BMC Nephrology最新文献

Background: Difelikefalin is a selective kappa opioid receptor agonist that is approved for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis (HD). In this study, we assessed the pharmacokinetics (PK) of intravenous (IV) difelikefalin in healthy subjects, in non-dialysis-dependent (NDD) subjects with varying stages of kidney disease, and in subjects with end-stage renal disease (ESRD) undergoing HD.

Methods: The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects. Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period).

Results: Single IV dosing of difelikefalin in NDD subjects (N = 36) with mild renal impairment demonstrated comparable exposure to healthy subjects with normal renal function, while subjects with moderate or severe renal impairment had higher total exposure. NDD subjects with severe renal impairment had higher total exposure compared with those with moderate renal impairment (i.e., exposure in severe NDD > moderate NDD > mild NDD ≈ healthy subjects). Clearance of difelikefalin correspondingly decreased with increasing renal impairment. In the multiple-dose study in subjects with ESRD undergoing HD (N = 19), IV difelikefalin demonstrated dose proportionality and was shown to be mostly cleared by dialysis; steady state was achieved with the second dose on day 3. Safety findings for all subjects were consistent with the known profile of IV difelikefalin.

Conclusions: IV difelikefalin was well tolerated. Similar exposure was observed in NDD subjects with mild renal impairment compared with healthy subjects with normal renal function, with reduced clearance and higher exposure in NDD subjects with moderate or severe renal impairment. Dose proportionality was demonstrated in subjects with ESRD undergoing HD administered IV difelikefalin 3 times per week following dialysis and was shown to be mostly cleared by dialysis.

Trial registration: Single-dose study: NA; multiple-dose study: ClinicalTrials.gov registration number NCT02229929, first registration 03/09/2014.

Background: The objective of the current study was to assess the effectiveness of stress management training, grounded in Lazarus and Folkman's stress management model, on reducing caregiving burden and perceived stress among family caregivers of patients on hemodialysis.

Methods: This two-group clinical trial study was conducted in parallel design among 60 family caregivers of patients on hemodialysis in 2023. The participants were divided into two groups of training and control using a random quadruple block allocation method. The intervention took place over two months, in six online group sessions of 35-45 min. Zarit Burden Inventory (ZBI) and Cohen's Perceived Stress Scale (PSS-14) were used to collect information before and two weeks after the intervention. The study data were analyzed using and analysis of covariance (ANCOVA), pair, and independent t-tests at a significance level of 0.05.

Results: At baseline, the two groups exhibited homogeneity in terms of mean scores for caregiving burden (Training group = 50.8 ± 4.9; Control group = 49.1 ± 6.0; P = 0.264) and perceived stress (Training group = 32.8 ± 4.7; Control group = 31.5 ± 2.4; P = 0.192). Nevertheless, following the intervention, there was a significant decrease in caregiving burden (Training group = 45.9 ± 4.1; Control group = 49.0 ± 5.8; P = 0.017) and perceived stress (Training group = 28.0 ± 4.4; Control group = 30.7 ± 3.5; P = 0.01) scores within the training group compared to the control group.

Conclusion: Based on the findings of the current study, given that family caregivers of patients on hemodialysis encounter psychological distress and contend with the negative aspects of care, it is advisable to implement psycho-educational interventions, such as stress management training. Incorporating these interventions into the care plan for hemodialysis could help mitigate these adverse consequences and provide valuable support for family caregivers.

Trial registration: Iranian Registry of Clinical Trials (IRCT), IRCT20180728040617N6. Registered on 17/04/2023.

Background: Primary aldosteronism (PA), which is present in 5-18% of hypertensive patients, is a leading cause of secondary hypertension. Adrenalectomy is often recommended for patients with unilateral primary aldosteronism (uPA), yielding good long-term outcomes. PA patients without hyperuricemia and chronic renal failure before adrenalectomy were enrolled in this cohort study. Serum uric acid (SUA) and renal filtration were measured one year post-adrenalectomy. Their relationships with pathologic features, histopathological subtype (classical or nonclassical (HISTALDO consensus)), and vessel stiffness were explored. The aim of this cohort study is to evaluate the correlation between post-adrenalectomy serum uric acid (SUA) levels and estimated glomerular filtration rate (eGFR) with the pathologic features delineated by the HISTALDO consensus. Additionally, the study seeks to assess the impact of these biochemical markers on peripheral vessel stiffness and brachial-ankle pulse wave velocity (baPWV) at a one-year follow-up visit.

Methods: This prospective cohort study included patients (N = 100) diagnosed with uPA who underwent adrenalectomy from Jan 1, 2007 to Dec 31, 2022.

Results: At follow-up, elevated SUA, hyperuricemia, and a > 25% eGFR decrease were significantly more common in the classical than the nonclassical group. The incidence of postoperative hyperuricemia, herein referred to as post-adrenalectomy hyperuricemia (PAHU), was 29% (29/100) overall, 34.8% (23/66) in the classical group and 17.6% (6/34) in the nonclassical group. The incidence of eGFR reduction > 25% was 33% (33/100), 43.9% (29/66), and 11.8% (4/34), respectively. baPWV decreased more in the classical group than the nonclassical group.

Conclusion: For PA patients with PAHU and/or renal impairment, we suggest monitoring SUA, pH, urine uric acid, and urine crystals and performing a KUB study and peripheral vascular and renal sonography (on which pure uric acid stones in the KUB are radiolucent) to determine whether drug intervention is required for cases of asymptomatic PAHU, especially patients in male gender, classical histopathology, or renal impairment.

Background: Chronic kidney disease (CKD) has become a concerning public health issue, affecting people regardless of their sex, age, or socioeconomic status. We aimed to analyze the burden of female CKD in Mexico between 1990 and 2021, expressed in terms of years lived with disability (YLDs), mortality, years of life lost (YLLs), and disability-adjusted life-years (DALYs). Additionally, we evaluated the relationship between DALYs and the Socio-Demographic Index (SDI) and the Healthcare Access and Quality Index (HAQI).

Methods: Secondary data analysis from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021. We used mortality, years of life lost due to premature mortality (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs to analyze CKD in women between 1990 and 2021. We used a log-linear segmented regression model to analyze trends in female CKD DALY rates over time. The information was disaggregated by age groups and sub-causes nationally and across the 32 states. Age-standardized rates (ASR) were used.

Results: Between 1990 and 2021, the ASR mortality and ASR-DALYs due to CKD increased significantly at the national level. The DALYs are almost entirely explained by YLLs, indicating that a large proportion of women with CKD in Mexico die prematurely. Disparities in the burden of this disease were observed across different states and age groups within the country. In 2021, the highest ASR-DALY rate was recorded in Tabasco (1,972.0), while the lowest was in Sinaloa (865.1). The SDI and HAQI were associated with the CKD DALYs in most states.

Conclusions: Mexican women experience a significant burden due to CKD, reflected in premature deaths and years lived with disability, while disparities between states need to be addressed to reduce inequities. Over the past 32 years, improvements in socioeconomic indicators and the quality and access to healthcare have not contributed to reducing the DALYs rate due to CKD, indicating a need to redirect policies to impact women's well-being and health positively.

Background: The objective of our research was to investigate the specific mechanism of FTO in diabetic kidney disease (DKD) progression.

Methods: The DKD model was established with renal tubular epithelial HK-2 cells and mice in vitro and in vivo. The N6-methyladenosine (m⁶A) content in cells was detected using dot plot assay and the m⁶A levels of NLRP3 was detected with the MeRIP assay. The mRNA and protein levels were tested with real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot. The IL-1β and IL-18 levels were assessed with enzyme-linked immunosorbent assay (ELISA). The cell viability was measured by cell counting kit (CCK)-8 assay and cell pyroptosis was determined with Annexin V and propidium iodide (PI) double staining followed by flow cytometry analysis. RNA-binding protein immunoprecipitation (RIP) and dual luciferase reporter assays were conducted to detect the interaction between FTO and NLRP3. m⁶A levels were detected by Me-RIP assay. The renal injury was measured by observing the renal morphology and urine and blood levels of relevant indicators.

Results: The results indicated that high glucose treatment induced HK-2 cell pyroptosis. m⁶A levels were prominently elevated in high glucose treated HK-2 cells while FTO expression were significantly down-regulated. FTO over-expression promoted cell viability but inhibited pyroptosis of HK-2 cells under high glucose (HG) treatment. Moreover, FTO could inhibit NLRP3 expression. RIP and Me-RIP assays indicated that FTO could bind with NLRP3 and regulate its m⁶A modification level. Further luciferase assay confirmed that FTO binds with the 233-237 bp region of NLRP3. NLRP3 neutralized the function of FTO in the HG stimulated HK-2 cells. In vivo, the H&E staining showed that FTO over-expression alleviated the kidney injury and suppressed the pyroptosis induced by DKD.

Conclusion: We found that FTO could inhibit the DKD progression in vivo and in vitro by regulated the m⁶A modification of NLRP3.

Kidney disease is a common complication of multiple myeloma (MM) and a risk factor for increased morbimortality. In this retrospective cohort study based on medical records, we analyzed the kidney function of patients with renal disease related to MM during the first year of treatment. All patients included were consecutively admitted to the outpatient services of two hospitals between January 2009 and January 2019 and met the diagnostic criteria for MM regardless of the reason for seeking medical help. We excluded patients who had kidney disease or who were on dialysis before MM diagnosis. We investigated the factors associated with renal function recovery using multivariate analysis. We evaluated 167 patients (median age of 66 ± 11.49 years). Almost half of the patients had arterial hypertension (76; 45.5%). The majority had International Staging System (ISS) grades 3 (73; 43.7%) or 2 (60; 35.9%). Seventy-four (44%) patients had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² at the time of MM diagnosis. Fifty-two patients (31%) underwent hematopoietic stem cell transplantation (HSCT). After 12 months, 4 (2.3%) patients needed dialysis, and 18 (10.7%) died. The factors associated with an eGFR < 60 ml/min/1.73 m² were anemia, hyperuricemia, 24-hour proteinuria > 1.0 g, and extramedullary plasmacytoma. However, only baseline renal function (eGFR > 60 ml/min/1.73 m²) and HSCT were associated with greater recovery of renal function at 12 months of follow-up.

Background: The rise in risk factors like obesity, hypertension, and diabetes mellitus has partly led to the increase in the number of patients affected by chronic kidney disease, affecting an estimated 843 million people, which is nearly 10% of the general population worldwide in 2017. Patients with CKD have an increased risk of functional difficulties and disability. This study aimed to assess the level of functional status and disability and its associated factors among patients with chronic kidney attending Saint Paul Hospital, Millennium Medical College, Addis Ababa, Ethiopia.

Methods: An institution-based cross-sectional study was conducted with 302 enrolled study participants through systematic random sampling techniques. Face-to-face interviews and chart reviews were used to collect data using a semi-structured questionnaire adapted from works of literature. The Health Assessment Questionnaire Disability Index (HAQ-DI) was used to assess the functional status and disability of the participants. Data was entered into EPI info version 7 and exported to SPSS version 23 for analysis. Bivariate logistic regression analysis was employed with a p-value less than 0.25. Finally, those variables with a p-value less than 0.05 in multivariate analysis were taken as statistically significant.

Results: A total of 219 (72.5%) CKD patients had moderate to severe functional limitation and disability (HAQ-Di > 0.5-3). Age > 50 years [AOR = 1.65; 95% CI (1.23, 3.15)], being at stage 2 and 3 CKD [AOR = 4.05; 95% CI (1.82, 9.21), being at stage 4 and 5 CKD [AOR = 2.47; 95% CI (1.87, 4.72)], and having MSK manifestations [AOR = 2.97; 95% CI (1.61, 5.55)] were significantly associated with functional status and disability.

Conclusion: The findings of this study suggest that CKD-associated functional disabilities are common. The advanced stage of CKD, higher age, and presence of musculoskeletal manifestations appear to be important variables predicting self-reported functional status. Healthcare professionals treating CKD shall be vigilant about the CKD-associated disability, the modifiable predictors, and interventions to limit the CKD-related disability.

Background: To evaluate the clearance of edoxaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations.

Methods: Edoxaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types, flow rates, and point of CVVH replacement fluid dilution. Concentrations of edoxaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters for edoxaban were estimated via noncompartmental analysis. Two and three-way analysis of variance (ANOVA) models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CL_CRRT. Linear regression was utilized to provide dosing estimations across CRRT effluent flow rates from 0.5 to 5 L/h. Optimal edoxaban doses were suggested using CL_CRRT and population non-renal clearance (CL_NR) to estimate total clearance and match the systemic AUC associated with efficacy in the treatment of venous thromboembolism.

Results: Edoxaban clearance from the CRRT circuit occurred primarily via hemofilter adsorption to the HF1400 and M150 filters at 74% and 65%, respectively, while mean percent protein binding was 41%. Multivariate analyses confirmed the lack of influence of CRRT mode, filter type, and point of dilution on the CL_CRRT of edoxaban allowing dosing recommendations to be made based on effluent flow rate. Edoxaban doses of 30-45 mg once daily were estimated to achieve target the AUC threshold for flow rates from 0.5 to 5 L/h.

Conclusion: For CRRT flow rates most employed in clinical practice, an edoxaban dose of 45 mg once daily is predicted to achieve target systemic exposure thresholds for venous thromboembolism treatment. The safety and efficacy of this proposed dosing warrants further investigation in clinical studies.

Background: Mutation of MMACHC gene causes cobalamin C disease (cblC), an inherited metabolic disorder, which presents as combined methylmalonic aciduria (MMA-uria) and hyperhomocysteinaemia in clinical. Renal complications may also be present in patients with this inborn deficiency. The most common histological change is thrombotic microangiopathy (TMA). However, to our acknowledge, renal tubular injury in the late-onset presentation of cblC is rarely been reported. This study provides a detailed description of the characteristics of kidney disease in cblC deficiency, aiming to improve the early recognition of this treatable disease for clinical nephrologists.

Case presentation: Here we described three teenage patients who presented with hematuria, proteinuria, and hypertension in clinical presentation. They were diagnosed with renal involvement due to cblC deficiency after laboratory tests revealing elevated serum and urine homocysteine, renal biopsy showing TMA and tubular injury, along with genetic testing showing heterogeneous compound mutations in MMACHC. Hydroxocobalamin, betaine, and L-carnitine were administered to these patients. All of them got improved, with decreased homocysteine, controlled blood pressure, and kidney outcomes recovered.

Conclusions: The clinical diagnosis of cblC disease associated with kidney injury should be considered in patients with unclear TMA accompanied by a high concentration of serum homocysteine, even in teenagers or adults. Early diagnosis and timely intervention are vital to improving the prognosis of cobalamin C disease.

Clinical trial number: Not applicable.