BACKGROUND:Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are a crucial therapy for chronic kidney disease (CKD), yet concerns persist regarding their impact on bone metabolism. This systematic review evaluates the skeletal safety and metabolic effects of SGLT2i in patients with CKD. METHODS:A systematic review of randomized controlled trials (RCTs) and observational cohort studies was conducted. Data on study design, population characteristics, baseline kidney function, bone-related comorbidities, and outcomes (osteoporosis, fractures, falls, amputations, and bone mineral markers) were summarized. Risk of bias was evaluated according to the included category. RESULTS:The analysis revealed that while one RCT and a cohort study reported a significantly increased risk of bone fracture and amputation, this finding was not replicated in other subsequent cohort studies and other RCTs, which generally showed non-significant differences. Of note, the reporting of bone-related outcomes was inconsistent throughout the literature, and a substantial proportion of the evidence derives from studies primarily designed for patients with type 2 diabetes, largely involving early-stage CKD subgroups. One study suggests that SGLT2i may favorably modulate markers of CKD-mineral bone disease (MBD), reporting reduced risk of hyperphosphatemia, hypocalcemia, high parathyroid hormone, and low vitamin D levels. The reviewed literature primarily included data on empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin. CONCLUSIONS:Mostly, SGLT2i demonstrated a possible reassuring skeletal safety profile in CKD. Initial safety concerns regarding fractures have not been consistently supported, although evidence in moderate-to-advanced CKD remains limited. Long-term, prospectively defined skeletal outcomes are needed to confirm these findings and clarify class effects.

Background Advanced chronic kidney disease (CKD) is associated with sleep disturbances, which in turn are linked to cardiovascular morbidity in the general population. However, few studies have examined these associations in individuals with mild to moderate CKD. We aimed to evaluate the association between mild to moderate CKD and sleep disturbances, and the association between sleep disorders and cardiovascular health in this population.Methods We conducted a retrospective study from a cohort of community-dwelling individuals aged 40 to 69 years old. Participants with an estimated glomerular filtration rate (eGFR) lower than 30 mL/min/1.73 m2 were excluded. The association between CKD and the risk of developing sleep disorders during follow-up, as identified through administrative health databases, was evaluated using Cox proportional hazards models adjusted for age, sex, lifestyle factors, and chronic comorbidities. The associations between sleep disorders or self-reported frequent sleeping difficulties at baseline and the risk of cardiovascular events were also examined using adjusted Cox models. All analyses were stratified according to eGFR categories.Results We included 19 973 individuals (mean age 54.2 ± 7.8 years, female 51.6%, 47.0% CKD stage G2, 3.9% CKD stage G3). There were 1299 diagnoses of sleep disorders after a median follow-up of 11.6 years. Stage G3 was associated with an increased risk of sleep disorders (Hazard Ratio [HR] = 1.30, 95% Confidernce Interval [CI]:1.01-1.65). We observed 2213 cardiovascular events during follow-up. Sleep disorders were associated with a higher risk of cardiovascular events in individuals with stage G2 (HR = 2.04, 95% CI:1.49-2.79), while having frequent sleeping difficulties "more than half of the days" was associated with cardiovascular event risk in individuals without CKD (HR = 1.42, 95% CI:1.16-1.72).Conclusions individuals with moderate CKD had a higher risk of sleep disorders. The cardiovascular risk associated with sleep disturbances was influenced by eGFR category.

We describe a family with 11 members affected by oral, facial and digital findings, as well as adult-onset multiple long bone insufficiency fractures mimicking atypical femur fractures (AFF) on radiographs. The analysis of the pedigree of this family suggested an X-linked dominant inheritance. We performed whole-exome sequencing in this family. A rare novel variant, p.Ala642Asp (NM_003611, c.1925C>A, hg19) of the OFD1 gene was the only candidate on the X chromosome segregating with the phenotype within the family. The OFD1 gene targeted sequencing was carried out on 49 patients with AFF and 100 healthy controls. We detected another rare variant, p.Lys668Asn (NM_003611, c.2004G>C, hg19) of the OFD1 gene, in a woman with AFF. The structure of OFD1 protein has been predicted by AlphaFold 3 (AF3). According to the AF3 model of OFD1, the destabilization of the dimerization of OFD1 by the p.Ala642Asp variant and the breaking of ionic bond by the p.Lys668Asn variant could be pathogenic. This family demonstrates that such insufficiency fractures of long bones may occur in patients with oral-facial-digital syndrome and provides novel insight into the pathophysiology of these fractures and their association with dental and facial hypoplasia.

INTRODUCTION:We aimed to assess whether Paget's disease of bone (PD) increases the risk of major adverse cardiovascular events (MACE) and arterial stiffness in middle-aged men and women. METHODS:We analyzed data from the CARTaGENE cohort, including individuals aged 40-69 years, recruited in the province of Quebec, Canada in 2009/2010, linked to healthcare administrative databases to identify PD and MACE (both before and after recruitment, 1997-2021). Comorbidities and arterial stiffness parameters (augmentation index, estimated pulse wave velocity) were measured at recruitment. Cardiovascular risk factors were compared in an age-standardized population. MACE was defined as 3-component (myocardial infarction, stroke, cardiovascular death) or 5- component (3-point + heart failure, unstable angina) variables. Time-to-event analyses (from birth) used Cox and Fine-Gray models in a 1:3 propensity-score matched population, and associations with arterial stiffness were tested with linear and logistic regressions. RESULTS:Among 19,990 participants, 101 (0.5%) had PD. PD participants were older (57.5 ± 7.7 vs 54.2 ± 7.9 years) and had a higher prevalence of diabetes (22.4% vs 9.9%) than participants without PD. Ten (10%) MACE-3 and 15 (15%) MACE-5 occurred in the PD group versus 18 (6%) and 24 (8%) in the matched sample (n = 303). Hazard ratios were 1.86 (95%CI 0.80-4.34) for MACE-3 and 2.06 (95%CI 1.06-4.04) for MACE-5. Competing risk models yielded similar results. No significant associations were observed with arterial stiffness parameters. CONCLUSION:PD was associated with an independently increased risk of MACE, but not with arterial stiffness.

Cardiovascular disease is the leading cause of mortality in patients with chronic kidney disease (CKD), and it is exacerbated by vascular calcification (VC). This pathological deposition of hydroxyapatite in blood vessels leads to arterial and organ dysfunction, yet no effective treatment is currently available. Herein, we developed poly(ethylene glycol)-b-poly(lactic acid) (PEG-PLA) nanoparticles functionalized with tetracycline to target VC, given the antibiotic's strong affinity for hydroxyapatite. In rats with CKD, rats with CKD and VC, or healthy animals, we compared the circulation and biodistribution profiles of nanoparticles, as well as the urinary elimination of PEG. Blood and organ analyses revealed similar blood and tissue exposures, with no significant nanoparticle or PEG accumulation in the body. In the same model, we demonstrated that encapsulating vitamin K, a possible inhibitor of VC, alters the pharmacokinetics of the model drug and may enhance its systemic exposure. We employed various methodologies to assess the terminal distribution of nanoparticles in the calcified vascular wall. This work advances our understanding of how kidney disease and vascular calcification can alter the pharmacology of nanoparticles. However, further studies will be necessary to refine tetracycline-based targeting strategies and optimize nanomedicine approaches for VC treatment.

PURPOSE:To assess the feasibility and safety of percutaneous peritoneal dialysis (PD) catheter insertion in obese patients. MATERIALS AND METHODS:This single-center retrospective study included 125 consecutive patients who underwent PD catheter insertion by an interventional radiologist. Patients were categorized by body mass index (BMI): <25 kg/m2 (normal weight, n = 61), 25-29.9 kg/m2 (overweight, n = 40), and ≥30 kg/m2 (obese, n = 24). Most obese patients had Class I obesity (BMI, 30-34.9 kg/m2), with only 2 having a BMI of >35 kg/m2. Catheter-related adverse events within 1 year were recorded. The primary outcome was catheter failure (replacement, surgical repositioning, or PD discontinuation due to dysfunction). Death, transplantation, and renal recovery were considered competing events. Failure risk was assessed using the cumulative incidence function, and the effect of BMI categories was estimated by a Fine and Gray model. Adverse events were analyzed using a robust Poisson method. RESULTS:Within 1 year, 36 catheter failures (28.8%) occurred, 3 patients died, and 7 underwent kidney transplantation before catheter failure. BMI was not significantly associated with catheter failure (subdistribution hazard ratios, overweight, 0.89 [95% CI, 0.45-1.78], and obese, 0.60 [95% CI, 0.23-1.59]). Sixty patients (48.0%) experienced at least 1 adverse event: 50.8%, 50.0%, and 37.5% in normal-weight, overweight, and obese patients, respectively (relative risk obese vs normal, 0.75 [95% CI, 0.41-1.36]). CONCLUSIONS:Class I obesity was not associated with a higher risk of adverse events, supporting the safety and feasibility of percutaneous PD catheter insertion. However, these findings should be interpreted with caution given the limited sample size.

ABSTRACT Background Frailty is a clinical syndrome that is particularly prevalent in patients with chronic kidney disease (CKD). We aimed to assess the associations between renal function and the presence of frailty criteria and to assess the association between frailty and bone outcomes. Methods We have conducted a retrospective study from a population-based cohort, which represents 1% of people aged 40–69 years in a Canadian province, excluding individuals with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2. Frailty was defined with Fried's criteria. Bone density was estimated with quantitative ultrasound at the calcaneus measuring speed of sound (SOS) and broadband ultrasound attenuation (BUA). Time to first fracture event was assessed and analyses were conducted using logistic regressions, multiple linear regressions and Cox models. Results Overall, 19 973 individuals were included: mean ± standard deviation age 54.2 ± 7.8 years, women 51.6%, 47.0% CKD stage G2, 3.9% CKD stage G3, 34.8% with at least one frailty criterion. We observed a U-shaped association between eGFR and the odds ratio (OR) of presenting at least one frailty criterion, with a minimum OR around 77 mL/min/1.73 m2 [per a 10 mL/min/1.73 m2 increase, respectively, for an eGFR <77 and >77, OR = 0.93, 95% confidence interval (CI) 0.86–1.01 and OR 1.09, 95% CI 1.06–1.13]. After a median follow-up of 5.8 years, there were 837 fracture events. Having at least one frailty criterion was negatively associated with SOS (β = –3.97, P < .0001) and BUA (β = –1.82, P < .0001). Having at least one frailty criterion was associated with a higher fracture risk (hazard ratio 1.23, 95% CI 1.07–1.42). Conclusion In conclusion, having at least one frailty criterion was associated with a higher risk of fracture and a lower bone mineral density.

Context:Quantitative ultrasound (QUS) can estimate bone mineral density and predict fracture risk, but its association with cardiovascular outcomes remains unclear. Objective:We aimed to assess the associations between bone QUS parameters and cardiovascular event risk, cardiovascular mortality (CVM) and all-cause mortality (ACM). Data Sources:Pubmed, Embase, Cochrane Library databases, and grey literature were searched. Study Selection:We considered studies including people aged >40 years who reported associations between bone QUS parameters (any bone site) and our outcomes. Data Extraction:Two reviewers selected eligible studies, extracted and analyzed data, and assessed risk of bias with the Risk of Bias in Non-randomized Studies of Exposure tool. Adjusted hazard ratios (HR) with 95% confidence intervals (CIs), estimated for 1 SD reduction of QUS parameters, were pooled using random effects meta-analyses. Data Synthesis:We included 9 studies with 275 to 477 683 (median = 3244) participants (follow-up duration range 2.8-12.8 years). All studies presented associations based on calcaneal QUS parameters; only 2 reported associations with cardiovascular events with discordant results. Seven studies reported associations with CVM and 7 with ACM. Meta-analyses based on 3 studies showed that broadband ultrasound attenuation (BUA) was inversely associated with CVM (HR = 1.22, 95% CI: 1.11-1.34, I 2 = 0%) and ACM (HR = 1.16, 95% CI: 1.10-1.23, I 2 = 0%). Meta-analyses, based on 4 and 3 studies, respectively, showed that speed of sound (SOS) was also inversely associated with CVM (HR = 1.19, 95% CI: 1.11-1.27, I 2 = 29%) and ACM (HR = 1.15, 95% CI: 1.07-1.23, I 2 = 0%). Conclusion:In a cohort of middle-aged individuals, a decrease in calcaneal BUA and SOS were both independently associated with higher cardiovascular and ACM.

Background:Adequate vitamin D is essential for maintaining optimal bone health, preventing and treating of osteoporosis. However, in recent years, large clinical trials and meta-analyses on the efficacy of vitamin D supplementation to prevent fractures in populations at different risks have been equivocal. The optimal level of 25-hydroxyvitamin D (25[OH]D) remains controversial. Recommendations vary between societies. The lack of standardized assays also poses a challenge in interpreting available research data. Methods:We systematically searched for articles in MEDLINE database through PubMed, which included meta-analysis, systematic reviews of randomized controlled trials (RCTs) and observational studies that assessed measurement, diagnosis and treatment about vitamin D deficiency. The experts evaluated the available literature, graded references according to the type of study and described the strength recommendations. Results:This expert consensus is based on the review of relevant clinical evidence and provides nine key recommendations on vitamin D deficiency in populations at different risks, especially in patients with osteoporosis. Supporting information is provided in the subsequent appendix box. Conclusions:This expert consensus is a practical tool for endocrinologists, general physicians for the diagnosis, assessment, and treatment of populations at different risks of vitamin D deficiency, especially in patients with osteoporosis. Clinicians should be aware of the evidence but make individualized decisions based on specific patients or situation.

A 63-year-old woman who had been on continuous cycling peritoneal dialysis (PD) for 24 months for end-stage kidney disease due to a homozygous required for meiotic nuclear division 1 homolog (RMND1) mutation was evaluated for a 3-kg weight gain and reduced dialysate effluent in less than a week. RMND1 mutation is a mitochondriopathy also leading to myopathy, leukopenia, ovarian insufficiency, and sensorineural hearing loss. Use of higher concentrations of dextrose solutions was unable to restore dry weight. Physical examination results were unremarkable, except for slight bilateral ankle edema. Notably, there was no evidence of cutaneous fluid accumulation over the abdomen and lumbar region. Biochemistry values were as usual. Peritoneal membrane permeability test did not suggest a membrane failure. Computed tomography scan with intraperitoneal contrast injection showed unusual dialysate leakage in the right anterior and posterior pararenal space (Figure 1a). The patient was temporarily transferred to hemodialysis. After 6 weeks, continuous cycling PD was progressively resumed over a 4-week period to the prior parameters. Computed tomography scan peritoneography performed 1 week and 1 month after PD restart did not reveal any leakage, and PD exchanges have been proceeding normally since then (Figure 1b). Dialysate leaks are common complications of PD but rarely manifest as retroperitoneal leakage in patients undergoing continuous cycling PD. As the patient was practicing physical exercises regularly, we suspect that abrupt increases in intra-abdominal pressure may have contributed to the occurrence of a communication between the parietal peritoneum and pararenal space. No association has yet been described between mitochondriopathy and peritoneal abnormalities. This case highlights the utility of computed tomography scan peritoneography for revealing dialysate leaks and the need to carefully investigate the possibility of retroperitoneal leak in patients undergoing PD. Finally, the occurrence of retroperitoneal leak should not discourage clinicians from resuming PD. All the authors declared no competing interests.

Purpose of Review This review aims to describe the pathogenic factors involved in bone-vessel anomalies in CKD which are the object of numerous experimental and clinical research. Recent Findings Knowledge on the pathophysiological mechanisms involved in the regulation of vascular calcification and mineral-bone disorders is evolving. Specific bone turnover anomalies influence the vascular health while recent studies demonstrate that factors released by the calcified vessels also contribute to bone deterioration in CKD. Current therapies used to control mineral dysregulations will impact both the vessels and bone metabolism. Available anti-osteoporotic treatments used in non-CKD population may negatively or positively affect vascular health in the context of CKD. It is essential to study the bone effects of the new therapeutic options that are currently under investigation to reduce vascular calcification. Summary Our paper highlights the complexity of the bone-vascular axis and discusses how current therapies may affect both organs in CKD.

Key Points Is performing a large definitive trial to establish the optimal anticoagulation strategy in dialysis recipients with atrial fibrillation feasible?One hundred fifty-one patients at 28 dialysis centers were enrolled and randomized to apixaban (n=51), warfarin (n=52), or no oral anticoagulation (n=48).Despite coronavirus disease–related pauses, recruitment was completed in 30 months, with 83% of participants completing follow-up in their assigned treatment arm. Background Atrial fibrillation is common in individuals receiving dialysis. The role of oral anticoagulation in this population is uncertain given its exclusion from previous seminal clinical trials. Our objective was to determine the feasibility of performing a large definitive trial to establish the optimal anticoagulation strategy in individuals with atrial fibrillation receiving dialysis. Methods The Strategies for the Management of Atrial Fibrillation in Patients Receiving Dialysis trial was a parallel-group, open-label, allocation-concealed, pilot randomized control trial that took place at 28 centers in Canada and Australia. The trial included adults (18 years or older) undergoing dialysis with a history of nonvalvular atrial fibrillation who met the CHADS-65 criteria. Participants were randomized 1:1:1 to receive dose-adjusted warfarin, apixaban 5 mg twice daily, or no oral anticoagulation and followed for 26 weeks. The primary outcomes evaluated the following measures of feasibility: (1) recruitment of the target population within 2 years from the start of the trial and (2) adherence of >80% of randomized patients to the allocated treatment strategy at the conclusion of follow-up. Secondary outcomes included stroke and bleeding. Results From December 2019 to June 2022, 151 patients were enrolled and randomized to apixaban (n=51), warfarin (n=52), or no oral anticoagulation (n=48). Allowing for pauses related to the coronavirus disease pandemic, recruitment was completed in 30 months, and 123 (83%) of participants completed follow-up in their allocated treatment arm. There was one adjudicated stroke event. Eight participants had a major bleeding event (four warfarin, two apixaban, two no oral anticoagulation). Death occurred in 15 participants (nine warfarin, two apixaban, four no oral anticoagulation). Time in the therapeutic range for warfarin recipients was 58% (interquartile range, 47%–70%). Conclusions We have demonstrated the feasibility of recruitment and adherence in a trial that compared different anticoagulation strategies in patients with atrial fibrillation receiving dialysis. Clinical Trial registry name and registration number: Strategies for the Management of Atrial Fibrillation in Patients Receiving Dialysis (SAFE-D), NCT03987711.

Background Atrial fibrillation is common in individuals receiving dialysis. The role of oral anticoagulation in this population is uncertain given its exclusion from previous seminal clinical trials. Our objective was to determine the feasibility of performing a large definitive trial to establish the optimal anticoagulation strategy in individuals with atrial fibrillation receiving dialysis. Methods The Strategies for the Management of Atrial Fibrillation in Patients Receiving Dialysis trial was a parallel-group, open-label, allocation-concealed, pilot randomized control trial that took place at 28 centers in Canada and Australia. The trial included adults (18 years or older) undergoing dialysis with a history of nonvalvular atrial fibrillation who met the CHADS-65 criteria. Participants were randomized 1:1:1 to receive dose-adjusted warfarin, apixaban 5 mg twice daily, or no oral anticoagulation and followed for 26 weeks. The primary outcomes evaluated the following measures of feasibility: (1) recruitment of the target population within 2 years from the start of the trial and (2) adherence of >80% of randomized patients to the allocated treatment strategy at the conclusion of follow-up. Secondary outcomes included stroke and bleeding. Results From December 2019 to June 2022, 151 patients were enrolled and randomized to apixaban (n=51), warfarin (n=52), or no oral anticoagulation (n=48). Allowing for pauses related to the coronavirus disease pandemic, recruitment was completed in 30 months, and 123 (83%) of participants completed follow-up in their allocated treatment arm. There was one adjudicated stroke event. Eight participants had a major bleeding event (four warfarin, two apixaban, two no oral anticoagulation). Death occurred in 15 participants (nine warfarin, two apixaban, four no oral anticoagulation). Time in the therapeutic range for warfarin recipients was 58% (interquartile range, 47%-70%). Conclusions We have demonstrated the feasibility of recruitment and adherence in a trial that compared different anticoagulation strategies in patients with atrial fibrillation receiving dialysis.

It is unclear if AGEs are involved in the bone fragility of type 1 diabetes (T1D). We evaluated whether skin AGEs by skin autofluorescence and serum AGEs (pentosidine, carboxymethyl-lysine [CML]) are independently associated with BMD by DXA (lumbar spine, hip, distal radius), trabecular bone score (TBS), serum bone turnover markers (BTMs: CTX; P1NP; osteocalcin), and sclerostin in participants with and without T1D. Linear regression models were used, with interaction terms to test effect modification by T1D status. In participants with T1D, correlations between skin and serum AGEs as well as between AGEs and 3-year HbA1C were evaluated using Spearman's correlations. Data are mean ± SD or median (interquartile range). We included individuals who participated in a cross-sectional study and had BMD and TBS assessment (106 T1D/65 controls, 53.2% women, age 43 ± 15 yr, BMI 26.6 ± 5.5 kg/m2). Participants with T1D had diabetes for 27.6 ± 12.3 yr, a mean 3-yr HbA1C of 7.5 ± 0.9% and skin AGEs of 2.15 ± 0.54 arbitrary units. A subgroup of 65 T1D/57 controls had BTMs and sclerostin measurements, and those with T1D also had serum pentosidine (16.8[8.2-32.0] ng/mL) and CML [48.0 ± 16.8] ng/mL) measured. Femoral neck BMD, TBS, and BTMs were lower, while sclerostin levels were similar in participants with T1D vs controls. T1D status did not modify the associations between AGEs and bone outcomes. Skin AGEs were significantly associated with total hip and femoral neck BMD, TBS, BTMs, and sclerostin before, but not after, adjustment for confounders. Serum AGEs were not associated with any bone outcome. There were no significant correlations between skin and serum AGEs or between AGEs and 3-yr HbA1C. In conclusion, skin and serum AGEs are not independently associated with BMD, TBS, BTMs, and sclerostin in participants with relatively well-controlled T1D and participants without diabetes.

In their cohort study, Kittrakulrat et al. reported that in patients with advanced chronic kidney disease (CKD), a shorter interval between HBV vaccination doses led to a significantly higher seroconversion rate 1Kittrakulrat J. Tiankanon K. Kerr S.J. et al.A Randomized Controlled Study of Efficacy and Safety of Accelerated Versus Standard Hepatitis B Vaccination in Patients With Advanced CKD.Kidney International Reports. 2024/04/01/ 2024; 9: 853-862https://doi.org/10.1016/j.ekir.2024.01.014Abstract Full Text Full Text PDF Scopus (0) Google Scholar. This finding is in line with our findings on the response rate to SARS-CoV-2 vaccinations in patients receiving hemodialysis. We conducted a prospective cohort study of chronic hemodialysis patients without prior SARS-CoV-2 infection from 7 centers. Patients received two doses of SARS-CoV-2 mRNA vaccine at variable dosing intervals (21 to 113 days) (Figure 1A). We assessed anti-receptor binding domain (RBD) IgG levels 3-6 weeks after each dose, and evaluated if dosing interval was associated with "positive anti-RBD response" (IgG level >10 relative light units (RLU)). In our cohort, 85/400 (21%) had positive anti-RBD response after one dose, compared to 19/20 healthy controls (p< p<0.0001). Of the 315 who did not respond to the first dose, 258 (82%) developed positive anti-RBD response after the second dose. Importantly, a longer interval between doses was associated with lower risk of eliciting anti-RBD IgG to the 2nd dose, contrary to what is observed in immunocompetent individuals 2Grunau B. Goldfarb D.M. Asamoah-Boaheng M. et al.Immunogenicity of Extended mRNA SARS-CoV-2 Vaccine Dosing Intervals.JAMA. 2021; https://doi.org/10.1001/jama.2021.21921Crossref Scopus (51) Google Scholar, 3Tauzin A. Gong S.Y. Beaudoin-Bussières G. et al.Strong humoral immune responses against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a 16-week interval between doses.Cell Host Microbe. Jan 12 2022; 30: 97-109.e5https://doi.org/10.1016/j.chom.2021.12.004Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 4Payne R.P. Longet S. Austin J.A. et al.Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine.Cell. Nov 11 2021; 184: 5699-5714.e11https://doi.org/10.1016/j.cell.2021.10.011Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar. In unadjusted analyses, dialysis duration, use of immunosuppressive medication, and dosing interval were each significantly associated with lower risk of developing anti-RBD IgG levels >10 RLU, whereas diabetes, age, and sex were not (Table S2). In multivariable analyses, an interval of >=8 weeks between doses was independently associated with lower odds of developing a positive anti-RBD IgG responses after the second dose (adjusted odds ratio 0.41, 95% CI 0.21-0.78, p=0.007) (Table S3). A positive anti-RBD response was observed in 120/137 (88%) who received the two doses <8 weeks apart, compared to 138/178 (78%) in those who received their doses >8 weeks apart, with median anti-RBD IgG levels significantly lower in the latter group (Figure 1B&C). In conclusion, our findings align with the current study, namely that shorter intervals between vaccine doses improve seroconversion rates in CKD and dialysis. Efforts to evaluate optimal vaccine dosing intervals in patients with kidney disease for all vaccinations should be encouraged. This work was funded by the Canadian Institutes of Health Research, grant no. 447760 to RSS, by le Ministère de l'Économie et de l'Innovation du Québec, Programme de soutien aux organismes de recherche et d'innovation to A.F. and by the Fondation du CHUM. This work was also supported by the following to A.F.: CIHR foundation grant #352417, CIHR operating Pandemic and Health Emergencies Research grant #177958, CIHR stream 1 and 2 for SARS-CoV-2 Variant Research, and Exceptional Fund COVID-19 from the Canada Foundation for Innovation (CFI) #41027. A.F. is the recipient of Canada Research Chair on Retroviral Entry no. RCHS0235 950-232424. D.E.K. is a FRQS Merit Research Scholar. RS, RG, ACNF, FM, CL and WBS were/are supported by the Fonds de Recherche du Québec – Santé (FRQS) Clinician-Researcher Awards. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.