Renal Failure Research Articles

Treatment discontinuation in adults with atypical hemolytic uremic syndrome (aHUS): a qualitative study of international experts' perspectives with associated cost-consequence analysis.

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) related to congenital mutations impeding control of the alternative pathway of complement. Following approval of the complement C5 inhibitor eculizumab by the European Medicines Agency and the US Food and Drug Administration, initial guidelines suggested lifelong therapy. Yet, growing evidence indicates that discontinuation of eculizumab, or its long-acting form ravulizumab, is possible for many patients. This mixed-methods study sought to explore international experts' perspectives and experiences related to treatment duration in adult patients with aHUS, while also estimating the financial and potential health consequences of early discontinuation. Between January and December 2023, we conducted 10 qualitative interviews with experts in the treatment of aHUS, based upon which we constructed a quantitative decision tree, designed to estimate time on treatment and treatment- and disease-related adverse events. Thematic analysis of the interview data identified four main themes: (1) Concerns and prior experience; (2) High-risk vs. low-risk groups; (3) Patient preference and adherence; and (4) Funding for monitoring and re-treatment. Although most interviewees were in favour of considering treatment discontinuation for many patients (citing the high cost, burden, and potential side effects of lifelong treatment as key reasons), a prior negative experience of discontinuation seemed to make others more reluctant to stop. Deciding which patients required lifelong treatment and which not involved consideration of a wide range of factors, including patient- and system-related factors. Cost-consequence analysis demonstrated the financial savings associated with early treatment discontinuation at the expense of increased risk of recurrent TMA events. Close monitoring for these events had the potential to minimise any long-term injury, primarily renal, with an estimated one event per 100 patient years. For patients at high risk of TMA and with poor adherence to monitoring, rates of renal injury rose to three events per 100 patient years. aHUS treatment protocols are changing globally in response to new clinical evidence. Against this backdrop, our mixed-methods study provides compelling evidence on the complexity of factors influencing treatment discontinuation decisions in aHUS, as well as the financial and health consequences of early discontinuation.

Chronic renal impairment predicts oncological outcomes in UTUC patients undergoing RNU.

This study aims to explore the relationship between pre-existing renal impairment and oncological outcomes in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU) using data from a multicentre international registry. Data on non-metastatic UTUC patients who underwent RNU were obtained from the Clinical Research Office of the Endourology Society Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry. Patients were categorised into normal pre-operative renal function and chronic renal impairment (CKD) groups, with CKD defined as an estimated glomerular filtration rate below 60 mL/kg/1.73m². Kaplan-Meier survival analysis was employed to investigate disease-free survival (DFS) and overall survival (OS). Multivariable Cox regression analysis was conducted to identify confounding variables. A total of 1393 patients diagnosed with UTUC who underwent RNU between 2014 and 2019 were analysed. 875 patients (62.4%) had normal renal function, whilst 528 patients (37.6%) had CKD prior to RNU. The two groups had similar proportions of bladder cancer history, comparable cardiovascular comorbidity, similar tumour stage, and comparable proportions receiving laparoscopic or robotic-assisted RNU. In multivariable cox regression analysis, CKD was found to be associated with inferior DFS (HR = 1.419; 95%CI = 1.060-1.898; p = 0.019). Upon multivariable analysis, pre-existing renal impairment and higher T stage (HR = 4.613; 95%CI = 1.829-4.712; p < 0.001) and the use of adjuvant chemotherapy (HR = 1.858; 95%CI = 1.229-2.807; p = 0.003) were also found to associate with worse DFS. Significant cardiovascular disease and higher T stage were associated with worse OS. Existing renal impairment at baseline did not have any significant associated with OS. In this multicentre registry, preoperative chronic renal impairment was identified as an independent predictor of inferior DFS in patients undergoing RNU for non-metastatic UTUC. Preoperative CKD could serve as a clinical predictor of poorer oncological outcomes.

Impaired Kidney Function and 10-Year Outcome After Percutaneous Coronary Intervention—Interaction with Age, Sex, Diabetic Status and Clinical Presentation

Background: Limited evidence exists regarding the association of chronic kidney disease (CKD) with long-term outcomes following percutaneous coronary intervention (PCI). We aimed to assess the association of CKD with 10-year outcome after PCI. Methods: This study included 5571 patients with coronary artery disease (CAD) undergoing PCI. Patients were categorized in groups according to the estimated glomerular filtration rate (eGFR) values: eGFR ≥ 90 mL/min/1.73 m2, (normal kidney function), 60 to &lt;90 mL/min/1.73 m2 (mild kidney impairment), 30 to &lt;60 mL/min/1.73 m2 (mild-to-moderate and moderate-to-severe kidney impairment) and &lt;30 mL/min/1.73 m2 (severe kidney impairment). The primary endpoint was all-cause mortality at 10 years. Results: All-cause deaths occurred in 155 patients (86.3%) with eGFR &lt; 30 mL/min/1.73 m2, 602 patients (59.1%) with eGFR 30 to &lt;60 mL/min/1.73 m2, 775 patients (31.3%) with eGFR 60 to &lt;90 mL/min/1.73 m2 and 220 patients (15.8%) with eGFR ≥ 90 mL/min/1.73 m2 (adjusted hazard ratio = 2.16, 95% confidence interval 1.84 to 2.54, p &lt; 0.001, for 30 mL/min/1.73 m2 decrement in the eGFR). There were CKD-by-age (Pint &lt; 0.001) and CKD–by-clinical presentation (Pint = 0.017) interactions showing a stronger association of CKD with mortality in younger patients and those presenting with acute coronary syndromes. The C statistic of the multivariable model for mortality increased from 0.748 [0.737–0.759] to 0.766 [0.755–0.777] (p &lt; 0.001) after the inclusion of eGFR in the model. Conclusions: In patients with CAD undergoing PCI, CKD was associated with higher mortality at 10 years compared with patients with preserved renal function. The association between CKD and mortality was stronger in patients of younger age and those presenting with acute coronary syndromes.

Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial.

Hyperthermic intraperitoneal chemotherapy (HIPEC) at interval cytoreductive surgery for ovarian cancer improves overall survival but its role in recurrent disease is uncertain. We aimed to compare outcomes in patients treated with or without HIPEC during surgery for recurrent ovarian cancer. The multicentre, open-label, randomised, phase 3 CHIPOR trial was conducted at 31 sites in France, Belgium, Spain, and Canada, and enrolled patients with first relapse of epithelial ovarian cancer at least 6 months after completing platinum-based chemotherapy. Eligible patients were aged 18 years or older with WHO performance status of less than 2. After six cycles of platinum-based chemotherapy (and optional bevacizumab), patients amenable to complete cytoreductive surgery were randomly assigned centrally in a 1:1 ratio, using a web-based system and a minimisation procedure, during surgery to receive HIPEC (cisplatin 75 mg/m2 in 2 L/m2 of serum at 41±1°C for 60 min) or not, stratified by centre, completeness of cytoreduction score, platinum-free interval, and latterly, planned poly(ADP-ribose) polymerase inhibitor use. The primary endpoint was overall survival, analysed on an intention-to-treat basis in all randomly assigned patients. This ongoing trial is registered with ClinicalTrials.gov, NCT01376752. Between May 11, 2011, and May 14, 2021, 415 female patients were randomly assigned (207 HIPEC, 208 no HIPEC). At the primary analysis (median follow-up 6·2 years, IQR 4·1-8·1), 268 (65%) patients had died (126 [61%] of 207 in the HIPEC group; 142 [68%] of 208 in the no-HIPEC group). Overall survival was significantly improved with HIPEC (stratified hazard ratio 0·73, 95% CI 0·56-0·96; p=0·024). Median overall survival was 54·3 months (95% CI 41·9-61·7) with HIPEC versus 45·8 months (38·9-54·2) without. Grade 3 or worse adverse events within 60 days after surgery occurred in 102 (49%) of 207 patients receiving HIPEC versus 56 (27%) of 208 receiving no HIPEC, the most common being anaemia (47 [23%] vs 30 [14%]), hepatotoxicity (23 [11%] vs 18 [9%]), electrolyte disturbance (28 [14%] vs two [1%]), and renal failure (20 [10%] vs three [1%]). There were three deaths within 60 days of surgery, all in the no-HIPEC group. Adding HIPEC to cytoreductive surgery after response to platinum-based chemotherapy at first epithelial ovarian cancer recurrence significantly improved overall survival. When treating patients with late first relapse of high-grade serous or high-grade endometrioid ovarian cancer amenable to complete cytoreductive surgery at specialist centres, platinum-based HIPEC should be considered to extend overall survival. French National Cancer Institute and French League Against Cancer.

HPB SO71 - Meta-Anaylsis of Early Endoscopic Retrograde Cholangiopancreatography versus conservative management for gallstone pancreatitis

Abstract Background Acute pancreatitis is one of the most common gastrointestinal causes of hospital admission. The most common cause is transient blockage of the bile or pancreatic duct (or both) by gallstones. Most of the time, pancreatitis responds to conservative management (CM) comprising intravenous fluid hydration and analgesia. ERCP +/_endoscopic sphincterotomy in acute gallstone pancreatitis has been advocated in the past to decrease the number of complications of this condition. However, the role and timing of this procedure are still contentious and an ongoing debate. Method The aim of this study is to compare the clinical outcomes of early urgent ERCP versus conservative management in biliary pancreatitis but not cholangitis. An online search of Medline, Embase, Science citation index, PubMed and Cochrane database of systematic reviews published between 1988 and 2022 was carried out for relevant studies. Statistical analysis was done using Revman 5.4 and Odds ratio with a 95% Confidence interval was used for outcome estimation. There was 14 studies included in the final study consisting a total of 1756 patients with 877 patients in ERCP group while 879 in CM group. Results With random effects model, data showed no significant reduction in mortality in ERCP group as compared to the CM group (OR 0.59, 95% CI 0.30-1.16; p=0.13). However there were overall more local or systemic complications (OR 0.51, 95% CI 0.36-0.71; p&amp;lt;0.002) in the CM group as compared to ERCP group. No statistically significant difference found amongst groups when comparing complications as renal failure(OR-0.99, 95% CI-0.41-2.41, p=0.98), cardiac failure (OR-0.77 95% CI 0.35-1.69, p=0.51) or biliary sepsis (OR-0.56 95%CI 0.15-2.10, p=0.39) but there was more incidence of pseudocyst in CM group patients(OR-0.47, 95% CI 0.25-0.87, p=0.02). Conclusion The above study did show that the mortality rate was not significantly higher in the CM group as compared to the ERCP group however the early ERCP was beneficial in reducing overall complications in the interventional group. Based on this fact, ERCP considered early in the management of acute pancreatitis despite of still being debatable in practice can be considered in severe pancreatitis cases and further high powered randomized controlled trials can be carried out to assess this point.

Successful Percutaneous Transcatheter Aortic Valve Replacement for Severe Aortic Regurgitation in a High-risk Patient with Cardiorenal Syndrome

The absence of a Food and Drug Administration-approved percutaneous valve technology for the treatment of severe aortic regurgitation (AR) presents a challenge for high-risk patients. In this report, we describe the successful treatment of an 84-year-old male patient suffering from severe symptomatic AR and concomitant cardiorenal syndrome with renal failure using a 34-mm Evolut R (Medtronic) self-expanding transcatheter aortic valve replacement. This intervention resulted in the resolution of AR, cardiorenal syndrome, and congestive heart failure symptoms.

The effectiveness and safety of posaconazole enteric-coated tablet versus oral suspension in invasive fungal infections.

Posaconazole enteric-coated tablet and oral suspension are two oral drugs in the treatment of invasive fungal infections (IFIs). This study compared the effectiveness and safety between posaconazole enteric-coated tablet and oral suspension, and provided a real world basis for the clinical practice. A retrospective cohort study was performed on IFIs patients treated with posaconazole enteric-coated tablet or oral suspension. The primary endpoints were in-hospital mortality, treatment discontinuation rate and clinical effective rate. The secondary endpoints were adverse events incidence (liver dysfunction, renal dysfunction and hypokalemia). One hundred and forty-four patients were totally included and divided into enteric-coated tablet group (n = 46) and oral suspension group (n = 98). There was no significant difference in effectiveness and safety between two groups. The female (OR = 0.130, P = 0.018) and diabetes mellitus (OR = 4.242, P = 0.003) were independently associated with combined in-hospital mortality/treatment discontinuation rate. The renal replacement therapy (OR = 10.071, P = 0.006), hypoalbuminemia (OR = 6.646, P = 0.002) and posaconazole duration (OR = 1.119, P = 0.002) were risk factors for liver dysfunction. The posaconazole enteric-coated tablet has comparable effectiveness and safety with oral suspension in IFIs, which need large-scale cases studies to confirm in the future.

Factors Influencing Self-Management Behaviors Among Patients with Post-Kidney Transplantation: A Qualitative Study of the Chronic Phase Transition

Background: Kidney transplantation is an effective treatment for patients with kidney failure. Despite the advances in technology, a certain number of patients still deteriorate due to improper management. The purpose of this study was to identify the promoting and inhibitory factors that influence recipients’ self-management behaviors after a kidney transplant. Methods: We enrolled participants who had kidney transplants for more than one year, aged ≥20 years from outpatient clinics in Japan. Face-to-face interviews were conducted between April and December 2016. Results: Nine participants were included in this study. By qualitative content analysis, 115 codes and 8 categories were extracted for the factors resulting in maintenance and the promotion of self-management behaviors; those were [attentiveness to changes in one’s own body], [good partnership with medical care providers], [past painful experiences], [establishment of lifestyle habits], [autonomy to protect one’s own body], [support from family and others], [gratitude for kidney donation], and [increased self-efficacy]. We also extracted three categories that inhibited self-management behavior: [fading threat of worsening disease], [shifting priorities], and [decreased motivation to control the disease]. Conclusions: The passage of time after transplant became a barrier to continue self-management. Providing knowledge about the importance of self-management can prevent the deterioration of kidney function over time after a transplant.

Gabapentinoids and Risk of Hip Fracture.

The increased use of gabapentinoids has been most pronounced in older people who are also susceptible to hip fractures. To investigate the overall association between gabapentinoids and the risk of hip fractures and the stratified association across age groups, frailty status, and history of chronic kidney disease. This was a case-case-time-control study in patients hospitalized for hip fracture in Victoria, Australia, between March 1, 2013, and June 30, 2018, with at least 1 prescription for a gabapentinoid before fracture. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% CI for gabapentinoid dispensing in the index (1-60 days prefracture) compared with the reference (121-180 days prefracture) period. To adjust for the underlying time trend in gabapentinoid use, each index case was matched with up to 5 controls, selected from future cases of the same age and sex. Subgroup analyses were conducted in subgroups with or without chronic kidney disease (CKD), frailty scores less than 5, and frailty scores 5 and above. Frailty was computed using the Hospital Frailty Risk Score (HFRS). Data were analyzed from November 2023 to April 2024. Gabapentinoids (pregabalin or gabapentin). Hip fracture. Of 28 293 patients hospitalized for hip fractures, 2946 (1752 [59.5%] aged ≥80 years; 2099 [71.2%] female) were dispensed a gabapentinoid before hip fracture. Gabapentinoid dispensing was associated with increased odds of hip fractures (OR, 1.96; 95% CI, 1.66-2.32). After adjusting for the exposure-time trend and concomitant use of other central nervous system medications, the odds of hip fractures remained elevated (OR, 1.30; 95% CI, 1.07-1.57). The association between gabapentinoid dispensing and hip fracture was higher in patients with HFRS 5 and above (OR, 1.75; 95% CI, 1.31-2.33) and CKD (OR, 2.41; 95% CI, 1.65-3.52). In this case-case-time-control study of Australian residents hospitalized for hip fracture, gabapentinoid use was associated with an increased risk of hip fractures, especially in patients who were frail or had chronic kidney disease. In addition to the known risk associated with kidney impairment, frailty status may be an important risk factor when considering use of gabapentinoids.

Normothermic Machine Perfusion Reconstitutes Porcine Kidney Tissue Metabolism But Induces an Inflammatory Response, Which Is Reduced by Complement C5 Inhibition

Normothermic machine perfusion (NMP) is a clinical strategy to reduce renal ischemia-reperfusion injury (IRI). Optimal NMP should restore metabolism and minimize IRI induced inflammatory responses. Microdialysis was used to evaluate renal metabolism. This study aimed to assess the effect of complement inhibition on NMP induced inflammatory responses. Twenty-two pig kidneys underwent 18 h of static cold storage (SCS) followed by 4 h of NMP using a closed-circuit system. Kidneys were randomized to receive a C5-inhibitor or placebo during SCS and NMP. Perfusion resulted in rapidly stabilized renal flow, low renal resistance, and urine production. During SCS, tissue microdialysate levels of glucose and pyruvate decreased significantly, whereas glycerol increased (p &amp;lt; 0.001). In the first hour of NMP, glucose and pyruvate increased while glycerol decreased (p &amp;lt; 0.001). After 4 h, all metabolites had returned to baseline. Inflammatory markers C3a, soluble C5b-9, TNF, IL-6, IL-1β, IL-8, and IL-10 increased significantly during NMP in perfusate and kidney tissue. C5-inhibition significantly decreased perfusate and urine soluble C5b-9 (p &amp;lt; 0.001; p = 0.002, respectively), and tissue IL-1β (p = 0.049), but did not alter other inflammatory markers. Microdialysis can accurately monitor the effect of NMP on renal metabolism. Closed-circuit NMP induces inflammation, which appeared partly complement-mediated. Targeting additional immune inhibitors should be the next step.

Total Gastrectomy for Gastric Malignancy: Trends Over 15 Years in Major Morbidity, Mortality, and Patient Selection From The National Surgical Quality Improvement Program.

We examined trends in major morbidity and mortality following total gastrectomy for malignancy in a national cohort. The National Surgical Quality Improvement Program was used to identify patients who underwent total gastrectomy for malignancy from 2007 to 2021. Joinpoint regression was used to determine annual percent changes (APCs) in thirty-day postoperative major morbidity, mortality, and length of stay (LOS). Major morbidity included deep and organ space surgical site infection, venous thromboembolism, cardiac event, pneumonia, acute renal failure, sepsis, and respiratory failure. Of 3515 patients, the median age was 65 years (IQR = 55-73), 59% were male, and 57.9% were White. Major morbidity was 23%, which did not change over time (APC = -1.4, 95% CI = -3.4 to 0.58), nor were there changes in individual morbidities with time. The most common morbidities were organ space surgical site infection (9.2%) and pneumonia (8.5%). Mortality rate in the study cohort was 2.7% and did not change (APC = -6.2, 95% CI = -13.0 to 1.1). LOS (median 9 days) also did not vary with time (APC = -2.3, 95% CI = -7.8 to 3.9). There was an increase in patients with diabetes (21.6% vs. 11.2%, p < 0.05), BMI ≥ 30 (31.1% vs. 18.2%, p < 0.05), and ASA IV-V status (11.6% vs. 3.5%, p < 0.05). Morbidity and mortality following total gastrectomy for malignancy have not significantly changed over the last fifteen years. While this may in part be explained by increased patient comorbidity, efforts should be made to improve patient selection and mitigate postoperative complications to allow for timely adjuvant therapies.

Cortical structural network characteristics in non-cognitive impairment end-stage renal disease

ObjectiveExplore alterations in topological features of gray matter volume (GMV) and structural networks in non-cognitive impairment end-stage renal disease (Non-CI ESRD).Materials and methodsUtilizing graph theory, we collected structural magnetic resonance imaging (sMRI) data from 38 Non-CI ESRD patients and 50 normal controls (NC). We compared, and extracted the GMV across subject groups, constructed corresponding structural covariance networks (SCNs), and investigated the alterations in SCNs feature parameters between groups.ResultsIn Non-CI ESRD patients, The GMV were reduced in several brain regions, predominantly on the left side (p &amp;lt; 0.05, FWE correction). The small-world network characteristics of the patient group’s brain networks showed a tendency toward regular. In a few densities, global network parameters, transitivity, (p &amp;lt; 0.05) was significantly increased in the ESRD group. Regional network measurements revealed inconsistent changes in regional efficiency across different brain areas. In the analysis of network hubs, the right temporal pole is likely a compensatory hub for Non-CI ESRD patients. The SCNs in Non-CI ESRD patients demonstrated reduced topological stability against targeted attacks.ConclusionThis study reveals that patients with renal failure exhibited subtle changes in brain network characteristics even before a decline in cognitive scores. These changes involve compensatory activation in certain brain regions, which enhances network transitivity to maintain the efficiency of whole-brain network information integration without significant loss. Additionally, the SCNs characteristics can serve as a neuroanatomical marker for brain alterations in Non-CI ESRD patients, offering new insights into the mechanisms of early brain injury in ESRD patients.

Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ.

Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing. Factors secreted by senescent cells affect their microenvironment and can induce spreading of senescence locally. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure. Why the latter occurs is poorly understood. Here we demonstrate senescence development in extrahepatic organs and associated organ dysfunction in response to liver senescence using liver injury models and genetic models of hepatocyte-specific senescence. In patients with severe acute liver failure, we show that the extent of hepatocellular senescence predicts disease outcome, the need for liver transplantation and the occurrence of extrahepatic organ failure. We identify the TGFβ pathway as a critical mediator of systemic spread of senescence and demonstrate that TGFβ inhibition in vivo blocks senescence transmission to other organs, preventing liver senescence induced renal dysfunction. Our results highlight the systemic consequences of organ-specific senescence, which, independent of ageing, contributes to multi-organ dysfunction.

PREVALENCE, Characteristics, and Awareness of Chronic Kidney Disease in Croatia: The EH-UH 2 Study

Background. National surveys have reported variable prevalence of chronic kidney disease (CKD), due to differences in the characteristics of the population, study design, equations used for the estimated glomerular filtration rate (eGFR), and definitions. The EH-UH 2 survey is the first study evaluating CKD prevalence, characteristics, and awareness in Croatia. Methods. This was a cross-sectional nationwide observational study designed to assess the prevalence of CKD and cardio–kidney–metabolic risk factors in Croatia, which included 1765 randomly selected subjects. We estimated the prevalence of CKD by means of the albumin-to-creatinine ratio (ACR) and eGFR (CKD-EPI equation). Comorbidities and anthropometric and social factors related to the prevalence of CKD were analyzed, and the CV risk profile was evaluated. Results. The weighted prevalence of CKD (any stage), CKD stage ≥G3A A2, and CKD defined only as an eGFR &lt;60 mL/min/1.73 m2 were estimated at 17.1%, 9.8%, and 7.9%, respectively. The prevalence was higher in men than in women (11.8% vs. 7.9%; p &lt; 0.001). The weighted prevalence of an ACR &gt;30 mg/g was 15.1%. Older age, male gender, diabetes, ePWV, and uric acid were independently associated with CKD prevalence. The awareness of CKD was 9.5%. Persons unaware of CKD were older with lower income, less education, more frequent diabetes, hypertension (less frequently controlled), and milder renal impairment. Conclusions. In Croatia, the estimated prevalence of CKD is high, being presented more frequently in men than in women. CKD patients have an unfavorable CV risk profile. The awareness of CKD is very low, reflecting poor health literacy in the general population but also in health-care workers.

Renal microangiopathy induced by lenvatinib in hepatocellular carcinoma: a case report and literature review

Lenvatinib, a multi-target inhibitor of receptor tyrosine kinases, has been increasingly used in the treatment of advanced hepatocellular carcinoma (HCC). However, its association with renal adverse effects, including proteinuria and renal microvascular complications, was not fully understood in HCC patients. We reported a case of a 68-year-old male with a history of hypertension, diabetes mellitus, and hepatitis C virus (HCV) infection, diagnosed with primary HCC in 2015. Despite previous treatments, he was started on lenvatinib due to tumor recurrence. Initially, he had mild proteinuria, which significantly worsened post-lenvatinib initiation, accompanied by fluctuating renal function and severe edema. The diagnosis of lenvatinib-induced renal microvascular damage was confirmed through renal biopsy, which showed glomerular sclerosis, tubulointerstitial changes, and arteriolosclerosis. Discontinuation of lenvatinib led to significant improvements in proteinuria and edema. Subsequent cancer recurrence was managed with microwave ablation and immunotherapy, with satisfactory recovery. The potential for lenvatinib to induce significant renal microvascular disease, as demonstrated in this case, emphasizes the importance of vigilant renal monitoring and personalized therapeutic strategies in patients treated with lenvatinib for HCC. Early intervention and dose adjustment may be crucial in preventing severe renal impairment, highlighting the significance of tailored treatment plans in the management of advanced HCC patients especially with pre-existing risk factors.

Mechanistic Insights Into Redox Damage of the Podocyte in Hypertension.

Podocytes are specialized cells within the glomerular filtration barrier, which are crucial for maintaining glomerular structural integrity and convective ultrafiltration. Podocytes exhibit a unique arborized morphology with foot processes interfacing by slit diaphragms, ladder-like, multimolecular sieves, which provide size and charge selectivity for ultrafiltration and transmembrane signaling. Podocyte dysfunction, resulting from oxidative stress, dysregulated prosurvival signaling, or structural damage, can drive the development of proteinuria and glomerulosclerosis in hypertensive nephropathy. Functionally, podocyte injury leads to actin cytoskeleton rearrangement, foot process effacement, dysregulated slit diaphragm protein expression, and impaired ultrafiltration. Notably, the renin-angiotensin system plays a pivotal role in podocyte function, with beneficial AT2R (angiotensin receptor 2)-mediated nitric oxide (NO) signaling to counteract AT1R (angiotensin receptor 1)-driven calcium (Ca2+) influx and oxidative stress. Disruption of this balance contributes significantly to podocyte dysfunction and drives albuminuria, a marker of kidney damage and overall disease progression. Oxidative stress can also lead to sustained ion channel-mediated Ca2+ influx and precipitate cytoskeletal disorganization. The complex interplay between GPCR signaling, ion channel activation, and redox injury pathways underscores the need for additional research aimed at identifying targeted therapies to protect podocytes and preserve glomerular function. Earlier detection of albuminuria and podocyte injury through routine noninvasive diagnostics will also be critical in populations at the highest risk for the development of hypertensive kidney disease. In this review, we highlight the established mechanisms of oxidative stress-mediated podocyte damage in proteinuric kidney diseases, with an emphasis on a hypertensive renal injury. We will also consider emerging therapies that have the potential to selectively protect podocytes from redox-related injury.

Single-point mutated lanmodulin as a high-performance MRI contrast agent for vascular and kidney imaging.

Magnetic resonance imaging contrast agents can enhance diagnostic precision but often face limitations such as short imaging windows, low tissue specificity, suboptimal contrast enhancement, or potential toxicity, which affect resolution and long-term monitoring. Here, we present a protein contrast agent based on lanmodulin, engineered with a single-point mutation at position 108 from N to D to yield maximum gadolinium binding sites. After loading with Gd3+ ions, the resulting protein complex, LanND-Gd, exhibits efficient renal clearance, high relaxivity, and prolonged renal retention compared to commercial agents. LanND-Gd enables high-performance visualization of whole-body structures and brain vasculature in male mice at a resolution finer than one hundred micrometers. In male ischemia mouse models, LanND-Gd also improves kidney dysfunction monitoring while minimizing risks of neural toxicity or immunogenic reactions. This protein-based contrast agent offers superior image quality, improved biocompatibility, and extended imaging timeframes, promising significant advancements in magnetic resonance-based diagnostics and patient outcomes.

Preparation and performance study of heparinized multi‐walled carbon nanotube/cellulose acetate hemodialysis membrane

AbstractCurrently, the incidence of kidney failure is increasing worldwide. Hemodialysis is the main method for the treatment of kidney diseases, and the continuous development of new hemodialysis membranes is the key to improve the treatment effect and the quality of life of patients. In this study, heparinized multi‐walled carbon nanotube/cellulose acetate (Hep/MWCNTs@CA) membranes were prepared by non‐solvent induced phase separation (NIPS). The morphology and pore structure of Hep/MWCNTs@CA membranes were characterized by scanning electron microscopy (SEM). The elongation at break and tensile strength of the membranes were characterized by a mechanical property universal tester. The results showed that mechanical properties of 0.1 wt% MWCNTs enhanced the membrane is best. The water contact angle test confirmed that MWCNTs can improve the membrane hydrophilicity, and combined with the adsorption test results for proteins, it was found that the hydrophilicity can reduce the adsorption of proteins to the composite membrane and improve the blood compatibility of the material. The dialysis performance of urea and lysozyme was tested by a self‐made simulated hemodialysis device, and the clearance rates of urea and lysozyme were 84% and 47.2%, respectively, which showed that the interfacial gap between MWCNTs and CA matrix can make the composite membrane retain a high retention rate of macromolecular proteins (92.3%) and further improved the clearance rate of small and medium molecular toxins. In addition, the good blood compatibility and biocompatible properties of the materials were confirmed by hemolysis, recalcification and cytotoxicity tests on Hep/MWCNTs@CA membranes. In conclusion, the prepared Hep/MWCNTs@CA holds great potential for application in the field of hemodialysis.

Role of epigenetic changes in the pathophysiology of diabetic kidney disease

Background: Diabetic kidney disease (DKD) is a global health issue. Epigenetic changes play an important role in the pathogenesis of this disease. Summary: DKD is currently the leading cause of kidney failure worldwide. Although much is known about the pathophysiology of DKD, the research field of epigenetics is relatively new. Several recent studies have demonstrated that diabetes-induced dysregulation of epigenetic mechanisms alters the expression of pathological genes in kidney cells. If these changes persist for a long time, the so-called “metabolic memory” could be established. In this review, we highlight diabetes-induced epigenetic modifications associated with DKD. While there is a substantial amount of literature on epigenetic changes, only a few studies describe the underlying molecular mechanisms. Detailed analyses have shown that epigenetic changes play an important role in known pathological features of DKD, such as podocyte injury, fibrosis, accumulation of extracellular matrix, or oxidative injury, all of which contribute to the pathophysiology of disease. The transforming growth factor-b plays a key role, as it is involved in all mentioned epigenetic types of regulation. Key messages: Epigenetic is crucial for the development and progression of diabetic kidney disease, but the detailed molecular mechanisms have to be further analyzed more in detail.

Clinicopathologic, Proteomic and Outcome Characteristics of Renal Apolipoprotein C-II Amyloidosis: A Case Series.

Amyloidosis derived from apolipoprotein C-II (AApoCII) is a recently discovered, rare form of amyloidosis. Data on clinical presentations and natural history are very limited. This study defines the clinicopathologic, proteomic and outcome characteristics of renal AApoCII. Case series. Twenty-five renal AApoCII cases were identified from the Mayo Clinic Tissue Proteomics Laboratory archives from January 2008 through January 2024. All patients were White, 19 were ≥65 years old at diagnosis, and 18 were female. Seven had a family history of CKD. Patients presented with proteinuria (median 3.3 g/day) and reduced kidney function (n=16, median creatinine 1.6 mg/dl). No patient had clinical evidence of other organ involvement by amyloidosis or features of monogenic hypertriglyceridemia. Histologically, amyloid deposits were often weakly positive for Congo red and involved glomeruli in all cases (with a nodular pattern in 22), whereas extraglomerular involvement was less common and generally mild. Proteomic analysis revealed abundant spectra for Apo C-II and for all 3 amyloid signature proteins (Apo E, Apo A-IV and SAP) in all cases, and detected an Apo C-II variant in 14 (K19T [p.Lys41Thr] in 12 and E47V [p.Glu69Val] in 2). Among 22 patients with follow-up available, there were 12 ESKD events and 2 deaths without ESKD during an average (SE) follow up of 75.5 (12.5) months. Retrospective design, small sample size, APOC2 gene sequencing performed in a smaller subset. AApoCII mostly affects the kidney, and manifests in the elderly with proteinuria and CKD. A minority of these patients had a family history of kidney disease. Kidney failure occurred in about half, whereas overall survival was more favorable.