Renal Failure Research Articles

Lactate dehydrogenase as a biochemical marker for prediction of maternal and perinatal outcomes in hypertensive disorders in pregnancy

Hypertensive disorder of pregnancy includes new onset hypertension in pregnancy that is gestational hypertension and already existing hypertension that is chronic hypertension and gestational hypertension sometimes worsened by preeclampsia. Preeclampsia can cause complications such as eclampsia, HELLP syndrome, renal failure, pulmonary edema, stroke, and left ventricular failure. We aim to assessthe predictive role ofLactate Dehydrogenase value in Hypertensive disorders in pregnancy.After obtaining the informed consent, pregnant patients who were visiting Tertiary care centre and who were more than 28 weeks period of gestation were enrolled. Patients from both antenatal OPD clinics and from those who were presenting in emergency were included in this study. Serum levels of LDH were tested. Patients were monitored till delivery and 6 weeks following childbirth.The Mean serum levels of lactate dehydrogenase (LDH) in eclamptic group was 1495.000±859.1230, 804.569±224.5519 in severely preeclamptic group and in mild preeclamptic group ,mean LDH levels were 520.062±110.3944. The difference between both the groups was statistically significant (p < 0.001).Women with serum LDH levels > 800 IU/L and LDH levels between 601-800 IU/L, experienced considerably greater complications in preeclamptic-eclamptic group as compared to those with serum LDH levels < 600 IU/L.Thepreeclamptic-eclamptic group of women had increased serum LDH levels. Greater LDH levels were linked to worse outcomes for mothers including placental abruption, hemolysis elevated liver enzymes low platelet count (HELLP syndrome), pulmonary edema and maternal death and they were also linked to fetal complications including intrauterine fetal death (IUFD), intrauterine growth restriction and neonatal intensive care unit (NICU) admission.

Tiliroside protects against diabetic nephropathy in streptozotocin-induced diabetes rats by attenuating oxidative stress and inflammation

BACKGROUND Diabetic nephropathy (DN), affecting half of diabetic patients and contributing significantly to end-stage kidney disease, poses a substantial medical challenge requiring dialysis or transplantation. The nuanced onset and clinical progression of kidney disease in diabetes involve consistent renal function decline and persistent albuminuria. AIM To investigate Tiliroside's (Til) protective effect against diabetic nephropathy (DN) in rats under diabetic conditions. METHODS Five groups of six rats each were included in this study: Rats treated with DMSO by intraperitoneal injection as controls, those treated with STZ by intraperitoneal injection, those treated with STZ + Til (25 mg/kg body weight [bwt]) or Til (50 mg/kg bwt), and those treated with anti-diabetic medication glibenclamide (600 μg/kg bwt). Biochemical markers, fasting blood glucose, food intake, kidney weight, antioxidant enzymes, inflammatory and fibrotic markers, and renal injury were monitored in different groups. Molecular docking analysis was performed to identify the interactions between Til and its targeted biomarkers. RESULTS Til significantly reduced biochemical markers, fasting blood glucose, food intake, and kidney weight and elevated antioxidant enzymes in diabetic rats. It also mitigated inflammatory and fibrotic markers, lessened renal injury, and displayed inhibitory potential against crucial markers associated with DN as demonstrated by molecular docking analysis. CONCLUSION These findings suggest Til's potential as a therapeutic agent for DN treatment, highlighting its promise for future drug development.

The renal-retinal connection - The eye in chronic kidney disease

Chronic kidney disease (CKD) is linked with several systemic complications, including ocular manifestations that can adversely affect quality of life. The prevalence and types of ocular changes in CKD patients, particularly their correlation with disease stages, are not well-documented. This study aims to evaluate the ocular manifestations in CKD and their association with different stages of the disease.A cross-sectional study on 70 CKD patients revealed a high prevalence of ocular abnormalities, including diabetic retinopathy, hypertensive retinopathy, and age-related macular degeneration. These conditions often worsened as CKD progressed, emphasizing the need for regular eye exams in CKD patients to prevent vision loss and address complications promptly. To investigate the prevalence and types of ocular manifestations in patients with chronic kidney disease (CKD) and to analyse their correlation with the stages of CKD. This cross-sectional, descriptive, non-interventional, hospital-based study was conducted over four months from May 2024 to August 2024 in the Department of Nephrology. Seventy patients with diagnosed CKD, aged 18 years and older, were included. Exclusion criteria were patients with reversible causes of renal failure, those who had undergone renal transplantation, and those who did not consent. A comprehensive ocular examination was performed on 140 eyes from the enrolled patients, assessing anterior and posterior segment findings, including visual acuity, eyelid conditions, conjunctival status, lens status, and fundus examination. The study included 38 males (54.3%) and 32 females (45.7%) with a mean age of 57 years. Hypertension and diabetes mellitus were the most common comorbidities, present in 71.4% and 64.3% of patients, respectively. Visual acuity deteriorated with advancing stages of CKD, with significant impairment and blindness observed predominantly in CKD stages 4 and 5. Anterior segment examination revealed that 62% of eyes had immature cataracts, and 38% were pseudophakic. Fundoscopic examination showed that 51.4% of patients had abnormal findings, including non-proliferative and proliferative diabetic retinopathy, hypertensive retinopathy, age-related macular degeneration, and glaucomatous disc changes. The severity of fundus abnormalities increased with the progression of CKD, highlighting a strong correlation between the degree of renal dysfunction and ocular health. Ocular manifestations are common in CKD patients and correlate with the severity of kidney disease. The prevalence of both anterior and posterior segment abnormalities underscores the need for regular ophthalmic evaluations in CKD patients to prevent vision loss and manage ocular complications early.

Oligomeric proanthocyanidin ameliorates sepsis-associated renal tubular injury: involvement of oxidative stress, inflammation, PI3K/AKT and NFκB signaling pathways

Oligomeric proanthocyanidin ameliorates sepsis-associated renal tubular injury: involvement of oxidative stress, inflammation, PI3K/AKT and NFκB signaling pathways

Urgent Reversal of Direct Oral Anticoagulants in Critical and Life-Threatening Bleeding: A Multidisciplinary Expert Consensus

Direct oral anticoagulants (DOACs) are increasingly being used due to their improved efficacy/safety ratio and lower clinical and economic burden when compared to vitamin K antagonists. However, bleeding is still the most frequent complication associated with DOACs, and although rare, bleeding episodes can be life-threatening or critical. The impact of DOAC anticoagulation activity during a bleeding event must be evaluated according to patient clinical assessment, dosage and time from last intake, the presence of comorbidities (especially kidney and liver dysfunction), and, whenever possible, coagulation tests. Unfortunately, DOACs’ anticoagulation activity is not easily or usually detectable in routine common coagulation testing. Specific DOAC tests allow for specific drug monitoring, but they are too time consuming, and are usually unavailable in routine emergency practice. If a clinically relevant DOAC plasma concentration is assumed or proven in a severe bleeding scenario, DOAC reversal is needed to restore hemostasis. This experts’ consensus provides a narrative review about DOAC reversal and practical life-threatening bleeding management in several scenarios (trauma, intracranial hemorrhage and gastrointestinal bleeding), focusing on the selection of patients to whom specific reversal agents should be given.

Chronic renal impairment predicts oncological outcomes in UTUC patients undergoing RNU

Abstract Objective 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. Patients and methods 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/1.73 m². 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. Results 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. Conclusion 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.

Development of cefepime‐induced encephalopathy in a patient with depression and rectal cancer: A case report

AbstractBackgroundCefepime, a fourth‐generation cephalosporin, has neurotoxic side effects such as encephalopathy. Baseline conditions, including blood–brain barrier (BBB) impairment and renal dysfunction, are known to associate with elevated central nervous concentration of cefepime. Although BBB dysfunction occurs with depression or cancer, currently, neither is regarded as a risk factor for cefepime‐induced encephalopathy.Case PresentationA 79‐year‐old woman with a history of depression and rectal cancer was hospitalized for a bacterial liver abscess. Brain metastasis and other causes for delirium were excluded, and no renal dysfunction was observed. However, 11 days after cefepime and metronidazole administration, the patient suddenly developed confusion, disorientation, and myoclonus, with no apparent changes on brain magnetic resonance imaging. Electroencephalography revealed a consistent tri‐phasic wave pattern. Clinical symptoms were well consistent with cefepime‐induced encephalopathy; hence, cefepime and metronidazole were discontinued, followed by rapid physical and mental recovery, with no aftereffects.ConclusionsIn terms of BBB dysfunction, depression and cancer might be possible occult risk factors for cefepime‐induced encephalopathy. Doctors need to pay attention to encephalopathy risk when administering cefepime in patients with depression or cancer because the psychiatric symptoms of encephalopathy, depression, and delirium from other causes are often confusing, leading to misdiagnosis and a poor prognosis.

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 <90 mL/min/1.73 m2 (mild kidney impairment), 30 to <60 mL/min/1.73 m2 (mild-to-moderate and moderate-to-severe kidney impairment) and <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 < 30 mL/min/1.73 m2, 602 patients (59.1%) with eGFR 30 to <60 mL/min/1.73 m2, 775 patients (31.3%) with eGFR 60 to <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 < 0.001, for 30 mL/min/1.73 m2 decrement in the eGFR). There were CKD-by-age (Pint < 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 < 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.

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<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.

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

ImportanceThe increased use of gabapentinoids has been most pronounced in older people who are also susceptible to hip fractures.ObjectiveTo 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.Design, Setting, and ParticipantsThis 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.ExposureGabapentinoids (pregabalin or gabapentin).Main Outcome and MeasureHip fracture.ResultsOf 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).Conclusions and relevanceIn 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 < 0.001). In the first hour of NMP, glucose and pyruvate increased while glycerol decreased (p < 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 < 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.

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 < 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 < 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

AbstractCellular 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 <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 < 0.001). The weighted prevalence of an ACR >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 (Ca 2+ ) 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 Ca 2+ 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

AbstractMagnetic 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.