Nephron最新文献

Introduction: Lysinuric protein intolerance (LPI) is a multisystemic inborn error of metabolism with a variable clinical expressivity that usually begins in childhood with growth failure and gastroenterological/neurological problems related to the altered urea cycle and, later, with complications involving the renal, pulmonary, and immunohematological systems.

Case report: We present the case of a 40-year-old woman suffering from chronic kidney disease in the context of a LPI, whose diagnosis was challenging because the signs of the disease were always blurred and the patient never manifested critical episodes typical of this multisystemic disease. In addition to renal disease, splenomegaly, thrombocytopenia, elevated lactate dehydrogenase (LDH), hyperferritinemia, and hypertriglyceridemia were also present. A thorough investigation of the patient's food preferences revealed her spontaneous aversion to protein-containing foods and excessive drowsiness during the occurrence of infectious episodes or on the rare occasions of excessive protein intake, although without ever coming to medical attention. These nuanced signs led us to suspect an impairment of the urea cycle and ultimately allowed us to narrow down the diagnosis to LPI through biochemical and genetic investigations.

Conclusion: Nephrologists should consider LPI in the differential diagnosis, whenever a patient presents with mixed proteinuria, tubular dysfunction, and/or chronic kidney disease of unknown origin. In these circumstances, we suggest looking for other signs such as growth failure, signs and symptoms ascribed to urea-cycle impairment, pulmonary involvement, hepatosplenomegaly, and laboratory alterations such as pancytopenia, hyperferritinemia, lipid abnormalities, and elevated LDH.

Objective: The aim of the study was to compare the direct healthcare cost and outcomes of a multidisciplinary care (MDC) program versus usual care for patients with advanced chronic kidney disease (CKD) in Singapore.

Methods: A retrospective study of patients with an estimated glomerular filtration rate (eGFR) less than 20 mL/min/1.73 m2, attending the MDC program or the usual care clinic in a tertiary hospital from 2016 to 2019. The usual care group was matched to the MDC group using propensity score matching based on age, gender, baseline eGFR, and diabetes mellitus. The primary outcome was the rate of emergent long-term kidney replacement therapy (KRT) initiation and the direct healthcare cost incurred from eGFR for less than 20 mL/min/1.73 m2 for the initiation of long-term KRT.

Results: There were 280 patients in each group. The MDC group had a lower rate of emergent KRT initiation than the usual care group (33.3 vs. 55.7 events per 100 patient-year, p = 0.003), shorter length of hospitalization stay (8.0 vs. 16.5 days per year, p = 0.004), lower number of emergency department visits (0.7 vs. 1.2 visits per year, p = 0.005), and higher number of renal clinic visits (14.5 vs. 13.0 visits per year, p = 0.009). The healthcare cost was lower in the MDC group than in the usual care group (SGD USD 18,408.83 (USD 13,664.51) vs. SGD USD 28,734.43 (USD 21,329.00) per patient-year, p = 0.016).

Conclusion: The MDC program for patients with advanced CKD in Singapore was associated with lower rate of emergent KRT initiation, shorter hospitalization stay, lower number of emergency department visit, and lower healthcare cost.

Introduction: Managing dialysis at home requires the involvement of the patient in decisions, treatment, and their illness and health. Evidence-based person-centered care interventions focus on listening to the patient's narrative, establishing a partnership between patients and healthcare professionals, and documenting care and treatment in a shared health plan. Therefore, a person-centered care intervention is expected to enhance the patient's ability to manage dialysis at home. This study aimed to identify and map evidence for person-centered interventions and home-based dialysis for individuals with kidney failure.

Methods: A scoping review was conducted based on the approach of Arksey and O'Malley. A systematic search was carried out in Medline, CINAHL, and Scopus for articles in all languages and without time restrictions. Person-centered care interventions concerning home dialysis were included. Two independent researchers assessed the literature. Data were extracted using NVIVO, and a relational analytical framework was employed to synthesize the data.

Results: The search identified 9,443 articles, of which 16 met the inclusion criteria. A total of 13 person-centered care interventions were identified. Eight interventions aimed to involve the patient in the decision regarding the type of dialysis modality, with six interventions identified to involve the patient in treatment, illness, and health. Only one intervention was identified to involve the patient in the decisions that follow once the patient has commenced dialysis treatment. Five interventions showed a correlation between a person-centered care intervention and the number of patients in home dialysis.

Conclusion: There is a need for interventions for patients in home dialysis to be adapted to a more person-centered care approach, particularly regarding the involvement of the patient in their treatment, illness, and health, as well as the decisions that follow the initiation of dialysis treatment.

Background: Fabry disease is an inherited metabolic disease that is caused by an abnormal accumulation of sphingolipids, including globotriaosylceramide (Gb3), in lysosomes. Patients with Fabry disease have insufficient levels or no total activity of an enzyme called α-galactosidase A, which catalyzes the removal of terminal α-galactose saccharides from substrates such as Gb3.

Summary: Because of the monogenetic nature of Fabry disease, the levels of enzyme activity correlate with disease outcome in patients, and thus enable genotype-phenotype predictions in the disease. Although Fabry disease results from reduced α-galactosidase A activity in the lysosome, there are many different molecular mechanisms for the loss of α-galactosidase A activity in Fabry disease patients, so it is of utmost importance to understand the journey and maturation of α-galactosidase A inside the cell. The proper synthesis of α-galactosidase A requires many steps, including the folding of the polypeptide, posttranslational modifications, trafficking of the enzyme to the lysosome, and substrate binding. Furthermore, researchers and clinicians benefit from extensive clinical data, with over 1,000 different mutations identified in patients, many of which are investigated by researchers. Finally, the availability of a pharmacological chaperone, which enhances the enzymatic activity of many α-galactosidase A variants, allows us to understand the biology better.

Key messages: This review will focus on the molecular steps that must be precisely orchestrated to properly synthesize the α-galactosidase A enzyme, and how failures in different maturation steps of α-galactosidase A lead to Fabry disease. We also describe how different treatment options address the loss of α-galactosidase A activity in the lysosome of patients.

Introduction: There is limited evidence regarding collapsing focal segmental glomerulosclerosis (cFSGS) after kidney transplantation. The aim of this study was to clarify the clinicopathological character of cFSGS.

Methods: Forty-two biopsies from 35 patients with cFSGS were included in the study. The cFSGS variant was determined according to the Colombia classification. The scoring of arteriosclerosis was evaluated as a score of 0-3 on the basis of the intimal fibrous thickening divided by the media, and other histological scoring was evaluated using the Banff score. Biopsies with a sclerosis score ≥3/4 were excluded from the study. Multivariate analysis was performed by a forward selection method using covariates significantly associated with cFSGS biopsies.

Results: Of 42 biopsies diagnosed with FSGS, 19 (45.2%) biopsies were cFSGS and 23 (54.8%) were non-collapsing FSGS (ncFSGS). The cFSGS group had a longer time after transplantation, lower eGFR, higher urine protein levels, and higher systolic blood pressure (all statistically significant) compared with the ncFSGS group. The Banff aah, ci, and arteriosclerosis scores were significantly higher in the cFSGS group compared with the ncFSGS group. There were no significant differences in the donor age or arteriosclerosis in 1-h biopsies between groups. Multivariate analysis showed that the arteriosclerosis score and Banff ci score were significantly associated with cFSGS using covariates that were statistically significant-related factors including systolic blood pressure, eGFR, proteinuria, ci score, aah score, and arteriosclerosis score. Graft survival after the time of biopsy was significantly worse in the cFSGS group compared with the ncFSGS group.

Conclusion: Collapsing FSGS was poor prognostic factor for allograft survival. Arteriosclerosis and chronic interstitial fibrosis may be related to cFSGS after kidney transplantation.

Background: Fabry disease (FD) is a rare, X-linked lysosomal storage disorder that affects both males and females. It is caused by pathogenic variants in the gene that encodes the enzyme α-galactosidase A, GLA. The classic form of the disease begins in childhood, presenting with a range of signs and symptoms that can lead to severe complications such as stroke, as well as cardiac and renal failure. In the late-onset form, the disease appears in adulthood, often with signs of cardiac involvement.

Summary: The N215S (p.Asn215Ser) missense mutation represents the most common late-onset variant in European countries. In these patients, cardiac involvement is usually more prominent than extracardiac signs and symptoms, which is why this form is often referred to as a cardiac variant. Renal involvement in the N215S variant has historically been considered infrequent and relatively mild, contributing little to the overall disease burden of late-onset FD, as it has not been thoroughly investigated.

Key messages: In this review, we examine Fabry nephropathy in patients with the late-onset N215S variant, providing an insight into the clinical and histopathologic aspects of renal involvement in these individuals.

Background: Ferroptosis is a novel form of iron-dependent programmed cell death, characterized by lipid peroxidation and the accumulation of reactive oxygen species. Dysregulation of iron metabolism, lipid metabolism, or the antioxidant system can trigger this process. Emerging evidence suggests that ferroptosis is implicated in the pathogenesis and progression of various kidney diseases.

Summary: This review explores the pathophysiological mechanisms of ferroptosis, focusing on its role in cellular damage and disease progression in kidney diseases. The roles of iron homeostasis, lipid peroxidation, and antioxidant defenses in ferroptosis are discussed. Studies have demonstrated that inhibiting ferroptosis can protect against kidney injury, highlighting its potential as a therapeutic target. Additionally, current findings on ferroptosis-targeted therapies, including preclinical studies and potential clinical applications, are summarized.

Key messages: Ferroptosis plays a critical role in the development and progression of kidney diseases. Understanding the mechanisms governing ferroptosis and its relationship with kidney pathology provides a foundation for novel diagnostic and therapeutic strategies. Further research is needed to identify specific molecular mechanisms and advance clinical trials to translate ferroptosis-targeted therapies into practice, paving the way for innovative therapeutic interventions in kidney diseases.

Background: Hypertension (HTN) is a common side effect of tacrolimus (Tac), the first-line antirejection medication for kidney transplant recipients. The impact of immediate-release tacrolimus (Tac IR) dosed twice daily versus extended-release tacrolimus (Tac ER) dosed once daily on long-term blood pressure control in kidney transplant recipients remains understudied. This study aims to compare the use of Tac IR versus Tac ER in kidney transplant recipients and evaluate the effects of the different formulations on systolic blood pressure (SBP), diastolic blood pressure (DBP), and HTN crisis.

Methods: This retrospective cohort study at a single institution collected baseline characteristics, time-varying exposure to Tac IR versus Tac ER, SBP, DBP, HTN crisis, and confounders at each posttransplant visit. A marginal structural linear mixed-effects model was employed to analyze the longitudinal blood pressure control in kidney transplant recipients receiving Tac IR and Tac ER.

Results: The final analysis included 654 patients, with mean ages of 52.0 years for Tac IR and 50.3 years for Tac ER. Males constituted 56.7% in Tac IR and 55.0% in Tac ER. Notably, the black population had 2.44 times higher odds of receiving Tac ER after adjusting for the rest of the baseline characteristics. No difference was found between longitudinal SBP (p = 0.386, 95% CI: -1.00, 2.57) or DBP (p = 0.797, 95% CI: -1.38, 1.06).

Conclusion: Our study indicates that posttransplant patients taking Tac ER exhibit no difference in chronic SBP and DBP controls compared to Tac IR.