Clinical nephrology最新文献

Background: Roxadustat is used for treating chronic kidney disease (CKD) patients, particularly those on hemodialysis with comorbid cancer. Some studies suggest a link between roxadustat and cancer progression, but the mechanisms remain unclear, highlighting the need for further investigation into potential causal links.

Materials and methods: We employed a two-sample Mendelian randomization (MR) analysis to explore associations between genetic variations in Roxadustat targets and 14 cancer types. Single-nucleotide polymorphisms (SNPs) in the Egl-9 family hypoxia inducible factor 1 (EGLN1) and Egl-9 family hypoxia inducible factor 2 EGLN2 genes, related to hemoglobin levels, were chosen as instrumental variables. Analyses used inverse variance-weighted (IVW)-MR and summary data-based MR (SMR) approaches, assessing horizontal pleiotropy with Mendelian randomization Egger (MR-Egger) and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and using the heterogeneity in dependent instrumental variables (HEIDI) test for SMR.

Results: Summary statistics were derived from three UK studies involving 172,925 individuals. IVW-MR revealed a positive association between EGLN1 variants and breast cancer (OR = 1.644) and lung adenocarcinoma (OR = 2.117), while negative associations were found for malignant non-melanoma skin cancer and kidney cancer. SMR confirmed the links to breast cancer and a decrease in skin cancer risk. EGLN2 expression was positively associated with prostate and lung cancers and negatively with estrogen receptor (ER)- breast and brain cancers.

Conclusion: Our findings support a potential causal relationship between the inhibition of EGLN1 and EGLN2 and the development of specific cancer types.

This review analyzes the pivotal but underrecognized contribution of Thomas Willis (1621 - 1675) to the foundations of kidney function in the 17^th century. By comparing his early work De Urinis (1659), which interpreted urinary diagnosis through humoral traditions, with his subsequent Pharmaceutice Rationalis (1674 - 1675) we document a paradigm shift: progress from considering the kidney a passive filter to proposing it as an active regulatory organ that balanced urinary salts through tubular function. Building on the cardiac pump and blood circulation model of William Harvey and the tubular structure of the kidney of Lorenzo Bellini, Willis rejected the Galenic physiology that the kidney attracted blood because it was in its nature to do so in favor of a mechanical model of "straining or percolation" driven by the force of circulating blood. Willis also considered diabetes a blood disorder rather than a kidney disease, noting that diabetic urine differed from imbibed fluids being sweet "as it were imbued with Honey or Sugar". These conceptual advances - developed without microscopic evidence or chemical analysis - reveal a remarkable inductive reasoning. Documented by subsequent observations, Willis' work established three critical principles: the blood-clearing function of the kidney depends on circulatory dynamics, tubules modify urine composition, and urinary changes reflect systemic physiology rather than just renal pathology. His renal model, though incomplete, provided the first systematic framework for homeostasis that would be developed in the 19^th century. His writings clearly mark the initial but fundamental first steps in the evolution of our current understanding of kidney function.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and have become an essential part of therapy, but their use is associated with immune-related adverse events (irAE). Specifically, nephrotoxicity is well documented in adult populations but data regarding irAEs are limited in pediatric populations. This review examines the renal manifestations of ICIs and relevant clinical measures and treatments.

Materials and methods: A comprehensive review of existing literature was conducted to assess the incidence, pathophysiology, and management of ICI-associated renal injuries in pediatric and adult populations.

Results: The most common renal irAE associated with ICIs is acute kidney injury; however, ICIs have been implicated in transplant rejection and electrolyte disturbances including hyponatremia, hyperkalemia, hypophosphatemia, and metabolic acidosis. Pediatric ICI manifestation patterns are similar to those in adults, but research suggests earlier onset compared to adults. Though corticosteroids are the primary treatment for irAEs, standardized pediatric management guidelines require further improvement.

Conclusion: ICIs carry concerning risks in pediatric populations, yet research in this area is lacking. This warrants further research into the recognition, treatment, and prevention of renal irAEs, particularly for the improvement of long-term outcomes.

Background: In the United States (U.S.), economically disadvantaged populations have reduced access to subspecialty care. To improve accessibility to nephrology care early in the clinical course of chronic kidney disease (CKD), we designed a feasibility pilot study for electronic consults (eCons).

Materials and methods: This retrospective cohort study evaluated eCons referral patterns, patient demographics, comorbidities, and rates of in-person visits following eCons. Our suggested referral criteria included CKD stages 1 - 3a with a urine albumin-creatinine ratio (UACR) < 300 mg/g, resistant hypertension, abnormal kidney imaging or urine sediment, electrolyte abnormalities, and nephrolithiasis.

Results: A total of 103 patients completed eCons over a 12-month period. 98% self-identified as African Americans, and 2% as Caucasians. The rates of subsequent in-person visits for patients with CKD stages 2, 3a, 3b, 4, and 5 were 5/9 (56%), 8/28 (29%), 34/38 (90%), 11/14 (79%), and 9/9 (100%), respectively. Among the 103 patients, 40 (39%) had macroalbuminuria (UACR > 300 mg/g), and 51 (50%) had diabetes mellitus. The rates of subsequent in-person visits for patients with macroalbuminuria and diabetes mellitus were 87.5% and 76%, respectively. Patients with macroalbuminuria had greater odds of subsequent in-person visits than did those without macroalbuminuria, adjusted for age and sex (AOR, 6.15; 95% confidence interval (CI), 2.08 - 18.16; p = 0.001). Patients with diabetes mellitus were also more likely to have subsequent in-person visits than were those without diabetes mellitus (OR, 2.38; 95% CI, 1.02 - 5.57; p = 0.04).

Conclusion: Electronic consultations are beneficial in the early CKD stages and in patients without diabetes or macroalbuminuria. In addition, both macroalbuminuria and diabetes influence the need for subsequent in-person evaluation.

Background: Mood disorders are common among patients with end-stage renal disease (ESRD) undergoing dialysis, with anxiety and depressive disorders being the most prevalent. The association of anxiety symptoms with sociodemographic and dialysis-related factors is less well understood in dialysis patients. The level of anxiety experienced during individual peritoneal dialysis (PD) remains unclear. This study examined the frequency and severity of anxiety and the association of anxiety symptoms with selected demographic and dialysis-related variables in patients receiving peritoneal dialysis in Isfahan, Iran.

Materials and methods: A cross-sectional study was conducted on 85 PD patients referred to Al-Zahra and Khorshid centers between October 2022 and April 2023, who had been undergoing PD for at least 3 months. Patients completed the Beck Anxiety Inventory questionnaire, which assessed the presence and severity of anxiety symptoms.

Results: The overall mean anxiety score was 10.65 ± 10.04. Minimal anxiety was reported by 50.6% of participants, 25.9% experienced mild anxiety, 14.1% had moderate anxiety, and 9.4% reported severe anxiety. No significant associations were found between anxiety and demographic or PD-related factors (p > 0.05).

Conclusion: According to this study, 50.6% of our participants reported minimal anxiety, and 49.4% had mild to severe anxiety. Early diagnosis and management of mood disorders in ESRD patients are crucial to improve their quality of life and prevent adverse outcomes. These findings underscore the need to plan and implement screening programs for mood disorders among high-risk chronic kidney disease patients to ensure timely and appropriate management.

Backgrounds: The present study aimed to explore the causal association between body composition indexes and primary membranous nephropathy (PMN) from a genetic perspective.

Materials and methods: A bidirectional two-sample Mendelian randomization (MR) analysis was conducted in the present study. Genetic data were obtained from published genome-wide association studies on PMN (n = 7,979) and body composition indexes, including weight (n = 797,859), body mass index (n = 461,460), body fat percentage (n = 454,633), waist circumference (n = 568,740), hip circumference (n = 336,601), and basal metabolic rate (n = 454,874) in European populations. The inverse variance weighted (IVW) random-effects MR method was performed as the main analysis, with MR-Egger and weighted median methods used as supplemental methods. Several sensitivity analyses were used to examine the reliability of the findings.

Results: The MR analysis results showed that weight (MRC-IEU: odds ratio (OR) = 1.578, 95% confidence interval (CI) = 1.047 - 2.379, and IVW p = 0.029; Neale Lab: OR = 1.745, 95% CI = 1.204 - 2.529, and IVW p = 0.003), body fat percentage (OR = 2.487, 95% CI = 1.349 - 4.583, and IVW p = 0.003), waist circumference (Neale Lab: OR = 1.700, 95% CI = 1.042 - 2.774, and IVW p = 0.034; GIANT: OR = 1.915, 95% CI = 1.030 - 3.559, and IVW p = 0.040), and hip circumference (OR = 1.410, 95% CI = 1.021 - 1.948, and IVW p = 0.037) were causally related to an increased risk of PMN. Sensitivity analysis verified and indicated the robustness of these results. Reverse MR analysis indicated no causal relationship between PMN and the body composition indexes.

Conclusion: The present study demonstrated causal relationships between body composition indexes and PMN, suggesting the potential value of these factors in helping to understand PMN and develop intervention strategies.

Background: Autosomal recessive polycystic kidney disease (ARPKD) is a rare disorder mainly caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene. This study aimed to analyze the genotypes, clinical phenotypes, and their correlations of PKHD1 gene mutations in such patients.

Materials and methods: A retrospective analysis was conducted using the clinical data of 11 patients diagnosed with or suspected of having ARPKD from August 2019 to September 2024. The clinical phenotypes and laboratory evaluation results of PKHD1 gene mutations were analyzed. Whole exome sequencing and Sanger sequencing were used for the analysis of mutation gene loci and family verification.

Results: The average age of the 11 patients was 28.1 ± 8.3 years old, with 7 females (63.6%). All patients (100%) had heterozygous PKHD1 mutations, and the c.2507T>C (p.Val836Ala) variant site was detected in 3 patients (14.3%). The main clinical symptoms were chronic kidney disease stage 1 - 2 in 7/11 cases (63.6%), and systemic hypertension in 6/11 cases (54.5%). Additionally, missense mutations were present on the majority of alleles (11/19), and 7 (36.8%) were novel variant sites.

Conclusion: The clinical phenotypes of patients with ARPKD were highly variable. For suspected cases, genetic testing should be conducted as early as possible for diagnosis, which is of great significance for the prognosis of patients and genetic counseling of their families.

Background: Renal interstitial inflammation (RII) is a frequent pathological feature in IgA nephropathy (IgAN), but its prognostic value remains uncertain. This study investigated the effect of RII on renal outcomes and developed a machine learning-based model incorporating RII for individualized prognosis.

Materials and methods: We retrospectively analyzed 540 IgAN patients diagnosed by renal biopsy at Zhongda Hospital and the First People's Hospital of Huai'an (2012 - 2023). The endpoint was a ≥ 50% decline in eGFR or end-stage renal disease, with follow-up to June 2024. Predictors included demographics, clinical/laboratory parameters (blood tests, serum biochemistry, 24-hour urine protein), and histopathology (Oxford MEST-C and RII scores). Variable selection used random forest, extreme gradient boosting, artificial neural networks, and LASSO regression. A logistic regression model and nomogram were developed and validated internally and externally.

Results: Of 540 patients (mean age 40.8 years; 50.6% male), 273 were in the derivation, 117 in the internal validation, and 150 in the external validation cohort. Patients with progression had lower baseline serum albumin (p = 0.023), lower estimated glomerular filtration rate (eGFR) (p < 0.001), and higher systolic blood pressure (SBP) and proteinuria (all p < 0.001). In multivariate analysis, RIIS1 (odds ratio (OR) 4.16, 95% CI 0.91 - 24.51, p = 0.048) and RIIS2 (OR 6.80, 95% CI 0.98 - 54.49, p = 0.039) independently predicted adverse outcomes. Use of renin-angiotensin-aldosterone system inhibitors was protective (OR 0.34, p = 0.026), while higher SBP increased risk (OR 1.04, p < 0.001). The nomogram achieved C-indices of 0.91, 0.90, and 0.92 in the derivation, internal, and external validation cohorts, respectively.

Conclusion: RII is an independent predictor of renal progression in IgAN. The developed model and nomogram may assist in individualized risk stratification.

Background: Refractory hypertension is a common and serious complication in patients with end-stage renal disease (ESRD), and conventional medications and catheter-based renal denervation (RDN) have limited efficacy in some patients. Laparoscopic-based renal sympathetic nerve denervation (L-RDN), an emerging noninvasive treatment, may offer new treatment options for selected patients by directly exposing the outer surface of the renal artery for ablation.

Materials and methods: This study enrolled 3 patients with ESRD and refractory hypertension who underwent L-RDN. Postoperatively, blood pressure was monitored to assess the changes before and after the procedure, as well as to evaluate the feasibility, safety, and short-term efficacy of this intervention.

Results: All 3 patients successfully underwent surgical treatment. Postoperative follow-up revealed that 2 patients completed a full 12-month follow-up, while the remaining patient completed a 6-month interim follow-up. Blood pressure levels in all patients were significantly reduced compared to preoperative levels 1 week after surgery and remained relatively stable throughout the follow-up period. Specifically, the systolic and diastolic blood pressures of the 3 patients decreased by an average of 25 and 21 mmHg, respectively, at 1 week postoperatively, and no significant rebound or fluctuation in blood pressure was observed during the follow-up period. One patient developed a lymphatic fistula 1 month after surgery, which was successfully managed with conservative treatment, while the other 2 patients experienced no significant postoperative complications. This result suggests that the procedure is effective in significantly reducing blood pressure in the short term and may contribute to long-term blood pressure stabilization.

Conclusion: This case series demonstrates that L-RDN may represent a safe and effective therapeutic modality, offering a potential alternative treatment option for patients with vascular pathologies or contraindications to intravascular interventions. However, given the limited sample size, further prospective studies are necessary to validate its long-term efficacy and safety.