Kidney & blood pressure research最新文献

Introduction: Hypertension (HTN) is a major cardiovascular disease that can cause and be worsened by renal damage and inflammation. We previously reported that renal lymphatic endothelial cells (LECs) increase in response to HTN and that augmenting lymphangiogenesis in the kidneys reduces blood pressure and renal pro-inflammatory immune cells in mice with various forms of HTN. Our aim was to evaluate the specific changes that renal LECs undergo in HTN.

Methods: We performed single-cell RNA sequencing. Using the angiotensin II-induced and salt-sensitive mouse models of HTN, we isolated renal CD31+ and podoplanin+ cells.

Results: Sequencing of these cells revealed three distinct cell types with unique expression profiles, including LECs. The number and transcriptional diversity of LECs increased in samples from mice with HTN, as demonstrated by 597 differentially expressed genes (p < 0.01), 274 significantly enriched pathways (p < 0.01), and 331 regulons with specific enrichment in HTN LECs. These changes demonstrate a profound inflammatory response in renal LECs in HTN, leading to an increase in genes and pathways associated with inflammation-driven growth and immune checkpoint activity in LECs.

Conclusion: These results reinforce and help to further explain the benefits of renal LECs and lymphangiogenesis in HTN.

Introduction: The prevalence of hypertension among patients with end-stage kidney disease (ESKD) undergoing hemodialysis (HD) ranges from 72 to 88% depending on applied diagnostic criteria and the chosen method of blood pressure measurement. Despite the guidelines recommending the widespread use of renin-angiotensin system blockers (RASBs) in patients with kidney disease, their utilization in patients on HD may be suboptimal, especially in patients with preserved diuresis. This hesitance that often steams from concern is often due to fear of a decrease in eGFR and a subsequent decrease in diuresis. The aim of this study was to compare clinical characteristics, blood pressure, safety, and HD adequacy indices in hypertensive HD patients on multiple antihypertensive drug regimens, including diuretic treated with RASB (RASB group) or without RASB (no-RASB) with preserved residual diuresis. We sought to examine the real-life use of RASB in HD patients in relation to their clinical characteristics, blood pressure, safety, and HD adequacy.

Methods: From a database of 5,879 patients receiving HD (mean age 65.2 ± 14.2 years, 60% of males) of the largest provider of HD in the country, we selected the subgroup treated with at least three antihypertensive medications including diuretics. We compared patients treated with RASB to counterparts without RASB (no-RASB).

Results: The RASB group has similar age and gender proportions as well as BMI and bioimpedance compared to counterparts. However, dry body mass was significantly lower in the RASB group (78.1 ± 18.3 kg vs. 80.0 ± 18.2 kg, p < 0.017). Prevalence of diabetes mellitus was similar in both groups, but RASB-treated patients have cardiovascular diseases more frequently (70.1 vs. 60.8%; p < 0.001). Systolic blood pressure and the number of antihypertensive drugs used were significantly higher in RASB patients than in counterparts (146 ± 16 mm Hg vs. 144 ± 15 mm Hg; p < 0.001 and 4.1 ± 0.9 vs. 3.5 ± 0.5; p < 0001, respectively). RASB-treated patients have significantly longer dialysis vintage (52.7 ± 44.4 months vs. 40.2 ± 40.9 months; p < 0.001) and dialysis time (722 ± 87.1 min/week vs. 713 ± 93.4 min/week; p < 0.017) than counterparts. Serum potassium was slightly but significantly higher in RASB (5.3 ± 0.8 mmol/L vs. 5.1 ± 0.7 mmol/L; p < 0.01).

Conclusions: In the real world setting, RASB can be safely used in HD patients treated with diuretics with preserved residual diuresis. Given that many HD patients present numerous multimorbidities, RASB should not only be considered as an additional hypotensive drug in poorly controlled hypertension but also in other compelling indications in HD patients. The tendency toward hyperkalemia in HD patients could be effectively managed with appropriate diet and HD prescription adjustments.

Introduction: Biomarkers are urgently required to identify peritoneal dialysis (PD) patients at risk of cardiovascular (CV) events. This study aimed to investigate the predictive value of soluble suppression of tumorigenicity-2 (sST2) for CV events in patients undergoing incident PD.

Methods: In this prospective cohort study, incident PD patients were enrolled. Blood samples to measure sST2 levels were obtained before PD catheter implantation. The patients underwent a standard peritoneal equilibration test (PET) after initiation of PD for 4-6 weeks. The sST2 levels in both serum and dialysate were determined using enzyme-linked immunosorbent assay. CV events were recorded during the follow-up period.

Results: A total of 137 patients were enrolled. During the follow-up period of 17.3 months, 49 (35.76%) patients experienced CV events. When patients were dichotomized based on the median values and the calculated cutoff values of sST2, the higher sST2 group had 2.980- and 3.048-fold increased risks of CV events, respectively, when compared with the lower sST2 group. Moreover, the prognostic value of sST2 remained significant as a continuous variable (per 1 standard deviation increase, hazard ratio [HR] = 1.037, 95% confidence interval [CI] 1.010-1.066, p = 0.008). N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were found to indicate a higher risk only when dichotomized based on the calculated cutoff values. Furthermore, serum sST2 and NT-proBNP levels simultaneously above the calculated cutoff values were associated with a higher risk of CV events (HR = 3.398, 95% CI 1.813-6.367, p < 0.001).

Conclusion: Baseline serum sST2 level is an independent predictor of the risk of CV events in patients receiving incident PD, and in combination with NT-proBNP level, it can provide a more accurate predictive value.

Introduction: IgA nephropathy (IgAN) is a prevalent worldwide glomerular disease with a complex pathophysiology that has significant economic implications. Despite the lack of successful research, this study aims to discover the potential competing endogenous RNA (ceRNA) network of autophagy-associated genes in IgAN and examine their correlation with immune cell infiltration.

Methods: Autophagy-related hub genes were discovered by assessing the GSE116626 dataset and constructing a protein-protein interaction network. Nephroseq v5 analysis engine was used to analyze correlations between hub genes and proteinuria, glomerular filtration rate (GFR), and serum creatinine levels. Then, a ceRNA network construction and the CIBERSORT tool for immune cell infiltration analysis were also performed. Additionally, the differentially expressed autophagy-related genes were used to predict potential targeted medications for IgAN.

Results: Overall, 1,396 differentially expressed genes were identified in IgAN along with 25 autophagy-related differentially expressed messenger RNAs. Enrichment analysis revealed significant involvement of autophagy and apoptosis in biological processes. Next, we evaluated the top hub nodes based on their highest degrees. The ability of IgAN discrimination was confirmed in the GSE35487 and GSE37460 datasets by validating the five hub genes: SIRT1, FOS, CCL2, CDKN1A, and MYC. In the Nephroseq v5 analysis engine, the clinical correlation of the five hub genes was confirmed. Furthermore, the ceRNA network identified 18 circular RNAs and 2 microRNAs associated with hub autophagy-related genes in IgAN. Our investigation identified hsa-miR-32-3p and hsa-let-7i-5p as having elevated expression levels and substantial diagnostic value. Finally, four distinctively infiltrated immune cells were found to be associated with the hub autophagy-related genes, and 67 drugs were identified as potential therapeutic options for IgAN.

Conclusion: This study sheds light on a novel ceRNA regulatory network mechanism associated with autophagy in IgAN development.

Background: A hereditary condition primarily affecting the kidneys and heart has newly been identified: the RRAGD-associated autosomal dominant kidney hypomagnesemia with cardiomyopathy (ADKH-RRAGD). This disorder is characterized by renal loss of magnesium and potassium, coupled with varying degrees of cardiac dysfunction. These range from arrhythmias to severe dilated cardiomyopathy, which may require heart transplantation. Mutations associated with RRAGD significantly disrupt the non-canonical branch of the mechanistic target of rapamycin complex 1 pathway. This disruption hinders the nuclear translocation and transcriptional activity of the transcription factor EB a crucial regulator of lysosomal and autophagic function.

Summary: All identified RRAGD variants compromise kidney function, leading to hypomagnesemia and hypokalemia of various severity. The renal phenotype for most of the variants (i.e., S76L, I221K, P119R, P119L) typically manifests in the second decade of life occasionally preceded by childhood symptoms of dilated cardiomyopathy. In contrast, the P88L variant is associated to dilated cardiomyopathy manifesting in adulthood. To date, the T97P variant has not been linked to cardiac involvement. The most severe manifestations of ADKH-RRAGD, particularly concerning electrolyte imbalance and heart dysfunction requiring transplantation in childhood appear to be associated with the S76L, I221K, P119R variants.

Key messages: This review aimed to provide an overview of the clinical presentation for ADKH-RRAGD, aiming to enhance awareness, promote early diagnosis, and facilitate proper treatment. It also reports on the limited experience in patient management with diuretics, magnesium and potassium supplements, metformin, or calcineurin and SGLT2 inhibitors.

Background: Chronic kidney disease (CKD) has a global prevalence of 9.1-13.4%. Comorbidities are abundant and may cause and affect CKD. Cardiovascular disease strongly correlates with CKD, increasing the burden of both diseases.

Summary: As a group of 15 clinical nephrologists primarily practicing in 12 Central/Eastern European countries, as well as Israel and Kazakhstan, herein we review the significant unmet needs for patients with CKD and recommend several key calls-to-action. Early diagnosis and treatment are imperative to ensure optimal outcomes for patients with CKD, with the potential to greatly reduce both morbidity and mortality. Lack of awareness of CKD, substandard indicators of kidney function, suboptimal screening rates, and geographical disparities in reimbursement often hamper access to effective care.

Key messages: Our key calls-to-action to address these unmet needs, thus improving the standard of care for patients with CKD, are the following: increase disease awareness, such as through education; encourage provision of financial support for patients; develop screening algorithms; revisit primary care physician referral practices; and create epidemiological databases that rectify the paucity of data on early-stage disease. By focusing attention on early detection, diagnosis, and treatment of high-risk and early-stage CKD populations, we aim to reduce the burdens, progression, and mortality of CKD.

Introduction: Osteoporosis poses a significant health concern, especially for individuals with chronic kidney disease (CKD). CKD disrupts mineral and bone metabolism, heightening the risk of fractures and complicating the management of osteoporosis. While anti-osteoporotic interventions aim to address bone health in CKD patients, ongoing research is essential to understand the comparative efficacy and safety of these medications, particularly in different CKD stages, notably in stages 4 and 5.

Methods: We searched PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials assessing the efficacy and safety of osteoporosis interventions in CKD up to June 15, 2024. The analysis utilized the pooled odds ratio (OR) along with the corresponding 95% confidence interval (CI), employing Comprehensive Meta-Analysis software, version 3.0. To assess heterogeneity in the results of individual studies, we used Cochran's Q statistic and the I2 statistic.

Results: We analyzed 12 randomized controlled trials involving 31,027 participants, revealing a significantly lower risk of vertebral fractures with anti-osteoporotic agents (teriparatide, denosumab, romosozumab, raloxifene) compared to placebo (pooled OR, 0.28 [95% CI, 0.22-0.36]). Stratification by CKD stages showed a lower risk in Stages 1-3 but no significant reduction in stages 4 and 5. Teriparatide, denosumab, and romosozumab were effective in lowering fracture risk, whereas Raloxifene showed no significant effect. The lumbar spine, femoral neck, and total hip BMD showed no significant differences between anti-osteoporotic agents (denosumab, raloxifene, risedronate, alendronate, teriparatide) and placebo. However, romosozumab demonstrated a significantly greater BMD change in all kidney function categories. No reported side effects were observed in CKD stages 1-5 across the trials.

Conclusions: Our meta-analysis highlights the effectiveness of anti-osteoporotic agents in lowering vertebral fracture risk in CKD patients, particularly in stages 1-3. However, this benefit is not apparent in stages 4 and 5, necessitating further research. Despite the absence of reported side effects in CKD patients, clinicians should carefully assess the suitability of these medications, considering individual risks and benefits.

Introduction: The effect of kidney transplantation on endothelial dysfunction and autonomic dysfunction in uremia remains controversial, and few studies have evaluated this question. Endothelial dysfunction and autonomic dysfunction, both, be assessed noninvasively using laser Doppler flowmetry (LDF). This study evaluated cutaneous microvascular blood flow and reactivity using LDF in patients undergoing kidney transplantation.

Methods: This prospective longitudinal cohort study involved 40 patients with chronic kidney disease (CKD) undergoing kidney transplantation, compared with 40 patients without kidney disease. Using LDF, post-occlusive reactive hyperemia (PORH) (resting flow [RF], peak flow, ratio between peak, and RF, hyperemic area, PORH index), and sympathetic constrictor response to inspiratory breath-hold (mean minimum inspiratory values) were evaluated.

Results: RF and sympathetic constrictor response to inspiratory breath-hold (mean minimum inspiratory values), were lower in the CKD group at 1 week and at 3 months after transplantation (p < 0.005). Mean minimum inspiratory values increase in the CKD group, 3 months after transplantation.

Conclusion: Compared with controls with no CKD, in CKD patients undergoing kidney transplantation, microcirculation by LDF shows improvement after 3 months.

Introduction: Transplant renal artery stenosis (TRAS) is a common post-renal transplant complication. Although endovascular treatment is widely used to treat TRAS, previous research has been limited by small sample sizes. This article aimed to present the clinical outcomes of endovascular treatment for TRAS in a large sample.

Methods: Between January 2010 and December 2019, this study included patients with TRAS who were admitted to our center. All patients' clinical symptoms, comorbidities, imaging data, treatment, and follow-up results were reviewed retrospectively.

Results: Seventy two patients participated in this study. The median time between renal transplantation and TRAS was 5.25 months. Out of 72 patients, 55 (76.4%) received balloon dilatation in conjunction with stent deployment, 10 (13.9%) received drug-coated balloon dilatation alone, and 7 (9.7%) received balloon dilatation alone. The median follow-up period was 27 months. Primary patency rates were 100%, 81.8%, 74.5%, 64.6%, and 61.8% at 1, 3, 6, 12, and 24 months. A total of 23 patients were found to have restenosis during follow-up, with 6 (26.1%) requiring reintervention and none remaining restenosis after the second treatment. In the subgroup analysis of the three types of stenosis, patients with transplant renal stenosis at the anastomosis had a significantly higher rate of primary patency. Between endovascular treatments, the primary patency rate, postoperative creatinine clearance, and mean systolic blood pressure did not differ significantly.

Conclusion: Endovascular treatment resulted in favorable short-term patency as well as effective relief of renal dysfunction and renal hypertension in TRAS patients.