Nephron最新文献

Introduction: In patients with chronic kidney disease (CKD) of diverse causes, obesity and metabolic syndrome (MS) accelerate disease progression. Therapeutic exercise could be effective in treating obesity and MS in patients with CKD. However, the evidence in this area is limited. The aim of this research was to evaluate the effect of an individualized exercise program on major metabolic and renal outcomes in patients with CKD, obesity, and MS.

Methods: This was an interventional exploratory study that included patients with established CKD - estimated glomerular filtration rate (GFR) ≥30 mL/min, obesity, and MS treated by therapeutic exercise (aerobic and resistance) for 6 months. We evaluated changes in renal outcomes - measured glomerular filtration rate (mGFR) with iohexol-DBS and albuminuria, and metabolic outcomes - weight and MS traits. Biochemical, anthropometric, and renal function were performed every 3 months.

Results: Forty patients were evaluated. All were overweight or obese, mGFR was 58 ± 20 mL/min, and the urine albumin-creatinine ratio (UACR) was 256 mg/g [IQR: 38-774]. Based on weight reduction (>5%), patients were classified as "responders" (n = 30) and "nonresponders" (n = 10). Responders had a major reduction in body mass index from 35 ± 4 to 31 ± 4 kg/m2 (p < 0.001), triglycerides, HbA1c, systolic and diastolic blood pressure, and UACR from 222 [20-610] to 89 [17-413] mg/g (p < 0.01), whereas mGFR diminished (≥7%) in half of them and remained stable in the other half. Nonresponders experienced no changes. No major side effects were observed.

Conclusion: In patients with CKD, obesity, and MS, exercise is an effective treatment to reduce weight, MS traits, and albuminuria. Changes in mGFR are heterogeneous. Understanding the impact of weight reduction on GFR changes is crucial in CKD. The role of exercise in nephrological care deserves further attention. The study trial registration number is NCT06576518.

Background: The management of kidney failure in older adults has increasingly adopted patient-centered approaches, with conservative kidney management (CKM) recognized as a valid alternative to dialysis in selected cases. Structured counseling is commonly used to support informed decision-making and align treatment with patient goals. However, evidence on its structured application and impact on treatment decisions in this population remains limited. This study evaluates the clinical characteristics, treatment choices, decision stability, and outcomes of older adults with kidney failure who, after a structured counseling session ("Welcome Meeting") at La Paz University Hospital, chose either CKM or dialysis.

Methods: This prospective, observational, single-center cohort study (April 2015 to December 2019) included participants aged >75 years with CKD-EPI <12 mL/min (<15 mL/min for those with diabetes), Charlson Comorbidity Index >5, and functional impairment (Barthel Index <95 or Palliative Performance Scale <60). All participants received a structured counseling session to support treatment decision-making. Participants then chose either dialysis or CKM. Predictors included treatment choice, clinical outcomes, symptom burden, and healthcare utilization. Decision stability was defined as sustained adherence to the initial treatment choice over the course of follow-up. Analyses were adjusted for potential confounders including age, sex, comorbidity, and functional status. Data were analyzed using SPSS version 27.

Results: A total of 103 participants were included (mean age: 84.9 ± 5.5 years); 72% chose CKM and 28% opted for dialysis. CKM participants were older, more often female (p = 0.009), and had greater functional and cognitive impairment (p < 0.001). They also reported more weakness or lack of energy (p = 0.03), constipation (p = 0.03), and poor mobility (p < 0.001) at baseline. At the standardized follow-up assessment, depressive symptoms measured with the IPOS-Renal scale showed a significant reduction in the dialysis group (p = 0.043), while vomiting (p = 0.021) and sore or dry mouth (p = 0.049) increased significantly in the CKM group. Healthcare utilization was higher among dialysis participants. Of the 69 deaths, 65 occurred in the CKM group. Decision stability revealed only 5% of CKM participants switching later to dialysis, with no treatment transitions observed in the dialysis group.

Conclusion: After a structured counseling session, elderly kidney failure participants who chose CKM were older, female, and presented greater cognitive and functional impairment. This approach supported informed choices and was associated with a high adherence to the initial treatment decision. Further studies are needed to expand this line of research.

Introduction: The number of spousal donor transplantation (SDT) has increased since the early 1990s. Although the SDT is performed successfully today, several concerns remain regarding compatibility. In particular, in husband-to-wife donations, donor-specific antibodies (DSAs) positivity may develop as a consequence of previous pregnancies, thereby posing a risk to graft survival. However, data on outcomes in recipients with a history of pregnancy and the development of DSA are limited. In this study, we aimed to compare the outcomes of transplantation between high-risk spouses and transplantation from living donors.

Methods: This study was conducted in our nephrology and transplantation department. It involved 59 spousal donors and 72 living-related donors with DSAs who were older than >18 years of age. We evaluated the consecutive patients who had kidney transplantation between 2010 and 2020.

Results: We analyzed data from 59 SDTs with 72 living-related donor transplants (LRDTs) with DSA positivity. Within the first year after transplantation, the acute rejection rate was highest in the husband-to-wife (H-to-W) group (p = 0.01). Compared with LRDT, H-to-W transplants were associated with an increased risk of acute rejection (OR [95% CI]: 4.231 [1.122-15.957], p = 0.03). Cox regression analysis demonstrated a higher risk of rejection in kidney transplants from H to W within the first year of kidney transplantation (HR: 3.734 [95% CI: 1.087-12.825], p = 0.03). There was no increase in creatinine doubling time between groups and no increase in risk of rejection in 5 years. During the follow-up period, graft loss was reported in 3 patients, comprising 2 in the LRDT group and 1 in the W-to-H group.

Conclusion: SDT, particularly when DSA has developed, appears to be associated with a higher risk of rejection during the first year compared with LRDT with similar DSA. Nevertheless, similar graft survival suggests that H-to-W spousal transplants appear to be safe in the long term.

Introduction: Type IV collagen trimers are major structural components of the kidney glomeruli and tubules. Several loss-of-function COL4A1 and COL4A2 variants have been reported to cause cerebral small vessel disease. However, there is little evidence to suggest that loss-of-function variants in these genes can cause kidney disease.

Case presentation: Here we report a case of a patient with thin basement membrane nephropathy and chronic kidney disease (CKD) who was found to bear a 1.9 Mb heterozygous contiguous gene deletion of chromosome 13q33.3-q34 that includes COL4A1 and a large region of COL4A2.

Conclusion: We propose that haploid expression of COL4A1 in combination with COL4A2 can lead to thin basement membrane nephropathy and CKD.

Introduction: Choosing the treatment for kidney failure, whether dialysis or conservative kidney management, is challenging. Many adults may experience regret about this decision, leading to poor quality of life. This review aimed to determine the proportion of patients who report decisional regret after making treatment choices for kidney failure, as well as to identify the factors that contribute to it.

Methods: This systematic review was conducted in accordance with PRISMA guidelines. A comprehensive search was performed through the databases PubMed, Web of Science, Scopus, APA PsycInfo, and through websites. The search strategy included terms of three main categories: adults with kidney failure or estimated glomerular filtration rate less than 30 mL/min/1.73 m2, kidney failure treatment, and decisional regret.

Results: Studies examining decisional regret in adults undergoing kidney replacement therapy, those in the pre-dialysis phase, or those receiving conservative kidney management were included. Initially, 1,712 articles were found by the reported research, and 22 of them were selected. The proportion of regret ranged from none to 62% and the factors most related to it were the lack of information, lack of patient autonomy, social and physical burden, and decisional conflict.

Conclusions: Decisional regret is a common experience among adults facing treatment choices for kidney failure, particularly when patient autonomy is compromised, or information is inadequate. Regret is also associated with decisional conflict, and with emotional, social and physical burden, impacting quality of life. Effective communication between healthcare professionals and patients plays a vital role in reducing decisional regret, leading to improved outcomes and greater patient satisfaction. Additionally, practical tools such decision aids can enhance shared decision-making and empower patients to make informed and autonomous choices.

Background: There are considerable sex and gender differences in the epidemiology of chronic kidney disease (CKD), with CKD stage 3, defined as a glomerular filtration rate (GFR) below 60, being more prevalent in women. This raises questions about whether sex differences in age-related GFR decline contribute to this paradox. Only a few studies have investigated this issue, and most of these studies used estimated GFR (eGFR) based on creatinine (eGFRcrea) or cystatin C.

Summary: This article reviews studies examining age-related GFR decline in men and women from the general population. The conflicting findings on sex differences in GFR decline are likely influenced by variations in study populations, including differences in comorbidities, as well as the methods used to assess GFR. Further research is essential to accurately address trajectories of GFR decline in men and women.

Key messages: Sex and gender differences in GFR levels and age-related GFR decline rates may influence the observed differences in CKD prevalence between men and women. Possible differences in age-related GFR decline between men and women may stem from a combination of biological factors, including sex hormones, different methods to assess GFR, and differences in the prevalence and impact of risk factors. Current eGFR equations may not accurately capture sex differences in measured GFR decline. Further research is needed to better understand these differences and their clinical implications.

Introduction: Mitophagy is central to acute kidney injury (AKI) pathogenesis. Elucidating its molecular interplay with AKI is crucial for novel therapeutics.

Methods: This study is based on transcriptome sequencing combined with single-cell sequencing and applies bioinformatics analysis. Finally, it is verified by in vitro, in vivo, and clinical specimen experiments.

Results: In transcriptome analysis, combining protein-protein interaction mapping with machine intelligence algorithms, we screened out two mitophagy-related differentially expressed genes (MitoDEGs), solute carrier family 3 member 2 (SLC3A2) and thioredoxin (TXN). The immunological analysis revealed a notable rise in monocyte infiltration in the immune microenvironment of ischemia-reperfusion injury (IRI)-AKI. Spearman analysis indicated hub MitoDEGs were positively correlated with pro-inflammatory immune cell infiltration and negatively correlated with anti-inflammatory or regulatory immune cell infiltration. Based on the highest binding score, 506-26-3 CTD (gamma-linolenic acid) was determined to be the top promising therapeutic candidate. At the single-cell level, hub MitoDEGs were mainly expressed in proximal tubular. In cell experiments, mitophagy was inhibited after hypoxia-reoxygenation, SLC3A2 matched earlier results, while TXN was contrary to the previous analysis results. In the IRI-AKI rat experiments, the findings regarding hub MitoDEGs aligned with our prior analysis, revealing a decrease in the expression of genes associated with mitophagy. Consequently, we directed our attention to the expression levels of SLC3A2 in clinical cases of AKI, where we observed a notable increase.

Conclusion: Our research indicates that SLC3A2 could be a crucial target for enhancing IRI-AKI through the modulation of the mitophagy pathway.

Background: Estimated glomerular filtration rate (eGFR) and proteinuria are the gold-standard markers for kidney function used traditionally to assess kidney outcomes. Increased evidence of tubule involvement in nearly all causes of chronic kidney disease (CKD) warrants exploring the association between markers of tubular function with clinical outcomes in patients with CKD.

Methods: We conducted a single-center retrospective cohort study in 626 patients with eGFR <60 mL/min/1.73 m2. We examined the association between spot urine-to-plasma (U/P) urea and the incidence of kidney failure, all-cause death, and their composite outcome using the Kaplan-Meier method and multivariable-adjusted Cox proportional hazard models.

Results: Our cohort predominantly consisted of males (96%) with a mean ± standard deviation age of 67.4 ± 10.8 years and eGFR of 23.6 ± 10.5 mL/min/1.73 m2. There were 448 composite outcome events (event rate: 159/1,000 patient-years; 95% confidence interval [CI]: 145-175) over a median follow-up of 4.5 years. Lower U/P urea was associated with a higher risk of the composite outcome in unadjusted (hazard ratio and 95% CI for 1 log-unit lower U/P urea: 1.98 [1.73-2.26], p < 0.001) and after multivariable adjustment (1.67 [1.37-2.07], p < 001). Associations were similar for kidney failure and for all-cause death.

Conclusion: Lower U/P urea, a marker of tubular dysfunction, is associated with a higher risk of adverse clinical outcomes in patients with moderate and advanced CKD, independent of eGFR and proteinuria.

Introduction: T-cell receptor αβ+CD4-CD8- (double-negative) T cells (DNT) exist as a small population of lymphocytes in the peripheral blood of healthy individuals, but have been reported to be increased in autoimmune lymphoproliferative syndrome (ALPS) and other collagen diseases, such as systemic lupus erythematosus (SLE), and to be involved in disease activity. However, there are no reports on their relationship with histological classification of lupus nephritis, influencing the management of SLE.

Methods: The study included 15 patients with SLE who underwent kidney biopsy for suspected lupus nephritis at Toranomon Hospital from June 2014 to March 2019 and also had their peripheral DNT cell levels measured. We defined high DNT as more than 1.5% DNT among peripheral blood lymphocytes, in accordance with the ALPS diagnostic criteria, and divided patients into a high and low DNT group.

Results: In the 15 cases analyzed, mild glomerular lesions tended to be more common in patients in the high DNT group than those in the low group (60% vs. 10%, respectively; p = 0.077, Fisher's exact test), as did moderate to severe leukocytic inflammation in the interstitium (100% vs. 20%, respectively; p = 0.004, Fisher's exact test).

Conclusions: Elevated peripheral DNT cell levels may be associated with mild glomerular lesions but moderate to severe interstitial inflammation in SLE patients. A prospective clinical study with a larger patient cohort is warranted to validate this possibility and investigate its potential causality.