Renal Failure Research Articles

Nephroprotective Effect of Ferula assa-foetida Oleo Gum Resin on Type 2 Diabetic Rats.

Diabetic nephropathy is one of the main causes of kidney failure in the end stage of diabetes worldwide. On the other hand, asafoetida is a gum whose hypoglycemic effects have been proven. The present study was conducted with the aim of using asafoetida to prevent diabetic nephropathy. Diabetes was induced by a high-fat diet (60%) and streptozotocin injection (35 mg/kg) in rats. Diabetic rats were treated with an oral dose of 50 mg/kg of asafoetida for 8 weeks. At the end of the experiment, serum and urine parameters were examined. Antioxidant enzymes and lipid peroxidation levels in the kidney were also determined along with its histological examination. The expression levels of tumor necrosis factor-alpha and Transforming growth factor beta genes were also evaluated. Glucose, cholesterol, triglyceride, and HbA1c concentrations were significantly reduced in the asafoetida 50. On the other hand, in the treatment group, serum creatinine, urea, and albumin levels decreased and increased in urine. Antioxidant enzymes in the kidney improved significantly, and the expression of tumour necrosis factor-alpha and transforming growth factor-beta genes decreased. Histopathological examination also showed that necrosis, epithelial damage, and leukocyte infiltration increased in the diabetic and the treatment group. The result of biochemical analysis, enzymatic, and histological examinations showed that asafoetida may delay the progression of diabetic nephropathy due to the presence of anti-inflammatory and antioxidant activities.

Acute kidney injury: the experience of a tertiary center of Pediatric Nephrology.

Acute kidney injury (AKI) is an abrupt deterioration of kidney function. The incidence of pediatric AKI is increasing worldwide, both in critically and non-critically ill settings. We aimed to characterize the presentation, etiology, evolution, and outcome of AKI in pediatric patients admitted to a tertiary care center. We performed a retrospective observational single-center study of patients aged 29 days to 17 years and 365 days admitted to our Pediatric Nephrology Unit from January 2012 to December 2021, with the diagnosis of AKI. AKI severity was categorized according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The outcomes considered were death or sequelae (proteinuria, hypertension, or changes in renal function at 3 to 6 months follow-up assessments). Forty-six patients with a median age of 13.0 (3.5-15.5) years were included. About half of the patients (n = 24, 52.2%) had an identifiable risk factor for the development of AKI. Thirteen patients (28.3%) were anuric, and all of those were categorized as AKI KDIGO stage 3 (p < 0.001). Almost one quarter (n = 10, 21.7%) of patients required renal replacement therapy. Approximately 60% of patients (n = 26) had at least one sequelae, with proteinuria being the most common (n = 15, 38.5%; median (P25-75) urinary protein-to-creatinine ratio 0.30 (0.27-0.44) mg/mg), followed by reduced glomerular filtration rate (GFR) (n = 11, 27.5%; median (P25-75) GFR 75 (62-83) mL/min/1.73 m2). Pediatric AKI is associated with substantial morbidity, with potential for proteinuria development and renal function impairment and a relevant impact on long-term prognosis.

The effect of lavender aromatherapy and deep breathing exercise on anxietas level in hemodialysis patients

Chronic kidney failure is a chronic disease that requires treatment and hemodialysis therapy. Hemodialysis therapy has physical and psychological impacts on patients, such as stress. Patients who experience stress require management techniques such as lavender aromatherapy and deep breathing relaxation. The purpose of the study was to compare the effects of lavender aromatherapy and deep breathing relaxation on patients receiving hemodialysis who were experiencing the stress of chronic kidney failure. The study's quasi-experimental design includes two groups for the pretest and posttest. The 32 patients with chronic renal failure receiving hemodialysis made up the research sample; 16 of them participated in the lavender aromatherapy intervention and 16 were part of the deep breathing relaxation group. The research instrument used is the perceived stress scale (PSS) questionnaire. With a p-value of 0.000, data analysis employing an independent t-test reveals a difference between the deep breathing relaxation and lavender aromatherapy interventions on the stress of chronic renal failure patients receiving hemodialysis. Lavender aromatherapy and breathing relaxation can reduce stress in chronic kidney failure patients undergoing hemodialysis. Lavender aromatherapy reduces stress in chronic kidney failure patients more effectively than deep breathing relaxation. Lavender aromatherapy can be an alternative therapy to reduce stress while undergoing hemodialysis.

Prevalence, impact and management of hypertension-mediated organ damage in type 2 diabetes patients

ObjectiveTo determine the prevalence, impact and management of hypertension-mediated organ damage (HMOD) according to the presence of type 2 diabetes (T2DM). MethodsIBERICAN is an ongoing multicenter, observational and prospective study, including outpatients aged 18–85 years who attended the Primary Care setting in Spain. In this study, the prevalence, impact and management of HMOD according to the presence of T2DM at baseline were analyzed. ResultsAt baseline, 8066 patients (20.2% T2DM, 28.6% HMOD) were analyzed. Among patients with T2DM, 31.7% had hypertension, 29.8% dyslipidemia and 29.4% obesity and 49.3% had ≥1 HMOD, mainly high pulse pressure (29.6%), albuminuria (16.2%) and moderate renal impairment (13.6%). The presence of T2DM significantly increased the risk of having CV risk factors and HMOD. Among T2DM population, patients with HMOD had more dyslipidemia (78.2% vs 70.5%; P=0.001), hypertension (75.4% vs 66.4%; P=0.001), any CV disease (39.6% vs 16.1%; P=0.001) and received more drugs. Despite the majority of types of glucose-lowering agents were more frequently taken by those patients with HMOD, compared to the total T2DM population, the use of SGLT2 inhibitors and GLP-1 receptor agonists was marginal. ConclusionsIn patients daily attended in primary care setting in Spain, one in five patients had T2DM and nearly half of these patients had HMOD. In patients with T2DM, the presence of HMOD was associated with a higher risk of CV risk factors and CV disease. Despite the very high CV risk, the use of glucose-lowering agents with proven CV benefit was markedly low.

Acute post-streptococcal glomerulonephritis with bilateral pleural effusion in a 12-year-old child in rural area: A case report

Background: Nephritic syndrome is a group of symptoms such as hematuria, hypertension, oliguria and edema. The most common cause of acute nephritic syndrome in children is acute glomerulonephritis after streptococcal infection. Case Presentation: A 12-year-old child came to the ER with shortness of breath for 3 days and swelling of the face. There was no history of fever or diarrhea. The patient had a history of itching of the feet 2 weeks earlier. Vital signs found blood pressure of 160/120 mmHg and edema was found on the face especially in the eyelids. Urine examination found a high number of leukocytes and erythrocytes and there was albumin +2 in the urine. Examination of kidney function showed an increase in urea and creatinine. Chest X-ray examination showed pulmonary edema and bilateral effusion. ASTO titer examination obtained a level of 200 IU/ml. The patient was given therapy in the form of antihypertensives, antibiotics and corticosteroids. After 1 week of hospitalization, the blood pressure target and clinical improved, the patient was able to leave the hospital, checked into the polyclinic to continue treatment and evaluated urine examination of kidney function every 2 weeks. Summary: Acute nephritic syndrome is a disease that is rarely found in pediatric patients, most of the causes are acute glomerulonephritis after streptococcal infection with clinical manifestations in the form of throat infection or skin infection in the form of impetigo. With proper diagnosis and management, this disease can be cured with perfect healing, but some cases can occur acute kidney failure so that monitoring is needed.

Mesoporous zinc-polyphenol nanozyme for attenuating renal ischemia-reperfusion injury.

Aim: To target the reactive oxygen species (ROS) accumulation and renal tubular epithelial cell (rTEC) death in renal ischemia-reperfusion injury (IRI), we constructed a nanoparticle that offers ROS scavenging and rTEC-death inhibition: mesoporous zinc-tannic acid nanozyme (ZnTA). Materials & methods: After successfully constructing ZnTA, we proceeded to examine its effect on ROS accumulation, cellular ferroptosisand apoptosis, as well as injury severity. Results: Malondialdehyde, Fe2+ amounts and 4-HNE staining demonstrated that ZnTA effectively attenuated rTEC ferroptosis. TUNEL staining confirmed that Zn2+ carried by ZnTA could effectively inhibit caspase 3 and caspase 9, mitigating apoptosis. Finally, it reduced renal IRI through the synergistic effect of ROSscavenging and cell-death inhibition. Conclusion: This study is expected to provide a paradigm for a combined therapeutic strategy for renal IRI.

The spectrum of co-existing disease in children with established kidney failure using registry and linked electronic health record data.

Children with established kidney failure may have additional medical conditions influencing kidney care and outcomes. This cross-sectional study aimed to examine the prevalence of co-existing diseases captured in the electronic hospital record compared to UK Renal Registry (UKRR) data and differences in coding. The study population comprised children aged < 18years receiving kidney replacement therapy (KRT) in England and Wales on 31/12/2016. Comorbidity data at KRT start was examined in the hospital record and compared to UKRR data. Agreement was assessed by the kappa statistic. Associations between patient and clinical factors and likelihood of coding were examined using multivariable logistic regression. A total of 869 children (62.5% male) had data linkage for inclusion. UKRR records generally reported a higher prevalence of co-existing disease than electronic health records; congenital, non-kidney disease was most commonly reported across both datasets. The highest sensitivity in the hospital record was seen for congenital heart disease (odds ratio (OR) 0.65, 95% confidence interval (CI) 0.51, 0.78) and malignancy (OR 0.63, 95% CI 0.41, 0.85). At best, moderate agreement (kappa ≥ 0.41) was seen between the datasets. Factors associated with higher odds of coding in hospital records included age, while kidney disease and a higher number of comorbidities were associated with lower odds of coding. Health records generally under-reported co-existing disease compared to registry data with fair-moderate agreement between datasets. Electronic health records offer a non-selective overview of co-existing disease facilitating audit and research, but registry processes are still required to capture paediatric-specific variables pertinent to kidney disease.

Epigenetic mechanisms differentially regulate blood pressure and renal dysfunction in male and female Npr1 haplotype mice.

We determined the epigenetic mechanisms regulating mean arterial pressure (MAP) and renal dysfunction in guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene-targeted mice. The Npr1 (encoding NPRA) gene-targeted mice were treated with class 1 specific histone deacetylase inhibitor (HDACi) mocetinostat (MGCD) to determine the epigenetic changes in a sex-specific manner. Adult male and female Npr1 haplotype (1-copy; Npr1+/-), wild-type (2-copy; Npr1+/+), and gene-duplicated heterozygous (3-copy; Npr1++/+) mice were intraperitoneally injected with MGCD (2 mg/kg) for 14 days. BP, renal function, histopathology, and epigenetic changes were measured. One-copy male mice showed significantly increased MAP, renal dysfunction, and fibrosis than 2-copy and 3-copy mice. Furthermore, HDAC1/2, collagen1alpha-2 (Col1α-2), and alpha smooth muscle actin (α-SMA) were significantly increased in 1-copy mice compared with 2-copy controls. The expression of antifibrotic microRNA-133a was attenuated in 1-copy mice but to a greater extent in males than females. NF-κB was localized at significantly lower levels in cytoplasm than in the nucleus with stronger DNA binding activity in 1-copy mice. MGCD significantly lowered BP, improved creatinine clearance, and repaired renal histopathology. The inhibition of class I HDACs led to a sex-dependent distinctive stimulation of acetylated positive histone marks and inhibition of methylated repressive histone marks in Npr1 1-copy mice; however, it epigenetically lowered MAP, repaired renal fibrosis, and proteinuria and suppressed NF-kB differentially in males versus females. Our results suggest a role for epigenetic targets affecting hypertension and renal dysfunction in a sex-specific manner.

Metolazone vs chlorothiazide in acute heart failure patients with diuretic resistance and renal dysfunction: a retrospective cohort study.

Guidelines recommend intravenous (IV) loop diuretics as first-line therapy for patients hospitalized with acute heart failure (AHF) and volume overload. Additional agents can be utilized for augmentation but there is limited guidance on agent selection. The study objective was to determine if chlorothiazide or metolazone is associated with differences in diuretic efficacy or safety in loop diuretic-resistant patients with AHF and renal dysfunction. We conducted a multi-center, retrospective cohort study of patients hospitalized with AHF and renal dysfunction who received metolazone or chlorothiazide in addition to IV loop diuretics. The primary endpoint was a comparison of 24-hour urine output (UOP) between the 24 hours before and after thiazide administration. Secondary and safety endpoints included weight change, requirement for vasopressors or inotropes, electrolyte abnormalities, and changes in renal function. A total of 223 patients were included. The mean daily diuretic doses were chlorothiazide 632 mg and metolazone 7 mg. Mean 24-hour UOP increased more among chlorothiazide- (1668 to 3826 mL) versus metolazone-treated patients (1672 to 2834 mL) (p<0.001) after addition of the second diuretic. No statistically significant differences in weight or serum creatinine changes were observed. More hypomagnesemia was observed in the chlorothiazide group; no differences in other electrolytes or serum creatinine were observed. Chlorothiazide was associated with a greater increase in 24-hour UOP than metolazone without an excess of potassium or serum creatinine derangements. However, weight changes did not differ significantly between groups. Future prospective studies are needed to confirm potential differences in diuretic response and safety.

Alliin mitigates the acute kidney injury by suppressing ferroptosis via regulating the Nrf2/GPX4 axis.

Acute kidney injury (AKI) is a clinical syndrome that is characterized by a sudden loss of kidney function, leading to severe metabolic disorders, multiple organ failure, and even death. Recent studies have strengthened the evidence for ferroptosis in AKI development. Alliin, a sulfur-containing amino acid with multiple pharmacological functions, was claimed with promising antioxidant and anti-inflammation effects in protecting organ damages. Herein, Alliin's potential in AKI treatment was investigated by exploring its impact on ferroptosis, providing a new strategy for clinical AKI treatments. Cecal ligation and puncture (CLP) modeling was performed on rats, followed by treated with 7.5 and 15mg/kg/day of alliin for 6days. A declined survival rate, severe renal pathological changes, renal dysfunction, and enhanced inflammatory state were observed in CLP-treated rats, which were remarkably alleviated by alliin. Moreover, increased MDA levels, declined SOD activity, and downregulated Nrf2, GPX4, and xCT in CLP-treated rats were notably reversed by alliin. To explore potential mechanisms of alliin, NRK-52E cells were stimulated with 1μg/mL LPS for 24h, followed by culturing with 30 and 100μM of alliin for 24h. Reduced cell viability, enhanced apoptosis, increased ROS production, boosted MDA level, and declined SOD activity were observed in LPS-stimulated NRK-52E cells, accompanied by downregulated Nrf2, GPX4, and xCT, which were strikingly ameliorated by alliin. Additionally, the influence of alliin on cell viability, oxidative stress (OS), and ferroptosis in LPS-stimulated NRK-52E cells were markedly abolished by silencing Nrf2. Collectively, alliin mitigated AKI by suppressing ferroptosis via regulating the Nrf2/GPX4 axis.

Lithium in the time of COVID: forever vigilant

BackgroundThere have been case reports of renal dysfunction with lithium toxicity among severely ill COVID-19 patients. Lithium levels may be affected by comorbid conditions and the presence of infective disease states like the SARS-CoV-2 which clearly adds systemic health burden. This study aimed to review the effect SARS-CoV-2 has on serum Li levels and the possible mechanism underlying it.MethodsRetrospective data from all clinical service encounters within the University of Michigan health system between September 2019 and September 2023 were reviewed. The study cohort included 98 patients with an average age of 45 years (62% female) who were diagnosed with any subtype of bipolar disorder, actively taking Li, and infected with SARS-CoV-2 during the study timeframe.ResultsThere was no overarching effect of a SARS-CoV-2 infection on Li chemistry in the overall sample. Higher serum Li levels were not significantly associated with SARS-CoV-2 infection nor total comorbidity index. However, higher Li levels were observed in males while infected with SARS-CoV-2 when compared with no infection. eGFR remained unassociated with serum Li level. Receiving COVID vaccination was associated with lower serum Li levels (Coeff. = − 0.88, p = 0.048).ConclusionsPatients with a diagnosis of BD, treated with Li, and infected with SARS-CoV-2 were not likely to present with elevated Li levels unless they are male or unvaccinated. Elevated serum Li level was not associated with significant renal dysfunction in this cohort. The case reports of severe renal complications and Li toxicity may be among cases of greater overall clinical severity of COVID-19. These findings are reassuring that Li may be used in the context of a COVID-19 illness but emphasize the ongoing need for clinical vigilance.

Kidney Blood Flow and Renin-Angiotensin-Aldosterone System Measurements Associated With Kidney and Cardiovascular Dysfunction in Pediatric Shock.

Pediatric acute kidney injury (AKI) is a prevalent and morbid complication of shock. Its pathogenesis and early identification remain elusive. We aim to determine whether renal blood flow (RBF) measurements by point-of-care ultrasound (POCUS) and renin-angiotensin-aldosterone system (RAAS) hormones in pediatric shock associate with vasoactive requirements and AKI. This is a single-center prospective, noninterventional observational cohort study in one tertiary PICU in North American from 2020 to 2022 that enrolled children younger than 18 years with shock without preexisting end-stage renal disease. RBF was measured by POCUS on hospital days 1 and 3 and plasma RAAS hormone levels were measured on day 1. The primary outcome was the presence of AKI by Kidney Disease Improving Global Outcomes criteria at first ultrasound with key secondary outcomes of creatinine, blood urea nitrogen (BUN), Vasoactive-Inotrope Score (VIS), and norepinephrine equivalent dosing (NED) 48 hours after first ultrasound. Fifty patients were recruited (20 with AKI, mean age 10.5 yr, 48% female). POCUS RBF showed lower qualitative blood flow (power Doppler ultrasound [PDU] score) and higher regional vascular resistance (renal resistive index [RRI]) in children with AKI (p = 0.017 and p = 0.0007). Renin and aldosterone levels were higher in the AKI cohort (p = 0.003 and p = 0.007). Admission RRI and PDU associated with higher day 3 VIS and NED after adjusting for age, day 1 VIS, and RAAS hormones. Admission renin associated with higher day 3 creatinine and BUN after adjusting for age, day 1 VIS, and the ultrasound parameters. In pediatric shock, kidney blood flow was abnormal and renin and aldosterone were elevated in those with AKI. Kidney blood flow abnormalities are independently associated with future cardiovascular dysfunction; renin elevations are independently associated with future kidney dysfunction. Kidney blood flow by POCUS may identify children who will have persistent as opposed to resolving AKI. RAAS perturbations may drive AKI in pediatric shock.

Occupational Priorities of People on Hemodialysis Who Participated in Energy Management Education.

Background. People with kidney failure who undergo hemodialysis treatment and experience chronic fatigue identify negative effects on occupational performance and participation as a key aspect of their illness experience. Purpose. To describe the occupational performance and participation problems of people treated with hemodialysis who live with debilitating fatigue. Method. Fifteen participants, who were randomized to participate in an energy management intervention as part of a randomized controlled trial, completed two occupation-based assessments at baseline and chose three priority occupational performance or participation problems to address as goals during the intervention. Results were analyzed using descriptive statistics (counts and percentages). Findings. Fifteen participants (mean age 60, 53% male) completed the occupation-based assessments. Participants stated that they wanted or needed more energy for a median of 22 of 55 occupations. Going out for food/drinks (n = 11), going to a movie/concert/performance (n = 10), and food preparation/clean-up (n = 10) were the top occupations for which participants required more energy. Prioritized occupational performance and participation problems most often fell within the household management (14 goals), self-care (6 goals), and hobbies (5 goals) domains. Conclusion. Occupational performance and participation problems are extensive among people treated with hemodialysis who live with debilitating fatigue. There is a clear need for occupation-based interventions that optimize occupational performance and participation in this population.

Prevalence and determinants of failure to thrive in children with vesico-ureteral reflux.

To assess the prevalence and determinants of failure to thrive (FTT) among patients with vesico-ureteral reflux (VUR) and evaluating the effects of supplementation on growth in patients with urinary solute losses. We retrospectively enrolled 1277 patients with VUR (mean age at diagnosis = 6.5 months). Patients with FTT were screened for renal tubular function impairment (TFI). If fractional excretion of sodium (FENa) >2% or blood bicarbonate <20 mmol/L, supplementation was provided. Among 1277 patients, 56 (4.4%) had FTT. Of these, 42 (75%) presented extrarenal causes of FTT, 3 (5.4%) had chronic kidney disease (CKD), 9 (16.1%) had TFI, and 2 (3.5%) had CKD and TFI. FTT occurred in 8/208 patients (3.8%) with and in 48/1069 patients (4.5%) without (p = 0.68) recurrent urinary tract infections (UTIs). At multiple logistic regression, birthweight <10th percentile, preterm birth, TFI, identified or suspected syndromes and other diseases were predictors of FTT. Eleven (19.6%) patients with FTT had TFI; five with increased FENa and/or acidosis received supplementation and showed catch-up growth. The remaining six patients exhibited spontaneous catch-up growth. FTT was found in <5% of children with VUR. It was not determined by recurrent UTIs and was mainly associated with extrarenal causes. Supplementation with sodium and bicarbonates could be useful in selected cases.

Levosimendan: A New Therapeutical Strategy in Patients with Renal Insufficiency.

Levosimendan, a Ca2 + sensitizer with positive inotropic effects, is primarily employed for the short-term treatment of acute decompensated heart failure (ADHF). Levosimendan exerts renal function protection through various mechanisms, including anti-apoptosis, anti-inflammatory, and antioxidant effects in vivo. Additionally, levosimendan may have a protective effect on individuals with heart failure and renal insufficiency, as well as on renal function impairment after cardiac surgery. However, the application of levosimendan in patients with severe renal dysfunction remains controversial. This article delves into the use of levosimendan in severe renal insufficiency, explores its impact on renal function, and provides a comprehensive overview of its impact on renal function after cardiac surgery.

Effects of the S1P/S1PR1 Signaling Pathway on High Glucose-Induced NRK-52E Epithelial-Mesenchymal Transition Via Regulation of ROS/NLRP3.

Diabetic kidney disease (DKD) is the most significant complication in diabetic patients, ultimately leading to renal fibrosis. The most important manifestation of DKD is the epithelial-mesenchymal transition (EMT) of renal tubular cells, which can lead to renal fibrosis and inflammatory injury in special situations. Sphingosine 1-phosphate (S1P) is involved in various signal transduction pathways and plays a role through G protein-coupled receptors. Research has demonstrated that blocking the S1P / S1PR2pathway inhibits inflammation and fibrosis. However, the interaction between S1P/S1PR1and the pathophysiology of EMT remains ambiguous. The purpose of this study was to investigate the mechanism of S1P/S1PR1 on high glucose (HG)-induced renal EMT. We found that HG markedly increased the S1P and EMT marker levels in renal tubular epithelial cells. At the same time, HG could stimulate NF-κB/ROS/NLRP3 expression, but these phenomena were reversed after blocking S1PR1. In mice models of DKD, FTY720 (S1P antagonist) could significantly improve renal function and reduce the infiltration of inflammatory cells. ROS, as well as NLPR3 inflammasome, were markedly decreased in the treatment group. FTY720 inhibits extracellular matrix synthesis and improves renal fibrosis. In brief, the HG stimulates S1P/S1PR1 synthesis and activates the S1P/S1PR1 pathway. Through the S1P/S1PR1 pathway, activates NF-κB, promotes ROS generation and NLRP3 inflammasome activation, and ultimately causes EMT.

Acute kidney injury in a child treated with cisplatin and amphotericin B.

Cisplatin and amphotericin B are both known to be potentially nephrotoxic. We describe acute kidney injury due to the combination of Liposomal amphotericin B and cisplatin in an adolescent with osteosarcoma. Acute kidney injury (peak creatinine 431 µmol/L) consistent with drug-induced acute tubulointerstitial nephritis was observed a few days after concomitant administration of cisplatin and amphotericin B. Kidney function nearly normalised during follow-up. The timing of the concomitant administration of amphotericin B and cisplatin led us to presume that the combination was the cause of renal failure, and we conclude that concurrent administration of cisplatin and amphotericin B should be avoided.

Signal of dementia with proton pump inhibitor after minimizing competition bias: an updated disproportionality analysis

ABSTRACT Objective The association between proton pump inhibitor (PPI) and dementia was controversial. The aim of the current study was to perform an updated pharmacovigilance analysis of the association between dementia event and PPI treatment after minimizing competition bias. Methods We gathered cases reported with PPI treatment based on the United States Food and Drug Administration Adverse Event Reporting System database from 2004 to 2023. We employed disproportionality algorithms, including reporting odds ratio (ROR) and the information component (IC), to detect the association between dementia event and PPI. We investigated the affection of event competition bias on the current disproportionality signal detection. Results We finally included a total of 776,191 PPI cases, and 1813 cases in the dementia group. Analyzing primary suspect PPIs, we detected a significant association between dementia and PPI (ROR = 1.38, 95%CI 1.22 to 1.56; IC = 0.46, 95%CI 0.04 to 0.86). After excluding the PPI case with renal injury events, the strength of the dementia signal increased. Omeprazole (589 cases), pantoprazole (514 cases), and esomeprazole (386 cases) were the top three PPI reported with dementia events. Conclusion The current pharmacovigilance study identified a significant association between dementia and PPIs, except vonoprazan and tegoprazan, especially taking competition bias into account. Further high-quality prospective study still needed.

Kidney transplantation in children and adolescents with C3 glomerulopathy or immune complex membranoproliferative glomerulonephritis: a real-world study within the CERTAIN research network.

Complement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are ultra-rare chronic kidney diseases with an overall poor prognosis, with approximately 40-50% of patients progressing to kidney failure within 10years of diagnosis. C3G is characterized by a high rate of disease recurrence in the transplanted kidney. However, there is a lack of published data on clinical outcomes in the pediatric population following transplantation. In this multicenter longitudinal cohort study of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, we compared the post-transplant outcomes of pediatric patients with C3G (n = 17) or IC-MPGN (n = 3) with a matched case-control group (n = 20). Eleven of 20 children (55%) with C3G or IC-MPGN experienced a recurrence within 5years post-transplant. Patients with C3G or IC-MPGN had a 5-year graft survival of 61.4%, which was significantly (P = 0.029) lower than the 5-year graft survival of 90% in controls; five patients with C3G or IC-MPGN lost their graft due to recurrence during this observation period. Both the 1-year (20%) and the 5-year (42%) rates of biopsy-proven acute rejection episodes were comparable between patients and controls. Complement-targeted therapy with eculizumab, either as prophylaxis or treatment, did not appear to be effective. These data in pediatric patients with C3G or IC-MPGN show a high risk of post-transplant disease recurrence (55%) and a significantly lower 5-year graft survival compared to matched controls with other primary kidney diseases. These data underscore the need for post-transplant patients for effective and specific therapies that target the underlying disease mechanism.

Mortality risk for kidney transplant candidates with diabetes: a population cohort study.

It is unclear whether kidney transplant candidates with diabetes have equitable transplantation opportunities or have divergent survival probabilities stratified by kidney replacement therapy. The aim of this study was to investigate these two issues using national transplant registry data in the UK. A cohort study was undertaken of prospectively collected registry data of all wait-listed people with kidney failure receiving dialysis in the UK. All people listed for their first kidney-alone transplant between 2000 and 2019 were included. Stratification was done for cause of kidney failure. Primary outcome was all-cause mortality. Time-to-death from listing was analysed using adjusted non-proportional hazard Cox regression models, with transplantation handled as a time-dependent covariate. A total of 47,917 wait-listed people with kidney failure formed the total study cohort, of whom 6594 (13.8%) had diabetes classified as cause of kidney failure. People with kidney failure with diabetes comprised 27.6% of the cohort (n=3681/13,359) that did not proceed to transplantation vs only 8.4% (n=2913/34,558) of the cohort that received a transplant (p<0.001). Kidney transplant candidates with diabetes were more likely to be older, of male sex and of ethnic minority background compared with those without diabetes. In an adjusted analysis, compared with remaining on dialysis, any kidney transplant provided survival benefit for wait-listed kidney transplant candidates regardless of diabetes as cause of kidney failure (RR 0.26 [95% CI 0.25, 0.27], p<0.001). Kidney transplant candidates with diabetes have a lower chance of transplantation despite better survival after kidney transplantation vs remaining on dialysis. The reasons for this require further investigation to ensure equal transplantation opportunities.