Chronic End-stage Renal Disease Research Articles

Urticarial vasculitis

Purpose of review Urticarial vasculitis is a rare condition manifesting with a variety of clinical presentations ranging from skin limited lesions to life-threatening systemic illnesses. This review aims to highlight the recent findings on the etiology, diagnostic modalities, and therapeutic strategies and course of urticarial vasculitis. Recent findings In addition to well established triggers, urticarial vasculitis (UV) cases associated with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) disease and COVID-19 vaccines, vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, and adenosine deaminase (ADA) deficiency have been reported. A clinical-dermoscopic model for differentiating urticarial vasculitis has been developed with purpuric patches and globules favoring UV diagnosis and thus diminishing the need for histopathology. The efficacy of treatment modalities has been reviewed, and antihistamines, systemic corticosteroids, omalizumab, cyclophosphamide, tocilizumab, anti-interleukin (IL)-1 agents, and rituximab were shown to have the highest success rates. Regarding the durability of remission, rituximab, dapsone, and MMF were related to long-lasting treatment free responses. The course of hypocomplementemic urticarial vasculitis was investigated in an epidemiological study, revealing 5- and 10-year survival rates of 92% and 83%, respectively. Chronic obstructive pulmonary disease, septicemia, and end-stage renal disease were identified as causes of mortality. Summary With the aid of dermoscopy, a noninvasive tool, differentiation from chronic spontaneous urticaria can be made, and the need for histopathological examination can be diminished. Although clear definitions and consensus criteria for performing disease severity are lacking, careful screening is needed to tailor the treatment on an individual basis. Emerging infections like SARS-CoV 2, vaccines, and autoinflammatory disorders like VEXAS syndrome and ADA deficiency are new associations. The optimal use of well established agents like systemic corticosteroids and immunomodulators are mainstay treatment modalities, whereas IL-1 inhibitors, omalizumab, rituximab and Janus Kinase inhibitors may represent viable alternatives in selected cases.

Relationship of body mass index and kidney outcomes in patients with primary glomerulonephritis: A systematic review and meta-analysis.

Primary glomerulonephritis, is a major contributor to the development of chronic kidney disease and end-stage renal disease. Previous studies on the relationship between overweight/obesity with primary glomerulonephritis in the chronic kidney disease was inconsistent. This study aimed to systematically review and meta-analyze the relationship between body mass index and adverse kidney outcomes in patients with primary glomerulonephritis. PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure were searched. Patients were divided into an overweight/obesity group (group O) and a non-overweight/obesity group (group N) according to their body mass index values. Twenty-six studies with 11,038 patients were selected. Patients in group O had deteriorated baseline characteristics, including worse baseline estimated glomerular filtration rate (weighted mean differences [WMD] = -5.99), higher Scr (WMD = 7.34), uric acid (WMD = 47.53), 24-hour proteinuria (WMD = 0.40), and a higher prevalence rate of hypertension (odds ratio, OR = 2.70) and diabetes mellitus (OR = 2.644). On the histopathologic level, patients in group O had a significantly lower total glomerular number (WMD = -2.30); however, no difference was observed in mesangial cell proliferation, endocapillary hypercellularity, crescents, sclerosis, and tubular atrophy/interstitial fibrosis between the 2 groups. The incidence of adverse renal outcomes in the 2 groups was similar (OR = 0.96). The meta-analysis of hazard ratios from Cox regressions indicated a strong association between overweight/obesity and poor renal outcomes in glomerulonephritis (HR = 1.17). Overweight/obesity glomerulonephritis patients had remarkably poor baseline clinicopathological characteristics. Being overweight or obesity would likely impact the progression of primary glomerulonephritis but not serious enough to contribute to significant poor renal outcomes, which could be prevented by aggressive therapy.

Cardiac Implantable Electronic Device Infections in Patients with Renal Insufficiency: A Systematic Review and Meta-Analysis.

(1) Background: Renal insufficiency is a risk factor for cardiac implantable electronic device (CIED) infection. (2) Methods: A comprehensive search was conducted from multiple electronic databases to identify studies. Using the random effects model, we calculated the pooled rates of CIED infection and their 95% confidence intervals. We also calculated the pooled odds ratios to determine the risk of CIED infections due to chronic kidney disease (CKD) and end-stage renal disease (ESRD). We utilized the Cochran Q and I2 statistics to detect and quantify heterogeneity. (3) Results: A total of 17 studies comprising 359,784 patients with renal insufficiency were added to the meta-analysis. Out of these, 263,819 were CKD patients and 89,617 were ESRD patients. The pooled rate of CIED infection in patients with CKD was 4.3% (95% CI: 2-8.8; I2: 95.7), and in patients with ESRD, it was 4.8% (95% CI: 2.6-8.7; I2: 99.4). The pooled risk of CIED infection in the CKD population was OR 2.5 (95% CI: 1.9-3.3; p < 0.001; I2: 21.1), and in the ESRD population, it was OR 2.4 (95% CI: 1.01-5.7; p = 0.046; I2: 88.8). ESRD was associated with higher mortality, OR 2.5 (95% CI: 1.4-4.4.8; p = 0.001; I2: 95). (4) Conclusions: The presence of renal insufficiency increases the number of CIED infections. In particular, patients with ESRD have an increased risk of mortality.

Concurrent chronic kidney disease in patients with inflammatory bowel disease, a systematic review and meta-analysis.

Inflammatory bowel disease (IBD) is a multi-organ autoimmune disease that commonly affects the gastrointestinal tract, but can also affect other organs throughout the body. Less is known, however, about kidney involvement in IBD. Although IBD has been associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD), these results have been inconsistent. The present study analyzed the prevalence of concurrent CKD and ESRD in patients with IBD. PubMed, Cochrane, Web of Science, and Embase were searched for studies published through October 2023 on IBD patients with concurrent CKD or ESRD. Outcomes included the incidence rates and odds ratios (OR) of concurrent CKD and ESRD in IBD patients. The quality of included studies was assessed using the Newcastle-Ottawa Scale, and sequential sensitivity was analyzed. Publication bias was evaluated using Egger's test. Nine studies were included in this meta-analysis. The combined results of eight studies, which included 239,042 IBD patients, showed that the prevalence of CKD in IBD patients was 5% (95% confidence interval [CI]: 1-9%). The combined results of two studies, which included 40,341 IBD patients, showed that the prevalence of ESRD in IBD patients was 0.2% (95% CI: -0.08-0.12%). The combined results of six case-control studies reported that the risk of CKD was significantly higher in patients with than without IBD (OR 1.36, 95% CI: 1.08-1.70, p = 0.008). Although studies have shown an increased risk of CKD in IBD, due to the small number of included studies and high heterogeneity across studies, it is not enough to definitively conclude that CKD is more common in patients with IBD. But patients with IBD should be regularly monitored for CKD. https://www.crd.york.ac.uk/PROSPERO/.

Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation.

This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV). Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified. Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury (AKI) group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (P<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (P<0.05). This study elucidated the optimal tacrolimus through level and highlighted the impact of IPV on the CKD and ESRD development post-LT.

Frequency and risk factors of congestive heart failure in hemodialysis patients in Assiut University Hospital

Background Cardiac failure is a leading cause of death for patients with chronic kidney disease and end-stage renal disease (ESRD). This study aimed to assess the prevalence of congestive heart failure (HF) in ESRD patients and evaluate its main risk factors. This data will help to provide better care to our patients and improve the outcome. Patients and methods A descriptive observational study was carried out on 290 individuals with ESRD who were on regular hemodialysis. The patients were categorized into two groups based on cardiac failure. The first group consisted of individuals diagnosed with HF, whereas the second group included people who showed no signs of HF. Results Logistic regression analysis revealed that smoking, hemoglobin level, ultrafiltration rate, ischemic heart disease, and ejection fraction were considered independent predictors for HF ESRD patients. Conclusion Congestive HF is prevalent among people undergoing hemodialysis. The main reasons for this high occurrence included the high prevalence of cardiovascular risk factors such as diabetes and hypertension, along with complications of renal failure such as anemia.

Comprehensive insights into diabetic nephropathy: pathophysiology, clinical features, and emerging treatments

Diabetic nephropathy (DN) is a leading cause of chronic kidney disease and end-stage renal disease globally, affecting 20–50% of diabetic patients. DN is characterized by albuminuria, retinopathy, and progressive reduction in glomerular filtration rate. The pathophysiology involves chronic hyperglycemia, protein glycosylation, mesangial matrix deposition, glomerular hemodynamic alterations, cytokine release, and renin-angiotensin-aldosterone system activation, leading to kidney damage. Differences in DN mechanisms between type 1 and type 2 diabetes are influenced by additional factors such as aging, obesity, and dyslipidemia. Prevention strategies focus on lifestyle modifications and regular screening. Pharmacological management includes tight glycemic control, blood pressure regulation, renin-angiotensin-aldosterone system blockade, and novel agents like sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists. Emerging therapies targeting inflammatory pathways and innovative medications offer promising avenues for future research. Comprehensive management integrating early detection and advanced pharmacological interventions is crucial to mitigating DN progression and improving patient outcomes.

Serum Potassium Monitoring UsingAI-Enabled Smartwatch Electrocardiograms.

Hyperkalemia, characterized by elevated serum potassium levels, heightens the risk of sudden cardiac death, particularly increasing risk for individuals with chronic kidney disease and end-stage renal disease (ESRD). Traditional laboratory test monitoring is resource-heavy, invasive, and unable to provide continuous tracking. Wearable technologies like smartwatches with electrocardiogram (ECG) capabilities are emerging as valuable tools for remote monitoring, potentially allowing for personalized monitoring with artificial intelligence (AI)-ECG interpretation. The purpose of this study was to develop an AI-ECG algorithm to predict serum potassium level in ESRD patients with smartwatch-generated ECG waveforms. A cohort of 152,508 patients with 293,557 ECGs paired serum potassium levels obtained within 1 hour at Cedars Sinai Medical Center was used to train an AI-ECG model ("Kardio-Net") to predict serum potassium level. The model was further fine-tuned on 4,337 ECGs from 1,463 patients with ESRD using inputs from 12- and single-lead ECGs. Kardio-Net was evaluated in held-out test cohorts from Cedars Sinai Medical Center and Stanford Healthcare (SHC) as well as a prospective international cohort of 40 ESRD patients with smartwatch ECGs at Chang Gung Memorial Hospital. The Kardio-Net, when applied to 12-lead ECGs, identified severe hyperkalemia (>6.5 mEq/L) with an AUC of 0.852 (95%CI: 0.745-0.956) and a mean absolute error (MAE) of 0.527 mEq/L. In external validation at SHC, the model achieved an AUC of 0.849 (95%CI: 0.823-0.875) and an MAE of 0.599 mEq/L. For single-lead ECGs, Kardio-Net detected severe hyperkalemia with an AUC of 0.876 (95%CI: 0.765-0.987) in the primary cohort and had an MAE of 0.575 mEq/L. In the external SHC validation, the AUC was 0.807 (95%CI: 0.778-0.835) with an MAE of 0.740 mEq/L. Using prospectively obtained smartwatch data, the AUC was 0.831 (95%CI: 0.693-0.975), with an MAE of 0.580 mEq/L. We validate a deep learning model to predict serum potassium levels from both 12-lead ECGs and single-lead smartwatch data, demonstrating its utility for remote monitoring of hyperkalemia.

Molecular Therapeutics for Diabetic Kidney Disease: An Update.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes mellitus (DM). With the increasing prevalence of DM worldwide, the incidence of DKD remains high. If DKD is not well controlled, it can develop into chronic kidney disease or end-stage renal disease (ESRD), which places considerable economic pressure on society. Traditional therapies, including glycemic control, blood pressure control, blood lipid control, the use of renin-angiotensin system blockers and novel drugs, such as sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor inhibitors and glucagon-like peptide-1 receptor agonists, have been used in DKD patients. Although the above treatment strategies can delay the progression of DKD, most DKD patients still ultimately progress to ESRD. Therefore, new and multimodal treatment methods need to be explored. In recent years, researchers have continuously developed new treatment methods and targets to delay the progression of DKD, including miRNA therapy, stem cell therapy, gene therapy, gut microbiota-targeted therapy and lifestyle intervention. These new molecular therapy methods constitute opportunities to better understand and treat DKD. In this review, we summarize the progress of molecular therapeutics for DKD, leading to new treatment strategies.

The Analysis Study of Association of Intestinal Microbiota and Kidney Disease: A Comprehensive Systematic Review

Background: Disruptions in gut microbiota compositiosn (dysbiosis) in kidney diseases can lead to worsened kidney function. Dysbiosis may increase intestinal permeability and systemic inflammation, allowing bacterial toxins to enter the bloodstream and exacerbate CKD and its complications. This systematic review aims to evaluate the association of intestinal microbiota and kidney disease by analyzing available studies of the last 10 years. Methods: The study adhered to PRISMA 2020 standards, examining English literature from 2014 to 2024. It excluded editorials, reviews from the same journal, and submissions without a DOI. PubMed, SagePub, SpringerLink, and Google Scholar were utilized as literature sources. Result: Initially retrieving 360 articles from online databases (PubMed, SagePub, SpringerLink and Google Scholar) eight relevant papers were selected after three rounds of screening for full-text analysis. Conclusion: Gut microbiota alterations are closely linked to chronic kidney disease (CKD) and end-stage renal disease (ESRD), impacting inflammation and disease progression. Microbial shifts offer potential diagnostic and therapeutic insights, though further research is needed for clinical application.

The association between klotho and kidney and cardiovascular outcomes: a comprehensive systematic review and meta-analysis.

Chronic kidney disease (CKD) and end-stage renal disease (ESKD) are significant global health challenges associated with progressive kidney dysfunction and numerous complications, including cardiovascular disease and mortality. This study aims to explore the potential association between plasma klotho levels and various prognostic outcomes in CKD and ESKD, including all-cause mortality, cardiovascular events, metabolic syndrome development and adverse renal events necessitating renal replacement therapies. A literature search was conducted through 3 June 2024 using the electronic databases Cochrane Library, Ovid MEDLINE, CINAHL, Web of Science, SCOPUS and PubMed. This systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Fourteen studies were included. For all-cause mortality, comparing CKD patients with low versus high klotho levels showed a significant association {odds ratio [OR] 1.81 [95% confidence interval (CI) 1.34-2.44], P=.0001}, with substantial heterogeneity (I 2=69%). Excluding one study reduced heterogeneity (I 2=43%) while maintaining significance [OR 1.97 (95% CI 1.45-2.66), P<.0001]. Cardiovascular mortality was higher in patients with low klotho levels [OR 2.11 (95% CI 1.61-2.76), P<.00001], with low heterogeneity (I 2=25%). Excluding one study eliminated heterogeneity (I 2=0%) while maintaining significance [OR 2.39 (95% CI 1.83-3.12), P<.00001]. Composite cardiovascular events did not differ significantly between low and high klotho groups [OR 1.51 (95% CI 0.82-2.77), P=.18], but with high heterogeneity (I 2=72%). Patients with low klotho levels had a higher risk of adverse renal events [OR 2.36 (95% CI 1.37-4.08), P=.002], with moderate heterogeneity (I 2=61%). Sensitivity analysis reduced heterogeneity (I 2=0%) while maintaining significance [OR 3.08 (95% CI 1.96-4.85), P<.00001]. Specifically, for ESKD or kidney replacement therapy risk, low klotho levels were associated with an increased risk [OR 2.30 (95% CI 1.26-4.21), P=.007]. Similarly, CKD progression risk was higher in patients with lower klotho levels [OR 2.48 (95% CI 1.45-4.23), P=.0009]. Lower serum klotho levels serve as a significant predictor of adverse outcomes, including increased risks of all-cause mortality, cardiovascular mortality and progression to end-stage kidney disease among CKD patients.

Histological evaluation of renal progenitor/stem cells, renal mesenchymal stem-like cells, and endothelial progenitor cells in chronic kidney disease and end-stage renal disease, and molecular docking analysis of drug-receptor interactions

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are prevalent and debilitating conditions with a significant impact on patients' quality of life. In this study, we conducted a comprehensive investigation into the histological characteristics of renal progenitor/stem cells (RPCs), renal mesenchymal stem-like cells, and endothelial progenitor cells (EPCs) in CKD and ESRD patients. Additionally, we performed a molecular docking analysis to explore potential drug-receptor interactions involving common medications prescribed to CKD patients. Our histological examination revealed a noteworthy increase in the number of CD24- and CD133-positive cells in CKD and ESRD patients, representing RPCs. These cells are implicated in kidney repair and regeneration, underscoring their potential role in CKD management. Moreover, we observed an elevation in the number of EPCs within the kidneys of CKD and ESRD patients, suggesting a protective role of EPCs in kidney preservation. The molecular docking analysis unveiled intriguing insights into potential drug interventions. Notably, digoxin exhibited the highest in-silico binding affinity to numerous receptors associated with the functions of RPCs, renal mesenchymal stem-like cells, and EPCs, emphasizing the potential multifaceted effects of this cardiac glycoside in CKD patients. Other drugs, including apixaban, glimepiride, and glibenclamide, also displayed strong in-silico affinities to specific receptors, indicating their potential influence on various renal cell functions. In conclusion, this study provides valuable insights into the histological alterations in renal cell populations in CKD and ESRD patients and underscores the potential roles of RPCs and EPCs in kidney repair and preservation. The molecular docking analysis reveals the complex interactions between common drugs and renal cells, suggesting the need for further in-vitro and in-vivo research to fully understand these relationships. These findings contribute to our understanding of CKD and offer new avenues for research into potential therapeutic interventions.

Sex Disparity in the In-Hospital Outcomes of Patients with Kidney Disease Admitted for Myocardial Infarction: Insights from a Large National Database.

There is limited evidence as to the effect of sex on the outcomes of patients admitted for ST-elevation myocardial infarction (STEMI) who have a concomitant diagnosis of chronic kidney disease (CKD) and end-stage renal disease (ESRD). We aimed to determine if there are differences in the outcomes between males and females in these patient populations. Data were obtained from the National Inpatient Sample database and patients were selected using the International Classification of Diseases, Ninth and Tenth Revision (ICD-9 and -10) codes. Hospitalizations for patients with CKD who had STEMI from 2012 to 2020 were included. The primary outcome of interest was in-hospital mortality. Secondary outcomes evaluated included ischemic stroke, major bleeding complications, pressor requirement, permanent pacemaker implantation, percutaneous coronary intervention, coronary artery bypass grafting, surgery, pericardiocentesis, mechanical circulatory support, and mechanical ventilation. A total of 1,283,255 STEMI patients without CKD, 158,715 STEMI patients with CKD, and 22,690 STEMI patients with ESRD were identified and analyzed. Among patients with STEMI and CKD, females demonstrated higher in-hospital mortality compared to male counterparts (16.7% vs. 12.7%, aOR = 1.13, 95% CI: 1.05-1.21, p &lt; 0.01). While there was no sex difference in the in-hospital mortality among STEMI patients with ESRD, female patients in this group were less likely to receive coronary artery bypass grafting and mechanical circulatory support. Increased in-hospital mortality rates were shown for females admitted for STEMI with CKD. Among patients with ESRD who had STEMI, females were less likely to receive coronary artery bypass grafting and mechanical circulatory support. Further research needs to be conducted to better explain this said difference in outcomes.

Mendelian randomization based on immune cells in diabetic nephropathy.

DKD, a leading cause of chronic kidney and end-stage renal disease, lacks robust immunological research. Recent GWAS utilizing SNPs and CNVs has shed light on immune mechanisms of kidney diseases. However, DKD's immunological basis remains elusive. Our goal is to unravel cause-effect relationships between immune cells and DKD using Mendelian randomization. We analyzed FinnGen data (1032 DKD cases, 451,248 controls) with 731 immunocyte GWAS summaries (MP=32, MFI=389, AC=118, RC=192). We employed forward and reverse Mendelian randomization to explore causal links between immune cell traits and DKD. Sensitivity analysis ensured robustness, heterogeneity checks, and FDR correction minimized false positives. Our study explored the causal link between diabetic nephropathy (DKD) and immunophenotypes using two-sample Mendelian Randomization (MR) with IVW. Nine immunophenotypes were significantly associated with DKD at p<0.05 after FDR correction. Elevated CD24, CD3 in Treg subsets, CD39+ CD4+, and CD33- HLA DR- AC correlated positively with DKD risk, while CD27 in B cells and SSC-A in CD4+ inversely correlated. Notably, while none showed significant protection, further research on immune cells' role in DKD may provide valuable insights. The results of this study show that the immune cells are closely related to DKD, which may be helpful in the future clinical study.

Vaccarin suppresses diabetic nephropathy through inhibiting the EGFR/ERK1/2 signaling pathway.

Diabetic nephropathy (DN) is recognized as one of the primary causes of chronic kidney disease and end-stage renal disease. Vaccarin (VAC) confers favorable effects on cardiovascular and metabolic diseases, including type 2 diabetes mellitus (T2DM). Nonetheless, the potential role and mechanism of VAC in the etiology of DN have yet to be completely elucidated. In this study, a classical mouse model of T2DM is experimentally induced via a high-fat diet (HFD)/streptozocin (STZ) regimen. Renal histological changes are assessed via H&E staining. Masson staining and immunohistochemistry (IHC) are employed to assess renal fibrosis. RT-PCR is utilized to quantify the mRNA levels of renal fibrosis, oxidative stress and inflammation markers. The levels of malondialdehyde (MDA) and reactive oxygen species (ROS), as well as the content of glutathione peroxidase (GSH-Px), are measured. The protein expressions of collagen I, TGF-β1, α-SMA, E-cadherin, Nrf2, catalase, SOD3, SOD2, SOD1, p-ERK, p-EGFR (Y845), p-EGFR (Y1173), p-NFκB P65, t-ERK, t-EGFR and t-NFκB P65 are detected by western blot analysis. Our results reveal that VAC has a beneficial effect on DN mice by improving renal function and mitigating histological damage. This is achieved through its inhibition of renal fibrosis, inflammatory cytokine overproduction, and ROS generation. Moreover, VAC treatment effectively suppresses the process of epithelial-mesenchymal transition (EMT), a crucial characteristic of renal fibrosis, in high glucose (HG)-induced HK-2 cells. Network pharmacology analysis and molecular docking identify epidermal growth factor receptor (EGFR) as a potential target for VAC. Amino acid site mutations reveal that Lys-879, Ile-918, and Ala-920 of EGFR may mediate the direct binding of VAC to EGFR. In support of these findings, VAC reduces the phosphorylation levels of both EGFR and its downstream mediator, extracellular signal-regulated kinase 1/2 (ERK1/2), in diabetic kidneys and HG-treated HK-2 cells. Notably, blocking either EGFR or ERK1/2 yields renal benefits similar to those observed with VAC treatment. Therefore, this study reveals that VAC attenuates renal damage via inactivation of the EGFR/ERK1/2 signaling axis in T2DM patients.

Mitochondrial dysfunction in diabetic nephropathy: insights and therapeutic avenues from traditional Chinese medicine.

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus. The progressive damage to glomeruli, tubules, and interstitium in the kidneys can lead to the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Most of the energy we need comes from mitochondria. Mitochondria are best known as the sites for production of respiratory ATP and are essential for eukaryotic life. The pathogenesis of DN involves a variety of factors, such as altered haemodynamics, oxidative stress, and inflammation, and studies from animal models suggest that mitochondrial dysfunction plays an important role in the development of DN. Traditional Chinese medicine (TCM) has a history of more than 2,500 years and has rich experience and remarkable efficacy in the treatment of DN. Recent studies have found that TCM may have great potential in regulating mitochondrial dysfunction in the treatment of DN. This review will elucidate the main causes of mitochondrial dysfunction and the relationship with DN, and explore in depth the potential mechanisms of TCM to protect the kidney by improving mitochondrial dysfunction. Current pharmacological treatments for patients with DN do not prevent the inevitable progression to ESRD. With the rich variety of Chinese herbs, TCM is expected to be the most promising candidate for the treatment of DN as we continue to learn more about the mechanisms of DN and incorporate the current advances in extraction techniques.

Targeting senescence to prevent diabetic kidney disease: Exploring molecular mechanisms and potential therapeutic targets for disease management.

As a microvascular complication, diabetic kidney disease is the leading cause of chronic kidney disease and end-stage renal disease worldwide. While the underlying pathophysiology driving transition of diabetic kidney disease to renal failure is yet to be fully understood, recent studies suggest that cellular senescence is central in disease development and progression. Consequently, understanding the molecular mechanisms which initiate and drive senescence in response to the diabetic milieu is crucial in developing targeted therapies that halt progression of renal disease. To understand the mechanistic pathways underpinning cellular senescence in the context of diabetic kidney disease, we reviewed the literature using PubMed for English language articles that contained key words related to senescence, inflammation, fibrosis, senescence-associated secretory phenotype (SASP), autophagy, and diabetes. Aberrant accumulation of metabolically active senescent cells is a notable event in the progression of diabetic kidney disease. Through autocrine- and paracrine-mediated mechanisms, resident senescent cells potentiate inflammation and fibrosis through increased expression and secretion of pro-inflammatory cytokines, chemoattractants, recruitment of immune cells, myofibroblast activation, and extracellular matrix remodelling. Compounds that eliminate senescent cells and/or target the SASP - including senolytic and senomorphics drugs - demonstrate promising results in reducing the senescent cell burden and associated pro-inflammatory effect. Here we evidence the link between senescence and diabetic kidney disease and highlight underlying molecular mechanisms and potential therapeutic targets that could be exploited to delay disease progression and improve outcomes for individuals with the disease. Trials are now required to translate their therapeutic potential to a clinical setting.

Impact of chronic kidney disease and end-stage renal disease on the mid-term adverse outcomes in diabetic patients with cardiovascular diseases

The evidence for the impact of renal dysfunction in patients with diabetes mellitus (DM) and first cardiovascular diseases on mid-term adverse outcomes remain scarce. This study included the data of patients with DM having first atherosclerotic cardiovascular disease (ASCVD) or congestive heart failure (CHF) from the Taipei Medical University Clinical Research Database. A Cox proportional hazards regression model was used to assess the impact of chronic kidney disease (CKD) or end-stage renal disease (ESRD) on the 1-year mortality and recurrent ASCVD/CHF outcomes. We enrolled 21,320 patients with DM hospitalized for ASCVD or CHF; of them, 18,185, 2639, and 496 were assigned to the non-CKD, CKD, and ESRD groups, respectively. After propensity score matching, compared with the non-CKD group, the CKD and ESRD groups had higher mid-term all-cause mortality (adjusted hazard ratio 1.72 [95% confidence interval 1.48–1.99] and 2.77 [2.05–3.73], respectively), cardiovascular death (1.84 [1.44–2.35] and 1.87 [1.08–3.24], respectively), and recurrent hospitalization for ASCVD (1.44 [1.24–1.68] and 2.33 [1.69–3.23], respectively) and CHF (2.08 [1.75–2.47] and 1.50 [1.04–2.17], respectively). The advancing age was associated with mortality in CKD/ESRD groups. In CKD group, male sex was associated with all-cause mortality and recurrent ASCVD risk; the diuretics usage was associated with mortality and recurrent CHF risks. Our findings suggest that CKD and ESRD are significant risk factors for mid-term adverse outcomes in patients with DM and established cardiovascular diseases. Additionally, old age, male sex and diuretics usage requires attention. Further good quality studies are needed in the future.

Urological outcomes in adult females born with anorectal malformation or Hirschsprung disease.

Women born with anorectal malformation (ARM) or Hirschsprung disease (HD) may have impaired urologic function resulting in sequelae in adulthood. This study assessed and compared self-reported urinary outcomes in adult females born with ARM or HD to a reference population. This was an IRB approved, cross-sectional study of female-born patients with ARM or HD, who completed surveys between November 2021 and August 2022. Female patients between the ages of 18 and 80years were included. Lower Urinary Tract Symptom Questionnaires were administered through REDCap and the responses were compared to a reference population using Chi-squared or Fisher's exact tests. Sixty-six born female patients answered the questionnaires, two of them identified as non-binary. The response rate was 76%. Median age was 31.6years. The majority were born with cloaca (56.3%), followed by other type of ARMs (28.1%), complex malformation (9.4%), and HD (6.3%). A history of bladder reconstruction was present for 26.6%. Catheterization through a channel or native urethra was present in 18.8%. Two had ureterostomies and were excluded from the analysis. Seven had chronic kidney disease or end-stage renal disease, three with a history of kidney transplantation. Patients with cloaca had significantly higher rates of urinary incontinence, urinary tract infection, and social problems due to impaired urological functioning, when compared to an age-matched reference population (Table3). This study emphasizes the need for a multi-disciplinary team that includes urology and nephrology following patients with ARM long term, especially within the subgroup of cloaca. III.

Accessibility and Affordability Issues for Renal Replacement Therapy Remain Challenges in Resource-Limited Healthcare Settings: A Case Report and Critique of Literature for Chronic Kidney and End-Stage Renal Disease

Accessibility and Affordability Issues for Renal Replacement Therapy Remain Challenges in Resource-Limited Healthcare Settings: A Case Report and Critique of Literature for Chronic Kidney and End-Stage Renal Disease