes of HTN vary across different post-transplant phases: (1) In the immediate period, peri-transplant hypervolemia, induction immunosuppressive therapy, rebound HTN, and inadequate pain control are key contributors[83]; (2) In the early period, weight gain, CNIs, glucocorticoids, hypertensive donor kidneys, and transplant renal artery stenosis (TRAS) are predominant; and (3) In the late period, chronic allograft dysfunction, elevated fibroblast growth factor (FGF23) levels, OSA, residual native kidney function, and persistent sympathetic overactivity are major causes.

Among immunosuppressive agents, glucocorticoids elevate BP mainly through fluid retention and renin-angiotensin-aldosterone system activation, while CNIs such as CsA and TAC increase BP via sodium retention and vasoconstriction, with TAC generally exerting milder effects than CsA. In contrast, purine synthesis inhibitors (MMF, AZA) and mTOR inhibitors (everolimus, sirolimus) typically do not affect BP regulation. TRAS is a reversible cause of post-transplant HTN, occurring in 1%-23% of cases, most often at the arterial anastomosis site. It usually presents between 3 months and 2 years after transplantation with worsening HTN, hypokalemia, and declining kidney function, particularly when treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Early recognition and timely intervention are crucial to improving patient outcomes[84].

Management strategies

Lifestyle modifications, including dietary changes, regular physical activity, and stress reduction, should always be incorporated into the management of HTN in KTRs. However, because most patients have pre-transplant HTN requiring ongoing medication (persistent HTN), and only a minority achieve normotension without therapy (recovered HTN), pharmacological treatment remains the primary approach to BP control in this group.

The role of ACE inhibitors and ARBs is somewhat controversial. A recent meta-analysis demonstrated a 38% reduction in graft loss risk with these agents, but no significant impact on nonfatal cardiovascular outcomes or overall mortality, while noting an increased risk of hyperkalemia. In contrast, dihydropyridine calcium channel blockers have consistently shown favorable effects, including improved graft survival and attenuation of CNIs-induced vasoconstriction. The same meta-analysis reported that calcium channel blockers reduced graft loss risk by 42% and increased eGFR by 11.11 mL/minute compared to ACE inhibitors/ARBs, supporting their use as a preferred option in the early post-transplant period. Thiazide and thiazide-like diuretics are also beneficial, particularly in addressing CsA-related sodium retention.

For resistant HTN, targeted interventions should be considered, such as angioplasty with or without stenting for TRAS and treatment of OSA. Renal sympathetic denervation of native kidneys, either through bilateral nephrectomy or catheter-based ablation, may also be effective in select cases[84,85]. At present, there is no definitive evidence regarding the long-term impact of antihypertensive medications on graft survival.

HYPERURICEMIA IN KIDNEY TRANSPLANT

Hyperuricemia is a frequent complication after KT. It is a metabolic disorder characterized by excessive uric acid (UA) production or reduced excretion due to abnormal purine metabolism, as well as elevated blood UA levels resulting from excessive intake of exogenous purines. Reduced UA excretion after KT may also lead to gout in some patients[86]. Serum UA levels exceeding 7.0 mg/dL in men and 6.0 mg/dL in women are considered hyperuricemia[87].

The incidence of hyperuricemia in KTRs is significantly higher than in the general population, affecting approximately 40%-60% of recipients, and rising to as high as 80% with CsA use. Moreover, a study involving 9589 participants suggested that incorporating UA into the definition of metabolic syndrome is crucial when assessing mortality risk in KTRs[88]. Risk factors for post-transplant hyperuricemia include older age, male gender, CNIs therapy (particularly CsA), diuretics, hypercalcemia, reduced eGFR, long-term pre-transplant dialysis, and pre-existing hyperuricemia[86].

Although the pathophysiological mechanisms of kidney damage caused by hyperuricemia are not yet fully understood, current research suggests the involvement of oxidative stress, endothelial dysfunction, renal fibrosis, and inflammation caused by sodium urate crystal deposition[89]. The extracellular matrix plays a pivotal role in the progression of interstitial fibrosis in the kidney, while epithelial-mesenchymal transition promotes extracellular matrix production[90].

Elevated UA levels are associated with progressive decline in graft function, increased graft loss, reduced survival, and higher risks of CVD and mortality[91]. These complications not only impair quality of life but also impose a substantial economic burden on KTRs, particularly in the presence of comorbidities such as impaired kidney function, HTN, diabetes, and CVD.

Gout may develop de novo after transplantation or recur in patients with a prior history of gout. In most transplant recipients, the clinical features of gout are similar to those in non-transplant patients but may be more severe[92]. In KTRs presenting with new-onset symptoms suggestive of a first gout flare, arthrocentesis with synovial fluid analysis and culture should be performed to confirm monosodium urate crystals and exclude septic arthritis. In KTRs with a documented history of gout flares who develop recurrent acute joint inflammation, treatment is often initiated without arthrocentesis if the presentation is typical and there are no signs of infection such as fever or chills[93].

Treatment of gout flares

In transplant patients with new-onset gout and no evidence of infection, management depends on the extent of joint involvement. For one or two inflamed joints, arthrocentesis with aspiration followed by intra-articular glucocorticoid injection is preferred. If multiple joints are affected or intra-articular therapy is not feasible, oral glucocorticoids are recommended, with low-dose colchicine or nonsteroidal anti-inflammatory drugs such as naproxen or indomethacin as alternatives when glucocorticoids are contraindicated[94,95]. Colchicine should be avoided in KTRs receiving CsA or other strong CYP3A4/P-glycoprotein inhibitors, those with severe kidney impairment (eGFR < 30 mL/minute/1.73 m²), moderate to severe hepatic impairment, or any degree of combined kidney and liver dysfunction. For patients unable to take oral medications, parenteral glucocorticoids or off-label use of the interleukin-1 beta inhibitor anakinra may be considered[96]. In patients with a prior history of gout, flare management is similar, but past treatment responses and flare frequency guide therapy choice. Urate-lowering medications should be continued during flares.

Prevention and long-term management

Prevention involves initiating urate-lowering therapy in patients with recurrent flares, tophi, or radiologic evidence of joint damage, with the goal of maintaining serum urate < 6 mg/dL. Therapy should begin at a low dose and be continued indefinitely. Allopurinol, a xanthine oxidase inhibitor (XOI), is first-line therapy, with human leukocyte antigen-B*58: 01 testing recommended in high-risk ethnic groups[97]. Dosing should be adjusted according to eGFR[95]. Severe anemia, though uncommon, can result from AZA-related myelosuppression, primarily due to its interaction with allopurinol, which inhibits the xanthine oxidase pathway of AZA metabolism[98]. To reduce toxicity, a lower AZA dose with weekly blood count monitoring during the first month is recommended when combined with allopurinol[98]. Febuxostat, a novel nonpurine-selective XOI, is an alternative for patients intolerant to allopurinol, provided they are not receiving AZA and have no high cardiovascular risk[99]. It is metabolized mainly through hepatic glucuronidation and oxidation, effectively inhibiting both oxidized and reduced xanthine oxidase at low concentrations, with no dose adjustment needed in mild to moderate kidney impairment. While caution is advised in severe kidney dysfunction (glomerular filtration rate < 30 mL/minute), its metabolic profile offers advantages over allopurinol[99]. Combination therapy with an XOI and a uricosuric agent (benzbromarone or probenecid) may be used if urate targets are not achieved. Uricosuric monotherapy is reserved for patients intolerant to XOIs and with adequate kidney function[95]. Prophylaxis during urate-lowering initiation typically involves oral colchicine; if not tolerated, low-dose glucocorticoids may be used, while nonsteroidal anti-inflammatory drugs are avoided in transplant recipients.

PERSISTENT HPT AFTER KT

Persistent HPT after KT occurs when parathyroid hormone (PTH) levels remain elevated despite the restoration of kidney function, leading to ongoing calcium and phosphate imbalances. This condition is a common complication in transplant recipients and can negatively impact bone health, cardiovascular risk, and graft survival. KTRs are therefore particularly vulnerable to persistent HPT.

Pathophysiology of HPT

Most patients with CKD develop secondary HPT by the time they require kidney replacement therapies, as reduced glomerular filtration rate leads to disturbances in mineral metabolism, persistent stimulation of PTH secretion, and parathyroid gland hyperplasia[100]. In mild cases, this condition often resolves after KT when kidney function improves. However, persistent HPT is observed in 8%-50% of transplant recipients because structural changes such as hyperplasia and adenoma formation remain despite removal of the original stimulus[101].

In transplant patients, the clinical picture resembles primary HPT, with hypercalcemia and hypophosphatemia due to PTH effects on the kidney, whereas non-transplant CKD patients typically present with hypocalcemia and hyperphosphatemia. Some patients may show only elevated PTH without other abnormalities[102]. Additional contributors to hypercalcemia in transplant recipients include increased calcitriol production, mobilization of calcium from soft-tissue deposits, and mild rises in albumin-bound calcium, while glucocorticoid therapy may mask hypercalcemia until doses are tapered[101].

Hypophosphatemia after transplantation results from both persistent HPT and excess FGF-23 secretion, which is elevated in CKD due to reduced phosphate clearance and may remain high initially after transplantation. Early post-transplant phosphate wasting reflects both PTH and FGF-23 excess, leading to high urinary concentrations of calcium and phosphate, which may cause calcium-phosphate deposition and acute tubular necrosis[101]. Beyond one year, persistent HPT becomes the predominant cause[103]. Other factors, such as mTOR inhibitors and high-dose glucocorticoids, may also contribute to hypophosphatemia, though evidence remains variable[104].

Clinical manifestations and kidney transplant survival

Unlike non-transplant CKD patients, symptoms such as bone pain, pruritus, nephrolithiasis, and myopathy are less common but may occur if HPT is severe and persistent. Symptomatic hypercalcemia most often arises in the early post-transplant period, usually within the first three months[105]. In one study of 1165 transplant recipients, the prevalence of hypercalcemia from any cause was 31% during the first year after transplantation and 12% at five years post-transplant[106]. Severe hypercalcemia can lead to graft vasoconstriction, volume contraction, acute kidney injury, or, rarely, calciphylaxis[107].

Hypophosphatemia is reported in 40%-90% of patients soon after transplantation, typically improving over time but persisting in some cases. One study found hypophosphatemia in 40% of patients during the first year and 11% during years 4 and 5[106]. Severe hypophosphatemia may cause muscle weakness and, occasionally, osteomalacia. Pre-transplant serum total alkaline phosphatase levels have also been associated with an increased risk of unfavorable outcomes after KT[108].

Evidence on the impact of persistent HPT on long-term graft and patient survival is limited and conflicting. The mechanisms remain unclear but may involve vasoconstriction and tubulointerstitial calcification[109,110]. Studies on pre-transplant PTH levels also show mixed results: Some link high levels to increased graft failure[109-111], while large retrospective analyses (> 10000 KTRs) found no association with death or graft loss[112]. Uncontrolled HPT also raises the risk of post-transplant bone disease and fractures. In a study of 143 KTRs, a PTH level > 130 pg/mL at three months post-transplant was associated with a 7.5-fold increased fracture risk over five years (hazard ratio: 7.5)[113].

Prevention and long-term management

Optimal management of HPT before KT may reduce the risk of persistent HPT afterward. In ESKD, cinacalcet and etelcalcetide are widely used for refractory HPT, but their use in transplant candidates varies. Some centers avoid calcimimetics unless parathyroidectomy is contraindicated, as discontinuation of cinacalcet at transplantation can cause rebound hypercalcemia and hypophosphatemia. Others routinely use calcimimetics, reserving parathyroidectomy for refractory or intolerant cases[114-116]. Clear guidelines on parathyroidectomy in dialysis patients with severe HPT are lacking, with no consensus on optimal PTH targets or timing[117].

After KT, routine monitoring of calcium, phosphorus, and PTH is essential, as persistent HPT requires tailored management based on clinical presentation. Mild to moderate hypercalcemia is typically treated with cinacalcet, with surgery reserved for patients who fail to respond. Prospective studies have shown that cinacalcet effectively lowers PTH and calcium without short-term harm to allograft function[118,119], though retrospective data suggest parathyroidectomy is associated with lower allograft failure rates compared with cinacalcet (9% vs 33%)[120]. Cinacalcet may also reduce blood TAC concentrations, while CsA and mycophenolate pharmacokinetics remain unaffected[121]. Severe or prolonged hypercalcemia generally warrants parathyroidectomy, with evidence from a randomized trial showing higher rates of normocalcemia at 12 months compared with cinacalcet (100% vs 67%)[119].

Hypophosphatemia management depends on severity, PTH level, and calcium status: Mild to moderate cases are addressed by treating HPT and increasing dietary phosphate intake, while severe cases require oral phosphate supplementation and, if not hypercalcemic, vitamin D derivatives. In patients with elevated PTH but normal calcium, vitamin D deficiency is corrected with cholecalciferol, and activated vitamin D derivatives are used if PTH remains high. Parathyroidectomy or cinacalcet is not indicated in isolated PTH elevation without hypercalcemia. This stepwise approach balances medical therapy with surgical intervention to optimize graft survival and patient outcomes[122]. Table 5 summarizes the management of HPT in KT, including strategies for prevention, monitoring, and treatment.

Table 5 Hyperparathyroidism in kidney transplantation: Prevention, monitoring and treatment.

Stage/condition	Risk factors	Drug contributions	Potential benefits of newer therapies
Pre-transplant	Long dialysis vintage, severe CKD-MBD	Steroids worsen bone loss	Calcimimetics (cinacalcet, etelcalcetide) as bridge to transplant
Post-transplant monitoring	Vitamin D deficiency, persistent hyperparathyroidism	Steroids, loop diuretics	Vitamin D analogs. Cholecalciferol supplementation
Persistent hyperparathyroidism	High PTH, hypercalcemia, hypophosphatemia	Steroids, immunosuppressants	Cinacalcet (medical therapy). Parathyroidectomy (definitive)
Late complications	Chronic graft dysfunction, bone disease	Steroids, CNIs	Denosumab. Bisphosphonates (bone protection)

CKD-MBD: Chronic kidney disease-mineral and bone disorder; PTH: Parathyroid hormone; CNIs: Calcineurin inhibitors.

OBESITY IN KT

Obesity is a major challenge for patients with ESKD, both before and after KT. For candidates awaiting transplantation, obesity is a well-documented barrier to waitlisting and surgical eligibility[123]. The prevalence of obesity in the ESKD population and among transplant candidates continues to rise. Current estimates suggest that 39%-46% of patients on the waitlist are obese[124]. Post-transplant, weight gain is common: Nearly one-third of recipients gain at least 10% of their body weight in the first year, driven by factors such as maintenance immunosuppression, liberalized dietary restrictions, increased appetite, and reduced physical activity[125]. On average, patients gain 4.5 kg within the first year, with over 70% experiencing some degree of weight increase. This trend mirrors the global obesity epidemic, which has tripled in prevalence across many countries in the World Health Organization European Region since the 1980s[126]. Between 1990 and 2017, the proportion of KTRs classified as obese (BMI ≥ 30 kg/m²) at the time of transplantation more than tripled, rising from 10.5% to 32.8%[124]. Such increases have significant implications for transplant program practices, as obesity is now recognized as one of the greatest global health threats of the 21^st century. In the context of ESKD and transplantation, obesity adds layers of complexity. It is frequently associated with metabolic disorders such as HTN, insulin resistance, dyslipidemia, atherosclerosis, and cardiovascular or cerebrovascular complications.

Determinant of transplant candidacy

Obesity poses substantial challenges in KT evaluation, as lower referral and wait-listing rates reduce access to transplantation. In some centers, a BMI greater than 35 kg/m² is considered a contraindication, raising ethical concerns about equitable access for obese patients[123,127]. In patients with ESKD undergoing maintenance hemodialysis, Park et al[128] first described the “obesity paradox”, in which higher BMI was incrementally associated with improved survival. This phenomenon, often termed “reverse epidemiology”, has been consistently observed in maintenance hemodialysis but remains less clear in peritoneal dialysis populations. The paradox has fueled skepticism among transplant clinicians, given the well-documented risks in obese recipients, including CVD, wound complications, and impaired healing. Nevertheless, recent evidence demonstrates that transplantation confers a clear survival advantage over dialysis in most obese individuals, thereby challenging BMI-based exclusion practices[129].

Post-transplant outcomes and complications

Obesity significantly influences post-transplant outcomes, contributing to both short- and long-term complications in KTRs. Elevated BMI is associated with higher risks of delayed graft function, reoperations, wound infections, hernia, impaired healing, surgical complications such as lymphocele formation, and increased resource utilization[130]. Gill et al[131] reported that the obesity paradox does not extend to the post-transplant setting, with obese recipients deriving lower survival benefits compared to non-obese counterparts, whereas Krishnan et al[132] found that although obese patients had reduced post-transplant survival relative to non-obese recipients, they still achieved significantly better 1- and 5-year survival rates across all BMI categories compared with patients remaining on dialysis. While the overall survival benefits of KT remain controversial, recent evidence suggests that obese KTRs may have comparable long-term outcomes to non-obese recipients[123,124].

In the long term, obesity is associated with an increased incidence of CVD, accounting for approximately 17% of deaths in KTRs[129], and although specific research on CKM syndrome in the context of obesity and transplantation is limited, several studies highlight the interplay between obesity, cardiovascular risk, and metabolic complications post-transplant[6]. Post-transplant weight gain, particularly in visceral fat, is linked to insulin resistance and new-onset diabetes after transplantation[125], while obesity also predisposes patients to metabolic syndrome, which exacerbates chronic allograft dysfunction and accelerates graft loss. Therefore, managing obesity in transplant recipients requires a comprehensive, multidisciplinary approach, one that maximizes the life-saving benefits of transplantation while minimizing the vulnerabilities introduced by excess weight.

Management strategies

The management of obesity in KT requires a comprehensive and multidisciplinary approach aimed at optimizing transplant candidacy, reducing perioperative risks, and improving long-term outcomes. Lifestyle modification remains the cornerstone, with nutritional counseling, structured physical activity, and behavioral support playing critical roles in achieving sustainable weight loss. Pre-transplant weight reduction strategies may improve short-term outcomes, although their impact on long-term results remains debated[133]. Recent research has highlighted the potential of pharmacological interventions in managing obesity and CKM syndrome in KTRs. SGLT2 inhibitors show promise in improving diabetes control, reducing obesity, and preserving kidney function, though they may increase the risk of urinary tract infections. GLP-1 receptor agonists contribute to weight loss and glycemic control, with potential graft-protective effects, and their combination with SGLT2 inhibitors is being explored for CKM syndrome management in kidney recipients[134,135]. Careful monitoring is essential, however, due to possible interactions with immunosuppressive therapy. In patients with severe obesity who fail conservative measures, bariatric surgery, particularly sleeve gastrectomy, has emerged as a viable option either before transplantation to improve candidacy or after transplantation to mitigate complications, with evidence suggesting improved access and favorable long-term outcomes despite perioperative risks. Post-transplant close monitoring for weight gain is critical, especially during the first year[136], as visceral fat accumulation is strongly associated with insulin resistance, new-onset diabetes, and metabolic syndrome, all of which contribute to chronic allograft dysfunction and graft loss. Therefore, individualized assessment, careful perioperative management, and targeted interventions such as weight optimization and lifestyle modification are necessary to maximize the life-saving benefits of transplantation while minimizing the vulnerabilities introduced by excess weight.

CONCLUSION

Metabolic disturbances continue to pose a significant challenge in KTRs, exerting a profound impact on graft durability and long-term patient prognosis. Conditions such as post-transplant diabetes, dyslipidemia, HTN, hyperuricemia, secondary hyperparathyroidism, and obesity emerge from the convergence of underlying predispositions and the metabolic consequences of immunosuppressive therapy. Proactive surveillance, individualized adjustment of immunosuppressive regimens, and coordinated multidisciplinary care are pivotal to reducing complications, safeguarding graft function, and improving overall survival outcomes.