Clinical Kidney Journal最新文献

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.

Background: Obesity is a leading risk factor for chronic kidney disease, with glomerular hyperfiltration as one of its earliest manifestations. However, absolute glomerular filtration rate (GFR) does not distinguish well between a pressure-driven hyperfiltration and the physiological forms. Insulin resistance and endothelial dysfunction have been proposed as key correlates of maladaptive renal haemodynamics, but their interplay remains unclear.

Methods: Cross-sectional pilot study involving 27 adults with severe obesity (mean body mass index of 43.9 kg/m²). Measured GFR (mGFR) was assessed by iohexol plasma clearance and effective renal plasma flow (ERPF) by ¹²³I-ortho-iodohippurate clearance. A hyperfiltration index (P-score) was derived as the standardized difference between filtration fraction and effective renal plasma flow with higher values reflecting a maladaptive phenotype. Endothelial function was assessed by brachial artery flow-mediated dilation and insulin sensitivity by oral glucose insulin sensitivity.

Results: Participants were stratified into tertiles of P-score. Across tertiles, mGFR did not differ, but ERPF declined (756 ± 113 vs 505 ± 130 mL/min, P = .001) and of filtration fraction increased (16 ± 3% vs 26 ± 5%, P = .001) from the lowest to the highest tertile. Insulin sensitivity significantly decreased with higher P-score (384 ± 50 vs 308 ± 33, P = .019). Endothelial function was reduced in the highest vs lowest tertile (3.44 ± 1.49 vs 6.21 ± 1.76%, P = .014), while responses to nitroglycerin did not differ. In univariate analyses, P-score was inversely associated with insulin sensitivity (r = -0.36, P = .036) and endothelial dysfunction (r = -0.40, P = .022), whereas measured mGFR showed no associations. In multivariable models, the link between P-score and insulin sensitivity remained significant after adjustment.

Conclusion: A maladaptive phenotype characterized by elevated filtration fraction relative to renal plasma flow clustered with insulin resistance and endothelial dysfunction, whereas mGFR alone failed to capture these relationships. Comprehensive haemodynamic profiling may help to refine risk stratification in obesity.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of kidney failure globally, and a significant cause of morbidity and mortality. It is now recognized that it may result from both major and minor genes with associated differences in disease penetrance, symptom burden and clinical outcomes. Genetic testing is now readily available to discriminate between different genotypes and is being increasingly utilized for diagnostic and prognostic indications. In this short review, we summarize the reasons why testing should become part of standard care for ADPKD patients where available and highlight some current limitations and challenges to testing. Defining the genetic landscape in ADPKD for all ethnic groups will be key to the future development and deployment of individualized patient-centered management in this condition.

Background: Cystinuria is a rare autosomal recessive disorder characterized by impaired renal reabsorption of cystine and dibasic amino acids, leading to recurrent nephrolithiasis. While dietary salt and protein restriction are commonly recommended, evidence supporting their effectiveness in reducing urinary cystine excretion is limited. This study investigated whether intra-individual changes in dietary salt and protein intake are associated with changes in cystine excretion over time.

Methods: We conducted a retrospective cohort study of 41 adult patients with recurrent cystine stones treated at a tertiary kidney stone clinic between 2004 and 2023. All patients underwent five 24-hour urine collections at intervals of 6-12 months. Urinary sodium and urea excretions were used as surrogates for salt and protein intake, respectively. Mixed-effects linear regression models assessed within-person associations between dietary intake and urinary cystine excretion, adjusting for age, sex, and time.

Results: Cystine excretion showed considerable intra-individual variability (intraclass correlation coefficient: 0.457). An increase in urinary urea of 3.5 g/24 h (reflecting ∼10 g/day higher protein intake) was associated with a 164 µmol/24 h increase in cystine excretion (95% CI: 57 to 271, P = .003). In contrast, a 17 mmol/24 h increase in urinary sodium (∼1 g/day salt intake) was associated with a non-significant 46 µmol/24 h increase in cystine excretion (95% CI: -5 to 97, P = .081).

Conclusions: Protein intake is moderately associated with urinary cystine excretion, whereas salt intake has minimal effect. These findings suggest that, while protein moderation may contribute to cystine reduction, fluid intake and urine alkalinization remain the primary determinants of urinary cystine levels.

Background: Intradialytic hypotension (IDH) is a serious complication of chronic hemodialysis (HD). BestShape is a novel artificial intelligence-driven system developed recently for real-time prediction of IDH. This study aimed to report the clinical results and health-economic benefits following the implementation of BestShape.

Methods: Medical records from two institutions in Taiwan that incorporated BestShape into all HD practices were retrospectively reviewed. Data from HD sessions from January 2020 to December 2023, following BestShape implementation, constituted the "BestShape group." Data from January 2016 through the end of 2019 served as the historical control group. The primary outcome was IDH frequency, and secondary outcomes were rates of cardiopulmonary resuscitation (CPR), falls, mortality, medical personnel satisfaction, and estimated cost reduction.

Results: In total, 213 071 HD sessions of 18 141 patients were included (BestShape 152 792 sessions; control 60 279 sessions). The mean monthly IDH rate significantly reduced from 27% in 2019 to 21% in 2023 (P < .001). The need for CPR during dialysis decreased from eight to three times per month, and post-dialysis falls decreased from 21 to seven times. The estimated annual cost savings by implementing BestShape were USD 115 658. The mortality rate during HD was not significantly different before and after BestShape implementation (8% vs 9.3%, P = .260). Medical personnel expressed satisfaction with BestShape, with a mean satisfaction score of 86.

Conclusion: Preliminary clinical data show BestShape is associated with reductions in IDH, CPR, and falls in patients undergoing HD, and a reduction in healthcare costs and high medical personnel satisfaction.

The debate over whether to use age-adapted or age-independent estimated glomerular filtration rate (eGFR) cut-offs for diagnosing chronic kidney disease (CKD) reflects a fundamental tension between physiological understanding and clinical pragmatism. Age-adapted proponents highlight robust evidence that GFR declines naturally with age, with many healthy older adults falling below the traditional 60 ml/min/1.73 m² threshold. They argue that fixed cut-offs risk overdiagnosing CKD in the elderly, potentially leading to unnecessary anxiety and treatment, while underrecognizing risk in younger individuals whose GFRs are abnormal for their age. Physiological and longitudinal studies support this view, suggesting age-specific percentiles may better reflect true pathology. Conversely, advocates for age-independent thresholds emphasize that age-related GFR decline is not benign. Large epidemiological studies show that older adults with an eGFR of 45-59 ml/min/1.73 m² are at increased risk of kidney failure, cardiovascular events and mortality, even in the absence of albuminuria. They caution that redefining CKD based on age could exclude high-risk older adults from beneficial therapies and research and that 'healthy' reference populations may harbour undiagnosed disease. A balanced approach recognizes the physiological realities of aging while not ignoring the clinical risks associated with reduced kidney function in older adults. Individualized risk prediction tools and shared decision-making can help tailor diagnosis and management. Ultimately, moving beyond arbitrary thresholds toward a patient-centred, risk-based strategy may best serve individuals across their lifespans, ensuring that CKD diagnosis and care are both scientifically sound and clinically meaningful.