Managing diabetes in patients on peritoneal dialysis (PD) is challenging due to the combined effects of dietary glucose, glucose from dialysate, and other medical complications. Advances in technology that enable continuous biological data collection are transforming traditional management approaches. This review explores how multiomics technologies and artificial intelligence (AI) are enhancing glucose management in this patient population. Continuous glucose monitoring (CGM) offers significant advantages over traditional markers, such as hemoglobin A1c (HbA1c). Unlike HbA1c, which reflects an mean glucose level, CGM provides real-time, dynamic glucose data that allow clinicians to make timely adjustments, leading to better glycemic control and outcomes. Multiomics approaches are valuable for understanding genetic factors that influence susceptibility to diabetic complications, particularly those related to advanced glycation end products (AGEs). Identifying genetic polymorphisms that modify a patient's response to AGEs allows for personalized treatments, potentially reducing the severity of diabetes-related pathologies. Metabolomic analyses of PD effluent are also promising, as they help identify early biomarkers of metabolic dysregulation. Early detection can lead to timely interventions and more tailored treatment strategies, improving long-term patient care. AI integration is revolutionizing diabetes management for PD patients by processing vast datasets from CGM, genetic, metabolic, and microbiome profiles. AI can identify patterns and predict outcomes that may be difficult for humans to detect, enabling highly personalized recommendations for diet, medication, and dialysis management. Furthermore, AI can assist clinicians by automating data interpretation, improving treatment plans, and enhancing patient education. Despite the promise of these technologies, there are limitations. CGM, multiomics, and AI require significant investment in infrastructure, training, and validation studies. Additionally, integrating these approaches into clinical practice presents logistical and financial challenges. Nevertheless, personalized, data-driven strategies offer great potential for improving outcomes in diabetes management for PD patients.

Abstract Background Hyperuricemia influences lipid metabolism, yet relationships between urate-lowering therapy with allopurinol, serum urate, and lipid levels in patients with chronic kidney disease (CKD) remain underexplored. Methods This was a post-hoc analysis of 1,970 participants of the CAN AIM to PREVENT who had pre-dialysis CKD and were not receiving lipid-lowering therapy or febuxostat. Joint generalized structural equation modelling was used to investigate associations between allopurinol use (yes or no), serum urate (as a continuous or categorical variable (target if <6 mg/dL or high if ≥6 mg/dL)), and lipid levels (total cholesterol, LDL-C, HDL-C, and triglycerides) assessed every 6 months for up to 3 years, along with time-to-event outcomes (death or initiation of renal replacement therapy), adjusting for demographic and clinical factors. Mediation analysis was used to determine allopurinol's direct and indirect effects (via urate) on lipid levels. Results Allopurinol use independently predicted lower total cholesterol (-7.94%, 95% CI: -12.13% to -3.54%, p<0.001)) and LDL-C (-13.84%, (-21.14 to -5.87), p=0.001). Serum urate independently predicted a small increase in LDL-C (0.02% per mg/dL (0.009 to 0.03), p<0.001). Patients on allopurinol with target urate had lower LDL-C compared to those not on allopurinol with target urate (-4.46% (-8.25 to -0.50), p=0.027) and those on allopurinol with high urate (-10.15% (-13.16 to -7.04), p<0.001. Mediation analysis showed that serum urate indirectly mediated only 24% of the effect of allopurinol on LDL-C. Conclusion Allopurinol use predicted lower total and especially LDL cholesterol independently of serum urate in this cohort of patients with pre-dialysis CKD. Future studies could investigate underlying mechanisms, evaluate clinical implications, and confirm these findings in this and other populations.

BACKGROUND:The main barriers to arterio-venous fistula (AVF) utilization are primary failure, long maturation duration, and low secondary patency rates. METHODS:In this retrospective cohort study, primary, secondary, functional primary, and functional secondary patency rates were calculated and compared between two age groups (< 75 years and > = 75 years) and between radiocephalic (RC-) and upper arm (UA-) AVFs, and factors determining the duration of functional secondary patency were evaluated. RESULTS:Between 2016 and 2020, 206 predialysis patients whose AVFs had been created previously initiated renal replacement treatment. RC-AVFs comprised 23.3% and were created after favorable analysis of the forearm vasculature. Overall, the primary failure rate was 8.3, and 84.7% started hemodialysis with a functioning AVF. Functional secondary patency rates of primary AVFs were better with RC-AVFs [1,3 and 5 year rates of 95.8, 81.9 and 81.9% versus 83.4, 71.8 and 59.2% for UA-AVFs (log rank p: 0.041)]. There was no difference between the two age groups for any of the AVF outcomes assessed. Among patients whose AVF was abandoned, 40.3% had gone on to have a second fistula created. This was significantly less likely in the older group (p < 0.01). IN CONCLUSION:(1) UA-AVFs were placed more commonly than RC-AVFs; (2) a selection bias existed whereby RC-AVFs were only created after favorable forearm vasculature was demonstrated or suspected; (3) superior functional secondary patency rates were observed with RC-AV's, perhaps stemming from this selection bias; (4) the elderly were more likely to have only one AVF creation attempt.

Introduction: QTc interval prolongation is increasingly frequent as CKD advances and predicts death in dialysis. However, predictors and mortality-risk in predialysis CKD are understudied. FGF23 induces left ventricular hypertrophy (LVH) which is associated with QTc interval prolongation and death, suggesting a possible pathway from FGF23 to death that entails LVH and QTc prolongation. We looked for links between FGF23 and prolonged QTc intervals mediated by LVH, and for deaths associated with QTc prolongation in a prospective observational cohort of patients with predialysis CKD. Methods: Participants underwent protocolized baseline and semi-annual FGF23 testing, baseline and study end echocardiograms, and baseline and annual electrocardiograms over three years. Results: 2,254 participants (34.1% female; mean age 68.7 years; mean glomerular filtration rate 41.4 ml/min/m2) enrolled. Baseline LVH (left ventricular mass index >131 g/m2 (>100 g/m2 if female)) was present in 10.8% and prolonged QTc intervals (>=500 ms) in 1.5%. One hundred thirty-eight (6.1%) participants died during the study. In generalized mixed effects regression, each unit increase in the natural log of FGF23 - but not LVH - predicted an odds ratio of 1.76 (1.15, 2.70, p=0.009) for prolonged QTc intervals independently of 15 other covariates. Mediation analysis showed that only 13% of FGF23's total effect on prolonged QTc intervals was mediated by LVH. Patients with prolonged QTc intervals had higher unadjusted (log rank p<0.001) and adjusted (hazard ratio 3.15 (1.38, 7.16, p=0.006)) mortality rates than those with QTc intervals <500 ms. Conclusions: QTc interval prolongation ≥500 ms was prospectively associated with FGF23 independently of LVH, and with a tripling of mortality-risk in patients with predialysis CKD.

Background: Dysregulated serum calcium and FGF23 are associated with increased mortality and morbidity rates in patients receiving hemodialysis. Preliminary data suggest serum calcium regulates FGF23 secretion independently of serum phosphate, parathyroid hormone, and 25-OH vitamin D. It is unclear to what extent dietary and prescription sources of calcium influence calcium and FGF23 levels, and whether they confound this relationship. In this cross-sectional analysis of a multi-ethnic cohort of prevalent hemodialysis patients, association of dietary calcium and prescribed calcium were examined against serum calcium and FGF23. Bi- and multivariable linear regression was used for all analyses. Results: 81 patients (mean age 58 years, dialysis vintage 2 years, 51 men) participated. Dietary calcium was inversely associated with FGF23 (p = 0.04) however association of FGF23 with prescribed calcium did not reach statistical significance (0.08). In multivariable models, dietary calcium and prescribed calcium were associated in opposing directions with serum calcium (prescribed calcium; ß-coefficient = −0.35, p = 0.005 versus dietary calcium; ß-coefficient = 0.35, p = 0.03). FGF23 was independently associated with serum calcium (p = 0.007). Conclusions: We found differing, sometimes opposing, associations between serum calcium and FGF23 levels when considering prescribed versus dietary sources of calcium. Serum calcium and FGF23 were strongly correlated regardless of possible confounders examined in this hemodialysis cohort. Dietary calcium was associated with higher serum calcium and lower FGF23 concentrations, while prescribed calcium was only inversely associated with serum calcium. Further studies are required to confirm these associations and determine causality.

Although echocardiograms are often performed when peritoneal dialysis is started, associations between commonly reported findings and prospective changes in renal function remain understudied. Ninety-nine of 101 patients in the Trio Trial had transthoracic echocardiograms within 6 months of dialysis initiation, and measurements of residual renal function every six weeks for up to two years. Generalized mixed modelling linear regression in STATA was used to examine associations between left atrial size, left ventricular hypertrophy, left ventricular ejection fraction, right ventricular systolic pressure, and left valvular calcification with subsequent slopes in renal function. After echocardiography (performed a median of 16 days following peritoneal dialysis initiation) right ventricular systolic pressure was associated with faster, while declining left ventricular ejection fraction and valvular calcification were associated with slower declines in residual renal function. Future studies could be conducted to confirm these findings, and identify pathophysiological mechanisms.

Background and objective Residual renal function (RRF) correlates with mortality and morbidity rates in patients receiving peritoneal dialysis (PD). We examined the effect of a biocompatible PD solution (Gambrosol Trio; Gambro Lundia AB, Lund, Sweden) with lower concentrations of glucose degradation products on rates of decline in RRF. Design, setting, participants, and measurements Incident patients at 2 centers in Canada and 1 in Hong Kong were randomized (by minimization) in an open-label parallel group trial to receive Gambrosol Trio or standard PD solution (Dianeal; Baxter Healthcare, Mississauga, Canada) for 2 years. Primary outcome was slope of RRF. Secondary outcomes were urine volumes, fluid and nutrition indices, PD and membrane characteristics, peritonitis rates, adverse events, and PD technique survival. Results Residual renal function declined by 0.132 mL/minute/1.73 m2/month in 51 patients allocated to biocompatible, and 0.174 mL/minute/1.73 m2/month in 50 patients allocated to standard PD solution (difference 0.042 mL/minute/1.73 m2/month, p = 0.001). Urine volume, body mass index, normalized protein catabolic rates, and fat mass were higher; total body water, peritoneal ultrafiltration, and D/P creatinine did not differ; and serum phosphate, rates of icodextrin, and automated cycler use were lower with Gambrosol Trio use. There were more peritonitis events with Gambrosol Trio use, while PD technique survival did not differ between groups. Conclusions The use of the biocompatible PD solution Gambrosol Trio was associated with slower rates of decline in RRF, fluid and nutrition benefits, and increased peritonitis rates. Trial Number: ISRCTN26252543

Background Despite adverse effects such as constipation, vascular calcification, and hypercalcemia, calcium-based salts are relatively affordable and effective phosphate binders that remain in widespread use in the dialysis population. We conducted a pilot study examining whether the use of a combined magnesium/calcium-based binder was as effective as calcium carbonate at lowering serum phosphate levels in peritoneal dialysis (PD) patients. Methods This was a cross-over, investigator-masked pilot study in which prevalent PD patients received calcium carbonate alone (200 mg calcium per tablet) or calcium magnesium carbonate (100 mg calcium, 85 mg magnesium per tablet). Primary outcome was serum phosphate level at 3 months. Analysis was as per protocol. Results Twenty patients were recruited, 17 completed the study. Mean starting dose was 11.35 ± 7.04 pills per day of MgCaCO3 and 9.00 ± 4.97 pills per day of CaCO3. Mean phosphate levels fell from 2.13 mmol/L to 2.01 mmol/L (95% confidence interval (CI): 1.76 – 2.30, p = 0.361) in the MgCaCO3 group, and 1.81 mmol/L (95% CI: 1.56 – 2.0, p = 0.026) in the CaCO3 alone group. Six (35%) patients taking MgCaCO3 and 9 (54%) taking CaCO3 alone achieved Kidney Disease Outcomes Quality Initiative (KDOQI) serum phosphate targets at 3 months. Diarrhea developed in 9 patients taking MgCaCO3 and 3 taking CaCO3. Serum magnesium exceeded 1.4 mmol/L in 5 patients taking MgCaCO3 while serum calcium exceeded 2.65 mmol/L in 3 patients receiving CaCO3. When compared to the initial dose, the prescribed dose at 3 months was reduced by 44% (to 6.41 tablets/day) in the MgCaCO3 group and by 8% (to 8.24 pills per day) in the CaCO3 alone group. Conclusion Compared with CaCO3 alone, the preparation and dose of MgCaCO3 used in this pilot study was no better at lowering serum phosphate levels in PD patients, and was associated with more dose-limiting side effects.

A52-year-old man was admitted to the hospital with severe dyspnea. He had a history of mild chronic obstructive pulmonary disease, tertiary hyperparathyroidism, type II diabetes mellitus, and end-stage renal disease treated with hemodialysis for 4 years. He had stopped a 12-year habit of smoking 10 cigarettes per day 8 years previously. A living unrelated renal transplantation was performed 8 months before admission. It was complicated by massive intraoperative hemorrhage and required transfusion of approximately 40 U of packed red cells, and prolonged ventilatory and inotropic support. A thrombectomy to salvage a thrombosed arteriovenous fistula resulted in a large pulmonary embolus and cardiac arrest. He remained dialysis dependent throughout. Exertional dyspnea developed soon after discharge and 6 months before admission to our hospital. A chest radiograph and subsequent high-definition computed tomography scan of the thorax revealed focal calcification in the apices of both lungs. Laboratory data revealed a serum parathyroid hormone of 3373.33 pg/mL, phosphate of 5.14 mg/dL, and calcium of 10.56 mg/dL. Pulmonary function tests (PFTs) disclosed severe restrictive lung disease in association with severe reduction in oxygen diffusion capacity (Fig. 1). A transthoracic echocardiogram showed normal left ventricular systolic function. Nuclear bone scanning with singlephoton emission computed tomography revealed advanced metabolic bone disease and large foci of uptake within the apices of both lungs. His dyspnea progressed despite therapy with home oxygen, corticosteroids, bronchodilators, and increased ultrafiltration at hemodialysis. He was admitted when restdyspnea ensued. He could speak in only oneor two-word sentences and was bed bound. Sodium thiosulfate (STS) 1250 mg administered intravenously after each thrice-weekly hemodialysis treatment was administered on admission. After 2 weeks, this was changed to STS 600 mg orally two times daily. Oral prednisone, cinacalcet, and lanthanum carbonate were continued. He began to notice improvement in his breathing and ability to weight-bear after 2 weeks. He then sustained a nontraumatic intratrochanteric fracture and required cemented bipolar hemiarthroplasty repair under spinal anesthesia. Two weeks later, he had a nontraumatic fracture of his contralateral intratronchanter and again required operative repair. STS was held when his fracture risk on bone scanning was found to be extreme (hip T score, Y3.9; lumbar spine Tscore, Y4.9), and resumed after a parathyroidectomy approximately 3 months later. One year later, he walked 252 m and maintained oxygen saturations of 97% during a 6-min walk test. Serial PFT results are shown in Figure 1. A follow-up computed tomography scan did not show evidence for radiographic improvement in the pulmonary calcification or nodules. Metastatic pulmonary calcification (MPC) occurs in 60% to 80% of patients receiving chronic hemodialysis and is usually asymptomatic being diagnosed incidentally on thoracic computed tomography or postmortem analysis (1). Occasionally, pulmonary calcification is associated with pulmonary restriction, respiratory failure, and death (1, 2). Risk factors for fulminant MPC-associated respiratory failure include recent renal transplantation (whether successful or not), corticosteroid use, elevated serum calcium and phosphate concentrations, and hyperparathyroidism (1Y6). Outside of supportive care and attempts to improve these metabolic aberrations, there is no treatment currently available for respiratory failure in the setting of MPC. Pulmonary calciphylaxis is an exceedingly rare condition that is also characterized by abnormal alveolar septal wall deposits of calcium. It differs from MPC in that the deposits have been described as unstable, softer, and associated with

After absorption from the gut or entry into the circulation from the skin, vitamin D is hydroxylated to 25(OH)D by 25-hydroxylase enzyme in the liver and then to 1α,25(OH)D3 (or calcitriol) by 1α-hydroxylase enzyme in the kidney and in many cells. The hormonal or active form of vitamin D, that is, 1,25(OH)2D3 acts through a nuclear receptor (VDR) to carry out its many functions. The receptor has been recognized in a wide variety of tissues such as in osteoblasts, distal renal tubular cells, parathyroid gland cells, skin keratinocytes, lymphocytes, enterocytes, prostate, colon, pituitary gland, and ovaries. Many tissues in the body, express 1-hydroxylase and synthesize 1,25(OH)2D3 locally. Vitamin D has at least 2 distinct groups of functions. One is classically endocrine functions regulating PTH secretion and hence its own production. The other is autocrine functions (or paracrine): the cells or tissues concerned make and degrade active vitamin D locally to regulate their own proliferation and differentiation. Vitamin D supplementation can affect many aspects of health because function. Many epidemiologic studies have shown that chronic vitamin D deficiency is associated with an increased risk of diseases such as dementia, hypertension, multiple sclerosis, rheumatoid arthritis, cancer of the colon, prostate, breast, and ovary, and types 1 and 2 diabetes. In the general population and especially in patients with chronic kidney disease (CKD) has been reported. The reasons for hypovitaminosis D in CKD are not known but likely include reduced oral intake of vitamin D because of dietary restrictions and/or anorexia. In this special issue about vitamin D and kidney, Nordenstrom evaluated vitamin D status in patients operated for primary hyperparathyroidism (PHPT) and compared the patients from southern and northern Europe. These authors found that postmenopausal women with PHPT from Spain had lower preoperative levels of 25(OH)D and more severe PHPT Swedish patients, and patients with PHPT and vitamin D deficiency gained more bone density at some sites one year after parathyroidectomy. The effects of vitamin D on gentamicin-induced acute kidney injury in an experimental rat model were investigated by Hur et al. The authors reported that vitamin D does not seem to affect histological findings although some beneficial effects via Renin Angiotensin System and a promising effect on antioxidant system. Cardiometabolic risk factors related to vitamin D and adiponectin in obese children and adolescents were evaluated by Kardas et al. The authors showed that lower vitamin D and adiponectin levels were strongly associated with metabolic risk factors and obesity in children and adolescents. Kidney disease was found to be a major risk factor for vitamin D deficiency population study of both hospitalized and non-admitted patients. Significant independent predictors of vitamin D deficiency in inpatients and outpatients of a nephrology unit were retrospectively studied by Bentli. These authors showed that vitamin D deficiency is an important problem in both inpatients and outpatients of nephrology. Monitoring serum 25(OH)D concentrations regularly and replacement of vitamin D are important. Finally, Yildirim et al. report their findings on the association between inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, and leukocyte count) and the presence of CKD in vitamin D-deficient patients sedimentation rate, and leukocyte count, in vitamin D deficient patients with and without chronic kidney disease.

Hypovitaminosis D is associated with reduced survival, increased cardiovascular events, and impaired bone-mineral balance in dialysis. The KDOQI guidelines do not have specific recommendations regarding vitamin D (VitD) intake in dialysis patients. The purpose of this study was to determine whether stable prevalent hemodialysis (HD) patients, for whom standard clinical dietary restrictions had been recommended, were able to meet their Recommended Daily Allowance (RDA) for VitD. An observational study was conducted to examine serum 25-OHD levels in relation to 3-day diet analysis, supplementation, anthropometrics and nutritional status (using Malnutrition Inflammation Score (MIS)) in 81 HD patients. Sixty-nine completed 3-day dietary intake records (1 dialysis day, 1 non-dialysis day, 1 weekend-non-dialysis day). Mean dietary VitD intake of the group was 2.5 μg/day SD±3.6, which is less than 15% of RDA of ∼17 μg/day. Only 2 out of 69 subjects (3%) met the RDA for VitD with mean intakes of 20.8±2.6 μg/day that corresponded with mean serum 25OHD of 43.5±17.6 nmol/L. Mean serum 25OHD levels for the group were 42.4 ±23.1 nmol/L, with 19 classified as deficient (28% <27.5 nmol/L), 43 insufficient (62%=27.5–75 nmol/L) and only 7 sufficient (10% >75nmol/L) in terms of 25OHD levels. 20 of the 69 (29%) took a VitD supplement and had significantly higher serum 25OHD than ones who did not take any (53.7±17.3 nmol/L vs 38.7±22.4 nmol/L, p-value=0.013). Multiple regression analysis revealed dietary calcium (p=0.001), and dietary protein (p=0.006) were positively related and HD-vintage (p=0.037), inversely related to dietary VitD whereas total kilocalories, dietary phosphate, MIS and dry body mass did not relate to it. Thus, inadequate intake of VitD is a common (97%) and modifiable risk factor for hypovitaminosis D in HD patietns. Factors affecting reduced intake of VitD in our patients included dietary protein and calcium but not dietary phosphorous. VitD levels were low even in the face of adequate VitD intake through supplementation and/or dietary sources, and would need monitoring if target levels are to be met by the renal dietitians and nephrologists.

OBJECTIVE:Chronic kidney disease (CKD) is staged by glomerular filtration rate (GFR). CKD stages sometimes vary between routine office visits, and it is unknown if this impacts renal and patient survival separately from a cross-sectional CKD stage value. We quantified and categorized CKD stage variability in a large group of outpatients and correlated this with clinical and demographic features and with renal and patient survival.METHODS:All estimated GFRs were staged in the first observation period. CKD stages were then categorized as static, improving, worsening, or fluctuating. Logistic regression analysis was performed to identify clinical variables associated with CKD stage variability. Death and dialysis progression rates were then collected and analyzed using Cox proportional regression.RESULTS:During a 1.1-year observation period, 1,262 patients (mean age 71.25 years) had a mean 5 eGFR's. CKD stages were static in 60.4%, worsened in 14.4%, improved in 7.4%, and fluctuated in 17.2% of patients. Secondary analysis revealed heavy proteinuria and East Asian ethnicity to be negatively, and diabetes mellitus and previous acute kidney injury to be positively associated with improving CKD stages. Cox proportional regression of 902 patients analyzed 2.3 years later revealed a negative association with improving CKD stage and subsequent need for dialysis.CONCLUSIONS:CKD stage changed in 40% of 1,262 elderly patients when determined 5 times in just over 1 year. Improving CKD stage was the only variability pattern significantly associated with any of the clinical outcomes when assessed 2.3 years later, being unlikely to be linked with subsequent need for dialysis.

The adverse effects arising from late referral to a nephrologist of patients with chronic kidney disease (CKD) are well known. Retrospectively we examined the initial characteristics of patients referred in various stages of CKD to our nephrology division and tried to identify potential baseline factors associated with subsequent changes in estimated glomerular filtration rate (eGFR).

Background: We report our center's experience with the Toronto Western Hospital (TWH) catheter, and discuss our catheter survival and complication rates.Methods: Retrospective chart review of patients receiving peritoneal dialysis therapy via a TWH catheter. Catheter complication rates of peritonitis, exit site infection, obstruction, leak, and malfunction were assessed. A catheter was considered failed if removed because of exit site infection, obstruction, or malfunction. All other catheters, even if removed for other reasons, were considered censured. Survival was defined as the period from insertion to failure or censure date, and reported using Kaplan Meier analysis.Results: 192 patients with a total of 208 TWH catheters (4,845.3 catheter months) were analyzed. Our overall 1- and 3-year catheter survival rates were identical at 0.9182. Our catheter complication rates (expressed as number of catheter months per event) were 31.3 for peritonitis, 42.9 for exit site infection, 72.3 for obstruction, 538.4 for malfunction, and 969.1 for catheter leak. Our findings were similar to those reported in the literature for TWH and other peritoneal catheters.