In chronic kidney disease (CKD), intestinal phosphate absorption stays largely constant even as the kidneys lose the ability to excrete phosphate, creating a tendency toward positive phosphate balance. Rising fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) keep serum phosphate near normal until advanced CKD, but these same adaptations can cause systemic harm long before overt hyperphosphatemia develops. Ultra-processed foods worsen this burden through phosphate additives (Pi-additives) used as preservatives, emulsifiers, stabilizers, leavening agents, and moisture retainers. These additives are absorbed more readily than natural food phosphate and are poorly captured by nutrient databases. Therefore, true phosphorus exposure is easily underestimated. This perspective outlines 2 pathways of harm. The direct pathway involves PTH and FGF23 activation, vascular and soft-tissue calcification, endothelial dysfunction, disordered bone remodeling, faster CKD progression, and cellular senescence-effects documented in CKD and possibly relevant even with preserved kidney function. The indirect pathway reflects that Pi-additives rarely occur alone: they accompany added sugars, non-nutritive sweeteners, nitrites, emulsifiers, and preservatives in ultra-processed foods, combinations that may drive gut dysbiosis, intestinal barrier dysfunction, oxidative stress, inflammation, and the formation of advanced glycation endproducts and other gut-derived toxins. We synthesize current understanding of phosphate homeostasis with mechanistic and epidemiologic evidence linking Pi-additives-alone and combined with other additives-to cardiovascular, skeletal, renal, and metabolic disease. Future research should move beyond single-additive safety testing toward evaluating additive mixtures, cumulative exposure, and food-matrix interactions. Better exposure assessment and transparent phosphorus labeling are essential to clarify the long-term health effects of these ubiquitous additives.

Over 750 million individuals worldwide experience chronic kidney disease (CKD), which is a major contributor to cardiovascular disease and kidney failure as well as increased morbidity and mortality. Diet is a key lifestyle factor in CKD risk prevention and management. Overall public dietary quality and sodium intake have shown limited improvement despite decades of public health efforts. Excessive sodium consumption is a challenging dietary risk factor because exposure is largely passively embedded within the modern food environment. Furthermore, the consequences of overconsumption of dietary sodium are often delayed, invisible, or difficult for patients to recognize. The complexity of dietary behavior approaches coupled with conventional education approaches also contributes to persistently high sodium intake across the CKD spectrum. In this review, we discuss three major overarching challenges to sodium reduction, which comprise the invisible nature of sodium-related risk, the ubiquity of sodium within commercially prepared and processed foods, and the limitations of knowledge-based interventions alone. We also highlight subsequent opportunities to improve implementation. These include practical, patient-centered, and personalized nutrition strategies; food environment and food supply improvements that make lower-sodium choices the default; and expansion of Food Is Medicine and culinary medicine approaches. Reducing dietary sodium exposure and its consequences requires coordinated efforts that extend beyond individual patients and health care providers to include multidisciplinary collaboration across health care systems, public health, industry, community organizations, professional societies, and policymakers. Such multilevel approaches offer important opportunities to improve kidney health trajectories as well as cardiovascular health. Semin Nephrol 36:x-xx © 20XX Elsevier Inc. All rights reserved.

Reducing dietary potassium (K) and phosphorus (P) intake is considered a cornerstone for managing hyperkalemia and hyperphosphatemia in adults with chronic kidney disease (CKD). K and P additives in processed foods are a growing concern as hidden sources of these minerals, yet their prevalence is unknown. The objective of this study was to investigate the characteristics of foods purchased by individuals with CKD, including the prevalence and types of K and P additives and the food categories most associated with these additives. This observational cohort study involved adults with CKD who collected grocery receipts over 4 weeks. Receipts were used to identify foods that may contain K or P additives. Ingredient lists of processed and ultra-processed foods were reviewed to identify items containing these additives. Statistical analysis was performed using IBM SPSS Statistics 31.0. Thirteen adults with CKD aged 54-80 (53.8% female, 84.6% of European descent) participated. A total of 889 food items were identified from 115 receipts, including 429 (48.3%) processed foods. Among these, 51 (11.9%) contained K additives only, 120 (28.0%) contained P additives only, and 34 (7.9%) contained both K and P additives. The most common K additive was K sorbate (57.3%), whereas the most common P additive was lecithin (42.6%). K additives were predominantly found in beverages (28.2%), sauces/salad dressings (20.0%), and ready-to-eat foods (20.0%). P additives were common in snacks (34.4%) and ready-to-eat foods (22.1%). Of 108 excluded foods, 65 items (60.2%) lacked food labels, with 25 (38.5%) being deli items and 23 (35.4%) being bakery items. Adults with CKD frequently purchased foods containing K and P additives. Educating patients about how to avoid these additives may help manage hyperkalemia and hyperphosphatemia. Future research is needed to validate the observed levels of additive exposure.

Potassium- and phosphorus-containing food additives represent large and functionally diverse classes of ingredients used to control flavor, texture, water dynamics, emulsification, pH, leavening, and shelf stability. Potassium-based additives, numbering over 70 approved compounds in the United States and European Union, are used as functional salts, buffering agents, antimicrobial preservatives, nonnutritive sweeteners, and leavening components, with expanding application in reformulated and reduced-sodium food products. Phosphorus-containing additives, encompassing more than 50 approved inorganic and organic phosphate compounds, constitute another major category of multifunctional ingredients used for emulsification, leavening, moisture retention, pH control, metal ion sequestration, and nutrient supplementation. Among these ingredients, many contain both potassium and phosphorus. These myriad additives differ substantially in chemical form, reactivity, solubility, and technological function, leading to distinct formulation roles and regulatory classifications. Despite their prevalence, dietary intake of potassium and phosphorus can be under-recognized, as ingredient labels typically declare additive names without quantifying the associated potassium or phosphorus contents. This review provides a structured reference for industry professionals and researchers by systematically categorizing potassium- and phosphorus-containing food additives according to technological function, food usage, chemistry, and regulatory status across major food safety authorities.

IgAN is the most common primary glomerular disease worldwide. It is characterized by high heterogeneity and poor long-term prognosis. Integrated traditional Chinese medicine and Western medicine (TCM-WM) has become a distinct and effective strategy for the treatment of IgAN in China. This review summarizes recent evidence-based research into integrated TCM-WM in IgAN management and its contribution to our understanding of IgAN etiology, current clinical practices, and the therapeutic mechanisms of TCM-WM treatments. Western explanations for IgAN pathogenesis center on aberrant IgA1 glycosylation, mucosal immune abnormalities, and inflammatory injury. These correspond to the traditional Chinese medicine (TCM) explanation of wind pathogen invading the kidney, inducing deficiency, stasis, and toxicity. Integrated TCM-WM management follows a staged approach to syndrome differentiation, and interventions aim to regulate the immune response, modulate the gut-kidney axis, and reduce inflammation and fibrosis. High-quality clinical evidence supports the efficacy and safety of several representative Chinese medicines. Based on long-term research, we have established a combined TCM five-syndrome typing and Western medicine five-stage pathologic blockade framework and propose an integrated five-sphere disease-syndrome-symptom-stage-biological characterization model. Supported by multiomics and artificial intelligence, this model bridges TCM syndromes and molecular pathologic mechanisms and facilitates precision therapy. Integrated TCM-WM effectively improves clinical remission and delays disease progression in IgAN. Future studies should focus on further biological integration of TCM syndrome dynamics and core molecular mechanisms to establish standardized precision protocols that promote the global application of integrated TCM-WM in IgAN management.

Potassium homeostasis is maintained primarily by the kidney, yet potassium is increasingly recognized not only as a regulated electrolyte but also as a key determinant of renal physiology and kidney health. Experimental, epidemiologic, and clinical evidence supports a reciprocal relationship in which kidney function governs potassium balance, whereas dietary potassium intake and plasma potassium concentration influence renal sodium transport, blood pressure regulation, and susceptibility to kidney injury. Both potassium deficiency and excess are associated with adverse cardiorenal outcomes, emphasizing the importance of maintaining potassium within an optimal physiologic range. Evidence suggests that the kidney adapts to changes in potassium availability through coordinated feedforward and feedback mechanisms, including a putative gut-kidney signaling axis and nephron-intrinsic potassium-sensing pathways. Along the nephron, inwardly rectifying potassium channels function as extracellular potassium sensors that couple changes in potassium concentration to alterations in epithelial transport and metabolism. Recent studies have identified potassium-responsive signaling pathways in the proximal tubule that regulate sodium transport, cellular growth, and kidney injury during potassium deficiency. In the distal convoluted tubule, related mechanisms regulate the thiazide-sensitive sodium-chloride cotransporter through the renal "potassium switch," linking potassium balance to sodium handling and blood pressure control. These mechanistic advances have renewed interest in potassium supplementation and potassium-containing additives as therapeutic interventions. Epidemiologic and emerging clinical data suggest that physiologically appropriate potassium intake, particularly from potassium-rich diets or bicarbonate/citrate-containing supplements, may provide cardiovascular and renal benefits. However, because impaired potassium excretion increases susceptibility to hyperkalemia in advanced chronic kidney disease, potassium supplementation and restriction should be individualized according to kidney function and patient risk.

Chronic kidney disease is a major global health burden with limited treatment options. Abelmoschus manihot (L.) Medicus (AM), a traditional Chinese medicine, has been used for centuries for edema and related disorders. Since the 1980s, it has been systematically applied in clinical nephrology, leading to the development of Huangkui capsules, an AM extract now widely used to treat proteinuria. Several high-quality clinical trials led by Chinese researchers show that AM preparations, alone or with standard therapy, significantly reduce proteinuria and preserve renal function in patients with kidney disease. The renoprotective effects of AM are attributed to its bioactive flavonoids. Its core mechanisms involve potent anti-inflammatory and antifibrotic actions alongside direct protection of renal parenchymal cells. Emerging research also highlights benefits in reducing oxidative stress, modulating gut microbiota, regulating programmed cell death, and alleviating dyslipidemia. Increasing evidence demonstrates that AM exemplifies a successful transition from traditional application to evidence-based medicine, supported by robust clinical trials and preclinical studies revealing its multitargeted mechanisms against key chronic kidney disease drivers. Further research will continue to expand its therapeutic application and refine crucial therapeutic targets. Semin Nephrol 36:x-xx © 20XX Elsevier Inc. All rights reserved.

Hyperkalemia is a consequential complication of chronic kidney disease (CKD), and clinical guidance has traditionally restricted potassium-rich foods despite the potential benefits of plant-rich diets. This guidance also does not address potassium added during food processing, such as potassium chloride, phosphate, citrate, and lactate. This review examines potassium intake and clinical outcomes in CKD in the context of food additives, drawing on three indirect bodies of evidence: (1) dietary potassium intake and clinical outcomes, (2) potassium source and serum potassium response, and (3) trials of potassium-based salt substitutes. Measured potassium intake is more often associated with neutral or favorable outcomes than harm across mortality, cardiovascular events, and CKD progression, providing little support for blanket restriction of potassium-rich whole foods. Total dietary potassium is a poor predictor of serum potassium, whereas soluble potassium salts are more bioavailable and can more readily raise serum potassium, with cardiovascular benefit from salt substitution in low-risk populations but hyperkalemia risk in susceptible patients. These findings argue against treating dietary potassium as a uniform exposure in CKD, and potassium source, not total intake alone, should guide counseling. Direct evidence on additive-derived potassium and clinical outcomes remains needed to guide practice, research, and food policy.

Lupus nephritis (LN) represents one of the most severe organ manifestations of systemic lupus erythematosus and remains a leading cause of morbidity and mortality in affected patients. Its pathogenesis is highly complex, involving multifaceted immune dysregulation and posing substantial challenges for clinical management. According to Traditional Chinese Medicine (TCM), LN is characterized by root deficiency and branch excess, with kidney deficiency as the base and heat-toxins combined with blood stasis driving disease progression. Furthermore, clinical manifestations of LN vary significantly across disease stages and are often complicated by conventional pharmacotherapies. Accumulating clinical evidence increasingly supports the therapeutic efficacy of TCM intervention in LN management. Pharmacologic investigations have further elucidated their multi-target, pleiotropic actions, including modulating immune responses and regulating critical molecular pathways implicated in the pathogenesis of LN. This review systematically outlines the TCM conceptualization of LN pathogenesis; catalogs commonly employed compound formulas, single herbs, and bioactive extracts used in clinical practice; and delineates their underlying pharmacologic mechanisms, thereby providing a rigorous scientific foundation for rational TCM formulation design and facilitating the development of integrated, evidence-informed, and optimized therapeutic strategies for LN.

Dietary management of chronic kidney disease (CKD) has evolved from reductionist nutrient restriction toward healthy dietary pattern advice. However, current guidance does not distinguish between nutrients intrinsic to whole foods and those delivered as isolated inorganic food additives. This distinction matters. Inorganic phosphorus and potassium additives are highly bioavailable, rapidly absorbed, and produce postprandial metabolic responses that differ substantially from their organic, food-bound counterparts. As ultra-processed foods now contribute around half of caloric intake globally, additive-derived nutrient exposure is both substantial and largely invisible. It is also inadequately captured by food composition databases, nutrition information panels, and ingredient declarations. This article proposes the concept of additive-aware dietary guidance in CKD: an approach that explicitly accounts for the chemical form and source of nutrients, their bioavailability and absorption kinetics, food matrix effects, co-exposure and additive stacking, and the contribution of unreported processing aids. We argue that this represents a necessary extension of existing dietary paradigms, not a replacement for them. This article outlines 4 practical strategies for clinical translation: (1) identifying additive exposure, (2) building ingredient literacy, (3) applying tiered risk-stratified counselling, and (4) using accessible behavioral framing. It also outlines implementation challenges, including cognitive burden, health literacy, socioeconomic equity, and the risk of nutritional inadequacy. Advancing additive-aware dietary guidance in CKD will require education of the multidisciplinary team, improved additive labelling regulation, standardized exposure assessment tools, mechanistic studies in CKD populations, and pragmatic intervention trials. Additive-aware dietary guidance represents a clinically relevant, achievable evolution in CKD nutrition care that better reflects the realities of the modern food supply.

Chronic kidney disease (CKD) is a global public health problem affecting 15% to 20% of adults worldwide. Vascular calcification (VC) is mediated by CKD-related mineral and bone disorders. However, no established therapy can reverse VC, making the exploration of effective treatment strategies particularly urgent. Traditional Chinese Medicine (TCM) has shown potential to improve renal function, correct calcium-phosphate metabolism disorders, and delay the progression of VC through long-term clinical practice and scientific research. This article systematically reviews clinical and basic studies on TCM for CKD-associated VC. It highlights 17 randomized controlled trials and 30 basic studies involving TCM decoctions, traditional Chinese patent medicines, single Chinese herbs, Chinese herb pairs, and the bioactive ingredients of TCM, summarizing their therapeutic effects and underlying molecular mechanisms. The review aims to provide new therapeutic options for the prevention and treatment of VC in patients with CKD.

Kidney injury molecule 1 (KIM-1), encoded by HAVCR1, was initially identified as one of the most highly induced proteins in injured proximal tubule epithelial cells and subsequently established as a sensitive tissue, urinary, and circulating biomarker of kidney injury. Yet KIM-1 is not just a marker of epithelial damage. It is a phosphatidylserine receptor that enables injured proximal tubule cells to recognize and internalize apoptotic cells and luminal cargo. This process engages intracellular trafficking, autophagy-related processing, and immune regulatory pathways, with consequences that are highly context-dependent. Transient KIM-1 expression can promote debris clearance and limit inflammation after acute injury, whereas sustained expression and uptake of protein- and lipid-rich cargo can contribute to cellular stress, maladaptive repair, inflammation, and fibrosis. Beyond kidney injury, KIM-1 is expressed and shed by renal cell carcinomas, in which circulating levels carry diagnostic, prognostic, and potentially treatment-stratifying information. KIM-1 is also emerging as both a molecular address for targeted therapeutic delivery and a candidate for functional inhibition or degradation. This review traces how KIM-1 evolved from an injury-induced transcript to a biomarker, signaling receptor, disease mediator, and therapeutic target. We propose a framework in which expression duration, cargo identity, receptor processing, intracellular trafficking, and disease context determine whether KIM-1 supports repair or promotes pathology, highlighting unresolved questions essential for translating its complex biology into more precise diagnostic and therapeutic strategies.

Membranous nephropathy (MN) is a common pathologic subtype of nephrotic syndrome in adults. Current clinical treatment strategies for MN are limited and are associated with high incidence rates of adverse reactions and risk of recurrence. Consequently, Traditional Chinese Medicine (TCM) has gradually emerged as an alternative option for patients. In recent years, TCM has accumulated substantial clinical experience in the management of MN. This review summarizes the latest research progress on TCM interventions in MN, aiming to provide additional evidence-based medical support for its clinical treatment. The proposed mechanisms of TCM in MN primarily involve immune regulation, anti-inflammation, podocyte protection, and anti-fibrosis, as well as modulation of lipid metabolism and the renal-intestinal microecosystem.

Regardless of recent progress, there is still unmet need for the treatment of chronic kidney disease (CKD). This has led to increased interest in using alternative medicine, such as Traditional Chinese Medicine (TCM), to treat CKD, particularly in China and other Asia countries. Indeed, many CKD patients experience improvement of proteinuria and renal function with appropriate TCM management. However, TCM practice is mostly based on the experiences accumulated over years, which has not been proven by modern well-designed clinical trials. Even though the number of TCM-related randomized controlled trials has been increasing in recent years, these studies still suffer from issues such as small sample sizes, inadequate randomization, and a lack of long-term follow-up. Also, trials with TCM in combination with recently approved new drugs have not been done. Additionally, the complexity and variability of TCM formulas, combined with a lack of standardized quality control for herbs and the heterogeneity of TCM practices, make the study designs very challenging. Safety concerns also arise owing to insufficient systematic monitoring and reporting of potential adverse herb-drug interactions and the nephrotoxicity of certain herbs. TCM uses a holistic medical approach; however, the underlying molecular mechanisms remain unclear. Most published studies are limited to examining the anti-inflammatory and antioxidative stress effects without knowing the exact targets of these drugs and the precise bioactive compounds are often not well defined. In this review, we discuss the challenges and opportunities related to the clinical and basic science research in the field of TCM and describe the pros and cons of several new approaches that have been used in recent years to discover new drugs from TCM.