Hyperkalemia is a common complication of kidney disease and incidence increases as kidney function declines. Renin-angiotensin system blockade, which improves renal and cardiovascular outcomes, increases the risk of hyperkalemia. Unfortunately, hyperkalemia often leads to discontinuation of these medications, which can increase adverse outcomes. Treatment of chronic hyperkalemia includes diet and pharmacologic interventions. However, the association of dietary potassium intake with serum potassium levels is weak and does not consider important internal and external balance factors that affect serum levels. Traditional dietary interventions that limit dietary potassium lead to a restrictive diet that limits fruits and vegetables, whole-grains, and plant-based proteins. This restrictive approach may unnecessarily limit dietary quality and variety in a population already at risk for poor nutritional status and complications of chronic kidney disease (CKD). The management of hyperkalemia requires a comprehensive, individualized approach that moves beyond blanket dietary restriction. The objective of this review is to describe the role of diet and pharmacological approaches to manage hyperkalemia, highlighting newer dietary approaches.

Protein is a unique, essential component of our diet. There is currently great emphasis on high protein diets, not only in the commercial food market and social media, but also in the scientific literature, with a continuous debate on the need of changing current protein recommendations, in particular in older adults. Here we provide an updated perspective on the debate on high protein intakes for maintaining muscle mass and function, with focus on people who are affected by kidney diseases. Several conditions such as aging, inactivity, and many chronic conditions including dialysis-treated chronic kidney disease are characterized by anabolic resistance, i.e. the need of ingesting higher amounts of protein to maximally stimulate muscle protein synthesis. In addition, sedentarianism and inactivity, conditions very common in developed countries, contribute to decreased muscle mass and strenght. Protein intake and physical activity as the major anabolic stimuli for muscle health and function. However, protein ingestion is associated with oxidation of excess amino acids, ureagenesis, and production of toxins. In addition, protein supplementation in the absence of resistance training produces relatively marginal effects on strength and performance in healthy subjects and older adults. On these grounds, for persons who are inactive, muscle mass and function can be better maintained by physical exercise without the use of high protein diets.

Hypophosphatemia is a frequent complication of chimeric antigen receptor T-cell therapy. In this setting, hypophosphatemia has been previously associated with cytokine release syndrome. The mechanisms underlying this electrolyte derangement are not fully understood. Extracellular phosphate consumption by chimeric antigen receptor T-cells was demonstrated in vitro, but inflammation is also thought to play a contributing role. We present a case of severe, refractory hypophosphatemia with renal phosphate wasting triggered by hemophagocytic lymphohistiocytosis in acute lymphoblastic leukemia. The diagnosis of phosphate wasting was made at the onset of leukemia and a clinical exacerbation occurred after chimeric antigen receptor T-cell therapy. Diagnostic workup revealed very high FGF23 levels in the absence of recognized, acquired or genetic causes of impaired FGF23 cleavage. This case suggests that inflammation associated with hemophagocytic lymphohistiocytosis may induce FGF23 as a potential mechanism for hypophosphatemia. In this context, we recommend evaluation of renal phosphate wasting and subsequently FGF23 in patients with persistent hypophosphatemia despite standard supplementation.

Kidney disease affects approximately half of patients with multiple myeloma (MM), and kidney failure is associated with poor prognosis. Kidney transplantation is rarely pursued in MM due to concerns of relapse, infection, and allograft rejection. However, advances in therapy, including B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy, have led to deep and durable hematologic responses, creating new opportunities for transplantation in select patients. We report a 71-year-old man with stage III MM and high-risk cytogenetics [del(17p)] who developed end-stage kidney disease requiring hemodialysis during his treatment course. Despite multiple lines of therapy, he had never achieved a deep remission until he received ciltacabtagene autoleucel (cilta-cel) CAR T-cell therapy, which led to minimal residual disease (MRD)-negative disease status. One year following CAR T-cell therapy, he underwent living donor kidney transplantation with basiliximab induction, and tacrolimus/mycophenolate maintenance immunosuppression. His course was complicated by hypogammaglobulinemia, cytopenia, BK viremia, and acute rejection, all managed with immunosuppression adjustment and supportive therapies. At 17 months post-transplant, allograft function remains stable (creatinine 1.8 mg/dL), and he has achieved an MRD-negative, complete hematologic remission. This case highlights both the feasibility and the challenges of kidney transplantation after CAR T-cell therapy in MM.

The current dialysis care model is largely disease-focused, designed to preserve longevity and minimize sequelae of end-stage kidney disease (ESKD), often with a goal of transplantation. As many patients living with ESKD experience high rates of comorbidity, frailty, and mortality, these goals may not be realistic nor align with their priorities and preferences. Instead, these patients benefit from a person-centered approach to care which emphasizes quality of life; minimizes disease and treatment-associated burdens; and promotes timely transitions to end of life care. Palliative dialysis aims to align dialysis treatment with patients' goals and preferences to optimize quality of life and adapt to patients' evolving individual needs throughout the disease course including at end of life. This narrative review describes person-centered care throughout the dialysis care continuum using palliative dialysis. We describe innovative end of life care models such as concurrent hospice and dialysis care. We then outline necessary steps for implementation of person-centered dialysis care at a system and policy level.

Whilst observational evidence suggests that metabolic acidosis in chronic kidney disease (CKD) is a driver of CKD progression, there remains significant debate regarding the quantity and quality of published evidence to support treatment. The Kidney Disease: Improving Global Outcomes (KDIGO) guidance on metabolic acidosis in CKD highlighted this controversy by publishing practice points, not recommendations, based primarily on placebo-controlled randomized controlled trials. These practice points suggest considering treatment to prevent metabolic acidosis with a proposed cut-off for serum bicarbonate < 18 mmol/L. However, this approach means a substantial number of individuals with CKD may now remain untreated for their metabolic acidosis which may impact CKD progression and associated adverse health outcomes. Additionally, the guidance does not include all the available evidence. From our critical appraisal we suggest that the evidence cited could have been interpreted differently. We recommend that the practice points published are revised based upon critical appraisal of the cited evidence to inform the clinical management of individuals with metabolic acidosis in CKD. We also suggest a research agenda for future studies to help resolve this issue.

Ketoacidosis is a metabolic state characterized by overproduction and accumulation of ketone bodies (ketoacids), leading to potentially life-threatening drops in blood pH. Common to these disorders is a reduction in the insulin-glucagon ratio signaling a lack of available cellular fuel. This change promotes lipolysis and subsequent hepatic β-oxidation of fatty acids, yielding acetyl-CoA that is converted into ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone). Additionally, increased levels of other counterregulatory hormones (eg, catecholamines, cortisol, and growth hormone) often play a key role in exacerbating ketogenesis and the catabolic state. This core curriculum explores the physiological and pathological spectrum of ketoacidosis, beginning with the benign state of starvation ketosis. Diabetic ketoacidosis is a severe complication of diabetes mellitus resulting from profound absolute or relative insulin deficiency and counterregulatory hormone excess. Other forms discussed include pregnancy-associated ketoacidosis (often triggered by starvation or illness), alcoholic ketoacidosis (resulting from the metabolism of alcohol in association with reduced food intake), ketoacidosis associated with chronic salicylate poisoning, sodium/glucose cotransporter 2 inhibitor-induced ketoacidosis, and development of euglycemic ketoacidosis in patients undergoing continuous kidney replacement therapy. Understanding the distinct pathophysiology of each condition is crucial for accurate diagnosis and timely, targeted therapeutic intervention.

Mitochondrial alterations are increasingly recognized as central to the pathogenesis of chronic kidney disease (CKD), contributing to impaired energy metabolism, oxidative stress, and maladaptive cellular responses. This review highlights recent advances in our understanding of mitochondrial remodeling in both diabetic and non-diabetic CKD (NDKD), including changes in bioenergetics, dynamics, redox balance, and biogenesis. We discuss state-of-the-art approaches to assess mitochondrial health, ranging from high-resolution respirometry and metabolomic profiling to transcriptomic analysis and advanced imaging techniques such as functional magnetic resonance imaging (MRI) and positron emission tomography (PET) radiotracers with metabolic readouts. Therapeutically, several agents show promise in modulating mitochondrial pathways, including sodium glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and non-steroidal mineralocorticoid receptor antagonists (nsMRAs), as well as emerging interventions such as glucose-dependent insulinotropic polypeptide and glucagon receptor agonist, nicotinamide adenine dinucleotide (NAD[+]) boosters, and coenzyme Q10 (CoQ10) derivatives. Multi-omics integration and spatial profiling are enabling precision phenotyping and the development of mitochondrial health scores to guide individualized therapy. Targeting mitochondrial adaptation offers a compelling avenue to improve outcomes in CKD.