Search Results (11,798)

Background: Native nephrectomy is frequently required in autosomal-dominant polycystic kidney disease (ADPKD) before or during transplantation, but the optimal minimally invasive approach is unsettled, and it is unclear whether the pattern of post-operative complications tracks with operative technique. We report a retrospective single-centre experience of hand-assisted laparoscopic (HAL) native nephrectomy and, alongside it, a technique-stratified scoping review of complications. Methods: We retrospectively reviewed all consecutive adults undergoing HAL native nephrectomy—with an infra-umbilical midline hand-port and free intraperitoneal cyst rupture—in preparation for transplantation in the period between December 2019 and December 2025. In parallel, we performed a PRISMA-ScR-compliant scoping review (MEDLINE, Embase, Scopus) of minimally invasive ADPKD nephrectomy, with duplicate independent screening and extraction, stratifying complications by operative approach and cyst-decompression method. No quantitative pooling was undertaken. Results: Twenty-three patients (mean age 52.8 ± 9.9 years; 87% dialysis-dependent; 78% for transplant preparation) were included. Median operative time was 102 min (IQR 90–122) with minimal blood loss, one transfusion (4%), and no open conversion. Complications occurred in 8/23 (35%) and were bowel-predominant: one small-bowel perforation, two obstructions, and one ileus—three of Clavien–Dindo grade IIIb, all in right-sided nephrectomies and independent of specimen weight. Peri-operative mortality was 1/23 (4%), from a non-technique-related mycotic aortic dissection. Of 481 records screened, 19 studies met inclusion; the cyst-decompression method was reported in only 7 (37%). Bowel events clustered in series using free intraperitoneal cyst rupture or puncture and were largely absent where decompression was contained, a pattern crossing platform boundaries and that is mechanistically consistent with intraperitoneal spillage of cyst contents. Conclusions: HAL native nephrectomy is a rapid and feasible means of removing massively enlarged polycystic kidneys before transplantation but, in our experience, carries a bowel-predominant morbidity that clustered in right-sided procedures and was independent of specimen weight. The sparse literature is consistent with—but cannot confirm—a relationship to intraperitoneal cyst spillage rather than to the hand-assisted approach itself. Whether contained cyst decompression can preserve operative efficiency while reducing bowel morbidity is a hypothesis warranting prospective study. Full article

Diabetic kidney disease (DKD) is characterized by progressive renal dysfunction driven by oxidative stress, inflammation, and hemodynamic alterations. Photobiomodulation (PBM) has emerged as a potential non-invasive therapeutic strategy targeting these pathways. To evaluate the effects of PBM on kidney function, hemodynamics, oxidative stress, and inflammatory profile in a rat model of DKD. Adult male Wistar rats were randomly assigned to four groups: control (Ct), Ct + PBM, DKD, and DKD + PBM. Diabetes was induced by streptozotocin (60 mg/kg, i.v.). PBM (808 nm, 100 mW) was applied transcutaneously (3 J per point; 30.48 J/cm²), bilaterally over the renal region, three times per week for six weeks. Kidney function (inulin clearance, serum creatinine, albuminuria), hemodynamics (mean arterial pressure, renal blood flow, renal vascular resistance), oxidative stress markers (urinary H₂O₂, NOx, thiols, Nrf2), and IL-1β levels were evaluated. DKD animals showed impaired kidney function, increased oxidative stress, and elevated inflammatory markers. PBM treatment significantly improved inulin clearance, reduced albuminuria and serum creatinine, increased renal blood flow, and decreased mean arterial pressure and vascular resistance. Oxidative stress markers and IL-1β levels were attenuated, with partial restoration of antioxidant capacity. No significant histological differences were observed. PBM improves kidney function and modulates redox and inflammatory pathways in experimental DKD, supporting its potential as a non-invasive adjunct therapy. Full article

Background: Cetuximab-based therapies continue to play an important role in the management of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) despite the increasing use of immunotherapy. However, data regarding treatment outcomes and prognostic factors remain limited. This study aimed to evaluate treatment outcomes and prognostic factors associated with survival in patients with R/M HNSCC treated with cetuximab-based regimens. Methods: This retrospective single-center cohort study included patients with recurrent/metastatic HNSCC who received cetuximab-based systemic therapy at the Department of Medical Oncology, Manisa Celal Bayar University Faculty of Medicine, between May 2012 and September 2025. Demographic, clinical, laboratory, and PET/CT data were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with survival were evaluated using univariable and multivariable Cox proportional hazards regression analyses. Results: A total of 57 patients were included in the study. The median age was 65 years, and 91.2% of patients were male. Most patients had ECOG performance status 0–1 (94.7%) and stage IV disease (71.9%). The larynx was the most common primary tumor site (50.9%), while distant lymph node metastasis (63.2%) and lung metastasis (61.4%) were the predominant metastatic sites. Median PFS and OS were 4.6 months and 13.8 months, respectively. Kaplan–Meier analysis demonstrated that patients with a body mass index (BMI) > 25 had longer OS, whereas chronic kidney disease (CKD), primary tumor localization, and best response to first-line treatment were significantly associated with survival. In multivariable Cox regression analysis, chronic kidney disease (CKD) (HR: 5.15, p = 0.004), oral cavity primary tumor localization (HR: 2.55, p = 0.013), progressive disease as the best response to first-line treatment (HR: 4.44, p < 0.001) and the absence of grade 1–2 cetuximab-related dermatologic toxicity (HR: 3.20, p = 0.027) remained independent adverse prognostic factors. BMI was not independently associated with survival in multivariable analysis. Conclusions: Cetuximab-based therapy demonstrated clinically meaningful activity in patients with R/M HNSCC. Comorbidities, primary tumor localization, the absence of grade 1–2 cetuximab-related dermatologic toxicity and treatment response appear to substantially influence survival outcomes. Larger prospective studies are warranted to validate these findings. Full article

Background and Clinical Significance: Anti–myelin-associated glycoprotein (MAG) antibody polyneuropathy is a rare, chronic IgM-mediated demyelinating peripheral neuropathy predominantly affecting sensory nerves in older adults, commonly in association with monoclonal gammopathy of undetermined significance. Reports describing anesthetic management in patients with this condition remain extremely limited, and no specific guidelines currently exist regarding neuromuscular blocking agent (NMBA) use or neuromuscular monitoring in this population. Case Presentation: A 79-year-old man with anti-MAG antibody polyneuropathy (diagnosed in 2007) and IgM monoclonal gammopathy of undetermined significance developed disproportionate progressive lower-extremity weakness and became wheelchair-dependent following COVID-19 infection in 2020. Preoperative evaluation revealed mildly reduced left ventricular function (ejection fraction 49%), mild chronic kidney disease, and marked intrinsic hand muscle atrophy with absent deep tendon reflexes. He was scheduled for robot-assisted radical cystectomy with ileal conduit diversion under combined general and thoracic epidural anesthesia. Before NMBA administration, neuromuscular monitoring was systematically attempted at the ulnar nerve (electromyography and acceleromyography, up to 60 mA/300 μs) and the corrugator supercilii; despite visible muscle contractions following peripheral nerve stimulation, neither modality produced reliable responses at either site. Given the inability to establish reliable monitoring, the administration of NMBAs was considered to carry an unacceptable risk of a prolonged, undetectable blockade. Anesthesia was maintained with deep sevoflurane (2.0–2.5% end-tidal) and remifentanil infusion without NMBAs, titrated to a bispectral index of 40–60. Tracheal intubation was accomplished via video laryngoscopy without NMBA. The 7 h and 30 min surgery was completed without patient movement or surgical compromise. Postoperatively, the patient developed transient upper airway obstruction attributed to glossoptosis, managed successfully with head elevation and nasopharyngeal airway insertion; supplemental oxygen was required until postoperative day 3, and the patient was discharged from the high-dependency unit on postoperative day 5. Conclusions: No measurable quantitative neuromuscular response could be obtained in this patient with advanced anti-MAG antibody neuropathy, despite appropriate application of electromyography- and acceleromyography-based monitoring and the presence of visible muscle contractions following peripheral nerve stimulation. In such circumstances, avoiding NMBA administration in favor of deep volatile or intravenous anesthesia with opioid supplementation may represent a reasonable, hypothesis-generating approach in carefully selected patients; this observation does not establish the general superiority of an NMBA-free strategy, and caution is warranted before generalizing it to procedures such as robotic surgery, in which profound neuromuscular blockade is often considered desirable. Full article

Background: Despite the increased infection-related morbidity of patients with chronic kidney disease (CKD), their vaccination coverage is low. Cocooning strategy has not been adequately researched in this group. Our aim was to evaluate vaccination coverage of CKD pediatric and adult patients and their families. Methods: In this prospective, single-center study, we recorded the vaccination coverage of CKD pediatric and adult patients and their families who attend a tertiary University Hospital. Vaccination rates were calculated according to the national vaccination program. Vaccination of pediatric CKD patients was compared to a control group of healthy children. Results: The vaccination rate of 63 hemodialysis patients was low for influenza (61.9%), COVID-19 (79.4% primary, 3.2% booster doses), RSV (50%), herpes zoster (42.4%), hepatitis B (41.3%), Streptococcus pneumoniae (25.4%), tetanus–pertussis (3.2%), and HPV (0%). Their 30 underaged relatives had low vaccination rates for influenza (13.3%), DTaP/Tdap (80%), and Men B (50%), with adequate vaccination for other pathogens. The 53 children with CKD were poorly vaccinated for influenza (20.8%), COVID-19 (0%), Streptococcus pneumoniae (15.4%), Men B (30.2%), DTaP/Tdap (67.9%), MMR (78.8%) and VZV (86.5%), but their vaccination rates for influenza were significantly higher compared to controls. Their 108 adult relatives were inadequately vaccinated for influenza (27.8%), COVID-19 (1.9%), and Tdap (1.9%). Their 35 underaged relatives were poorly vaccinated for influenza (22.9%) and DTaP (80%). Conclusions: Vaccination coverage of CKD patients is suboptimal for vaccines particularly important for their condition and their family members are insufficiently informed about potential contribution to their protection by cocooning strategy. Full article

Background and Objectives: Sarcopenia is highly prevalent among older adults with chronic kidney disease (CKD) and is associated with adverse clinical outcomes. The finger-ring (Yubi-wakka) test is a simple anthropometric screening tool based on calf circumference; however, its performance in older adults with CKD remains unclear. This study aimed to investigate the association of the finger-ring test with low muscle mass, sarcopenia, and comprehensive geriatric assessment parameters and to evaluate its diagnostic performance for identifying low muscle mass in older adults with CKD. Materials and Methods: This cross-sectional study included 115 patients aged ≥65 years with CKD who were evaluated in geriatric and nephrology inpatient services. After excluding two participants with missing finger-ring measurements, 113 individuals were analyzed. Muscle mass was assessed using bioelectrical impedance analysis and low muscle mass was defined according to EWGSOP2-based Turkish cut-off values. Demographic characteristics, anthropometric measurements, laboratory findings, and comprehensive geriatric assessment parameters were recorded. Correlation analyses, logistic regression models, receiver operating characteristic (ROC) analyses, and likelihood-ratio tests were performed. Results: Among 113 participants, 62 were classified as finger-ring positive (FR = 0) and 51 as finger-ring negative (FR = 1). Low muscle mass was significantly more frequent in the FR = 0 group than in the FR = 1 group (51.6% vs. 24.0%, p = 0.005). Finger-ring test results showed strong correlations with calf circumference (rho = 0.689, p < 0.001) and body mass index (BMI) (rho = 0.631, p < 0.001), whereas the correlation with muscle mass was modest (rho = 0.250, p = 0.008). For detecting low muscle mass, the finger-ring test demonstrated an area under the curve (AUC) of 0.643 (95% CI 0.554–0.732), sensitivity of 72.7%, specificity of 55.9%, positive predictive value of 51.6%, and negative predictive value of 76.0%. In multivariable analyses, BMI remained the strongest independent determinant of finger-ring test results, whereas the association with muscle mass lost statistical significance after BMI adjustment. Adding age and sex significantly improved discrimination, while the contribution of nutritional status was limited. Conclusions: The finger-ring test is associated with low muscle mass in older adults with CKD; however, its diagnostic performance is modest and appears to be substantially influenced by body size and calf circumference. Therefore, the finger-ring test should be considered a simple adjunctive screening tool rather than a stand-alone method for identifying low muscle mass in this population. Full article

Vascular calcification is an ectopic calcium salt deposition process that lacks effective treatment under pathological conditions such as chronic kidney disease, diabetes, and aging. This review, for the first time, systematically categorizes miRNAs involved in the regulation of vascular calcification according to signaling pathways, clearly revealing the regulatory nodes and crosstalk among different pathways (Wnt/β catenin, BMP/Smad, NF κB, etc.), thereby providing a pathway-level theoretical basis for precision targeting. It also dissects the functional duality and microenvironment dependency of miRNAs—the same miRNA can exert opposite effects in different contexts, suggesting that miRNA-based drug development must focus on disease-selective targeted delivery to avoid the risk of functional reversal. This article further comprehensively summarizes the heterogeneous regulatory patterns of lncRNAs, the unique regulatory modes of circRNAs, and preliminary evidence suggesting the involvement of emerging non-coding RNAs (piRNAs, tsRNAs) and integrates the potential of circulating non-coding RNAs as non-invasive biomarkers and prospects for targeted therapeutic translation. This review provides a panoramic view of the network-based regulation of vascular calcification by non-coding RNAs, laying a theoretical foundation for precision diagnosis and multi-target combination intervention. Full article

Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of pediatric chronic kidney disease (CKD) and comprise a heterogeneous group of developmental disorders with a substantial genetic contribution. Advances in next-generation sequencing have facilitated the identification of numerous candidate genes and rare variants associated with CAKUT. However, establishing causality and defining the biological functions of implicated genes remain major challenges. Functional validation is therefore essential to bridge the gap between gene discovery and mechanistic understanding, enabling the interpretation of genetic variation within the context of kidney development and disease. The zebrafish (Danio rerio) has emerged as a powerful in vivo model for studying renal development and interrogating the function of CAKUT-associated genes. Its utility stems from a high degree of genetic and developmental conservation with humans, conserved nephrogenic pathways, optical transparency during embryogenesis, and the relative ease of genetic manipulation. In this review, we provide an overview of zebrafish kidney development within the broader context of vertebrate nephrogenesis, highlighting the key genetic programs governing intermediate mesoderm specification, nephron segmentation, and pronephric morphogenesis. We then systematically examine CAKUT-associated genes that have been modeled in zebrafish, focusing on studies that have linked genetic perturbations to renal development and structural phenotypes. Finally, we discuss the strengths and limitations of zebrafish models for functional genomics and variant interpretation and consider their emerging role in bridging genetic discovery with mechanistic insights into CAKUT pathogenesis. Full article

Dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) is considered a marker of vitamin K status and vascular calcification risk in chronic kidney disease. This study assessed the association of serum dp-ucMGP, alone and combined with albumin, with all-cause and cardiovascular mortality in maintenance hemodialysis patients. This single-center observational cohort study included 133 maintenance hemodialysis patients with a two-year survival follow-up. Analyses involving dp-ucMGP and albumin were performed in 113 patients with complete biomarker data. Baseline serum dp-ucMGP, albumin, inflammatory markers, and routine laboratory parameters were measured. Associations with all-cause and cardiovascular mortality were evaluated using group comparisons, ROC curve analysis, Kaplan–Meier analysis, and Cox regression. Patients who died had significantly lower dp-ucMGP and albumin levels and higher inflammatory and hematological indices than survivors, with similar findings for cardiovascular mortality. The combined dp-ucMGP–albumin model showed higher apparent discriminatory performance than either marker alone for all-cause mortality (AUC 0.793, 95% CI 0.708–0.878, p < 0.001) and cardiovascular mortality (AUC 0.778, 95% CI 0.687–0.868, p < 0.001). Lower dp-ucMGP levels were associated with worse survival. In multivariable Cox regression, higher dp-ucMGP and albumin were independently associated with lower mortality. Combined dp-ucMGP and albumin assessment may provide complementary prognostic information in hemodialysis patients but requires validation in larger cohorts. Full article

Background: Autoimmune diseases (AIDs) are associated with increased cardiovascular risk. However, specific protein mediators linking AIDs to major adverse cardiovascular events (MACE) and cardiovascular death (CV death) remain unexplored. This study identifies proteomic mediators linking AIDs to MACE via high-dimensional mediation analysis in the UK Biobank. Methods: We used UK Biobank data with proteomic profiling by Olink platform. Participants with prevalent myocardial infarction (MI), stroke, and heart failure at baseline were excluded. AIDs were categorized into musculoskeletal (MSK), vasculitis, gastrointestinal (GI), neurologic, and rheumatic fever subsets. Fine–Gray models assessed associations between AIDs and MACE and CV death. Proteome-wide association studies identified proteins associated with both AIDs and cardiovascular outcomes. High-dimensional mediation analysis (HIMA) explored protein-mediated pathways. All models adjusted for age, sex, lipids, BMI, smoking, hypertension, diabetes, chronic kidney disease, atrial fibrillation, and coronary artery disease. Results: Among 400,633 participants (median follow-up 14.5 years, 44.8% male), AIDs were present in 28,754 (7.2%). All AID categories were associated with increased MACE (sHR: MSK 1.34, vasculitis 1.67, GI 1.20, neurologic 1.33, rheumatic fever 1.38; all p < 0.001). For CV death, MSK, vasculitis, and rheumatic fever showed increased risk (sHR 1.34, 1.78, 1.51; all p ≤ 0.004), but not GI or neurologic AIDs. In 43,599 participants with proteomic data, HIMA identified 66 and 32 unique potential mediators linking AIDs to MACE and CV death, respectively. Four proteins (Growth Differentiation Factor 15, Interleukin-15, urokinase plasminogen activator receptor, and Tenascin C) mediated the AID-MACE relationship across multiple AID categories. Growth Differentiation Factor 15 and Interleukin-15 were shared mediators for CV death. Conclusions: This proteomic analysis identifies specific proteins that may mediate the association between AIDs and adverse cardiovascular outcomes, offering mechanistic insights into immune-related cardiovascular risk. These findings are hypothesis-generating and require replication and validation before the identified proteins can be considered causal mediators or adopted for clinical risk stratification. Full article

Background: Chronic kidney disease (CKD) is a major global health burden, affecting more than 850 million people worldwide. Increasing evidence implicates engulfment and cell motility 1 (ELMO1), a cytoplasmic adaptor protein that regulates cytoskeletal remodeling, phagocytosis, and immune responses through the ELMO1–DOCK1–Rac1 signaling axis, in renal injury and disease progression. Methods: This narrative review identified relevant publications through searches of PubMed, Web of Science, and Google Scholar using combinations of the terms “ELMO1,” “kidney disease,” “diabetic kidney disease,” “IgA nephropathy,” “focal segmental glomerulosclerosis,” “acute kidney injury,” and “renal fibrosis.” English-language original research articles, genetic association studies, mechanistic investigations, and selected review articles were preferentially included according to their relevance to ELMO1 in kidney diseases. Results: Genetic association studies have implicated the ELMO1 locus in susceptibility to diabetic kidney disease (DKD), although associated variants and effect sizes differ across populations. Experimental studies suggest that ELMO1 regulates cytoskeletal remodeling, inflammatory responses, oxidative stress, and extracellular matrix deposition through the canonical ELMO1–DOCK1–Rac1 signaling pathway as well as Rac1-independent mechanisms. Available evidence supports a role for ELMO1 in DKD and renal fibrotic remodeling. In focal segmental glomerulosclerosis, the relevance of ELMO1 is primarily inferred from Rac1-associated podocyte injury pathways, whereas evidence in acute kidney injury remains limited and context-dependent. ELMO1 may contribute to inflammatory injury in ischemia–reperfusion settings but may also support efferocytosis and tissue repair in nephrotoxic injury models. In IgA nephropathy, evidence for a direct role of ELMO1 remains limited and is currently based largely on indirect mechanistic observations involving mucosal immunity and glomerular injury responses. Conclusions: ELMO1 is a context-dependent regulator of cytoskeletal, inflammatory, oxidative, and matrix-remodeling processes relevant to kidney disease. The strongest evidence currently supports its involvement in DKD, whereas its roles in other kidney diseases remain to be further defined in disease-specific, cell-type-specific, and stage-specific experimental models. Further studies are required to clarify its potential as a biomarker or therapeutic target in CKD. Full article

Feline chronic gingivostomatitis (FCGS) is a chronic inflammatory disease of the oral mucosa. Mesenchymal stem cell (MSC) treatments have been investigated as a potential treatment for this condition; however, the biodistribution profile of MSCs remains poorly understood. The goal of this study was to assess the relative pharmacokinetics of MSCs by comparing their biodistribution in healthy cats to that in cats suffering from FCGS. Two studies were performed to evaluate the biodistribution of radiolabelled equine peripheral blood-derived mesenchymal stem cells (ePB-MSCs) following intravenous and subcutaneous administration in healthy cats (n = 3) and in cats with FCGS (n = 4). Total body scintigraphic scans were obtained using a gamma camera. Free ^99mTechnetium accumulation was primarily observed in the heart, lungs, stomach, bladder, thyroid, and salivary glands. Following intravenous administration of radiolabelled ePB-MSCs, increased radiopharmaceutical uptake (IRU) was mainly detected in the lungs, liver, kidneys, and bladder. After subcutaneous administration, IRU was predominantly observed at the injection site. In cats affected by FCGS, a higher radiotracer signal was observed in the rostral oral region following intravenous administration, with a mean 3.4-fold increase compared with healthy cats. The biodistribution pattern of radiolabelled ePB-MSCs differed from that of free ^99mTechnetium. These findings provide preliminary information regarding the biodistribution of radiolabelled ePB-MSCs in cats. Full article

Acute kidney injury (AKI) is a major global health challenge associated with substantial morbidity, mortality, and progression to chronic kidney disease. Increasing evidence indicates that oxidative stress, mitochondrial dysfunction, inflammatory signaling, regulated cell death, and maladaptive tissue repair play central roles in AKI pathogenesis, yet effective disease-modifying pharmacological therapies remain unavailable. This narrative review critically evaluated current evidence regarding the pharmacological characteristics, molecular mechanisms, and translational potential of alpha-mangostin (AM), the principal prenylated xanthone isolated from the pericarp of Garcinia mangostana L., through a comprehensive synthesis of experimental and mechanistic studies. Available preclinical evidence consistently demonstrates that AM improves renal function and attenuates histopathological injury, particularly in cisplatin-induced nephrotoxicity and glycerol-induced rhabdomyolysis models. These renoprotective effects are primarily associated with suppression of oxidative stress, activation of the Nrf2/HO-1 antioxidant pathway, inhibition of NF-κB-mediated inflammatory signaling, preservation of mitochondrial function, and attenuation of apoptosis. Several emerging pathways may also contribute to AM-mediated renoprotective effects; however, current evidence remains indirect, and their roles require validation in kidney-specific models. Clinical translation remains limited by poor oral bioavailability, insufficient pharmacokinetic data, lack of standardized formulations, and the absence of human clinical trials. Overall, current evidence suggests that AM has preliminary renoprotective potential in experimental AKI models. However, the limited number of available studies, predominance of cisplatin-induced nephrotoxicity models, insufficient pharmacokinetic and safety data, and absence of human clinical studies preclude conclusions regarding its clinical efficacy or translational readiness. Further validation in diverse and clinically relevant AKI models is required before clinical investigation can be considered. Full article

Chronic kidney disease (CKD) is a major public health problem worldwide, affecting over 10% of the global population, and its prevalence continues to increase. In addition to classic comorbidities, including cardiovascular and metabolic disorders, cognitive impairment (CI) has recently been recognized as a serious complication of CKD. CI can be observed across the entire spectrum of CKD, from G1 to G5 stages, independent of age-related changes. The kidney–brain axis seems to provide a conceptual framework in which microvascular disease, blood–brain barrier disruption, uremic toxins, oxidative stress, systemic inflammation, and consequent neuroinflammation converge to promote CI. This narrative review aims to synthesize the existing evidence on stage-dependent molecular mechanisms of CI in CKD, integrating clinical observations with proposed molecular and pathophysiological mechanisms. Because most studies investigating CI in CKD rely primarily on eGFR-based staging, our analysis was structured around GFR categories, assessing early-to-moderate CKD, defined according to KDIGO as G1–G3 stages, advanced CKD stages, including G4–G5 not yet requiring kidney replacement therapies, and kidney failure treated with different modalities of kidney replacement therapy, such as peritoneal dialysis, hemodialysis, and kidney transplantation. In addition to clinical observations and the burden of CI in CKD, we describe the potential stage-dependent pathomechanisms underlying vascular-executive, uremic-toxic, inflammatory, dialysis-hemodynamic, and post-transplant medication-related profiles as a continuum of cognitive disorders in individuals with CKD. Full article

Background: Pregnancy-associated plasma protein-A (PAPP-A)-derived N- and C-terminal fragments of IGF-binding protein-4 (NT- and CT-IGFBP-4) are released from vulnerable atherosclerotic plaques. This study investigated the prognostic value of PAPP-A and IGFBP-4 fragments in patients with acute myocardial infarction (AMI), especially in those combined with chronic kidney disease (CKD). Methods: This prospective study measured admission levels of PAPP-A, NT- and CT-IGFBP-4 in 341 consecutive AMI patients. Of these patients, 232 were diagnosed with CKD (AMI and CKD), which consisted predominantly of early-stage cases. The primary outcome was one-year major adverse cardiovascular and cerebrovascular events (MACCE), a composite of cardiovascular death, non-fatal MI, and stroke. Results: In the whole AMI cohort and the AMI and CKD subgroup, serum PAPP-A and NT-IGFBP-4 levels in patients with MACCE were both significantly higher than those in patients without MACCE, whereas CT-IGFBP-4 levels were similar. Multivariable Cox regression analysis revealed that increased levels of PAPP-A (HR, 2.48; 95% CI, 1.09–5.63; p = 0.030) and NT-IGFBP-4 (HR, 2.48; 95% CI, 1.03–6.02; p = 0.044) were associated with MACCE in the whole AMI cohort. The areas under the receiver operating characteristic (ROC) curve for PAPP-A and NT-IGFBP-4 were 0.637 and 0.633, respectively. However, in the AMI and CKD subgroups, only NT-IGFBP-4 was identified as an independent predictor of MACCE (HR, 2.72; 95% CI, 1.16–6.41; p = 0.021) and cardiovascular death (HR, 2.63; 95% CI, 1.01–6.84; p = 0.048). Conclusions: PAPP-A and NT-IGFBP-4 were independently associated with one-year MACCE. NT-IGFBP-4 may be a promising prognostic marker in AMI patients with early-stage CKD. Full article