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

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.

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.

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.

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.

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.