Introduction Parathyroid hormone remains the primary biomarker used to classify and monitor CKD-MBD, yet its reliability for risk stratification and treatment guidance is limited. Multidimensional biomarker clustering that integrates indicators of bone turnover, vascular calcification, inflammatory and oxidative stress, may better capture the heterogeneity of clinical phenotypes, improve risk stratification, and inform on new therapeutic approaches in dialysis care. Methods We conducted a computational analysis of a multicentric cohort study including 471 hemodialysis patients. The Partitioning Around Medoids algorithm was used to cluster the cohort by a pathophysiology-based biomarker panel (noxPTH®, iPTH, OPG, sRANKL, ImAnOx®, PerOx®, β-Crosslaps and hsCRP) at baseline. The cluster phenotypes were characterized by anthropometrics, imaging and clinical data. Cluster-specific outcomes and event patterns were assessed after one year. Results Four distinct clusters were identified – Cluster 1 reflected a high bone turnover state with high antioxidative capacity and high bone-specific alkaline phosphatase. Cluster 2 showed low bone turnover with high antioxidative capacity and high sclerostin levels. Cluster 3 exhibited an inflammatory–oxidative phenotype, the highest one-year mortality and cluster membership improved prediction of events beyond clinical covariates. This phenotype was marked by high aortic calcium burden, vascular disease, markers of vitamin D degradation, low vaccine response, and hepatic steatosis. Cluster 4 showed a balanced biomarker profile and the highest rate of reclassification after one year. Conclusions Multidimensional biomarker clustering captures heterogeneity in bone and vascular disease phenotypes of CKD-MBD exhibiting differential mortality risk and event patterns, highlighting inflammation as an important pathway for further studies.

Epidemiological investigations have shown that approximately 2-3% of all Austrians have diabetes mellitus with renal involvement (diabetic kidney disease, DKD). Therefore, this concerns approximately 250,000 people in Austria. The risk of occurrence and progression of DKD can be attenuated by lifestyle interventions as well as optimization of blood pressure, blood glucose control and specific drug classes. These guidelines represent the joint recommendations of the Austrian Diabetes Association and the Austrian Society of Nephrology for the definition, diagnostics and treatment strategies of DKD.

Background:The identification of causative antigens for membranous nephropathy (MN) has revolutionized the comprehension of the pathophysiology of this autoimmune disease and its management. Recently, some studies described protocadherin FAT1 (FAT1) as a causal antigen in the context of hematopoietic stem cell transplantation (HSCT). The aim of this study was to investigate the large Viennese kidney biopsy collection at the Department of Pathology of the Medical University of Vienna and explore MN cases after HSCT for the causative antigen. Methods:Fifteen patients were identified with MN in diagnostic renal biopsies for proteinuria/nephrotic syndrome after HSCT between 2001 and 2024. Cases were reviewed and tested for the expression of FAT1 by immunofluorescence specifically. Results:Immunofluorescence showed that 12 out of 15 patients with MN had FAT1 expression, appearing 2.3 years after HSCT. In three patients without FAT1 expression, MN appeared 3.8 years after HSCT, with one testing positive for phospholipase A2 receptor (PLA2R) and two with unknown antigens. Serum creatinine for FAT1+ MN was 1.2 mg/dl, while FAT1- MN was 1.3 mg/dl. Proteinuria was 8 g/g compared to 10.4 g/g, respectively. IgG4 positivity was seen in 30% of FAT1+ MN cases. Over a follow up of 5.2 years, of the seven FAT1+ MN patients treated with rituximab, four achieved complete remission, two partial remission, and one was non-responsive. Conclusion:This hitherto largest single-center-cohort solidifies FAT1 as a causative antigen for MN in the setting of HSCT. However, not all post-HSCT-MN are related to FAT1.

Epidemiologische Untersuchungen zeigen, dass etwa 2–3

Die chronische Nierenkrankheit (CKD) betrifft weltweit über 800 Mio. Menschen, wobei nur etwa 6–10

Background:Short calciprotein crystallization time (low T50) is directly associated with an increased risk of cardiovascular events and mortality. Here, we investigated whether increases in dialysate bicarbonate concentrations increase T50 times in dialysis patients. Methods:In a prospective, single-center, single-arm, interventional trial in hemodialysis patients (N = 29), dialysate bicarbonate was decreased from baseline settings to 27 mmol/L (D-Bic 27) followed by an increase to 37 mmol/L (D-Bic 37), over the course of 6 weeks. The primary endpoint was the change in T50 time between the D-Bic 27 and D-Bic 37 phases. Measurements of endogenous calciprotein monomers (CPM), primary (CPP-1) and secondary (CPP-2) calciprotein particles were pre-specified secondary outcomes. Results:Twenty-four patients completed the study per protocol. T50 time increased significantly from 246 ± 77 to 282 ± 81 min from the D-Bic 27 to the D-Bic 37 phase (P < .0001). The hydrodynamic radius (size) of secondary calciprotein particles generated in the T50 test (CPP-2Rh) did not differ significantly between study phases (251 ± 75 vs 240 ± 78 nm, P = .27). Comparing the D-Bic 27 with the D-Bic 37 phase, CPM (16.8 × 10³ vs 16.2 × 10³ AU/µL, P = .9) and CPP-1 (4.6 × 105 vs 4.5 × 105 counts/mL, P = .7) did not change significantly, but there was a significant decrease in CPP-2 levels (5.9 × 104 vs 3.2 × 104 counts/mL, P < .0003). Intradialytically, T50 increased, CPM and CPP-1 decreased, while CPP-2 remained stable. Conclusions:Raising dialysate bicarbonate resulted in a significant increase in T50 time and a reduction of CPP-2 levels.

Chronic kidney disease (CKD)-associated osteoporosis increases fracture risk, yet clinical guidance remains unclear. A survey of 89 Italian nephrologists revealed heterogeneous biomarker availability and varied treatment approaches. Denosumab was the preferred antiresorptive agent, while anabolic drugs were rarely used. Findings highlight progress in CKD-related bone health management despite existing uncertainties. CKD-associated osteoporosis comprises the skeletal effects of a complex mineral and bone disorder causing increased risks of fragility fractures (FF), cardiovascular events, and mortality. Existing clinical guidance about CKD-associated osteoporosis is vague, leading us to hypothesize that a treatment gap exists and that clinical practice is dependent on local availability of diagnostic tools. The aim of the current survey was to determine current attitudes and practices among Italian nephrologists regarding the evaluation and management of CKD-associated osteoporosis. An online survey was designed, consisting of 9 thematic groups with a set of 16 closed questions regarding the availability of biomarkers and BTMs at reference laboratories and their use for the diagnosis and treatment of CKD-associated osteoporosis in patients with different stages of CKD, including CKD stages G4-5 and dialysis patients. Results were compared to a previous survey on the use of BTMs from 2022. Eighty-nine Italian nephrologists participated in the survey, reporting that parathyroid hormone (PTH), alkaline phosphatase, and 25-hydroxy-vitamin D measurements were available in 92–100

Proteinuria is an established biomarker in native kidney disease, there is, however, a lack of data on its significance for assessing organ quality in the setting of deceased kidney donors. Donor urinary protein-to-creatinine ratio (UPCR) has been associated with the extent of chronic lesions in pre-transplant kidney graft biopsies in a prospective single center study. Validating this association in a larger multicenter cohort and assessing its value in addition to known clinical predictors might help to improve evaluation of organ quality and organ utilization. We are currently conducting a prospective observational multi-center study recruiting 300 consecutive adult deceased kidney donor and kidney graft recipient pairs procured and transplanted in all four Austrian transplant centers. The primary aim is to validate donor UPCR for assessing graft quality of kidney grafts from deceased donors by examining the association of donor UPCR with the extent of chronic lesions in pre-implant kidney grafts (glomerulosclerosis, arteriosclerosis/arteriolosclerosis, interstitial fibrosis and tubular atrophy = total chronic lesion score). The secondary objective is the evaluation of donor UPCR for the prediction of graft function after one year, and building of a donor urine biobank. The study in currently ongoing; the expected end of study is by the last quarter of 2027. The trial centers at Vienna, Linz, Graz and Innsbruck have started including patients and samples in January 2023, March 2024, April 2024 and June 2024, respectively. To date, 125 donor-recipient pairs have been included, with an estimated inclusion of the last patient by July 2026. While proteinuria in donor reports is often noted semi-quantitatively and not linked to graft quality, a preliminary study has shown that a quantitative and qualitative assessment of donor proteinuria can predict chronic graft damage. Confirming these findings through a large multicenter study, alongside known graft quality predictors, could help develop better prediction models for graft quality. These models have the potential to enhance pre-implant risk assessment and organ utilization. Establishing a large comprehensive donor urine bio-database will enable further research.

Histomorphometric analysis of an iliac bone biopsy remains the gold standard for the diagnosis of renal osteodystrophy (ROD), which comprises various histological lesions induced by chronic kidney disease (CKD). ROD belongs to the framework of CKD-associated osteoporosis. The use of bone biopsy in the routine management of CKD-associated osteoporosis has decreased over the past decades for various reasons, including diminishing expertise in performing the procedure, and major variability in processing bone samples and reporting of results. In this context, the European Renal Osteodystrophy group, a part of the CKD-mineral and bone disorder working group of the European Renal Association launched an initiative to evaluate various issues related to bone histomorphometry in the context of ROD. To this effect, 28 experts from 14 European countries engaged in rounds of discussions to reach a consensus related to the bone biopsy procedure, sample handling, and reading and reporting findings. Key conclusions include a recommendation that all practitioners in this field move towards reporting diagnostic findings by the turnover, mineralization, and volume (TMV) classification and that external quality control is prioritized to ensure validity and reproducibility of results. The consensus group recognises that the lack of an accepted normative reference for bone histomorphometry is a barrier towards uniform diagnostic definitions and recommends further collaborative efforts in this area. Until these issues are solved, transparent reporting on the choice of reference and diagnostic definitions applied should be adhered to, both in clinical reports and research settings.

Peritubular capillaritis (ptc) is a hallmark lesion of antibody-mediated rejection (AMR), but the grading of its extent is historically based on arbitrary defined cut-offs. Molecular AMR diagnosis via intragraft gene expression measurements may provide evidence to challenge established ptc categories. We retrospectively included 38 renal allograft biopsies from clinical routine, performed because of suspicion of AMR. Biopsies were re-assessed by an experienced nephropathologist and intragraft gene expression was measured using the NanoString nCounter® platform. Ptc categories were correlated with AMR gene expression to identify a ptc extent cut-off with optimal prediction of molecular diagnosis of AMR [gene expression levels above first quartile (AMRQ>1)]. Finally, an independent validation cohort (n = 25, Erasmus MC, Rotterdam, The Netherlands) was included to reproduce the results. Re-assessment of biopsies revealed AMR in 26/68.4%, mixed rejection in 5/13.2%, and T-cell-mediated rejection in 3/7.9%. Biopsies with diffuse ptc had significantly higher AMR gene expression compared to biopsies with focal ptc and biopsies with no ptc (64.0/53.3–84.0 vs. 31.5/27.0–49.5, p = 0.023 and 27.0/14.3–31.8, p = 0.003, median/IQR). Sensitivity analysis revealed that a ≥35% ptc cut-off resulted in higher AUCs for predicting AMRQ>1 compared to ptc50% (AUC 0.78, 95% CI: 0.63–0.93, p = 0.009 versus AUC: 0.74, CI: 0.56–0.90, p = 0.03). In the validation cohort, only the ptc35–, but not the ptc50%, cut-off significantly predicted AMRQ>1 (AUC 0.75, 95% CI: 0.54–0.96 p = 0.04 vs. AUC 0.69, CI: 0.46–0.93, p = 0.13). Using intragraft gene expression measurement, we identified a new ptc extent threshold with better prediction of molecular AMR. The newly proposed cut-off of ≥35% could potentially improve diagnostic evaluation and prognostication in cases with suspected or diagnosed AMR.

Chronic kidney disease (CKD) affects over 800 million people worldwide, yet only about 6-10% of those affected are aware of their condition. Limited public awareness and insufficient structural measures in the healthcare system lead to the fact that CKD is frequently not diagnosed or diagnosed after a delay and therefore insufficiently treated. Current projections estimate that CKD could become the fifth leading cause of death worldwide by 2040, if timely and effective measures to increase awareness and early detection are not implemented. This article presents practice-oriented guidelines for the screening, diagnostics and treatment of CKD in Austria. It outlines for which risk groups screening is recommended and describes how physicians can diagnose and treat CKD across all medical specialties. A key aspect of these guidelines is the presentation of pharmacological treatment options that slow disease progression, with specific indications and practical clinical recommendations for their use. Furthermore, the recommendations address nationally defined referral criteria to nephrology specialists in Austria and discusses possible CKD-related complications along with appropriate treatment strategies.

Annual mortality still exceeds 15% in patients receiving maintenance hemodialysis, mainly driven by cardiovascular disease (CVD) burden. Therapies targeting calcium, phosphate and bone metabolism are still lacking evidence for consistent benefits, warranting new approaches to guide treatment decisions. A prospective, observational study was conducted across three Austrian hemodialysis centers including stable maintenance hemodialysis patients. Blood samples were collected at study entry. Biochemical markers of bone metabolism (iPTH, noxPTH®, betacrosslaps, osteoprotegerin, sRANKL), antioxidative capacity (ImAnOx®) and oxidative stress (PerOx®) were measured with standardized assays provided by Immundiagnostik AG. Unsupervised K-means machine learning algorithm was employed to cluster the dataset based on these biochemical variables. The 1-year mortality rates, treatment-related data and CVD burden were then compared between clusters. A total of n = 363 patients were included. Basic demographic data include a median age of 72 years, median hemodialysis vintage of 27.5 months and a male preponderance of 63%. Four distinct clusters were identified (Fig. 1A and B). Cluster 0 was defined by low noxPTH® (median 139 pg/mL), low sRANKL levels and high oxidative stress with the highest 1-year mortality rate (24.9%). In contrast, higher antioxidative capacity and beta-crosslap levels distinguished Clusters 1 and 2 with lower mortality rates (13.2% and 0% respectively). Cluster 3 was defined by high noxPTH levels (median 441 pg/mL) and showed an intermediate 1-year mortality rate (17.8%), yet the highest CVD burden (81%). Calcimimetic treatment was highest in Cluster 3 (57.8%), however, over 23% of patients in the low-noxPTH® Cluster 0 were inadequately treated with calcimimetics. Unsupervised cluster analysis allowed risk-stratification of hemodialysis patients by biochemical profiles, reflecting low-turnover bone disease and oxidative stress as features with unfavourable outcome. This strategy could improve treatment categorization in future trials.

Calciphylaxis, or calcific uraemic arteriolopathy, is a rare and life-threatening condition predominantly affecting people receiving dialysis. Characterized by painful necrotic skin lesions due to arteriolar calcification and thrombosis, calciphylaxis is associated with high morbidity and mortality. Diagnosis is frequently delayed due to misdiagnosis and an absence of specific diagnostic tests. Current treatment approaches are largely based on registry data and small uncontrolled studies. This update brings together the latest understanding of calciphylaxis pathogenesis, diagnostic approaches and management, highlighting recent advances and future directions. Pathophysiological mechanisms include vascular smooth muscle cell osteogenic transformation, loss of endogenous calcification inhibitors (fetuin-A, matrix Gla protein, pyrophosphate), systemic inflammation and thrombosis. The potential prognostic role of biomarkers, including the calciprotein particle crystallization test (T50) and plasma pyrophosphate, are also discussed. Management remains complex, with no proven treatments. A multifaceted, and multi-professional team approach is fundamental. Sodium thiosulfate remains widely used despite the lack of trial evidence. Recent investigational therapies, including SNF472 and INZ-701, target key calcification pathways and offer promise. The Better Evidence and Translation for Calciphylaxis (BEAT-Calci) adaptive platform trial represents a landmark step in evaluating multiple therapies systematically. National registries remain vital for informing prevalence estimates and improving real-world outcome data. Looking ahead, future research should prioritize the development and validation of diagnostic criteria, and prognostic tools integrating clinical risk factors with biomarkers. In addition, we propose the routine inclusion of patient-reported experience measures in calciphylaxis studies to better capture treatment impact in this vulnerable population.

ABSTRACT Background This study investigated whether parathyroid hormone (PTH) lowering with etelcalcetide, and the consequent effects on mineral and bone metabolism, could improve serum calcification propensity (T50 time) and decrease calciprotein particle (CPP) load in hemodialysis patients with secondary hyperparathyroidism. Methods In this single-arm, prospective, dose-escalation proof-of-principle study, hemodialysis patients received etelcalcetide at 2.5 mg/dialysis session with increments of 2.5 mg every 4 weeks to a maximum dose of 15 mg three times a week or until a pre-specified safety endpoint was reached, followed by an 8-week wash-out phase. Results Out of 36 patients recruited (81% male, 62 ± 13 years), 16 patients completed the study per protocol with a mean maximum tolerated dose of etelcalcetide of 9.5 ± 2.9 mg/dialysis session. With escalating doses of etelcalcetide, PTH and serum calcium levels significantly decreased (P < 0.0001). While there was no significant change in T50 times or serum phosphate levels, etelcalcetide did yield significant and consistent reductions in serum levels of endogenous calciprotein monomers [−35.4 (−44.4 to −26.5)%, P < 0.0001], primary [−22.4 (−34.5 to −10.3)%, P < 0.01] and secondary CPP [−29.1 (−45.7 to −12.4)%, P < 0.01], an effect that was reversed after therapy withdrawal. Serum levels of osteoclastic markers significantly decreased with escalating doses of etelcalcetide, while levels of the osteoblastic marker remained stable. Conclusions Lowering of PTH with etelcalcetide did not result in statistically significant changes in T50. By contrast, homogenous reductions in serum levels of calciprotein monomers, primary and secondary CPP were observed.

Focal segmental glomerulosclerosis (FSGS) combines a heterogeneous group of different etiologies with defined glomerular histopathology and accounts for approximately 10% of nephrotic syndrome cases in adults and 20% of cases in children in Europe. Currently, there is no specific therapy available for FSGS, with the majority of patients being treated with systemic corticosteroids, calcineurin inhibitors and renin-angiotensin-system (RAS) inhibitors.1 While some patients respond to therapy, a significant proportion remains unresponsive, ultimately requiring kidney replacement therapy, resulting in a significant burden to the individual patient as well as to the health care system.

IntroductionIn living donor kidney transplantation (LDKT), vascular anastomosis is more difficult due to missing arterial patches and shorter renal veins. The surgical challenge is even more demanding in kidneys with multiple arteries. Although renal transplantation is feasible in most cases of complex donor vascular anatomy and similar results compared with standard LDKT are reported, the discussion on potentially increased complication rates and graft function continues. This prompted us to review our results of LDKT with multiple renal artery (MRA) grafts with a special concentration on complications and long-term function.Patients and methodsWe reviewed the records of all LDKT in our center from the beginning of the program in 2005 until 2022 for arterial vascular reconstructions. The cohort was divided into two groups: transplantation with vascular reconstruction (VR) and standard transplantation. These groups were compared for operative parameters and short- and long-term results.ResultsFrom 2005 to 2022, 211 LDKT were completed in our unit. In 32 (15.2%), a VR was performed, including single ostium side-to-side anastomosis, end-to-side anastomosis, patch reconstruction, and vein interposition. There was no significant difference in operative time (169 min vs. 180 min; p = 0.118) and time for anastomosis (28 min vs. 26 min; p = 0.59) between both groups. Postoperative complications (5.7% vs. 7.4%; p = 0.72) were not significantly different. During the follow-up period (110 months, range 10–204), the risk of organ loss was comparable after VR (13.625% vs. 11.56% p = 0.69).ConclusionIn LDKT, arterial vascular reconstructions for kidneys with MRA provide similar results compared to grafts with a single renal artery (SRA). Short- and long-term results are comparable with standard procedures.

Background Austria is among the countries with the highest incidence and prevalence of osteoporotic fractures worldwide. Guidelines for the prevention and management of osteoporosis were first published in 2010 under the auspices of the then Federation of Austrian Social Security Institutions and updated in 2017. The present comprehensively updated guidelines of the Austrian Society for Bone and Mineral Research are aimed at physicians of all specialties as well as decision makers and institutions in the Austrian healthcare system. The aim of these guidelines is to strengthen and improve the quality of medical care of patients with osteoporosis and osteoporotic fractures in Austria. Methods These evidence-based recommendations were compiled taking randomized controlled trials, systematic reviews and meta-analyses as well as European and international reference guidelines published before 1 June 2023 into consideration. The grading of recommendations used ("conditional" and "strong") are based on the strength of the evidence. The evidence levels used mutual conversions of SIGN (1++ to 3) to NOGG criteria (Ia to IV). Results The guidelines include all aspects associated with osteoporosis and osteoporotic fractures, such as secondary causes, prevention, diagnosis, estimation of the 10-year fracture risk using FRAX (R), determination of Austria-specific FRAX (R)-based intervention thresholds, drug-based and non-drug-based treatment options and treatment monitoring. Recommendations for the office-based setting and decision makers and institutions in the Austrian healthcare system consider structured care models and options for osteoporosis-specific screening. Conclusion The guidelines present comprehensive, evidence-based information and instructions for the treatment of osteoporosis. It is expected that the quality of medical care for patients with this clinical picture will be substantially improved at all levels of the Austrian healthcare system.