Clinical Kidney Journal最新文献

Background: Immunoglobulin A nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) and identifying early molecular signatures is crucial for IgAN risk stratification and timely intervention. In this study we used serum proteomics to investigate molecular differences between IgAN patients who progressed and those who remained stable before separation in kidney function became apparent.

Methods: Serum samples from 40 adults with biopsy-proven IgAN were analysed and classified as progressors (PRs; n = 13) or non-progressors (NPs; n = 27) based on the estimated glomerular filtration rate slope over a 5- to 6-year follow-up. Samples underwent protein depletion, SP3 digestion, tandem mass tag labelling and liquid chromatography-tandem mass spectrometry analysis. Differentially expressed proteins were identified using Welch's t-test. Enrichment analysis (Gene Ontology, Kyoto Encyclopedia of Genes and Genomes) was performed with ShinyGO and Cytoscape. Random forest machine learning was applied for classification modelling.

Results: Fifty-two proteins showed a significant differential abundance between PRs and NPs. Enrichment analysis revealed dysregulation in complement cascade, extracellular matrix signalling and renin-angiotensin system in PRs compared with NPs. Finally, the random forest model on this protein set achieved an accuracy of 85.0% and identified NCAM1, F7, ARG1, CLU and ANXA5 among the most important predictors.

Conclusions: Serum proteomic profiling identified early molecular differences between PR and NP IgAN patients. These findings support the utility of serum proteomics for early risk stratification in IgAN.

Background: The origin of chronic kidney disease (CKD) remains unknown in ≈16% of patients at the time of renal replacement therapy. The aim of this study was to assess the proportion of monogenic kidney diseases in kidney transplant candidates with kidney disease of unknown cause.

Methods: Transplant candidates, referred to a nephrogenetic outpatient clinic, had a molecular investigation and were included if they met the following inclusion criteria: absence of diagnosis (including presumed hypertensive nephropathy or vascular or focal segmental glomerulosclerosis lesions) and a glomerular filtration rate <30 ml/min/1.73 m² before 50 years of age and/or renal morphology abnormality (including renal hypotrophy, cysts and congenital anomalies of the kidney and urinary tract) and/or extrarenal involvement and/or family history of CKD.

Results: Eighty-nine patients were evaluated at the nephrogenetic consultation and 84 patients met the inclusion criteria and were tested and included. Half had a family history of CKD. Almost half of the patients (46.4%) had a morphological abnormality of the kidney. Twenty-eight (33.3%) had been biopsied: 21% had focal and segmental hyalinosis lesions and 25% had chronic interstitial nephropathy. Thirty patients (36%) had a positive genetic diagnosis. Of these, 9/30 (30%) had APOL1 high-risk alleles and 21/30 (70%) had monogenic nephropathy. Patients with a positive genetic diagnosis were significantly more likely to have a family history of kidney disease (70% versus 37%; P = .004).

Conclusions: Genetic testing enables a diagnosis to be established in 36% of patients, allowing genetic counselling and may help potential living donor evaluations.

Background: Contrast-associated acute kidney injury (CA-AKI) has been reported to occur in a significant proportion of patients undergoing percutaneous coronary intervention (PCI). The role of remote ischemic preconditioning (RIPC) in CA-AKI prevention remains unclear.

Methods: In this single-center double-blind randomized controlled trial, 420 eligible patients with high risk of CA-AKI admitted for PCI were randomized into two groups: RIPC and sham RIPC (control group). RIPC was performed by repeated cycles of inflation and deflation of an upper limb blood pressure cuff prior to PCI. Serum neutrophil gelatinase-associated lipocalin (NGAL) levels were measured at 2- and 6-h, and serum creatinine at 24- and 48-h post-PCI. The primary endpoint was the incidence of CA-AKI. Secondary endpoints were change in serum creatinine at 48 h, incidence of subclinical AKI (defined as an increase in NGAL values by 25% or more from baseline), change in NGAL at 2- and 6-h (delta NGAL), in-hospital mortality and major adverse cardiovascular events (MACE) at Day 30.

Results: CA-AKI occurred in 11.4% (n = 48), with AKI stage 1 in 10.2% (n = 42). The incidence of CA-AKI was significantly lower in the RIPC group, compared with control group [8.1% vs 15.0%, risk ratio (RR) 0.54, 95% confidence interval (CI) 0.31-0.94; P = .027]. There was no significant difference in change in creatinine at 48 h in both the groups (P = .158). The incidence of subclinical AKI was also numerically lower in the RIPC group; however, this was not statistically significant (36.2% vs 40.5%, RR 0.89, 95% CI 0.66-1.22; P = .158). Dialysis-requiring AKI, in-hospital mortality and 30-day MACE were similar in both groups. There were no RIPC-related adverse events.

Conclusions: In patients at high risk of developing CA-AKI after PCI, RIPC is an effective and safe preventive measure.

Background: Despite therapeutic strategies to manage comorbidities and risk factors associated with chronic kidney disease (CKD), a significant number of patients continue to progress toward kidney failure. The role of low protein diets (LPDs) in delaying the need for kidney replacement therapy (KRT) remains a subject of ongoing discussion. Real-world studies offer insights into the risks, implementation and feasibility of LPDs.

Methods: We retrospectively evaluated the efficacy of a moderate LPD (0.6-0.7 g/kg/day) proposed to all newly referred patients with advanced CKD. Survival and need for dialysis were compared between patients who choose an LPD and those who did not. Follow-up was otherwise identical in both groups.

Results: Between January 2021 and December 2023, 110 of 182 patients chose to follow an LPD, while 72 did not. No baseline difference in age, sex, kidney function and comorbidity were observed between the two groups. The decline in estimated glomerular filtration rate was faster in patients not adhering to a diet compared with those who followed it (-2.65 versus -0.89 ml/min/1.73 m²/year), with an 84% reduction in the need for KRT {hazard ratio [HR] 0.16 [95% confidence interval (CI) 0.07-0.39]}, 78% in all-cause mortality [HR 0.22 (95% CI 0.06-0.72)] and 81% in the composite outcome death or dialysis [HR 0.19 (95% CI 0.09-0.38)].

Conclusion: When offered the option of an LPD, >60% of patients agreed to and followed it. Choosing an LPD was associated with improved patient and renal survival. While this retrospective study cannot establish a causal relationship, our data provide reassurance regarding feasibility and suggest potential advantages of offering LPDs to unselected patients with CKD who choose this dietary approach.

Introduction: In patients with incident end-stage kidney disease (ESKD), hyperkalemia (HyperK) is a common indication for initiating kidney replacement therapy (KRT). Hemodialysis (HD) and peritoneal dialysis (PD) both effectively reduce serum potassium, but HD is often considered superior due to its perceived faster efficiency. However, evidence supporting this perception remains limited. We hypothesized that HD and PD would be equally effective for the management of severe HyperK during hospitalization.

Methods: We conducted a prospective cohort study at the Nephrology Department of Hospital Civil de Guadalajara. Consecutive, dialysis-naïve patients hospitalized with ESKD and severe HyperK (serum potassium >6.5 mEq/L at admission) between 2022 and 2024 were included. The modality of KRT (HD vs PD) was determined by the treating nephrology team. The primary outcome was the trajectory of serum potassium reduction between groups. Secondary outcomes included daily potassium trajectory, catheter dysfunction, length of stay and mortality.

Results: Eighty-two patients were included: 34 initiated PD, 37 HD and 11 received conservative management. Baseline demographic and clinical characteristics were similar across groups (P > .05). Median age was 65 years [interquartile range (IQR) 53-74], with diabetes in 33% and hypertension in 53%. Median admission potassium was 6.99 mEq/L (6.7-7.6), serum creatinine 15.9 mg/dL (11.5-23.1) and estimated glomerular filtration rate 2.91 mL/min/1.73 m² (1.80-4.09). The PD group underwent a mean of 45 (±15) exchanges during hospitalization, and the HD group received 4.6 (±1) sessions. Serum potassium decreased similarly in both groups (P > .05), with substantial reductions on Day 1 (PD 6.03 mEq/L; HD 5.90 mEq/L) and stabilization by Day 5 through Day 15. Catheter dysfunction occurred in 11% of patients, with similar rates between groups, hospitalization median was 5 days (IQR 3-8) and 12-month mortality was 26.8%, without differences between modalities.

Conclusions: In this prospective cohort of ESKD patients with severe HyperK, both PD and HD achieved comparable potassium reduction and clinical outcomes, supporting PD as an effective alternative for urgent-start KRT.

Background: Increased tissue sodium (Na⁺) concentration is associated with adverse clinical outcomes in people with chronic kidney disease (CKD) including hypertension, inflammation and increased cardiovascular disease (CVD). 23-Sodium magnetic resonance imaging (²³Na-MRI) can non-invasively quantify tissue Na⁺ concentration. However, in the CKD population, few studies have evaluated relationships between ²³Na-MRI-derived tissue Na⁺ concentrations and measures of Na⁺ metabolism, surrogate markers of CVD and other CKD-related health complications.

Methods: We conducted a cross-sectional cohort study, involving 51 participants with CKD (28 with non-dialysis CKD, 23 on dialysis), to explore relationships between ²³Na-MRI-derived tissue Na⁺ concentrations (including skin, bone, muscle and whole leg-tissue), measures of Na⁺ metabolism and CKD-related health outcomes. Multivariable regression and correlation analyses were used to assess associations.

Results: Skin and whole leg-tissue Na⁺ concentrations were positively associated with surrogate cardiovascular markers of troponin I and brain natriuretic peptide (P < .05). Bone and whole leg-tissue Na⁺ concentrations were negatively associated with bone mineral density. Higher muscle Na⁺ concentration was associated with lower levels of physical well-being. Tissue Na⁺ concentration was positively correlated with extracellular fluid volume as measured by proton (¹H) MRI (P ≤ .001) and body composition monitor (P < .05).

Conclusion: Whole leg-tissue Na⁺ in addition to skin Na⁺ concentration may be a useful clinical marker of body Na⁺ with related health outcomes. Tissue Na⁺ may play a role in CVD, bone health and quality of life in people with CKD, representing a potential therapeutic target to improve clinical outcomes.

Cystinuria is a rare autosomal recessive hereditary disorder characterized by increased urine cystine excretion and recurrent kidney stone formation. Acquired cystinuria after kidney transplantation is extremely rare, with, to our knowledge, a single case described in the literature, albeit without genetic explorations. We herein report a 59-year-old male kidney transplant recipient, without history of urolithiasis, who developed cystine stones in the allograft. Genetic studies revealed a homozygous pathogenic mutation in the SLC3A1 gene in the deceased donor. This case demonstrates the potential for transmission of cystinuria through the kidney allograft and underlines the value of genetic analysis in the donor.

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.

Chronic kidney disease (CKD) is a common condition and important cardiovascular risk factor. However, CKD remains underdiagnosed and evidence-based medicines underutilized. In most healthcare systems, most CKD is managed in primary care. Optimal management in this setting can only be achieved with integration of care including early identification, prioritization, and use of the tools and skill mix available. This narrative review focuses on the importance of screening and identification in primary care, looking at innovative solutions and methods from other long-term conditions, particularly cardio-renal-metabolic conditions. Integrated care virtual multidisciplinary reviews, have demonstrated clinical and economic benefits, improved medication optimization, and reduced unnecessary referrals. However, implementation remains inconsistent, and prescribing of both established and novel therapies remains sub-optimal. Optimizing CKD care requires a system-wide approach that reinforces primary-secondary care collaboration, prioritizes early detection, and facilitates timely, evidence-based interventions. The inclusion of urine albumin: creatinine ratio testing, integrated digital tools, and shared accountability frameworks must be urgently adopted to realize improved outcomes and reduce the burden of CKD on individuals and healthcare systems alike.

Introduction: Chronic kidney disease (CKD) is associated with systemic inflammation and elevated pro-inflammatory cytokines. While interleukin (IL)-8 has shown harmful cardiovascular effects in preclinical studies, its role in CKD remains underexplored. The study aimed to (i) determine serum IL-8 concentrations across CKD stages, (ii) identify factors associated with IL-8 concentrations, and (iii) evaluate its association with major adverse cardiovascular events (MACEs) and all-cause mortality.

Methods: The Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) prospective cohort includes CKD patients with an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m² not on kidney replacement therapy. Baseline serum IL-8 concentrations were centrally measured. MACE was defined as any cardiovascular death, myocardial infarction, stroke and hospital admission for heart failure. Multivariable linear regression was used to identify factors associated with IL-8 concentrations. Adjusted cause-specific Cox proportional hazard models were used to estimate hazard ratios [hazard ratio (HR) (95% confidence interval)] for the first MACE and for mortality.

Results: Among 2389 included patients (66% men; median age 68 years; mean eGFR 34.8 mL/min/1.73 m²), median serum IL-8 concentration was 12.2 pg/mL. Higher IL-8 levels correlated with more advanced CKD (P < .001), and were independently associated with lower eGFR, diabetes, prior cardiovascular disease, anemia, elevated C-reactive protein, more medications and lower serum albumin. Elevated baseline IL-8 was associated with a greater adjusted hazard of MACEs in women [HR for 1-unit change in log(IL-8): 1.75 (1.26; 2.43)] but not in men [HR 1.16 (0.93; 1.45)]. The adjusted HR for all-cause mortality was 1.70 (1.40; 2.06), with no difference between men and women.

Conclusion: In a large cohort of patients with moderate-to-advanced CKD, higher IL-8 levels were associated with a greater risk of MACEs in women (but not in men) and higher mortality in both sexes. Further research is needed to assess the potential of IL-8 as a cardiovascular risk biomarker, clarify the clinical significance of the sex difference observed here and determine whether targeting IL-8 could reduce cardiovascular risk in CKD.