BMC Nephrology最新文献

Background: Patients with chronic kidney disease (CKD) are susceptible to acquiring opportunistic parasites due to acquired immunodeficiency caused by uremia. Therefore, the present case-control study attempted to determine the prevalence of T. gondii infection and also associated risk factors among patients with CKD under hemodialysis and healthy controls who were registered at the Iranian National Registry Center for Toxoplasmosis (INRCT) in Mazandaran Province, northern Iran.

Methods: 212 cases with CKD and 200 healthy controls were enrolled in this study. Informed consent as well as a questionnaire were obtained from all subjects. Blood samples were collected from each participant and the serum was screened for anti-Toxoplasma antibodies (IgG and IgM). PCR assay was performed to detect circulating T. gondii in the blood samples of patients and controls using the primer pair targeting the RE gene.

Results: Out of 412 participants, 67.92% of patients and 15.5% of control subjects were positive for anti-Toxoplasma IgG, but all participants were negative for anti-Toxoplasma IgM. Also, considering PCR assays with RE target, the prevalence of T. gondii infection was 24.1% in case subjects, while none of the control subjects tested positive. Among the PCR positive, 34 (66.7%) had Toxoplasma IgG positivity. The results from the multiple multinomial logistic regression revealed that the seroprevalence of anti-T. gondii IgG antibodies in patients with CKD was 3.12 times higher than in healthy controls (OR = 3.12; 95% CI = 0.43, 14.8; P < 0.001). Also, there was a significant association between seroprevalence of T. gondii infection and age, having a cat at home, and level of glomerular filtration rate (GFR) in these patients.

Conclusion: Our findings demonstrate a highly significant association between latent T. gondii infection and CKD, mostly in the late stages. Thus, regular screening for T. gondii infection in these patients is strongly recommended to prevent the reactivation of latent infections. A combination of serological screening, chemoprophylaxis, and PCR follow-up for patients at risk of reactivation should effectively reduce the likelihood of latent infection reactivation.

Clinical trial number: Not applicable.

Purpose: Transcatheter arterial embolization (TAE) is increasingly utilized in the management of renal angiomyolipomas (AML). However, the growth in its application has not been matched by a proportional increase in the level of evidence validating its safety and efficacy. This meta-analysis aims to evaluate TAE in managing renal AMLs by examining the effects of tumour size reduction and technical success.

Methods: A literature search of several databases was conducted from inception to July 2023. Eligible studies reported adult patients (≥ 18 years old) who underwent TAE for renal AML. The pooled proportions were analyzed using a random-effects model. This review was registered in PROSPERO (CRD42023441331).

Results: A total of 32 studies comprising 1087 patients were included. The average preoperative tumour size across renal AMLs was 8.79 cm (95% CI: 7.64, 9.93; I² = 97%) and the post-operative tumour size was 6.47 cm (95% CI: 5.44, 7.50; I² = 98%). The mean decrease in tumour size was 1.85 cm (95% CI: 1.69, 2.00; I² = 23%), whereas the mean reduction in tumour size percentage was 43.30% (95% CI: 34.30, 52.30; I² = 98%). The technical success rate from 1059 embolizations was 95.70% (95% CI: 0.94, 0.97; I² = 44%), with 65 procedural failures reported.

Conclusion: This meta-analysis provides insights into the efficacy of TAE for renal AMLs, emphasizing notable tumour size reduction and a high technical success rate for selected patients. Despite identified biases, the findings support TAE as a valuable intervention, warranting further research to refine safety profiles and optimize patient outcomes.

Background: Angiotensin II (Ang II) plays a critical role in the progression of kidney disease. In addition to its direct signaling events, Ang II transactivates epidermal growth factor receptor (EGFR) and causes renal injury. CD148 is a transmembrane protein tyrosine phosphatase that dephosphorylates EGFR and strongly inhibits its activity. In this study, we have asked if CD148 agonistic antibody 18E1 mAb attenuates renal injury induced by chronic Ang II infusion to explore its therapeutic application.

Methods: Hypertensive nephropathy was induced in mice subjected to unilateral nephrectomy (UNx) by infusing Ang II (1.4 mg/kg per day) for 6 weeks using an osmotic minipump. The 18E1 mAb or isotype control IgG were intraperitoneally injected (15 mg/kg, three times per week) to the UNx + Ang II mice for 6 weeks, and their renal phenotype was investigated.

Results: Chronic Ang II infusion induced evident hypertension and renal injury that is indicated by elevation of plasma creatinine, urinary albumin excretion, renal hypertrophy, podocyte injury, macrophage infiltration, and the expression of alpha smooth muscle actin and collagen deposition. As compared with isotype control antibody, 18E1 mAb significantly reduced these renal changes, while it showed no effects on blood pressure. Furthermore, phospho-EGFR immunohistochemistry and immunoblotting demonstrated renal EGFR is activated in the mice that were subjected to UNx and Ang II infusion and 18E1 mAb significantly reduces EGFR phosphorylation in these kidneys as compared with isotype control treatment.

Conclusion: Agonistic CD148 antibody attenuates UNx + Ang II-induced renal injury, in part by reducing EGFR activity.

Background: Ensuring that patients, especially those in underserved areas, have access to specialized nephrology care is essential to addressing the increasing burden of chronic kidney disease. To address this, we developed the Telenephrology Dashboard for the 150,000 Veterans served by the Iowa City Veterans Affairs Health Care System (ICVAHCS). Our goal was to optimize the dashboard as a comprehensive and practical tool for end-users in order to monitor kidney health and facilitate remote nephrology consultations.

Methods: The optimization process adhered to the Human-Centered Design (HCD) framework, encompassing five stages: Empathize, Define, Ideate, Prototype and Test. Research team members spent 10 h observing nephrologists during remote consultations and supplemented these observations with semi-structured interviews with clinicians to gain insights into existing workflows and challenges. A rapid ideation workshop was then held to propose innovative solutions that balanced technical needs with user preferences. Subsequent prototyping and testing helped refine and evaluate the proposed designs, identifying key areas for improvement.

Results: The iterative design process identified three critical needs: (1) improved clarity in visual data representation, (2) enhanced data accuracy, and (3) a balance between standardized features and customization options. Five dashboard prototypes were created, tested, and iteratively refined into a final version. The completed Telenephrology Dashboard includes five core features: (1) graphical representation of kidney function trends, (2) tables summarizing key lab data, (3) functionality to examine specific events in detail, (4) customizable views tailored to user workflows, and (5) integration of predictive kidney disease progression models.

Conclusion: The Telenephrology Dashboard was developed using a Human-Centered Design approach to improve remote nephrology consultations. Future efforts will focus on evaluating its impact on user satisfaction, referring clinician satisfaction, access to nephrology care, and patient care outcomes.

Clinical trial number: Not applicable, as this is not a clinical trial.

Background: Sepsis-associated acute kidney injury (SA-AKI) is a prevalent and severe complication of sepsis, but its complex pathogenesis remains unclear. This study aims to identify potential biomarkers for SA-AKI by elucidating its molecular mechanisms through bioinformatics methods.

Methods: Transcriptional data related to SA-AKI were obtained from the Gene Expression Omnibus (GEO) database. We used differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) to identify characteristic genes associated with SA-AKI and conducted enrichment analyses. Hub genes were determined using protein-protein interaction (PPI) network analysis and the Least Absolute Shrinkage and Selection Operator (LASSO). Additionally, ROC curves were plotted to assess the diagnostic value of these core genes. Immune cell infiltration was analyzed using the CIBERSORT algorithm, and potential associations between the hub genes and clinicopathological features were explored based on the Nephroseq database. Finally, a murine model of SA-AKI was induced with lipopolysaccharide (LPS) to validate the findings, and mRNA abundance and protein production levels of pivotal genes were confirmed via RT-qPCR, Western blotting, and immunohistochemical methods.

Results: We identified 268 characteristic genes associated with SA-AKI that are enriched in immune and inflammation-related pathways. Utilizing machine learning techniques, three key genes were screened: GBP2, PSMB8 and PSMB9. The expression patterns of these three genes were well-validated through animal experiments and databases. Correlation between these genes and clinical indicators was confirmed using the Nephroseq database. Furthermore, immune infiltration analysis provided additional insights into their potential functions.

Conclusion: GBP2, PSMB8, and PSMB9 are promising candidate genes for SA-AKI, providing a novel perspective on its pathological mechanisms. Further exploration of the biological roles of these genes in the pathogenesis of SA-AKI is needed in the future.

Background: A major challenge of transplantation is the unavailability of organs. For a successful transplantation process, awareness and negative attitudes among potential donors need to be sought for and addressed. Our objective was to examine the knowledge, perception and information needs of family members of patients with chronic kidney disease (CKD) in Nigeria and factors associated with their likelihood to decide to donate a kidney.

Methods: This was a convergent parallel mixed method study that obtained information from family members of patients with CKD in Nigeria. Ordinal logistic regression was used to determine factors associated with the likelihood of donation. Thematic analysis was used for the qualitative analysis.

Results: Three hundred and six respondents with a mean age of 41.2 ± 12.9 years participated in the quantitative survey. About 30% of participants were not familiar with the concept of kidney donation; 63% had never sought information about kidney donation; about 75% felt inadequately informed about the risks, benefits, and requirements of kidney donation. About 26% of participants were unlikely to consider donating a kidney to a family member with CKD. The majority expressed medical risk (47%) as their primary concern with donation. The age group of respondents (OR 0.48, 95% CI 0.239-0.967, P = 0.04), parent/child relationship, (OR 2.42, 95%CI 1.198-4.886, P = 0.01), awareness of the suitable medical factors for donation (OR 2.07, 95%CI 1.127-3.796, P = 0.02), and provision of support or counsel to donors (OR 3.89, 95%CI 1.576-9.638, P = 0.003), were independently associated with decisions to donate. The qualitative analysis identified personal, socio-cultural, religious and psychological factors that could influence willingness to donate.

Conclusion: This study identified factors that influenced donations and brought to the fore the need to adequately educate and provide support for potential kidney donors.

Clinical trial number: Not applicable.

Background: Acute kidney injury (AKI) is a common complication in pediatric oncology patients, most often caused by nephrotoxic drugs. We aimed to assess whether levels of urinary kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), liver fatty acid binding protein (uL-FABP) and Vanin-1 (uVNN-1), individually and in combination-integrated could be early markers for cytotoxic treatment induced AKI.

Methods: Children with different malignant diseases treated with cisplatin (CIS) or ifosfamide (IFO) were included. AKI was defined using pediatric KDIGO (Kidney Disease Improving Global Outcomes) criteria by comparing pretreatment serum creatinine (sCr) values with those acquired at 48 h after the first or second chemotherapy cycle. Five serum (at baseline, 2, 6, 24 and 48 h after treatment) and four urine samples (at baseline, 2, 6 and 24 h after treatment) were obtained. Urinary biomarkers (uBm) were normalized to urine creatinine.

Results: Thirty-eight patients were assessed. Within 48 h following chemotherapy 6 (15.79%) patients experienced AKI. Patients with AKI were younger and tend to have lower baseline sCr values than patients without AKI, but these differences were not statistically significant. Compared to baselines, all uBm were significantly increased during the first 6 h while sCr concentrations did not change significantly during the study period. The median increases in uBm during the first 6 h after treatment were 529.8% (interquartile range - IQR, 63.9-1835.2%) - 2194.0% (IQR, 255.3-4695.5%) in AKI vs. 302.2% (IQR 114.6-561.2%) -429.8% (156.5-1467.0%) in non-AKI group depending of tested uBm. The magnitude of these changes over time didn't differ significantly between groups. The area under receiver operator curve (AUC) for uL-FABP and uNGAL at 24 h after chemotherapy were 0.81 and 0.72, respectively. The ROC analysis revealed that the other individual biomarkers' performance at any time-point wasn't statistically significant (AUC < 0.7). A model of integrated-combined uBm, 2 h (AUC 0.78), 6 h (AUC 0.85) and 24 h after (AUC 0.92) treatment with CIS and/or IFO showed good utility for early AKI prediction.

Conclusions: The results of this study support that the use of the uBm to improves early AKI prediction in patients receiving CIS and/or IFO containing chemotherapy. Further studies on larger comparable groups of patients are needed.

Complement-mediated thrombotic microangiopathies (CM-TMA) are rare and life-threatening disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. These conditions result from dysregulation of the alternative complement pathway, often due to genetic variants or autoantibodies. The clinical spectrum is broad, comprising varied presentations and triggers, including infections, malignancies, and pregnancy-related complications. Advances in understanding the genetic and immunological basis of CM-TMA have improved diagnosis and treatment. Diagnosis requires exclusion of other thrombotic microangiopathies like thrombotic thrombocytopenic purpura and secondary causes, with genetic testing recommended to identify underlying susceptibilities. The introduction of C5 inhibitors has transformed the management of CM-TMA, significantly improving outcomes compared to the pre-2011 era when therapeutic plasma exchange was the primary therapy. Despite these advances, challenges remain in determining the optimal duration of therapy. Prophylactic measures against infections, particularly meningococcal disease, are mandatory for patients receiving C5 inhibitors. This article underscores the need for a personalized, multidisciplinary approach in the diagnosis and management of CM-TMA. Advances in genetics and complement biology have led to improved therapeutic strategies, however ongoing research is essential to address unanswered questions regarding relapse risk, treatment duration, and long-term outcomes.

Background: Chronic kidney disease-associated pruritus (CKD-aP) can negatively impact quality of life and survival among patients receiving maintenance hemodialysis. Difelikefalin, a selective κ-opioid receptor agonist, is the first medication approved for treatment of moderate-to-severe CKD-aP among patients on chronic hemodialysis. This retrospective database study assessed the real-world safety and effectiveness of difelikefalin across a large US dialysis organization.

Methods: We analyzed de-identified data from 715 adult hemodialysis patients treated with difelikefalin who had a Worst Itching Intensity Numerical Rating Scale (WI-NRS) score (0 = no itching to 10 = worst itch imaginable) assessed before therapy. Patients were classified as having received at least 30 difelikefalin doses over 12 weeks (complete regimen group; CRG) or fewer doses over that time period (incomplete regimen group; IRG). Mean baseline and follow-up WI-NRS scores were compared and potential adverse events evaluated.

Results: Mean (SD) baseline WI-NRS scores were 8.5 (1.7), indicative of severe pruritic symptomatology. In the 22% of patients with follow-up data, mean WI-NRS scores improved by 2.9 points (8.4 [severe] to 5.4 [moderate]; P < 0.0001). This mean improvement was more pronounced in CRG patients (n = 84; 3.6) compared with IRG patients (n = 84; 2.2). Overall, 46% of patients experienced a 3-point reduction in itch severity. Difelikefalin initiation was not associated with changes in rates of nausea, diarrhea, vomiting, headache, or trouble walking. Dizziness and hyperkalemia were infrequent, but statistically significant with increases in dizziness (0.09% vs. 0.20%) and hyperkalemia (2.0% vs. 2.6%) were observed during treatment with difelikefalin.

Conclusions: In this analysis of real-world difelikefalin use in a US hemodialysis population, patients experienced significant reductions in CKD-aP, based on a validated measure of pruritus. Patients remaining on therapy for 12 weeks demonstrated greater symptom reductions than those patients receiving partial treatment. In combination with controlled trials, these data suggest that difelikefalin is an effective and well-tolerated treatment for the management of CKD-aP in adult patients receiving hemodialysis.

Background: End-stage renal disease is a significant global health issue, and Peritoneal Dialysis (PD) is a vital treatment modality. The study aims to assess the Quality of Life (QoL) and pain levels in PD patients and explore potential influencing factors.

Methods: A cross-sectional study was conducted in 2022 involving 76 PD patients at a referral tertiary dialysis center in Palestine. The study evaluated patient demographics, clinical data, laboratory measures, quality of life as assessed by the KDQOL-SF36, and pain levels as determined by the Brief Pain Inventory. Statistical analyses, including multivariate linear regression, were employed to identify relevant associations.

Results: This study included 76 PD disease patients, with 68.4% being under the age of 60 and 53.9% being male. Almost one-third of the participants (34.0%) reported mild to severe pain, and 23.7% reported low to high interference levels. Pain severity was negatively correlated with supplement doses for both vitamin D3 (p = 0.049) and calcium (p < 0.01). Female patients reported higher pain severity (p = 0.001) and interference (p < 0.007) levels. The study revealed relatively higher QoL among our cohort of PD patients compared to previously published findings in similar settings, specifically for HD populations. Factors such as age, comorbid conditions, and duration of dialysis influenced QoL (p < 0.05). Pain severity and interference were negatively correlated with QoL (p = 0.01).

Conclusion: This study provides valuable insights into the QoL and pain experiences of PD patients in Palestine. It underscores the importance of effective pain management strategies and holistic care to improve QoL in this patient population. Addressing psychological and emotional well-being is vital for optimizing treatment adherence and long-term outcomes.

Clinical trial number: Not applicable.