Search

Chronic kidney disease (CKD) is a prevalent global health concern affecting approximately 850 million people worldwide, with a significant and rising mortality rate. CKD often coexists with hyperuricemia (HSUA), which is also increasingly common due to its association with hypertension, obesity, and diabetes. The interplay between hyperuricemia and CKD is complex; while in vitro studies and animal models support a role for uric acid mediating glomerular and tubule-interstitial damage, and HSUA has been shown to predict the onset and progression of CKD, the expectations of renal protection by the use of urate lowering treatment (ULT) are inconsistent. A significant challenge in managing asymptomatic HSUA in CKD patients lies in determining the appropriate SUA threshold values. Recent research, including the URRAH project, has sought to identify SUA cut-offs predictive of cardiovascular mortality, but these thresholds may vary depending on the severity of CKD. This variability complicates the establishment of universal guidelines for treating asymptomatic HSUA, leading to a lack of specific recommendations in clinical practice. In conclusion, while hyperuricemia is recognized as a prognostic factor for CKD and cardiovascular risk, more research is needed to refine the threshold values for SUA and to identify which patients may benefit from ULT. Stratification based on glomerular filtration rate may be necessary to tailor the treatments and improve outcomes in this population.

Background The predictive role of blood pressure variability for all‐cause mortality and fatal and nonfatal cardiovascular events has been described in the general population and in patients with diabetes, independently of mean BP. Although systolic blood pressure variability has been proposed as an informative measure for predicting clinical outcomes in patients with chronic kidney disease, its role in kidney transplant recipients is still debatable. Methods and Results We performed a retrospective, observational, monocentric analysis of all kidney transplant recipients in follow‐up at the outpatient Nephrology Clinic of San Martino Hospital from January 1, 2016 to December 31, 2016, who underwent kidney transplantation >12 months. The primary outcome was a fatal or nonfatal cardiovascular event (myocardial infarction, unstable angina, stroke, and hospitalization for heart failure). Visit‐to‐visit systolic blood pressure variability was expressed as the SD of systolic blood pressure values recorded at baseline and 3 months up to 18 months. Among the 272 patients (mean age, 64±13; 63% men) included in the present analyses, for each increase of 2.7 mm Hg in systolic blood pressure SD, the risk for events increased 3‐fold (hazard ratio [HR], 3.1 [95% CI, 1.19–7.88]; P=0.02), and patients in the highest tertile of systolic blood pressure SD showed a 4‐fold increased risk (HR, 4.1 [95% CI, 1.34–12.43]; P=0.01). This relationship was maintained even after incremental adjustment for time‐averaged pulse pressure, age, diabetes, and prior cardiovascular event (HR, 3.2 [95% CI, 1.1–10.0]; P=0.04). Conclusions Long‐term blood pressure variability represents a risk factor for cardiovascular events in kidney transplant recipients, even independently by several confounding factors including blood pressure load.

IntroductionAcute kidney injury (AKI) in cancer patients receiving immune checkpoint inhibitors (ICIs) may recognize multiple causes. Here, we reviewed cases of biopsy-proven acute tubulointerstitial nephritis (ATIN) to describe the clinical characteristics and outcomes of this condition.MethodWe conducted a pooled analysis of clinical cases of ICI-related biopsy-proven ATIN up to 1 May 2022. We collected data on clinical characteristics, AKI, biopsy findings, laboratory examinations, and renal outcomes.ResultsEighty-five patients (61.4 ± 19 years, 56 male) were evaluated. Melanoma was the most prevalent diagnosis (51%), followed by non-small cell lung cancer (30%). ICI treatment consisted of PD-1, PDL-1 (nivolumab, pembrolizumab, atezolizumab), and CTLA-4 inhibitors (i) (ipilimumab) or combination PD-1i+CTLA4i. Renal toxicity developed after a median of four cycles of therapy. Fifty-one patients (65.5%) developed the most severe form of AKI- stage 3, including five patients requiring dialysis. All the 19 patients treated with dual ICI blockade developed AKI-stage 3, compared with 29 patients out of the 60 receiving a single agent (p

Although rare, C3 glomerulopathy (C3G) is increasingly recognized thanks to the currently available diagnostic skills. C3G is not a single disease but a group of disorders with distinct pathogenesis and progression. Thus, an essential step for its management remains an in-depth characterization of the specific form and the identification of underlying conditions, which may also impact treatment choices as well. Among these entities, an emerging condition is the association of C3G with monoclonal gammopathy, which confers poor outcomes. Overall, diagnosis of C3G remains challenging, and determining the appropriate treatment remains unclear. Conventional immunosuppressive therapy has proven ineffective in such cases, while clone-directed therapies have shown promising results in small interventional studies and case series. Here, we report a case of a patient affected by C3G with monoclonal gammopathy of renal significance who experienced rapid deterioration of kidney function requiring replacement therapy. After the failure of first-line treatment, a switch to the anti-CD38 therapy with daratumumab resulted in the progressive improvement of the patient’s kidney function, leading to the discontinuation of hemodialysis after approximately 10 months. Serial renal biopsies were also performed to study the disease’s evolution in response to the treatment. Based on the description of this single case, we have comprehensively reviewed available studies on daratumumab use in patients with C3G associated with monoclonal gammopathy to provide insights for the design of prospective studies which aim to enhance the management of such poor prognosis disease.

Background: Chronic kidney disease (CKD) is a progressive systemic condition characterized by numerous complications. Among these, alterations in skeletal muscle physiology, such as sarcopenia, are particularly significant, as they are associated with poor outcomes and reduced quality of life. Summary: Various interventions, including pharmacological approaches and lifestyle modifications have been investigated to slow CKD progression and prevent or treat its complications. Physical exercise, in particular, has emerged as a promising intervention with multiple beneficial effects. These include improvements in physical functioning, increased muscle mass, modulation of metabolic abnormalities, and reduced cardiovascular risk. However, the pathophysiology of physical exercise in patients with kidney disease is complex and remains only partially understood. A crucial advancement in understanding this phenomenon has been the identification of myokines – molecules expressed and released by skeletal muscle in response to physical activity. These myokines can exert both paracrine and systemic effects, influencing not only skeletal muscle physiology but also other processes such as energy metabolism and lipid regulation. Key Messages: The interplay among skeletal muscle, physical activity, and myokines may act as a pivotal regulator in various physiological processes, including aging, as well as in pathological conditions like cachexia and sarcopenia, frequently observed in CKD patients at different stages, including patients on dialysis. Despite the potential importance of this relationship, only a limited number of studies have explored the relationship between exercise and myokine, and the effect of this interaction on experimental models or individuals with kidney disease. In the following sections, we review and discuss this topic.

IntroductionRecent evidence suggests the blood-to-brain influx rate (K1) in TSPO PET imaging as a promising biomarker of blood–brain barrier (BBB) permeability alterations commonly associated with peripheral inflammation and heightened immune activity in the brain. However, standard compartmental modeling quantification is limited by the requirement of invasive and laborious procedures for extracting an arterial blood input function. In this study, we validate a simplified blood-free methodologic framework for K1 estimation by fitting the early phase tracer dynamics using a single irreversible compartment model and an image-derived input function (1T1K-IDIF).MethodsThe method is tested on a multi-site dataset containing 177 PET studies from two TSPO tracers ([11C]PBR28 and [18F]DPA714). Firstly, 1T1K-IDIF K1 estimates were compared in terms of both bias and correlation with standard kinetic methodology. Then, the method was tested on an independent sample of [11C]PBR28 scans before and after inflammatory interferon-α challenge, and on test–retest dataset of [18F]DPA714 scans.ResultsComparison with standard kinetic methodology showed good-to-excellent intra-subject correlation for regional 1T1K-IDIF-K1 (ρintra = 0.93 ± 0.08), although the bias was variable depending on IDIF ability to approximate blood input functions (0.03–0.39 mL/cm3/min). 1T1K-IDIF-K1 unveiled a significant reduction of BBB permeability after inflammatory interferon-α challenge, replicating results from standard quantification. High intra-subject correlation (ρ = 0.97 ± 0.01) was reported between K1 estimates of test and retest scans.DiscussionThis evidence supports 1T1K-IDIF as blood-free alternative to assess TSPO tracers’ unidirectional blood brain clearance. K1 investigation could complement more traditional measures in TSPO studies, and even allow further mechanistic insight in the interpretation of TSPO signal.

Abstract Background The need for arterial blood data in quantitative PET research limits the wider usability of this imaging method in clinical research settings. Image-derived input function (IDIF) approaches have been proposed as a cost-effective and non-invasive alternative to gold-standard arterial sampling. However, this approach comes with its own limitations—partial volume effects and radiometabolite correction among the most important—and varying rates of success, and the use of IDIF for brain PET has been particularly troublesome. Main body This paper summarizes the limitations of IDIF methods for quantitative PET imaging and discusses some of the advances that may make IDIF extraction more reliable. The introduction of automated pipelines (both commercial and open-source) for clinical PET scanners is discussed as a way to improve the reliability of IDIF approaches and their utility for quantitative purposes. Survey data gathered from the PET community are then presented to understand whether the field’s opinion of the usefulness and validity of IDIF is improving. Finally, as the introduction of next-generation PET scanners with long axial fields of view, ultra-high sensitivity, and improved spatial and temporal resolution, has also brought IDIF methods back into the spotlight, a discussion of the possibilities offered by these state-of-the-art scanners—inclusion of large vessels, less partial volume in small vessels, better description of the full IDIF kinetics, whole-body modeling of radiometabolite production—is included, providing a pathway for future use of IDIF. Conclusion Improvements in PET scanner technology and software for automated IDIF extraction may allow to solve some of the major limitations associated with IDIF, such as partial volume effects and poor temporal sampling, with the exciting potential for accurate estimation of single kinetic rates. Nevertheless, until individualized radiometabolite correction can be performed effectively, IDIF approaches remain confined at best to a few tracers.