The Thai Transplantation Society developed these clinical practice guidelines to establish a comprehensive standard for immunosuppressive therapy in adult kidney transplantation. While rooted in evidence-based medicine, the objective of this document extends beyond local application, serving as a practical model for low-to-middle-income countries, particularly within the Asia-Pacific and Southeast Asian regions, where specific genetic profiles and resource limitations require tailored management strategies. This publication addresses a critical need in the field, as there has been no updated comprehensive international consensus on immunosuppression since the KDIGO Clinical Practice Guideline in 2009, over 17 years ago. These guidelines bridge this gap by synthesizing modern clinical data with practical applicability. The scope of the guidelines is extensive, covering all aspects of immunosuppression usage including induction, maintenance, therapeutic drug monitoring, and the treatment of rejection. Uniquely, this document addresses specific challenges relevant to resource-limited settings, offering protocols for cost reduction through the use of generic drugs and the co-administration of cytochrome P450 3A4 and 3A5 inhibitors to minimize dosage requirements. Furthermore, it provides distinct guidance for immunosuppression in special clinical settings, including management during periods of fasting, pregnancy, and malignancy. This guideline ultimately benefits clinicians by offering a pragmatic, updated reference that balances therapeutic efficacy with economic sustainability.

Gluconeogenesis, nitrogen metabolism and acid-base regulation are fundamental for the maintenance of metabolic homeostasis. These three processes form an interconnected triangle, with liver-kidney crosstalk and the hormone glucagon at its core. Both kidney and liver perform gluconeogenesis, and they function in co-ordination to regulate the formation and excretion of the organic osmolyte urea and the acid equivalent ammonium, and to determine the usage and de novo generation of bicarbonate. Within the liver, glucagon promotes fasting-induced gluconeogenesis and the bicarbonate-consuming formation of urea from amino acid-derived ammonia in response to protein intake and catabolic states. Within the kidney, glucagon facilitates the excretion of urea. In metabolic acidosis, the liver shifts nitrogen metabolism from ureagenesis to glutamine formation for kidney ammoniagenesis. Liver and kidney disease interfere with whole-body homeostasis of glucose, nitrogen and acid-base by promoting hypo- or hyperglycaemia, ammonia and urea toxicity, and metabolic alkalosis or acidosis. Inhibitors of the sodium glucose cotransporter SGLT2 not only cause glucosuria and compensatory hepatic gluconeogenesis but also interfere with kidney bicarbonate reabsorption, leading to compensatory kidney ammoniagenesis, bicarbonate formation and gluconeogenesis, which mitigates lactate accumulation and is associated with improved kidney health. Glucagon receptor agonists, in combination with GLP1 receptor agonists, also hold therapeutic promise in obesity and fatty liver and potentially kidney disease, but a better understanding of their effects is needed in the pathophysiological setting.

The concept of cardiovascular-kidney-metabolic (CKM) syndrome integrates cardiovascular, kidney and metabolic disorders into a single pathophysiological continuum characterized by chronic inflammation, oxidative stress, fibrosis and progressive organ dysfunction. A central driver of CKM syndrome progression is inappropriate activation of the aldosterone-mineralocorticoid receptor (MR) pathway, which promotes adverse remodelling of the heart, kidney, vasculature, adipose tissue, liver and pancreas. Steroidal MR antagonists (MRAs) and non-steroidal MRAs mitigate maladaptive MR signalling and improve cardiorenal outcomes. Compared with steroidal MRAs, non-steroidal MRAs such as finerenone provide enhanced tissue selectivity and favourable safety profiles. Finerenone has been shown to reduce cardiovascular and renal events in patients with chronic kidney disease (CKD) and in patients with heart failure. Aldosterone synthase inhibitors represent a complementary approach that suppresses aldosterone production upstream of MR activation and has shown promising results in resistant hypertension and CKD. Preclinical and clinical data indicate that combined strategies targeting the aldosterone-MR axis can attenuate cardiorenal remodelling, insulin resistance and organ injury, offering a comprehensive therapeutic approach. Ongoing trials will clarify the efficacy of these combined therapies in non-diabetic CKD, resistant hypertension and broader CKM syndrome populations. Overall, targeting the aldosterone-MR pathway represents a central strategy to reduce organ dysfunction, improve metabolic homeostasis and limit progression of CKM syndrome.

Frailty is highly prevalent in patients with chronic kidney disease (CKD) and is associated with increased mortality, hospitalization and disability and with poorer quality of life. Despite its prognostic importance, substantial knowledge gaps remain with regard to the optimal tools for assessing frailty in CKD settings, the extent to which frailty can be reversed through targeted interventions, and how frailty should inform decision-making between conservative kidney management and kidney replacement therapy (KRT). This consensus report provides 63 consensus statements across four domains covering the assessment of frailty, interventions aimed at targeting the modifiable contributors to frailty in patients with CKD, considerations related to conservative kidney management and KRT, and the management of stage 5 CKD in the presence of frailty. Key recommendations include the need for routine frailty screening using multi-dimensional tools; the implementation of interventions to target physical activity with a focus on resistance training, adequate dietary protein intake, medication optimization and comprehensive geriatric assessment; a frailty-informed, person-centred framework for shared decision-making that emphasizes transparent communication, goal elicitation and cultural safety; and flexible KRT delivery - including less intensive dialysis schedules, assisted home dialysis and transplant eligibility assessment - guided by serial frailty measurement. The report concludes with priority research questions and a patient partner's reflections on the co-production of consensus statements.

Cardiovascular-kidney-metabolic (CKM) syndrome is a multisystem disorder in which obesity, diabetes, chronic kidney disease, and cardiovascular disease reinforce one another through shared pathobiological characteristics and bidirectional organ crosstalk. Rather than representing the mere coexistence of diseases, CKM syndrome can be understood as a mitochondrial systems disorder. In energy-intensive tissues such as the myocardium and renal tubules, chronic haemodynamic stress, substrate excess, hypoxia and neurohormonal activation converge on mitochondrial programmes governing oxidative phosphorylation, redox balance, organelle dynamics and quality control. Disruption of these programmes, including impaired fatty acid oxidation, suppressed biogenesis, defective mitophagy and mitochondrial DNA instability, reduces bioenergetic reserve and promotes reactive oxygen species generation, inflammatory signalling and progressive organ dysfunction. Mitochondrial dysfunction in other metabolic tissues further amplifies these processes. In the liver, reduced fatty acid oxidation promotes steatosis, insulin resistance and the release of lipids, whereas in skeletal muscle and adipose tissue, impaired oxidative capacity and insulin resistance increases lipid spillover and systemic inflammation. Mitochondria-derived signals - including FGF21, GDF15, succinate and circulating mitochondrial DNA - enable bidirectional communication between organs, reinforcing multi-organ decline in a positive-feedback loop. Advancing our understanding of mitochondrial dysfunction and inter-organ communication may provide new mechanistic insights into CKM syndrome progression and inform the development of mitochondria-targeted therapeutic strategies.