Andreas Kousios

Living donor kidney transplantation (LDKT) offers superior outcomes for most patients with end-stage kidney disease (ESKD), yet its uptake across Europe remains highly variable. This proceedings article summarizes key themes from a pan-European symposium held in November 2025 in Prague, organized by the European Kidney Transplant Association (EKITA) in collaboration with the DESCaRTES Working Group. Discussions highlighted substantial heterogeneity in LDKT activity across Europe, driven by differences in healthcare capacity, legal frameworks, donor evaluation practices, and access to kidney exchange programmes. Marked inequities persist between regions, particularly in the Balkans and Western Balkans, for women those who are socioeconomically disadvantaged, ethnic minority populations, paediatric and elderly patients and individuals with obesity. The symposium identified wide variation in donor selection criteria, risk assessment, informed consent practices, and long-term donor follow-up, despite existing international guidelines. Emerging strategies to address these challenges include harmonisation of donor evaluation and consent, expansion of paired and cross-border kidney exchange programmes, increased use of unspecified kidney donation, and adoption of innovative surgical and immunological approaches to safely broaden donor eligibility. Advances in outcome measurement, including validated surrogate endpoints, machine learning methods, and integrated, harmonised transplant registries, were discussed as critical tools to improve quality, transparency, and research efficiency. Collectively, the proceedings underscore the need for coordinated clinical, policy, and data-driven solutions to reduce inequities and unlock the full potential of LDKT across Europe, with implications for international transplant practice.

Monoclonal immunoglobulin deposition disease (MIDD) is a complication of plasma cell dyscrasias, resulting in abnormal immunoglobulin deposition along basement membranes. We describe a case of a 60-year-old male with a complex hospital admission, presenting with critical illness accompanied by acute kidney injury, nephrotic syndrome and moderately elevated serum free light chain (SFLC) ratio, on a background of well-controlled diabetes, hypertension and chronic kidney disease. There was no clear aetiology for his presentation following preliminary examination and investigations, which led to a biopsy diagnosis of heavy chain deposition disease (HCDD) in the context of monoclonal gammopathy of renal significance (MGRS). We explore the importance of understanding the disease course to allow timely biopsy diagnosis and treatment initiation. Our patient required very close follow-up and a wide multi-disciplinary approach, including haematologists, nephrologists and histopathologists, to guide management in a disease for which therapeutic strategies are poorly defined due to limited clinical trial data.

Systemic amyloid A amyloidosis is a progressive condition in which sustained elevation of serum amyloid A protein concentration leads to widespread amyloid

The term monoclonal gammopathies of renal significance (MGRS) encompasses a group of renal histopathological lesions fulfilling two criteria: (a) they are caused by nephrotoxic monoclonal immunoglobulins and (b) the monoclonal immunoglobulins are produced by small B-cell or plasma cell clones which do not meet the criteria for multiple myeloma or malignant lymphoma. Here, we provide a review of the MGRS definition and related terminology and elaborate on the diagnostic approach and treatment principles from the general physician perspective.

Light chain proximal tubulopathy (LCPT) is a rare form of paraprotein-related disease, occurring in two main histopathological forms: crystalline and non-crystalline. The clinicopathological features, treatment strategies and outcomes, especially of the non-crystalline form, are not well described. We conducted a single-centre retrospective case series of 12 LCPT patients, 5 crystalline and 7 non-crystalline, between 2005 and 2021. The median age was 69.5 years (range 47–80). Ten patients presented with CKD and significant proteinuria (median estimated glomerular filtration rate of 43.5 ml/min/1.73 m²; urine protein:creatinine ratio 328 mg/mmol). Only six patients had known haematological disease at the time of renal biopsy. Multiple myeloma (MM) was diagnosed in seven patients cases and monoclonal gammopathy of renal significance (MGRS) in five patients. A clone was detected in all cases combining serum/urine electrophoresis and free light chain (LC) assays. Crystalline and non-crystalline variants had similar clinical presentations. For the non-crystalline variant, a diagnosis was reached based on a combination of CKD without another cause, haematological workup, LC restriction on immunofluorescence and abnormalities on electron microscopy (EM). Nine of 12 patients received clone-directed treatment. Patients who achieved haematological response (including all non-crystalline LCPT) had improved renal outcomes over a median follow-up of 79 months. The non-crystalline variant may go unrecognised because of its subtle histopathological features and requires EM to distinguish it from ‘excessive LC resorption without tubular injury’. Clone-directed treatment with good haematological response improves renal outcomes in both variants but limited data exist in MGRS. Multicentre prospective studies are needed to better define the clinicopathological characteristics associated with poor outcomes and optimize treatment strategies in patients with MGRS.

Aim: Fibrates have proven efficacy in cardiovascular risk reduction and are commonly used, in addition to statins, to control hypertriglyceridaemia. Their use is often limited due to reduction in glomerular filtration rate at treatment initiation. However, recent studies suggest benign changes in kidney function and improvement of proteinuria, an established early marker of microvascular disease and kidney disease progression. We summarize the evidence from existing trials and provide a summary of effects of fibrates, alone or in combination, on kidney disease progression and proteinuria. Methods and Results: Systematic review and meta-analysis of randomized, controlled trials (PROSPERO CRD42020187764). Out of 12,243 potentially eligible studies, 29 were included in qualitative and quantitative analysis, with a total of 20,176 patients. Mean creatinine increased by 1.05 (95% CI (0.63 to 1.46)) units in patients receiving fibrates vs. comparator, and this was similar in all other subgroups. eGFR showed a bigger decrease in the fibrates arm (SMD −1.99; 95% CI (−3.49 to −0.48)) when all studies were pooled together. Notably, short-term serum creatinine and eGFR changes remained constant in the long-term. Pooled estimates show that fibrates improve albuminuria progression, RR 0.86; 95% CI (0.76 to 0.98); albuminuria regression, RR 1.19; 95% CI (1.08 to 1.310). Conclusions: Fibrates improve albuminuria in patients with and without diabetes when used to treat hyperlipidaemia. The modest creatinine increase should not be a limiting factor for fibrate initiation in people with preserved renal function or mild CKD. The long-term effects on kidney disease progression warrant further study.

Monoclonal Gammopathy of Renal Significance (MGRS) encompasses a wide spectrum of histopathology. Characterizing rare forms of MGRS‐related renal pathology remains work in progress. Light chain crystalline podocytopathy in the context of MGRS, either in isolation or combined with proximal tubulopathy (LCPT) has rarely been described. Unravelling MGRS pathologies is critical for patient management and often requires ancillary techniques for antigen retrieval to demonstrate light chain (LC) restriction on immunofluorescence (IF).

Background/Objectives: Fibrates reduce cardiovascular risk in the general population and in patients with chronic kidney disease (CKD). Although, they are commonly used as second-line agents in addition to statins for hypertriglyceridemia, their use in CKD is limited due to a decrease of glomerular filtration rate (GFR) at treatment initiation. This change in GFR is reversible with fibrate discontinuation. Importantly, randomised control trials with fibrate treatment have demonstrated reduction in proteinuria and benefit for microvascular diabetic complications. In addition, a number of experimental studies have shown nephroprotective effects with fibrates through attenuation of renal fibrosis and inflammation. Thus, the effect of fibrates on renal outcomes remains undetermined. The objective of this systematic review is to summarize the evidence from randomised controlled studies and provide pooled estimates on the effect of fibrates on short- and long-term renal outcomes. Methods/Design: The study will be contacted according to the Cochrane Collaboration principles for Systematic reviews. We will include randomised trials comparing fibrate to placebo or studies comparing the addition of fibrate on statin versus statin alone and reporting on the short- and long-term effects on renal function, CKD progression and proteinuria. We will examine studies including patients with established CKD and those studies including patients at risk of developing CKD, separately. A comprehensive summary of the evidence will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data from included studies suitable for metanalysis will be analyses accordingly to provide quantitative estimates using a random effects model. The Cochrane Collaboration tool for assessing the risk of bias in randomized clinical trials will be utilised. The quality of the evidence from included studies will be addressed descriptively using GRADE (Grading of Recommendations, Assessment, Development and Evaluations).Discussion: The results of this systematic review will be informative for clinicians. A summary of high-level evidence with robust estimates of the effect of fibrates on safety and renal outcomes may be used to inform clinical practice guideline development for dyslipidaemias and primary and secondary prevention of CVD. Systematic review registration: PROSPERO CRD42020187764

Purpose of the review: Validated tools to improve cardiovascular disease (CVD) risk assessment and mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) are lacking. Noninvasive measures of arteriosclerosis and subclinical atherosclerosis such as pulse wave velocity (PWV) and carotid intima-media thickness (cIMT), respectively, have emerged as promising risk stratification tools and potential modifiable biomarkers. Their wide use as surrogate markers in clinical research studies is based on the strong pathophysiological links with CVD. However, whether their effect as risk stratification or intervention targets is superior to established clinical approaches is uncertain. In this review, we examine the evidence on the utility of PWV, cIMT, and plaque assessment in routine practice and highlight unanswered questions from the clinician’s perspective. Sources of information: Electronic databases PubMed and Google Scholar were searched until February 2020. Methods: This narrative review is based on peer-reviewed meta-analyses, national and international societies’ guidelines, and on focused critical review of recent original studies and landmark studies in the field. Key findings: Although patients with CKD are considered in the high-risk CVD groups, there is still need for tools to improve risk stratification and individualized management strategies within this group of patients. Carotid intima-media thickness is associated with all-cause mortality, CVD mortality, and events in CKD and hemodialysis cohorts. However, the evidence that measurement of cIMT has a clinically meaningful role over and above existing risk scores and management strategies is limited. Plaque assessment is a better predictor than cIMT in non-CKD populations and it has been incorporated in recent nonrenal-specific guidelines. In the CKD population, one large observational study provided evidence for a potential role of plaque assessment in CKD similar to the non-CKD studies; however, whether it improves prediction and outcomes in CKD is largely understudied. Pulse wave velocity as a marker of arterial stiffness has a strong pathophysiological link with CVD in CKD and numerous observational studies demonstrated associations with increased cardiovascular risk. However, PWV did not improve CVD reclassification of dialysis patients when added to common risk factors in a reanalysis of ESRD cohorts with available PWV data. Therapeutic strategies to regress PWV, independently from blood pressure reduction, have not been studied in well-conducted randomized trials. Limitations: This study provides a comprehensive review based on extensive literature search and critical appraisal of included studies. Nevertheless, formal systematic literature review and quality assessment were not performed and the possibility of selection bias cannot be excluded. Implications: Larger, prospective, randomized studies with homogeneous approach, designed to answer specific clinical questions and taking into consideration special characteristics of CKD and dialysis, are needed to study the potentially beneficial role of cIMT/plaque assessment and PWV in routine practice.