Journal of Nephrology最新文献

Background: It is important to learn more about the prevalence, severity and characteristics (i.e., which cognitive abilities are especially affected) of cognitive impairment in kidney transplant patients. Furthermore, the impact of living vs. deceased donor renal transplantation on cognitive outcome in this patient group needs further studies.

Methods: Fifty-nine patients (43 men, age 55 ± 13 years) who received a deceased donor or living donor kidney transplant, completed a comprehensive neuropsychological test assessment. Neuropsychological tests explored the cognitive domains of verbal and visual memory, attention, and executive functions.

Results: Fifteen percent  of the patients had mild, 25% moderate, and 15% severe cognitive impairment. The level of domain-specific cognitive deficit differed between verbal memory, attention, and executive functions (χ²(2) = 7.11, p = 0.029). On average, patients showed the highest deficit in executive functions, and the lowest deficit in verbal memory. Patients who received a kidney graft from a deceased donor were more likely to have a cognitive impairment than those who received a kidney graft from a living donor (OR = 3.03, 95% CI [0.99,9.32], Wald χ²₍₁₎ = 3.74, p = 0.053). This effect was independent of time on dialysis as well as of creatinine levels, or creatinine clearance.

Conclusions: Our results show that in kidney transplant patients with cognitive impairment, the cognitive domain of executive functions is the most affected one. This might be detrimental for quality of life. The fact that patients who received living donor kidneys seem to do better in terms of cognition than patients with deceased donor kidneys deserves more attention in future research.

Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) effective in non- small cell lung cancer (NSCLC) with EGFR mutations. Since the drug is primally eliminated by the fecal route no dose adjustment is needed in patient with chronic-kidney disease (CKD); despite this there is limited data about its safety in cancer patients with end-stage renal disease (ESRD). Herein, we reported a case report of a 77-year-old woman, diagnosed in 2018 with lung adenocarcinoma EGFR mutated with lymph nodal and cerebral metastasis, who started Osimertinib 80 mg/day. She under- went 41 cycles of therapy with no Osimertinib interruptions, no severe toxicities and obtaining complete radiological response. We conclude that Osimertinib has an acceptable safety profile also in cancer patients with ESRD not undergoing hemodialysis (HD).

This review discusses genetic variants associated with cognitive dysfunction in chronic kidney disease (CKD) patients, emphasising the limited research in this area. Four studies have explored genetic markers of cognitive dysfunction in CKD, with findings suggesting shared genetic biomarkers between Alzheimer's Disease and CKD.Because of the limited specific research on genetic markers of cognitive dysfunction and dementia in CKD, we extracted data from the current literature studies on genetic markers in the general population that may be relevant to the CKD population. These markers include Apolipoprotein E (APOE), Complement Receptor 1 (CR1), Clusterin (CLU), Sortilin-related receptor 1 (SORL1), Catechol-O-methyltransferase (COMT), and Brain-derived neurotrophic factor (BDNF), all of which are known to be associated with cognitive dysfunction and dementia in other populations. These genes play various roles in lipid metabolism, inflammation, Aβ clearance, and neuronal function, making them potential candidates for studying cognitive decline in CKD patients.CKD-specific research is needed to understand the role of these genetic markers in CKD-related cognitive dysfunction. Investigating how these genes influence cognitive decline in CKD patients could provide valuable insights into early detection, targeted interventions, and personalised treatment strategies. Overall, genetic studies to enhance our understanding and management of cognitive dysfunction in CKD represent a clinical research priority in this population.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disorder that may progress to kidney failure, accounting for 5-10% of all patients with end-stage kidney disease (ESKD). Clinical data, as well as molecular genetics and advanced imaging techniques have provided surrogate prognostic biomarkers to predict rapid decline in kidney function, nonetheless enhanced tools for assessing prognosis for ADPKD are still needed. The aim of this study was to analyze specific microRNAs involved in the pathogenesis of ADPKD and in the development of renal fibrosis, evaluating their potential role as predictors of renal function loss.

Methods: We evaluated kidney function by estimated glomerular filtration rate (eGFR) in 32 ADPKD patients in different stages of kidney disease at T0 and after a 24-month follow up (T1). Patients were divided into two groups: Rapid disease progression ([RP], n 15) and Non-rapid disease progression ([NRP], n 17), according to the Mayo Clinic classification criteria. At T0, ADPKD patients underwent plasma sampling for quantitative analysis of h-miR-17-5p, h-miR-21-5p and h-miR-199a-5p microRNA expression, using the quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) method and a 3 T magnetic resonance imaging (MRI), using an advanced MRI imaging protocol, for the quantification of total kidney volume (TKV), total perfusion volume (TPV) and total fibrotic volume (TFV).

Results: The expression of h-miR17-5p was higher (p < 0.05) in ADPKD patients with rapid disease progression. h-miR-17-5p, h-miR-21-5p and h-mir-199-5p showed a positive and significant correlation with the eGFR slope (mL/min/1.73 m²/year) (p < 0.05) but not with the eGFR at both T0 and T1. Both total fibrotic volume (cm³) and height-adjusted total fibrotic volume (cm³/m) were positively and significantly correlated to h-miR 21-5p and h-miR 199-5p (p < 0.05), but not to total kidney volume (cm³) and height-adjusted total kidney volume (cm³/m).

Conclusions: The microRNAs we studied were associated with fibrosis and renal damage, suggesting their possible role as biomarkers able to identify ADPKD patients at high risk of disease progression regardless of the degree of kidney function, and therefore suitable for medical therapy, and may help uncovering new molecular mechanisms underlying cystogenesis.

Background: Cystinuria is a rare genetic disease characterized by impaired tubular transport of cystine. Clinical features of cystinuria mainly include nephrolithiasis and its complications, although cystinuric patients may present with other comorbidities. There are currently no data on bone features of patients with cystinuria. Our aim is to characterize bone mineral density (BMD) in cystinuria.

Methods: Our study included adult cystinuric patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m² followed at 3 specialized outpatient clinics in Italy (Rome, Naples and Verona). Markers of bone turnover were analyzed in a centralized laboratory. Clinical, biochemical and dual-energy X-ray absorptiometry (DEXA) data were collected from September 2021 to December 2022. Linear regression models were used to evaluate statistically significant deviations from zero of Z-scores.

Results: Twenty-seven patients were included in the study. Mean (SD) age was 37 (15) years, 41% were women. Mean estimated glomerular filtration rate was 99 mL/min/1.73 m². Serum parameters associated with bone turnover (parathyroid hormone, FGF23, calcium and phosphate) were all in the normal range, with only 4 patients showing mild hypophosphatemia. Prevalence of low bone mineral density, defined as Z-score ≤  - 2 at any site, was 15%. Average Z-scores were negative across most sites.

Conclusions: Our study suggests that cystinuric patients have lower bone mineral density compared with individuals of the same sex and age, even when their kidney function is normal.

Background: Chronic kidney disease (CKD) is associated with increased mortality. Individual mortality prediction could be of interest to improve individual clinical outcomes. Using an independent regional dataset, the aim of the present study was to externally validate the recently published 2-year all-cause mortality prediction tool developed using machine learning.

Methods: A validation dataset of stage 4 or 5 CKD outpatients was used. External validation performance of the prediction tool at the optimal cutoff-point was assessed by the area under the receiver operating characteristic curve (AUC-ROC), accuracy, sensitivity, and specificity. A survival analysis was then performed using the Kaplan-Meier method.

Results: Data of 527 outpatients with stage 4 or 5 CKD were analyzed. During the 2 years of follow-up, 91 patients died and 436 survived. Compared to the learning dataset, patients in the validation dataset were significantly younger, and the ratio of deceased patients in the validation dataset was significantly lower. The performance of the prediction tool at the optimal cutoff-point was: AUC-ROC = 0.72, accuracy = 63.6%, sensitivity = 72.5%, and specificity = 61.7%. The survival curves of the predicted survived and the predicted deceased groups were significantly different (p < 0.001).

Conclusion: The 2-year all-cause mortality prediction tool for patients with stage 4 or 5 CKD showed satisfactory discriminatory capacity with emphasis on sensitivity. The proposed prediction tool appears to be of clinical interest for further development.

Background: Chronic kidney disease (CKD) may affect women of childbearing age and may lead to substantial maternal and foetal morbidity and mortality in pregnancy. There is a lack of prediction models for  preeclampsia and adverse pregnancy outcomes in pregnant women with CKD. This study aimed to create a prediction nomogram for these issues.

Methods: This retrospective cohort study included clinical data from 627 women with CKD and their 627 pregnancies at Peking University First Hospital between January 1, 2009, and December 31, 2022. Multivariate logistic regression analysis was conducted to identify independent prognostic factors and develop a nomogram for predicting the occurrence of preeclampsia. The identified risk factors were utilised to construct the nomogram, which was subsequently internally validated using receiver operating characteristic (ROC) analysis and calibration curve assessment.

Results: According to our multivariate analysis, age, blood urea nitrogen (BUN), serum creatinine (Scr), mean arterial pressure (MAP), 24-h proteinuria, and CKD stage were identified as predictors of preeclampsia. Additionally, Scr, MAP, BUN, and 24-h proteinuria were found to be predictors of adverse pregnancy outcomes. The nomogram for predicting preeclampsia had an area under the ROC curve of 0.910, while the nomogram for predicting adverse pregnancy outcomes had an area under the ROC curve of 0.906. Both models demonstrated excellent discriminatory ability.

Conclusions: A nomogram based on 24-h proteinuria, serum creatinine, serum urea and age, and MAP allows predicting the occurrence of preeclampsia and other adverse pregnancy-related outcomes in CKD patients.

Diabetic kidney disease (DKD) affects 30-40% of all patients with diabetes and contributes significantly to the cardiovascular burden of chronic kidney disease (CKD). Despite the availability of evidence-based medications like finerenone and simple screening tests such as Urinary Albumin-to-Creatinine Ratio (UACR), more resources are still needed to care for DKD patients. Physician Associates (PAs) play a crucial role in the multidisciplinary team responsible for DKD diagnosis, monitoring, and management. A nonsteroidal mineralocorticoid receptor antagonist, namely finerenone, was approved by the FDA in adults with CKD associated with type 2 diabetes to reduce the risk of renal and cardiovascular outcomes. Finerenone is considered among the pillars of care for DKD, furthermore, the addition of finerenone in combination with renin-angiotensin system inhibitors and/or other renal protective medications may offer additional benefits. Primary care providers prescribe finerenone less frequently than specialized care providers, indicating a need to empower physician associates in medication prescription and other renal protection strategies. As part of a multidisciplinary team, physician associates can play an important role in evaluating risk factors that contribute to heart disease and metabolic health. They can also monitor not only kidney function by ordering tests, such as serum creatinine and urinary albumin-to-creatinine ratio every 3-12 months, but also serum potassium levels. Additionally, physician associates can encourage patients to take responsibility for their health by regularly monitoring their blood pressure, blood glucose levels, and body weight. With early detection and management, kidney failure and cardiovascular events may be preventable. Specialized physician associates also play a significant role in the comprehensive care of DKD patients, especially in the later stages. DKD care can be hindered by numerous factors such as lack of patient engagement during counseling, cost disparities, and a complex referral system that requires multidisciplinary guidelines to improve professional communication. It is necessary to re-envision the physician associates' role in primary care and empower them in goal-directed therapies.

Background: Chronic kidney disease (CKD) is commonly associated with psychosocial problems, especially depression, contributing to poor overall outcomes. Depression has not been given adequate priority in the management of CKD patients despite its significant adverse impact on all major outcomes. This systematic review and meta-analysis determined the pooled prevalence of clinical depression in the global CKD population and sub-populations.

Methods: PubMed, African Journals Online (AJOL), and EMBASE were systematically searched to identify published articles with relevant data. The pooled prevalence of clinical depression in the global CKD population was determined using random effects meta-analytic techniques. The study protocol was registered with PROSPERO (CRD42022382708).

Results: Sixty-five articles were included in this review, comprising 80,932 individuals with CKD from 27 countries. The participants' mean age ranged from 11.0 to 76.3 years. Most (70.4%) of the studies had medium methodological quality. The overall pooled prevalence of depression was 26.5% (95% CI 23.1-30.1%). Studies using the Diagnostic Statistical Manual for Mental Diseases (DSM) and International Classification of Disease (ICD) returned a pooled prevalence of 25.5% and 39.6%, respectively, p = 0.03. There was a significant difference in the pooled prevalence across regions; p = 0.002.The prevalence of depression was higher among individuals on chronic hemodialysis compared to pre-dialysis patients (29.9% versus 18.5%; p = 0.01) and among those on hemodialysis compared to peritoneal dialysis (30.6% versus 20.4%; p = 0.04). There was no significant difference between adults and children (26.8% versus 15.9%, p = 0.21). There was an increasing temporal trend in depression prevalence, though this did not achieve statistical significance (p = 0.16).

Conclusion: Depression is common in patients with CKD. The findings of this study highlight the need for clinicians to make efforts to evaluate individuals with CKD for depression, especially those with advanced stages of the disease.