Nephron最新文献

Background: The lysosomal autophagic pathway plays a fundamental role in cellular and tissue homeostasis, and its deregulation is linked to human pathologies including kidney diseases. Autophagy can randomly degrade cytoplasmic components in a nonselective manner commonly referred to as bulk autophagy. In contrast, selective forms of autophagy specifically target cytoplasmic structures such as organelles and protein aggregates, thereby being important for cellular quality control and organelle homeostasis.

Summary: Research during the past decades has begun to elucidate the role of selective autophagy in kidney physiology and kidney diseases.

Key messages: In this review, we will summarize the knowledge on lipophagy and mitophagy, two forms of selective autophagy important in renal epithelium homeostasis, and discuss how their deregulations contribute to renal disease progression.

Diabetic kidney disease is the most common driver of chronic kidney disease (CKD)-associated mortality and kidney replacement therapy. Despite recent therapeutic advances (sodium glucose co-transporter 2 [SGLT2] inhibitors, finerenone), the residual kidney and mortality risk remains high for patients already diagnosed of having CKD (i.e., estimated glomerular filtration rate <60 mL/min/1.73 m2 or urinary albumin:creatinine ratio >30 mg/g). The challenge for the near future is to identify patients at higher risk of developing CKD to initiate therapy before CKD develops (primary prevention of CKD) and to identify patients with CKD and high risk of progression or death, in order to intensify therapy. We now discuss recent advances in biomarkers that may contribute to the identification of such high-risk individuals for clinical trials of novel primary prevention or treatment approaches for CKD. The most advanced biomarker from a clinical development point of view is the urinary peptidomics classifier CKD273, that integrates prognostic information from 273 urinary peptides and identifies high-risk individuals before CKD develops.

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.

Background: Estimated GFR (eGFR) has shown poor agreement with measured GFR (mGFR) in several populations. We investigated the impact of age and body composition on the accuracy and precision of eGFR in heart transplant (HTx) recipients.

Methods: In a longitudinal, observational, retrospective study design, patients receiving first-time HTx with at least one registered mGFR value within 15 months after HTx and a corresponding plasma creatinine were included. GFR was measured by 51Cr-EDTA and eGFR calculated by creatinine-based CKD-EPI formula.

Results: A total of 150 patients with a total of 723 mGFR measurements were included. During the first year after HTx, mean weight increased by 4.2 kg (CI: 3.2 to 5.1) followed by an annual decrease of 0.35 kg/year (Cl: -0.05 to 0.74). mGFR increased by 7.5 mL/min (Cl: 3.2 to 11.8) the first year but was stable hereafter (0.0 mL/min/year; CI: -1.0 to 1.0). The initial weigh gain and increase in mGFR were most pronounced in patients <45 years. Neither eGFR adjusted nor unadjusted for BSA detected the initial increase in mGFR. At 1 year after HTx, limits of agreement on the Bland-Altman plot were -37.2 to 33.1 mL/min with a bias of -2.1 mL/min (Cl: -5.0 to 0.9). In patients <45 years, eGFR significantly overestimated mGFR by 7.1 mL/min (Cl: 1.0 to 13.2) and showed a significant lower precision than patients >45 years. There was no effect of BMI class, weight, BSA, or change in BMI class on the difference between eGFR and mGFR.

Conclusion: eGFR is, on average, accurate but imprecise in HTx patients. The agreement is affected by age but not body composition.

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.

Introduction: Acute renal infarction (ARI) is a relatively rare and underdiagnosed condition. Presenting symptoms are nonspecific, and imaging is the mainstay for diagnosis. This study attempts to characterize the profile of patients with ARI and identify possible risk factors.

Methods: All inpatients admitted with diagnosis of ARI between 2010 and 2022 were included in this single-center retrospective observational study. Patients with chronic renal infarction, iatrogenic causes, and without radiographic evidence of ARI were excluded. Clinical, laboratory, and radiological findings of patients were collected. Patients were grouped into three groups based on probable etiology: cardiovascular, hypercoagulable disorders, and idiopathic, and analyzed.

Results: Eighty-five patients were included. Mean age of patients was 61.6 ± 17.54 years. Cardiovascular group had the highest number of patients (49.4%) of which atrial fibrillation was the most common etiology (59.5%). Malignancy was the most common etiology in the hypercoagulable disorder group (69.3%). Patients in the idiopathic group were significantly younger and had higher mean body mass index than the other 2 groups at presentation. Smokers had 9 times higher risk of renal infarction in cardiovascular group and 1.7 times higher risk in hypercoagulable when compared to the idiopathic group. 48.2% of patients developed renal infarction though they were on antiplatelets/anticoagulants.

Conclusion: ARI is a rare and often underdiagnosed condition that can have residual renal dysfunction. It is important to consider ARI as a differential especially in young patients with risk factors even if they are on anticoagulation medication.

Introduction: Middle-aged and older individuals often face significant challenges in adopting digital health solutions, leading to a digital divide that hinders their ability to benefit from mobile health (mHealth) interventions. This study aimed to investigate the specific requirements of middle-aged and older patients with chronic kidney disease (CKD) for self-management through mobile health applications (mHealth apps), using the Kano model.

Methods: A multicenter cross-sectional survey was conducted from April to September 2023 in five hospitals across Sichuan, Shandong, Guangdong, and Shaanxi provinces in China. The Kano model was employed to analyze participants' preferences regarding mHealth apps for self-management.

Results: Out of 359 participants (57.1% men, predominantly aged 45-54), the study identified essential and desirable features for mHealth apps. Essential attributes include comprehensive CKD information and robust privacy protection. Key to enhancing user satisfaction is features like symptom and medication management, access to medical insurance information, and app interface simplicity. Additional attractive features for increasing app appeal include diet management, exercise guidance, and customizable text size.

Conclusion: This study identifies critical mHealth app features for self-management in middle-aged and older CKD patients, emphasizing the importance of user-centric design. The findings provide valuable insights for app developers to create tailored solutions that cater to the specific needs of this demographic, potentially enhancing their self-management capabilities.

Background: Diagnosing and monitoring kidney diseases traditionally rely on blood and urine analyses and invasive procedures such as kidney biopsies, the latter offering limited possibilities for longitudinal monitoring and a comprehensive understanding of disease dynamics. Current noninvasive methods lack specificity in capturing intrarenal molecular processes, hindering patient stratification and patient monitoring in clinical practice and clinical trials.

Summary: Molecular imaging enables noninvasive and quantitative assessment of physiological and pathological molecular processes. By using specific molecular probes and imaging technologies, e.g., magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, or ultrasound, molecular imaging allows the detection and longitudinal monitoring of disease activity with spatial and temporal resolution of different kidney diseases and disease-specific pathways. Several approaches have already shown promising results in kidneys and exploratory clinical studies, and validation is needed before implementation in clinical practice.

Key messages: Molecular imaging offers a noninvasive assessment of intrarenal molecular processes, overcoming the limitations of current diagnostic methods. It has the potential to serve as companion diagnostics, not only in clinical trials, aiding in patient stratification and treatment response assessment. By guiding therapeutic interventions, molecular imaging might contribute to the development of targeted therapies for kidney diseases.

Introduction: Previous randomized controlled trials have not demonstrated the benefits of renal artery stenting with respect to kidney function. However, these trials did not focus on patients with severely impaired kidney function caused by severe bilateral stenosis. Therefore, the efficacy of stenting in such patients remains unclear.

Case presentation: We report 4 cases of successful percutaneous transluminal renal angioplasty (PTRA) with severely impaired kidney function with rapid decline caused by bilateral atherosclerotic stenosis. The catheterization before irreversible parenchymal damages was useful in improving kidney function dramatically in these cases of severe bilateral renal artery stenosis. Furthermore, we examined the clinical characteristics of the 4 cases to identify the potential predictors of PTRA effectiveness. Notably, bilateral renal artery >90% stenosis, elevated plasma renin activity, estimated glomerular filtration rate <15 mL/min/1.73 m2 with an accelerated decline within 6 months before PTRA (>50 mL/min/1.73 m2/6 months), and resistance index (RI) <0.7 were identified as common findings.

Conclusion: PTRA should be considered a treatment strategy for patients with these features to preserve kidney function and avoid dialysis therapy.

Introduction: Previous randomized controlled trials have not demonstrated the benefits of renal artery stenting with respect to kidney function. However, these trials did not focus on patients with severely impaired kidney function caused by severe bilateral stenosis. Therefore, the efficacy of stenting in such patients remains unclear.

Case presentation: We report 4 cases of successful percutaneous transluminal renal angioplasty (PTRA) with severely impaired kidney function with rapid decline caused by bilateral atherosclerotic stenosis. The catheterization before irreversible parenchymal damages was useful in improving kidney function dramatically in these cases of severe bilateral renal artery stenosis. Furthermore, we examined the clinical characteristics of the 4 cases to identify the potential predictors of PTRA effectiveness. Notably, bilateral renal artery >90% stenosis, elevated plasma renin activity, estimated glomerular filtration rate <15 mL/min/1.73 m2 with an accelerated decline within 6 months before PTRA (>50 mL/min/1.73 m2/6 months), and resistance index (RI) <0.7 were identified as common findings.

Conclusion: PTRA should be considered a treatment strategy for patients with these features to preserve kidney function and avoid dialysis therapy.