Search Results (66)

Sepsis-associated acute kidney injury (SA-AKI) often requires renal replacement therapy (RRT), which markedly alters antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD). Novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations broaden options against multidrug-resistant Gram-negative bacteria, but dosing during RRT remains uncertain. This review summarizes PK/PD features, extracorporeal clearance, and practical dosing considerations about ceftolozane–tazobactam, ceftazidime–avibactam, aztreonam–avibactam, cefiderocol, meropenem–vaborbactam, imipenem–relebactam, and newer agents including sulbactam–durlobactam, cefepime–enmetazobactam, and cefepime–taniborbactam. Pharmacokinetic data, RRT impact, PK/PD targets, pediatric aspects, and clinical outcomes were extracted from experimental models, case reports, and clinical studies. Drug exposure varies with RRT modality, effluent flow, membrane properties, and patient-specific factors such as augmented renal clearance, hypoalbuminemia, and fluid overload. Standard renal-adjusted dosing often yields subtherapeutic concentrations in critically ill patients. Pediatric data remain scarce and largely limited to case reports. Optimal BL/BLI use in septic patients with SA-AKI on RRT requires individualized dosing that accounts for PK/PD variability and dialysis settings. Full-dose initiation during the first 24–48 h, followed by careful adjustment, appears prudent. Therapeutic drug monitoring should be used when available, and institution-specific protocols should be integrated into stewardship programs to improve efficacy and minimize resistance. Full article

Peritoneal dialysis (PD) is a widely used renal replacement therapy in which hyperosmolar solutions are instilled into the abdominal cavity to facilitate the removal of excess water, electrolytes, and metabolic waste products. During PD treatment, homeostasis is maintained through adaptive responses of the neuroendocrine system to high glucose exposure, changes in circulating blood volume, and shifts in electrolyte balance. Clinical observations and limited experimental studies suggest that these neurohormonal dynamics may influence both the complications and therapeutic efficacy of PD. However, systematic investigations remain scarce, largely because hormonal and neural responses are highly dynamic, involve complex interactions, and are substantially influenced by individual patient characteristics. In this review, we synthesize current clinical and experimental evidence linking PD-related complications with hidden hormone dynamics, with particular emphasis on hypothalamic hormones such as arginine vasopressin. We also discuss how the biocompatibility of PD solutions—traditionally assessed by their effects on peritoneal mesothelial cells—could be reconsidered when neuroendocrine aspects are taken into account. We propose that integrating both clinical insights and emerging basic research will provide a more comprehensive understanding of neuroendocrine regulation in PD and may contribute to the development of novel therapeutic strategies. Full article

Background: End-stage renal disease (ESRD) presents a substantial and growing global health challenge, where hemodialysis serves as an essential life-sustaining therapy for countless individuals. Despite its physiological necessity, the demanding treatment regimen can profoundly impact mental health and overall well-being, though gender-specific data and correlates within the Saudi population remain insufficiently explored. Methods: This cross-sectional study aimed to investigate this gap by assessing the prevalence of anxiety and depression, evaluating health-related quality of life (HRQoL), and analyzing associations with gender and treatment duration in a cohort of 250 hemodialysis patients from multiple centers in Madinah, Saudi Arabia. Validated instruments, namely, the Hospital Anxiety and Depression Scale (HADS) and the 36-Item Short Form Health Survey (SF-36), were employed. Results: The findings revealed a significant psychological burden, with 38% of patients exhibiting anxiety and 32% depression, with females disproportionately affected. HRQoL scores were severely diminished across all domains compared to healthy population norms. Furthermore, a longer dialysis vintage demonstrated a significant positive correlation with worsening psychological scores and a decline in physical HRQoL. Conclusions: These results underscore the critical need for a paradigm shift in standard care, advocating for the systematic integration of routine mental health screenings and the development of tailored, gender-sensitive psychosocial interventions to mitigate this considerable burden. Full article

Background/Objectives: Stage 5 chronic kidney disease (CKD), or end-stage renal disease (ESRD), requires renal replacement therapy, commonly hemodialysis (HD). This treatment necessitates dietary changes due to impaired excretory function and protein-energy wasting (PEW). A structured diet with adequate energy, protein, electrolytes, and fluids is essential. The aim was to characterize habitual dietary intake in adults on HD relative to KDOQI and ESPEN recommendations. Methods: In this cross-sectional study, 50 adults on maintenance HD at the Medical University of Warsaw completed a validated Food Frequency Questionnaire (55 items, nine frequency categories). The study was questionnaire-based and did not collect, link, or analyze dialysis efficacy indices, residual diuresis, or anthropometric measurements; all dietary estimates are independent of these clinical parameters. Estimated intakes of energy, macronutrients, fiber, electrolytes (Na, K, Ca, P), and fluids were compared with KDOQI 2020 and ESPEN 2021 recommendations. Sensitivity analyses included deterministic scenarios and Monte Carlo simulations. Results: Mean intakes were 2696.9 ± 1392.7 kcal and 87.7 ± 35.3 g protein; 64% and 82% met reference values. Sensitivity analyses revealed per-kg shortfalls in heavier patients (>75 kg): Monte Carlo medians were 37.8 kcal/kg/day and 1.28 g/kg/day. Diets were fat-dominant (~46%E), with low carbohydrates (~40%E) and low fiber, about 8 g per 1000 kcal. Sodium and phosphorus were elevated, about 1119 mg and 498 mg per 1000 kcal, while calcium was low (~346 mg/1000 kcal). Conclusions: Despite adequate mean intake, sensitivity analyses revealed per-kg energy/protein deficits and elevated sodium and phosphorus. Individualized counseling with electrolyte and fluid management, greater dietary diversity, and psychosocial support is warranted in HD. Full article

Background: Adherence to Medical Nutrition Therapy (MNT) is a key determinant of therapy success, particularly in chronic diseases like chronic kidney disease (CKD). MNT in CKD requires significant changes in patient’s dietary habits, which can affect long-term adherence. This study aims to evaluate the adherence to MNT in stage 5 CKD patients undergoing conservative kidney management (CKM), identifying potential challenges and strengths of nutritional intervention. Methods: We enrolled in 94 stage 5 CKD patients undergoing CKM at the University Hospital of Modena, Italy. We collect clinical data from medical and nutrition records. The inclusion criteria comprised patients of all genders, ages, and ethnicity with stage 5 chronic kidney disease (CKD), in pre-dialysis, enrolled in the nephrology and dietetics program, who had access to 24-h urine tests, anthropometric measurements, and dietary history records. Exclusion criteria included patients with CKD stages lower than 5, those who had not undergone at least one nutritional assessment, or lacked accessible 24-h urine data. The study utilized medical and dietary records from September 2017 to March 2025. The primary outcome was the assessment of adherence to medical nutrition therapy (MNT), comparing prescribed protein intake with actual intake, estimated from dietary history (DH). Protein intake was compared with normalized protein nitrogen appearance (nPNA) as stated by recent guidelines. Additional factors influencing adherence, such as age, gender, comorbidities, physical activity, and prior dietary interventions, were also evaluated. Anthropometric measurements and biochemical tests were collected, and dietary intake was assessed using a seven-day DH. Results: Data were analyzed using descriptive statistics, linear correlation models, univariate logistic regression, t-tests, paired t-tests, and chi-square tests, with significance set at p < 0.05. Most of the patients follow suggested energy and protein intakes limits; however, substantial individual variability emerged Bland–Altman analysis indicated a moderate bias and wide limits of agreement for energy intake (+116 kcal; limits of agreement –518.8 to +751.3 kcal), revealing frequent overestimation in self-reports. Protein intake showed less systematic error, but discrepancies between dietary recall and biochemical markers persisted. Protein intake decreased significantly over time (p < 0.001), while correlation with nPNA did not reach statistical significance (ρ = 0.224, p = 0.051). No significant associations were identified between adherence and most clinical or lifestyle factors, although diabetes was significantly associated with lower adherence to protein intake (p = 0.042) and a predominantly sedentary lifestyle showed a borderline association with energy intake adherence (p = 0.076), warranting further investigation. Longitudinal analysis found stable BMI and body weight, alongside notable reductions in sodium (p = 0.018), potassium (p = 0.045), and phosphorus intake (p < 0.001) over time. Conclusions: Assessing dietary adherence in CKD remains complex due to inconsistencies between self-reported and biochemical estimates. These findings highlight the need for more objective dietary assessment tools and ongoing, tailored nutritional support. Multifaceted interventions—combining education, personalized planning, regular monitoring, and promotion of physical activity—are recommended to enhance adherence and improve clinical outcomes in this vulnerable population. Full article

Background: Sepsis is a leading cause of morbidity and mortality among patients receiving maintenance hemodialysis (HD), reflecting a unique combination of immunologic dysfunction, comorbidities, and healthcare-related exposures. Despite advances in dialysis technology and infection control, outcomes for septic HD patients remain disproportionately poor. Objective: This review aims to synthesize current evidence on the epidemiology, risk factors, diagnostic challenges, and treatment considerations of sepsis in HD patients, highlighting persistent vulnerabilities and areas for clinical improvement. Methods: A structured narrative review was conducted, focusing on high-quality cohort studies, surveillance data, and pharmacologic analyses published over the past two decades. The literature search was performed using PubMed, Web of Science, and Google Scholar. A total of 37 studies were included in the final synthesis. Key themes were organized around epidemiologic trends, infection sources, risk modifiers, treatment outcomes, and antimicrobial considerations in the dialysis population. Results: The review found that sepsis in HD patients is multifactorial and systemic. Diabetes, advanced age, and central venous catheters remain strong risk factors, while a substantial proportion of infections arise from non-access-related sources. Mortality rates remain high, often due to delays in recognition, inappropriate empiric therapy, and challenges in antimicrobial dosing. Pharmacokinetic alterations in renal replacement therapy complicate treatment, requiring individualized approaches. Despite variations in infection rates across centers, systemic vulnerabilities—rather than dialysis modality alone—drive outcomes. Conclusions: Sepsis in hemodialysis patients is not solely a hardware-related complication but reflects deeper systemic and immunologic challenges. Improving outcomes will require earlier recognition, tailored antimicrobial strategies, standardized infection control protocols, and broader attention to patient-specific risk factors. Future research should focus on ESRD-adapted sepsis diagnostics and interventional models to reduce infection-related mortality in this high-risk group. Full article

The number of patients with end-stage renal disease continues to grow worldwide, placing increasing demands on dialysis technologies. Conventional hemodialysis remains the dominant modality but is often limited by frequent intradialytic hypotension and the insufficient removal of medium-sized toxins. Intermittent infusion hemodiafiltration (I-HDF) is an emerging, hybrid dialysis technique that combines standard hemodialysis with the cyclic backfiltration of ultrapure dialysate. This approach enables dynamic blood volume control and periodic backflushing of the dialyzer membrane. Recent clinical studies demonstrate that I-HDF can reduce intradialytic hypotension incidence, improve systemic and microcirculatory perfusion, and enhance the clearance of middle molecules such as β₂-microglobulin, while minimizing albumin loss. These benefits are particularly relevant to toxin clearance and hemodynamic stabilization, key priorities in optimizing dialysis outcomes. Large-scale cohort data suggest that I-HDF may be linked to improved long-term survival in dialysis patients. Given its physiological advantages and operational flexibility, I-HDF may also offer a practical solution in healthcare systems with limited access to high-volume online hemodiafiltration or kidney transplantation. Further research is warranted to develop individualized infusion protocols and validate its broader applicability. Full article

Background/Objectives: Secondary hyperparathyroidism (SHPT) is a prevalent complication in end-stage renal disease, often necessitating surgical intervention when refractory to medical therapy. The optimal surgical strategy—subtotal parathyroidectomy (SPTX) versus total parathyroidectomy with/without autotransplantation (TPTX ± AT)—remains debated, especially considering postoperative complications like persistent HPT and hungry bone syndrome (HBS). This study aimed to compare early surgical outcomes and identify predictors for postoperative complications in patients undergoing SPTX and TPTX + AT. Methods: We conducted a retrospective, single-center observational study involving 93 dialysis patients who underwent PTX for drug-refractory SHPT. Patients were analyzed according to surgical procedure (SPTX vs. TPTX + AT), focusing on postoperative complications such as cervical bleeding, reintervention rates, and the incidence of HBS. Multivariate logistic regression was utilized to identify predictors of these outcomes. Results: TPTX + AT demonstrated superior control of HPT, with significantly lower rates of reintervention compared to SPTX (7.1% vs. 23.5%, p = 0.037). However, TPTX + AT was associated with a higher incidence of HBS (57.1% vs. 35.3%, p = 0.039). Independent predictors of reintervention included absence of concomitant thymectomy, preoperative hypercalcemia, fewer visualized glands preoperatively, and preoperative PTH > 2000 pg/mL. Elevated alkaline phosphatase levels (>300 U/L), severe bone pain, and the TPTX procedure itself were significant predictors of HBS. Conclusions: Surgical strategy for SHPT should be individualized, balancing the lower recurrence risk associated with TPTX + AT against its higher likelihood of postoperative hypocalcemia. Preoperative biochemical markers and clinical features could potentially influence operative decision-making and optimize patient outcomes. Full article

Fracture risk is a serious yet underrecognized complication among patients with chronic kidney disease (CKD), especially in those with stages G3-G5D. The overlap between CKD-Mineral and Bone Disorder (CKD-MBD) and osteoporosis leads to complex bone changes that increase the likelihood of fragility fractures. Studies show that 18% to 32% of CKD patients also have osteoporosis, and these individuals are more than 2.5 times as likely to suffer from fractures compared to those without CKD. In the advanced stages of the disease, fracture risk is up to four times higher than in the general population, with the femur, forearm, and humerus being the most commonly affected sites. Hip fractures are of particular concern as they are linked to longer hospital stays and higher rates of morbidity and mortality. Furthermore, dialysis patients who experience hip fractures have a mortality rate 2.4 times higher than those in the general population with similar fractures. This increased risk underscores the need for proactive bone health maintenance in CKD patients to prevent fractures and related complications. This review explores the underlying pathophysiological mechanisms, diagnostic challenges, and treatment options related to bone fragility in CKD. Diagnostic tools, such as bone mineral density (BMD) assessments, the trabecular bone score (TBS), and biochemical markers, remain underused, especially in advanced CKD stages. Recent treatment strategies emphasize a multidisciplinary, stage-specific approach, incorporating calcium and vitamin D supplements, anti-resorptive agents like denosumab, and anabolic therapies such as teriparatide and romosozumab. Effective management needs to be tailored to the patient’s bone turnover status and stage of CKD. Despite progress in understanding bone fragility in CKD, significant gaps remain in both diagnosis and treatment. Personalized care, guided by updated KDIGO recommendations and based on an interdisciplinary approach, is essential to reduce fracture risk and improve outcomes in this vulnerable population. Further research is needed to validate risk assessment tools and refine therapeutic protocols. Full article

Chronic kidney disease-associated pruritus (CKD-aP) is a distressing symptom that affects both dialysis and non-dialysis patients, significantly impairing their quality of life. Despite its multifactorial pathophysiology, no gold-standard treatment has been established. This review explores various therapeutic options and evaluates their effectiveness based on recent clinical studies and meta-analyses. Therapies targeting novel mechanisms have evolved in recent years. Difelikefalin, a κ-opioid receptor agonist, represents a breakthrough in systemic treatment, demonstrating efficacy with a favorable safety profile. Another opioid-based therapy, nalfurafine, has shown notable symptom relief in multiple clinical studies, with a low risk of abuse. Sertraline, an antidepressant, offers another alternative, although its delayed onset remains a limitation. Nonpharmacologic approaches are also evolving. Phototherapy, particularly UV-B therapy, modulates the immune response, reduces inflammation, and effectively alleviates itching in hemodialysis patients. Personalized treatment strategies are crucial, as responses vary among patients. Further research, including comparative and long-term studies, is essential to refine treatment algorithms and improve patient outcomes. By integrating new pharmacologic and nonpharmacologic options, CKD-aP management is shifting toward a more tailored and effective approach that addresses the individual needs of each patient. Full article

Background: Chronic kidney disease (CKD) and its advanced stage, end-stage renal disease (ESRD), affect millions worldwide and are associated with a paradoxical hemostatic imbalance—marked by both increased thrombotic and bleeding risks—which complicates anticoagulant use and demands clearer, evidence-based clinical guidance. Design: This study is a critical review synthesizing the current literature on anticoagulant therapy in CKD and ESRD, with emphasis on altered pharmacokinetics, clinical complications, and therapeutic adjustments. Data Sources: PubMed, Scopus, and Google Scholar were searched for articles discussing anticoagulation in CKD/ESRD, focusing on pharmacokinetics, clinical outcomes, and dosing recommendations. Study Selection: Studies examining the safety, efficacy, and pharmacokinetics of anticoagulants—including heparin, low-molecular-weight heparin (LMWH), warfarin, and direct oral anticoagulants (DOACs)—in CKD and ESRD populations were included. Data Extraction and Synthesis: Key findings were summarized to highlight the dose modifications, therapeutic considerations, and clinical challenges in managing anticoagulation in CKD/patients with ESRD. Emphasis was placed on balancing thrombotic and bleeding risks and identifying gaps in existing guidelines. Results: Patients with CKD and ESRD exhibit a paradoxical hypercoagulable state marked by platelet dysfunction, altered coagulation factors, and vascular endothelial damage. This condition increases the risk of thrombotic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE), while simultaneously elevating bleeding risks. Hemodialysis and CKD-associated variables further complicate the management of coagulation. Among anticoagulants, unfractionated heparin (UFH) is preferred due to its short half-life and adjustability based on activated partial thromboplastin time (aPTT). Low-molecular-weight heparins (LMWHs) offer predictable pharmacokinetics but require dose adjustments in CKD stages 4 and 5 due to reduced clearance. Warfarin necessitates careful dosing based on the estimated glomerular filtration rate (eGFR) to maintain an international normalized ratio (INR) ≤ 4, minimizing bleeding risks. Direct oral anticoagulants (DOACs), particularly Apixaban, are recommended for patients with eGFR < 15 mL/min or those on dialysis, although data on other DOACs in CKD remain limited. The lack of comprehensive guidelines for anticoagulant use in CKD and ESRD highlights the need for individualized, patient-centered approaches that account for comorbidities, genetics, and clinical context. Conclusions: Managing anticoagulation in CKD/ESRD is challenging due to complex coagulation profiles and altered pharmacokinetics. Judicious dosing, close monitoring, and patient-centered care are critical. High-quality randomized controlled trials are needed to establish clear guidelines and optimize therapy for this vulnerable population. Full article

Background: Anemia represents a significant complication in patients with advanced chronic kidney disease (CKD) on hemodialysis, primarily caused by reduced renal erythropoietin production. Despite erythropoiesis-stimulating agents (ESAs) being the cornerstone of treatment, hyporesponsiveness to these agents remains a clinical challenge with implications for patient outcomes. Objective: To identify and quantify risk factors associated with hyporesponsiveness to erythropoietin in patients with CKD on hemodialysis who present with anemia. Methods: This multicenter case–control study analyzed data from 784 hemodialysis patients receiving erythropoietin therapy across six dialysis centers in Ecuador between January and December 2019. Hyporesponsiveness was defined as requiring ≥ 200 IU/kg/week of erythropoietin alfa for ≥3 consecutive months to maintain target hemoglobin levels (10–12 g/dL). Demographic, clinical, and laboratory parameters were compared between hyporesponsive cases (n = 123) and responsive controls (n = 661). Bivariate and multivariate logistic regression analyses were performed to identify independent risk factors. Results: The prevalence of erythropoietin hyporesponsiveness was 15.69%. A multivariate analysis identified female sex (adjusted OR = 1.96; 95% CI: 1.20–3.20; p < 0.001), age < 50 years (adjusted OR = 4.25; 95% CI: 2.42–7.47; p < 0.001), serum albumin < 4.0 g/dL (adjusted OR = 10.53; 95% CI: 6.53–16.98; p < 0.001), ferritin ≥ 800 ng/mL (adjusted OR = 7.28; 95% CI: 4.22–12.57; p < 0.001), transferrin saturation < 20% (adjusted OR = 9.27; 95% CI: 5.47–15.69; p < 0.001), parathyroid hormone ≥ 500 pg/mL (adjusted OR = 1.89; 95% CI: 1.16–3.09; p = 0.011), and use of renin–angiotensin system blockers (adjusted OR = 2.25; 95% CI: 1.36–3.71; p = 0.002) as independent risk factors for erythropoietin hyporesponsiveness. Conclusions: Multiple demographic, clinical, and laboratory factors independently contribute to erythropoietin hyporesponsiveness in hemodialysis patients. Identification of these risk factors may guide clinicians in developing individualized treatment approaches, optimizing erythropoietin dosing, and implementing targeted interventions to improve anemia management in this vulnerable population. Full article

Background/Objectives: Individuals with chronic kidney disease often face significant physical and clinical challenges, such as muscle weakness, fatigue, and reduced cardiorespiratory capacity, that impact their quality of life. Physical activity has emerged as an effective intervention to counteract these effects, with clinical guidelines recommending exercise as a standard treatment for kidney transplant recipients. The aim of this study was to assess pretransplant physical activity levels in a cohort of transplant patients and analyze their relationships with cardiovascular risk factors. Methods: A cross-sectional, analytical, and correlational study was conducted from September 2020 to June 2022 with a sample of 122 kidney transplant recipients assessed before kidney transplantation. Sociodemographic data, anthropometric data, comorbidities, renal replacement therapy types, and clinical and analytical data were collected from the patients’ clinical records. Physical activity was assessed via the International Physical Activity Questionnaire. Results: The average time spent waiting for transplantation was 423 ± 405 days, which was longer (387 ± 524) in the group of those under 65 years than in those over 65 years (194 ± 256) (p = 0.010). The median energy expenditure was 1742 (IQR = 1719) METs. In addition, 15.6% of the participants reported inactivity. Men reported higher physical activity levels (median: 2076 METs/week; IQR: 2037) than women did (median: 1386 METs/week; IQR: 1238). A higher level of physical activity was found in non-dialysis patients, overweight patients, and those with a history of stroke. A significant positive correlation was found between physical activity levels and serum urea. Conclusions: Increased physical activity levels were observed in men and in participants under 65 years of age. Patients with cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, overweight and obesity, reported lower activity levels, whereas those with a prior history of cerebrovascular accidents engaged in more physical activity. This study highlights the importance of assessing physical activity and promoting exercise for chronic kidney disease patients awaiting kidney transplantation. Further research is needed to explore the evolution of physical activity in this population and its impact post-transplantation. Full article

Background: Atypical hemolytic uremic syndrome (HUS) is a rare form of thrombotic microangiopathy (TMA) characterized by complement dysregulation. Cocaine use has been reported to be a potential trigger of TMA; however, the underlying mechanisms remain poorly elucidated. Proposed hypotheses include direct endothelial injury, activation of the complement cascade, and the unmasking of whether HUS is genetic or acquired. Case Report: We report the case of a 47-year-old man who presented with hypertensive emergency and acute kidney injury following intranasal cocaine use. The laboratory findings were consistent with microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and markedly elevated lactate dehydrogenase (LDH) levels. Renal biopsy (RB) revealed classic features of TMA, including glomerular capillary thrombosis, fibrinoid necrosis, and acute tubular injury. Complement studies demonstrated reduced levels of Factor I, indicative of complement dysregulation. The patient was treated with therapeutic plasma exchange and four weekly doses of eculizumab, resulting in hematologic remission and significant improvement in renal function, without the need for dialysis. Genetic testing for known atypical HUS-associated mutations was negative; therefore, maintenance therapy with eculizumab was discontinued without clinical relapses. Discussion: This case underscores cocaine as a rare but important precipitating factor for atypical HUS in predisposed individuals. Early diagnosis, RB, and complement evaluation were essential in determining the etiology and guiding targeted therapy. Complement inhibition with eculizumab was effective in halting disease progression and preventing long-term renal damage. Conclusions: This case highlights the relevance of considering cocaine use as a potential trigger of complement-mediated TMA. Early identification of aHUS features and prompt initiation of complement inhibition therapy may be critical to preventing irreversible kidney injury. Full article

Phosphorus is one of the most abundant minerals in the body and plays a critical role in numerous cellular and metabolic processes. Most of the phosphate is deposited in bones, 14% is present in soft tissues as various organic phosphates, and only 1% is found in extracellular space, mainly as inorganic phosphate. The plasma inorganic phosphate concentration is closely maintained between 2.5 and 4.5 mg/dL by intertwined interactions between fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), and vitamin D, which tightly regulate the phosphate trafficking across the gastrointestinal tract, kidneys, and bones. Disruption of the strict hemostatic control of phosphate balance can lead to altered cellular and organ functions that are associated with high morbidity and mortality. In the past three decades, there has been a steady increase in the prevalence of kidney failure (KF) among populations. Individuals with KF have unacceptably high mortality, and well over half of deaths are related to cardiovascular disease. Abnormal phosphate metabolism is one of the major factors that is independently associated with vascular calcification and cardiovascular mortality in KF. In early stages of CKD, adaptive processes involving FGF-23, PTH, and vitamin D occur in response to dietary phosphate load to maintain plasma phosphate level in the normal range. However, as the CKD progresses, these adaptive events are unable to overcome phosphate retention from continued dietary phosphate intake and overt hyperphosphatemia ensues. As these hormonal imbalances and the associated adverse consequences are driven by the underlying hyperphosphatemic state in KF, it appears logical to strictly control serum phosphate. Conventional dialysis is inadequate in removing phosphate and most patients require dietary restrictions and pharmacologic interventions to manage hyperphosphatemia. However, diet control comes with many challenges with adherence and may place patients at risk for inadequate protein intake and malnutrition. Phosphate binders help to reduce phosphate levels but come with a sizable pill burden and high financial costs and are associated with poor adherence and psychosocial issues. Additionally, long-term use of binders may increase the risk of calcium, lanthanum, or iron overload or promote gastrointestinal side effects that exacerbate malnutrition and affect quality of life. Given the aforesaid challenges with phosphorus binders, novel therapies targeting small intestinal phosphate absorption pathways have been investigated. Recently, tenapanor, an agent that blocks paracellular absorption of phosphate via inhibition of enteric sodium–hydrogen exchanger-3 (NHE3) was approved for the treatment of hyperphosphatemia in KF. While various clinical tools are now available to manage hyperphosphatemia, there is a lack of convincing clinical data to demonstrate improvement in outcomes in KF with the lowering of phosphorus level. Conceivably, deleterious effects associated with hyperphosphatemia could be attributable to disruptions in phosphorus-sensing mechanisms and hormonal imbalance thereof. Further exploration of mechanisms that precisely control phosphorus sensing and regulation may facilitate development of strategies to diminish the deleterious effects of phosphorus load and improve overall outcomes in KF. Full article