Background:Kidney transplant recipients face a high risk of adverse events, including fractures. Reported fracture rates post-transplant vary widely and may have changed over time. The consequences of a fracture, especially subsequent fractures, remain under-investigated. This study examined the risk and prognosis of fractures after kidney transplantation in the current era. Methods:This retrospective cohort study included all adults who received a first single-organ kidney transplant between 2000 and 2022 in Denmark. Nationwide healthcare registries were utilized to identify the study population and provide demographic data, diagnostic and procedural codes, and prescription data. Cumulative incidence (risk) of both first fracture and subsequent fracture was computed, treating death as a competing risk. Crude, and sex- and age-standardized incidence rates were estimated for different time periods. Results:The study included 3977 first kidney transplant recipients, of whom 788 sustained any post-transplant fracture. The 10-year risk of fracture was 21% (95% confidence interval 20-23). Crude incidence rates of any fracture remained unchanged over time, while standardized estimates showed a slight decline. Fractures were primarily located at the peripheral skeleton. Twenty-eight percent of patients with a fracture sustained a subsequent fracture, with the highest incidence at 6-12 months following the first event. Conclusions:Kidney transplant recipients remain at high fracture risk, with unchanged fracture rates over the past 20 years. The imminent fracture risk following a first fracture is high and largely unaddressed. Although formal guidelines have yet to be established, this knowledge should urge clinicians to perform risk assessment and consider intervention following a post-transplant fracture.

Skeletal fragility has long been overlooked by the nephrology community despite patients with chronic kidney disease (CKD) facing double the risk of hip fracture compared with the general population. Consequently, the term CKD-associated osteoporosis was recently coined to increase awareness. In this context, vertebral fractures are even less studied. Vertebral fractures predict increased fracture risk, and especially in advanced CKD, show a strong association with aortic and iliac vascular calcifications and cardiovascular events such as myocardial infarction. The scope of the present consensus paper is to comprehensively discuss the management of skeletal fragility in CKD patients, from diagnosis to treatment, with a particular focus on vertebral fractures in CKD G4-G5D.

This systematic review and meta-analysis evaluated complication rates and diagnostic yield reported in studies of adult native kidney biopsy using 16-gauge (16 G) or 18-gauge (18 G) needles. We included randomized trials and cohort studies of real-time ultrasound-guided biopsies, including case series. MEDLINE, Embase, and CENTRAL were searched through October 2024. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using Joanna Briggs Institute tools. Random-effects meta-analyses estimated pooled proportions with 95% confidence intervals (CI), and univariable random-effects meta-regression explored study-level associations with major complications, transfusion, or gross hematuria. We screened 4,499 titles and abstracts and reviewed 319 full-text articles; 62 studies comprising 68 biopsy series were included. The pooled major complication rate in studies using 16 G needles was 1.83% (95% CI: 1.20-2.79) and 1.29% (95% CI: 0.78-2.13) in studies using 18 G needles, with no statistically significant difference. Mean glomerular yield was 18.8 with 16 G and 17.5 with 18 G needles. In study-level meta-regression, studies with higher prevalence of acute kidney injury, lower mean estimated glomerular filtration rate, or lower mean hemoglobin reported higher pooled complication rates. Most studies were single-arm cohorts; between-needle differences therefore reflect indirect study-level contrasts. Interpretation is limited by retrospective design and heterogeneity across studies. Overall, studies using both needle sizes reported low complication rates and similar diagnostic yield, although definitions and reporting varied. Direct comparative studies are needed to determine whether meaningful differences exist.

Brief rationale: The impact of non-dialysis chronic kidney disease (CKD) on combined muscle and bone decline remains insufficiently described. Main result: Patients with CKD showed markedly higher rates of sarcopenia, osteoporosis, and osteosarcopenia than matched healthy controls. Significance of the paper: These findings support systematic evaluation of muscle and bone health in CKD management. Chronic kidney disease (CKD) negatively affects bone and muscle quality. The combination of sarcopenia and osteoporosis, osteosarcopenia, is associated with an increased risk of fractures and mortality. Yet, little is known about osteosarcopenia in patients with non-dialysis-dependent CKD compared to healthy controls. We hypothesized that patients with CKD have a higher prevalence of osteosarcopenia than healthy adults. In this cross-sectional study, 138 patients with CKD stages G4-5 were matched 1:1 on sex and age to healthy controls. We assessed appendicular lean mass and bone mineral density (BMD) at the hips and lumbar spine using dual-energy X-ray absorptiometry and evaluated muscle strength through handgrip strength, 30-s chair stands, and 10-m gait speed. Sarcopenia was defined using the criteria by the EWGSOP criteria, osteoporosis by the WHO criteria, and osteosarcopenia required the presence of both. CKD participants had weaker handgrip strength, poorer chair-stand performance, and slower gait speed compared to healthy controls. BMD was reduced in patients with CKD. The prevalence of sarcopenia (21.7

Currently, no consensus exists on either terminology, definition, or the biological significance of the phenomena intratrabecular tunneling. Despite this, observations of intratrabecular tunneling are frequently reported in literature covering diseases or treatments involving parathyroid hormone or kidneys. A few attempts to quantify this phenomena have been made mainly based on bone resorption, despite the concurrent presence of bone formation. This study demonstrates that intratrabecular tunneling is a previously unrecognized physiological mode of intratrabecular bone remodeling occurring across conditions and ages. Similar to intracortical remodeling, it is induced by PTH-treatment and creates an extensive interconnected tunnel-network that hollows out the trabeculae. This study primarily utilizes iliac crest bone biopsies collected from a clinical trial where patients with hypoparathyroidism were randomized to receive daily injections with either 100μg rhPTH(1-84) or placebo as add-on to conventional therapy for 6 months. In addition, further bone biopsies were collected from a 24-month open-label extension study, including patients receiving either only conventional treatment, continued rhPTH-treatment or discontinued rhPTH-treatment. Histomorphometry demonstrated that PTH-treatment induced an 18-fold and 36-fold increase in intratrabecular porosity after 6 and 30 months of treatment, respectively. After 6-months of PTH- versus conventional treatment, a median 7.7% versus 0.0% were eroded pores, 69.1% versus 0.0% were eroded-formative pores, 12.9% versus 0.0% were formative pores and 0.9% versus 81.2% were quiescent pores. PTH-treatment withdrawal normalized the intratrabecular remodeling to levels similar to conventional therapy. The intratrabecular remodeling mainly occurred in plates and junctions of trabeculae, and not in trabecular rods. Intratrabecular remodeling parameters showed a positive correlation with PTH-induced trabecular mineralization and a negative correlation with active vitamin D-supplementary doses. Dynamics of the PTH-induced intratrabecular remodeling could be tracked using time-lapsed synchrotron radiation μCT in a rabbit model and the complexity of the trabecular strain environment was confirmed with micro-finite-element analysis.

KEY POINTS:Far infrared radiation did not improve the proportion of interventions in arteriovenous fistulas in patients on hemodialysis after 12 months of treatment. No difference was seen between treatment groups in time to intervention, number of thrombosed fistulas, and change in access flow. This study does not support the effect of far infrared radiation on fistula survival as proposed in previous vascular access guidelines. INTRODUCTION:In patients on hemodialysis, the risk of arteriovenous fistula (AVF) failure is unacceptably high. Up to 67% of AVFs need an intervention within 1 year after placement. There are no effective treatments to prolong AVF longevity. Far infrared radiation (FIR) treatment has been suggested to enhance AVF survival. The present trial investigated the effect of FIR on the proportion of interventions in the AVF. METHODS:In a multicenter, randomized, controlled trial, patients were allocated to receive FIR treatment or no FIR. Eligible patients were patients on chronic hemodialysis with a well-functioning AVF. The FIR group received FIR above the skin of their AVF for 40 minutes at every hemodialysis session for 1 year. The primary outcome was the difference in the proportion of patients with at least one intervention (thrombectomy or percutaneous transluminal angioplasty) after 12 months. The chi-squared test analyzed the difference. Secondary outcomes included differences in the number of thrombosed AVFs, intervention rate, access flow at various time points, and time to first intervention between groups. RESULTS:A total of 115 patients were randomized to the FIR group ( n =58) or the control group ( n =57). Baseline characteristics were similar in both groups. There was no significant difference in the proportion of patients with interventions between the FIR and control groups (19% versus 28%, P = 0.25) or in the proportion with thrombosed AVFs (5% versus 3%, P = 0.26). Time to first intervention was 164 (interquartile range, 86-272) days in the FIR group and 127 (interquartile range, 44-164) days in the control group ( P = 0.26). No differences in the change of access flow occurred ( P = 0.86). CONCLUSION:During 12 months of treatment, FIR did not affect the overall patency of the AVF. No difference was found in the number of patients with interventions or in any of the secondary endpoints (Clinicaltrials.gov: NCT04011072 ). CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:Clinicaltrials.gov: NCT04011072.

AIMS:Respiratory syncytial virus (RSV) is a common cause of severe illness in older adults and may cause extra-pulmonary complications. Individuals with chronic kidney disease (CKD) are at increased risk of severe outcomes from respiratory infections, but RSV-specific data are limited. This prespecified analysis of the DAN-RSV trial evaluated the RSV prefusion F protein-based vaccine (RSVpreF) effectiveness (VE) in adults aged ≥60 years with and without CKD. METHODS AND RESULTS:The DAN-RSV trial was a pragmatic, open-label, parallel-group, individually randomized clinical trial conducted during 2024/25. Adults aged ≥60 years were randomized 1:1 to receive respiratory syncytial virus prefusion F (RSVpreF) or no vaccine. Chronic kidney disease was identified using diagnosis codes and biomarkers. Outcomes were assessed through nationwide registry linkage from 14 days post-randomization to 31 May 2025. The primary outcome was RSV-related respiratory tract disease hospitalization; secondary outcomes included respiratory, cardiovascular, and kidney-related hospitalizations, and all-cause mortality. Among 131 276 participants (65 642 RSVpreF; 65 634 controls), 13 364 (10.2%) had CKD. Chronic kidney disease participants were older and had more comorbidities. Hospitalization rates were consistently higher among those with CKD. RSVpreF compared with no vaccine reduced RSV-related respiratory tract disease hospitalization [overall VE: 83.3% (95% confidence interval, CI: 42.9-96.9%); CKD VE: 66.4% (95% CI: -85.2 to 96.7%); no CKD VE: 91.7% (95% CI: 43.7 to99.8%), Pinteraction = 0.29], and cardiorespiratory hospitalization, irrespective of CKD status. Among participants with CKD, a numerical imbalance in mortality was observed; however, event numbers were limited. CONCLUSION:In this analysis of the DAN-RSV trial, RSVpreF vaccination reduced RSV-related, broader respiratory and cardiorespiratory hospitalizations in older including those with CKD. No significant differences were observed for acute kidney outcomes.

PURPOSE OF REVIEW:Secondary hyperparathyroidism remains a universal complication of chronic kidney disease (CKD), yet evidence-based treatment targets for parathyroid hormone (PTH) are lacking. This review revisits the pathophysiology of secondary hyperparathyroidism with emphasis on PTH as a master regulator of both calcium and phosphate homeostasis and discusses emerging treatment targets beyond PTH. RECENT FINDINGS:Recent data reinforce the role of phosphate burden as a central driver of hyperparathyroidism in CKD. At the same time, publications from recent years highlight substantial heterogeneity in skeletal responsiveness to PTH with discordance between PTH levels and bone turnover. Observational data continue to demonstrate nonlinear associations between PTH levels and patient-relevant outcomes, while interventional trials defining optimal PTH targets remain scarce. Recent consensus statements propose the use of nonkidney-cleared bone turnover markers as a supplemental noninvasive tool to better assess skeletal remodeling activity and guide treatment decisions. SUMMARY:PTH levels do not adequately reflect skeletal remodeling in CKD. A broader approach that considers biochemical bone turnover markers alongside PTH may allow a more individualized management strategy. Future studies should focus on defining optimal treatment targets and should include clinically important and patient-relevant, rather than biochemical, outcomes.

INTRODUCTION:Minimal change disease (MCD) is a frequent cause of nephrotic syndrome in adults. Standard treatment consists of high-dose prednisolone (1 mg/kg/d), which induces remission in over 80% of patients but is associated with considerable glucocorticoid toxicity. Here, in the ADAPT trial, we investigated whether a lower dose of prednisolone combined with activated vitamin D (alfacalcidol) could be non-inferior to the standard high-dose regimen in achieving remission. METHODS:In this randomized, open-label, non-inferiority, multicenter trial, 67 adults with MCD were assigned to either lower-dose prednisolone with alfacalcidol or standard high-dose prednisolone. The primary endpoint was remission rate. Secondary endpoints included time to remission, relapse rate, time to relapse, incidence of serious adverse events and glucocorticoid-related toxicity. RESULTS:Although statistical non-inferiority was not established, rates, time to remission and relapse were comparable between groups. Remission was achieved in 88% (95% confidence interval: 74-96) of patients in the lower-dose prednisolone/alfacalcidol group and in 91% (78-98) of those receiving high-dose prednisolone. Median time to remission was 28 days [interquartile range 14-54] versus 23 days [13-47], respectively. Relapses occurred in 35% and 32% of patients, with median times to relapse of 195 days [100-275] and 179 days [161-206], respectively. The total cumulative doses of prednisolone were significantly less 3.7 g vs 8.0 g, respectively. The number of serious adverse events were less and glucocorticoid-related toxicities (46 [11-77] vs. 74 [30-119]) were significantly less in the lower-dose/ alfacalcidol group than the high-dose group, respectively. CONCLUSIONS:Non-inferiority was not reached for the combined intervention with lower dose prednisolone and alfacalcidol compared to standard prednisolone treatment. But the combined treatment offers a safer alternative to high-dose prednisolone for treatment of MCD, with similar efficacy but fewer serious adverse events and reduced glucocorticoid toxicity. TRIAL REGISTRATION:Registered at ClinicalTrials.gov with study number NCT03210688.

Bone turnover abnormalities are common in chronic kidney disease (CKD) and contribute to bone fragility. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) introduced the term CKD-associated osteoporosis to describe bone fragility in CKD and highlighted the role of bone turnover markers (BTM) in clinical evaluation and management of bone fragility. However, current clinical practice guidelines lack specific treatment targets for bone turnover in the setting of CKD. The aim of this consensus was to present recommendations for the use of BTM in the management of CKD-associated osteoporosis. The consensus was conducted by members of relevant working groups of the European Renal Association (ERA), International Osteoporosis Foundation (IOF), European Foundation for Clinical Chemistry and Laboratory Medicine (EFLM) and European Society of Pediatric Nephrology (ESPN). Bone-specific alkaline phosphatase and tartrate resistant acid phosphatase isoform 5b are not renally cleared and considered reliable diagnostic tools for bone evaluation in CKD-associated osteoporosis. Both have been proposed as reference BTM in CKD by a recent international consortium. Intact N-terminal telopeptide of type I collagen can also be used in CKD. The current consensus describes methodological considerations and the clinical usefulness of BTM in risk prediction, choice of therapeutic strategy, and treatment evaluation in CKD-associated osteoporosis. Specific diagnostic ranges for bone turnover abnormalities are provided. Future research should focus on the integration of these reference BTM with other diagnostic tools, establishment of concrete treatment targets, and development of treatment strategies to reach these targets.

Type 2 diabetes mellitus (T2DM) is common in patients with chronic kidney disease (CKD). Both conditions are associated with an increased fracture risk, with the proposed etiology including impaired bone quantity and quality. This cross-sectional study examined the bone phenotype in patients with T2DM and kidney failure and explored the role of glycemic control on the bone phenotype. To do so, laboratory parameters of mineral metabolism (including sclerostin) and bone turnover markers (BTM) (bone-specific alkaline phosphatase [BALP], trimeric pro-collagen type I N-terminal propeptide [intact P1NP], and tartrate-resistant acid phosphatase isoform 5b [TRACP5b]) were assessed in 647 patients with kidney failure, of which 102 had T2DM (median hemoglobin A1c [HbA1c] of 6.2%), at the time of kidney transplantation. Patients with type 1 DM were excluded. BMD (n = 555) by densitometry, and bone histomorphometry (n = 188) were available for subsets, and correlations between HbA1c and both BTM and BMD were examined. This study found that intact P1NP was lower (68 vs 82 μg/L, p = .03) while sclerostin was higher (2.1 vs 1.8 ng/mL, p = .04) in T2DM versus non-T2DM in an unadjusted analysis. BMD at the lumbar spine (Z-score: -0.066 vs -0.760, p < .001) and femoral neck (Z-score: -0.680 vs -0.965, p = .04) were higher in T2DM, and T2DM was in multivariable regression analysis identified as a significant determinant of lumbar spine BMD, independent of age, sex, and BMI. Bone histomorphometric parameters did not differ between groups. A correlation between HbA1c and BTM and BMD was present, but only in non-T2DM (BALP [ρ = -0.12, p = .007], intact P1NP [ρ = 0.14, p = .002], TRACP5b [ρ = -0.13, p = .003], BMD at the lumbar spine [ρ = 0.12, p = .008], femoral neck [ρ = 0.11, p = .02], and total hip [ρ = 0.17, p < .001]). In conclusion, patients with kidney failure and T2DM have preserved BMD compared with patients without diabetes. Our findings suggest a role for hyperglycemia as a determinant of the bone phenotype.

OBJECTIVE:Metabolic acidosis is a common complication in chronic kidney disease (CKD) and is associated with accelerated disease progression. Diets with a low potential renal acid load (PRAL) represent a promising non-pharmacological strategy to mitigate metabolic acidosis. The New Nordic Renal Diet (NNRD), a plant-focused, low-phosphorus diet, improves acid-base status in patients with CKD stage 3-4. This study evaluated the effects of a two-week, low-PRAL modified NNRD in patients with advanced CKD and chronic metabolic acidosis. DESIGN AND METHODS:Twelve patients with CKD stage 4-5 and metabolic acidosis completed a prospective, sequential dietary intervention consisting of three consecutive two-week periods: habitual diet (control), low-PRAL modified NNRD (intervention), and free-living follow-up without dietary guidance. The intervention consisted of individualized low-PRAL recipes. Fasting blood samples, 24-hour urine collections, and clinical measures were obtained throughout the study. RESULTS:During the intervention, PRAL and net endogenous acid production decreased significantly (-17.2 mmol/day, 95% CI: -23.1 to -11.3 and -17.4, 95% CI: -23.3 to -11.3, respectively). No changes in plasma tCO2 were observed. Net acid excretion decreased slightly (4.1 mmol/d, 95% CI: -8.2 to -0.1). Clinically meaningful reductions were noted in albuminuria (-22.1%, 95% CI: -32.3 to -10.4), and systolic blood pressure (-17 mmHg, 95% CI: -22 to -12). CONCLUSION:A two-week low-PRAL NNRD reduced dietary acid load but did not correct chronic metabolic acidosis in patients with CKD stage 4-5. This likely reflects severely diminished renal acid excretory capacity in late-stage CKD, where endogenous acid production still exceeds the renal capacity.

Although α-Klotho has gained attention as a promising biomarker of aging, its association with frailty and broader aging-related outcomes beyond chronic kidney disease–mineral and bone disorder remains incompletely characterized. This systematic review and meta-analysis aimed to investigate the association between circulating α-Klotho levels and aging-related outcomes, including frailty, effects of physical activity and exercise interventions, body composition, cognitive and neuropsychiatric status, sarcopenia, and bone mineral density (BMD). A comprehensive literature search was performed across multiple electronic databases, including Ovid MEDLINE, Web of Science, Scopus, PubMed, and the Cochrane Library, to identify relevant studies published up to April 30, 2025. Pooled analyses were conducted using random-effects models, with effect estimates synthesized as mean differences, odds ratios, or correlation coefficients, and heterogeneity assessed using the I2 statistic. Risk of bias was assessed using design-specific tools, including the Newcastle–Ottawa Scale, the Risk of Bias 2 tool (RoB2) of the Cochrane collaboration, and the Joanna Briggs Institute (JBI) checklists. A total of 109 studies met the inclusion criteria and were included. In our meta-analysis, higher circulating α-Klotho levels were significantly associated with lower odds of frailty (OR = 0.61, 95

Left ventricular diastolic dysfunction (LVDD) is common in chronic kidney disease (CKD) and is suggested to be linked to worse renal prognosis. We investigated the associations between both the ratio of early mitral inflow velocity to early diastolic tissue velocity (E/e’) and LVDD grades with the risk of end-stage kidney disease (ESKD). This prospective cohort study included individuals with non-dialysis-dependent CKD from the nephrology outpatient clinics at Rigshospitalet and Herlev-Gentofte hospital, Copenhagen. All participants underwent a thorough, protocolized echocardiographic examination. The outcome was time to ESKD (defined as dialysis treatment or kidney transplantation). A total of 731 participants were included. Mean age was 57 ± 13 years and 39

BACKGROUND:Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular (CV) events. Myocardial work indices represent novel echocardiographic measures that may reveal subtle but important abnormalities of left ventricular (LV) function. METHODS:Patients with CKD were included prospectively and underwent echocardiography, including pressure-strain loop analyses to acquire myocardial work indices. These included the global work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE). Their association to major adverse cardiovascular events (MACE) - defined as heart failure (HF) and ischemic heart disease - were investigated by Cox regression. Competing risk regression was performed to account for all-cause death as a competing event. RESULTS:We included 697 patients with CKD (mean age: 57 years, 60% men, median estimated glomerular filtration rate of 43 mL/min/1.73 m2), of whom 42 (6%) experienced MACE during a median follow-up of 3.9 (IQR: 3.4-4.5) years. In univariable analyses, all myocardial work indices were significantly associated with MACE. After multivariable adjustments, only GCW, GWW, and GWE remained significantly associated with MACE (GCW: HR 1.08 (1.00-1.17), per 100 mmHg% decrease; GWW: HR 1.05 (1.01-1.08), per 10 mmHg% increase; GWE: 1.15 (1.08-1.22), per 1% decrease), but only GWW and GWE were associated with MACE in multivariable competing risk regression. Notably, myocardial work indices were only associated with HF and not ischemic heart disease. CONCLUSION:In patients with non-dialysis dependent CKD, wasted work and work efficiency were independently associated with MACE. These findings were driven by their association with HF.