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Frontiers in Immunology 2023Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2... (Review)
Review
Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Kidney
PubMed: 37809091
DOI: 10.3389/fimmu.2023.1213473 -
Kidney International Feb 2022Chronic kidney disease (CKD) triggers the risk of developing uremic cardiomyopathy as characterized by cardiac hypertrophy, fibrosis and functional impairment.... (Meta-Analysis)
Meta-Analysis
Chronic kidney disease (CKD) triggers the risk of developing uremic cardiomyopathy as characterized by cardiac hypertrophy, fibrosis and functional impairment. Traditionally, animal studies are used to reveal the underlying pathological mechanism, although variable CKD models, mouse strains and readouts may reveal diverse results. Here, we systematically reviewed 88 studies and performed meta-analyses of 52 to support finding suitable animal models for future experimental studies on pathological kidney-heart crosstalk during uremic cardiomyopathy. We compared different mouse strains and the direct effect of CKD on cardiac hypertrophy, fibrosis and cardiac function in "single hit" strategies as well as cardiac effects of kidney injury combined with additional cardiovascular risk factors in "multifactorial hit" strategies. In C57BL/6 mice, CKD was associated with a mild increase in cardiac hypertrophy and fibrosis and marginal systolic dysfunction. Studies revealed high variability in results, especially regarding hypertrophy and systolic function. Cardiac hypertrophy in CKD was more consistently observed in 129/Sv mice, which express two instead of one renin gene and more consistently develop increased blood pressure upon CKD induction. Overall, "multifactorial hit" models more consistently induced cardiac hypertrophy and fibrosis compared to "single hit" kidney injury models. Thus, genetic factors and additional cardiovascular risk factors can "prime" for susceptibility to organ damage, with increased blood pressure, cardiac hypertrophy and early cardiac fibrosis more consistently observed in 129/Sv compared to C57BL/6 strains.
Topics: Animals; Cardiomyopathies; Disease Models, Animal; Fibrosis; Mice; Mice, Inbred C57BL; Renal Insufficiency, Chronic
PubMed: 34774555
DOI: 10.1016/j.kint.2021.10.025 -
Current Urology Reports Apr 2020To present the latest evidence related to the impact of ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) on the renal function.
PURPOSE OF REVIEW
To present the latest evidence related to the impact of ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) on the renal function.
RECENT FINDINGS
Our review suggests that the overall renal function is not detrimentally affected by endourological interventions (URS, PCNL). This is however influenced by the preoperative renal function, presence of comorbidities such as diabetes and hypertension. For PCNL procedures, tract multiplicity, preoperative UTI, and postoperative bleeding also contribute to a decline in renal function. This review suggests that endourological interventions do not adversely affect renal function and tend to improve it in patients who do not have a poor renal function prior to the procedure. Several factors including poor preoperative renal function, diabetes, hypertension, and multiple percutaneous tracts appear to predispose patients to declining renal function after procedure, and these patients should be counseled for and followed up appropriately.
Topics: Humans; Hypertension; Nephrolithotomy, Percutaneous; Nephrostomy, Percutaneous; Postoperative Complications; Renal Insufficiency; Ureteroscopy
PubMed: 32318942
DOI: 10.1007/s11934-020-00973-4 -
Scientific Reports Sep 2023The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney... (Meta-Analysis)
Meta-Analysis
The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney function groups. We conducted a systematic review and meta-analysis of randomized control trials (RCTs) with SGLT-2 inhibitors in patients with and without CKD. We performed a PubMed/Medline search of randomized, placebo-controlled, event-driven outcome trials of SGLT-2 inhibitors versus active or placebo control in patients with and without diabetes from inception to November 2022. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m (PROSPERO registration CRD4202016054). The primary outcome was cardiovascular death. Secondary outcomes included hospitalization for heart failure, major adverse cardiovascular events, CKD progression, all-cause mortality, treatment discontinuation, and acute kidney injury (AKI). The relative risk (RR) was estimated using a random-effects model. Twelve RCTs were included in this meta-analysis (89,191 patients, including 38,949 with eGFR < 60 ml/min/1.73m). Use of an SGLT-2 inhibitor in patients with CKD was associated with a lower incidence of cardiovascular death (RR 0.87; 95% CI 0.79-0.95) and of heart failure (RR 0.67; 95% CI 0.61-0.75), compared with placebo. Heart failure risk reduction with SGLT-2 inhibitors was larger among patients with CKD compared with patients without CKD (RR for the interaction 0.87, 95% CI 0.75-1.02, and p-value for interaction 0.08). SGLT-2 inhibitors were associated with a lower incidence of CKD progression among patients with pre-existing CKD: RR 0.77 (95% CI 0.68-0.88), compared with placebo. Among patients with CKD, a lower risk of AKI (RR 0.82; 95% CI 0.72-0.93) and treatment discontinuation was seen with SGLT-2 inhibitors compared with placebo. SGLT-2 inhibitors offer substantial protection against cardiovascular and renal outcomes in patients with CKD. These results strongly advocate in favor of using them in patients with CKD and keeping them as kidney function declines.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Heart Failure; Kidney; Acute Kidney Injury; Renal Insufficiency, Chronic
PubMed: 37741858
DOI: 10.1038/s41598-023-42989-z -
Journal of Human Hypertension Jan 2024The present study aims to evaluate the clinical outcomes following renal denervation (RDN) for hypertensive patients with chronic kidney disease (CKD). Prospective... (Meta-Analysis)
Meta-Analysis Review
The present study aims to evaluate the clinical outcomes following renal denervation (RDN) for hypertensive patients with chronic kidney disease (CKD). Prospective studies published between January 1, 2010 and November 15, 2022 where systematically identified for RDN outcomes on office and ambulatory blood pressure, estimated glomerular filtration rate (eGFR), creatinine and procedural characteristics from three online databases (Medline, PubMed, EMBASE). Random effects model to combine risk ratios and mean differences was used. Where possible, clinical outcomes were pooled and analyzed at 6, 12 and 24 months. Significance was set at p ≤ 0.05. 11 prospective trials, with a total of 226 patients with treatment resistant HTN receiving RDN met the inclusion criteria. Age ranged from 42.5 ± 13.8 to 66 ± 9. Main findings of this review included a reduction in systolic and diastolic office blood pressure at 6 [-19.8 (p < 0.00001)/-15.2 mm Hg (p < 0.00001)] and 12 months [-21.2 (p < 0.00001)/-9.86 mm Hg (p < 0.0005)] follow-up compared to baseline. This was also seen in systolic and diastolic 24-hour ambulatory blood pressure at 6 [-9.77 (p = 0.05)/-3.64 mm Hg (p = 0.09)] and 12 months [-13.42 (p = 0.0007)/-6.30 mm Hg (p = 0.001)] follow-up compared to baseline. The reduction in systolic and diastolic 24-hour ambulatory blood pressure was maintained to 24 months [(-16.30 (p = 0.0002)/-6.84 mm Hg (p = 0.0010)]. Analysis of kidney function through eGFR demonstrated non-significant results at 6 (+1.60 mL/min/1.73 m, p = 0.55), 12 (+5.27 mL/min/1.73 m, p = 0.17), and 24 months (+7.19 mL/min/1.73 m, p = 0.36) suggesting an interruption in natural CKD progression. Similar results were seen in analysis of serum creatinine at 6 (+0.120 mg/dL, p = 0.41), 12 (+0.100 mg/dL, p = 0.70), and 24 months (+0.07 mg/dL, p = 0.88). Assessment of procedural complications deemed RDN in a CKD cohort to be safe with an overall complication rate of 4.86%. With the current advances in RDN and its utility in multiple chronic diseases beyond hypertension, the current study summarizes critical findings that further substantiate the literature regarding the potential of such an intervention to be incorporated as an effective treatment for resistant hypertension and CKD.
Topics: Humans; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Denervation; Hypertension; Kidney; Prospective Studies; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 37666908
DOI: 10.1038/s41371-023-00857-3 -
Pharmaceutics Feb 2022Kidney function assessment in the critically ill overlooks the possibility for hyperfunctioning kidneys, known as augmented renal clearance (ARC), which could contribute... (Review)
Review
Kidney function assessment in the critically ill overlooks the possibility for hyperfunctioning kidneys, known as augmented renal clearance (ARC), which could contribute to therapeutic failures in the intensive care unit (ICU). The aim of this research is to conduct a systematic review and meta-analysis of prevalence and risk factors of ARC in the critically ill. MEDLINE, Embase, Cochrane Library, CINAHL, Scopus, ProQuest Dissertations and Theses Global databases were searched on 27 October 2020. We included studies conducted in critically ill adults who reported the prevalence and/or risk factors of ARC. We evaluated study quality using the Joanna Briggs Institute appraisal tool. Case reports, reviews, editorials and commentaries were excluded. We generated a random-effects meta-analytic model using the inverse variance method and visualized the pooled estimates using forest plots. Seventy studies were included. The pooled prevalence (95% CI) was 39% (34.9-43.3). Prevalence for neuro, trauma, mixed and sepsis ICUs were 74 (55-87), 58 (48-67), 36 (31-41) and 33 (21-48), respectively. Age, male sex and trauma were associated with ARC with pooled OR (95% CI) of 0.95 (0.93-0.96), 2.36 (1.28-4.36), 2.60 (1.21-5.58), respectively. Limitations included variations in ARC definition, inclusion and exclusion criteria and studies design. In conclusion, ARC is prevalent in critically ill patients, especially those in the neurocritical care and trauma ICU population. Young age, male sex and trauma are risk factors for ARC in those with apparently normal renal function. Further research on optimal dosing of drugs in the setting of ARC is warranted. (Prospero registration: CRD42021246417).
PubMed: 35214177
DOI: 10.3390/pharmaceutics14020445 -
PloS One 2014High blood pressure can cause kidney damage, which can increase blood pressure, leading to a vicious cycle. It is not clear whether the protective effects of T-type... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High blood pressure can cause kidney damage, which can increase blood pressure, leading to a vicious cycle. It is not clear whether the protective effects of T-type calcium channel blockers (T-type CCBs) on renal function are better than those of L-type CCBs or renin-angiotensin system (RAS) antagonists in patients with hypertension.
METHODS AND FINDINGS
PUBMED, MEDLINE, EMBASE, OVID, Web of Science, Cochrane, CNKI, MEDCH, VIP, and WANFANG databases were searched for clinical trials published in English or Chinese from January 1, 1990, to December 31, 2013. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated and reported. A total of 1494 reports were collected, of which 24 studies with 1,696 participants (including 809 reports comparing T-type CCBs versus L-type CCBs and 887 reports comparing T-type CCB versus RAS antagonists) met the inclusion criteria. Compared with L-type CCBs, T-type CCBs resulted in a significant decline in aldosterone (mean difference = -15.19, 95% CI -19.65 - -10.72, p<1×10(-5)), proteinuria (mean difference = -0.73, 95% CI -0.88 - -0.57, p<1×10(-5)), protein to creatinine ratio (mean difference = -0.22, 95% CI -0.41 - -0.03, p = 0.02), and urinary albumin to creatinine ratio (mean difference = -55.38, 95% CI -86.67 - -24.09, p = 0.0005); no significant difference was noted for systolic blood pressure (SBP) (p = 0.76) and diastolic blood pressure (DBP) (p = 0.16). The effects of T-type CCBs did not significantly differ from those of RAS antagonists for SBP (p = 0.98), DBP (p = 0.86), glomerular filtration rate (p = 0.93), albuminuria (p = 0.97), creatinine clearance rate (p = 0.24), and serum creatinine (p = 0.27) in patients with hypertension.
CONCLUSION
In a pooled analysis of data from 24 studies measuring the effects of T-type CCBs on renal function and aldosterone, the protective effects of T-type CCBs on renal function were enhanced compared with L-type CCBs but did not differ from RAS antagonists. Their protective effects on renal function were independent of blood pressure.
Topics: Adult; Aged; Aldosterone; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, T-Type; Case-Control Studies; Humans; Hypertension; Middle Aged; Proteinuria
PubMed: 25330103
DOI: 10.1371/journal.pone.0109834 -
SpringerPlus 2016Methadone is commonly administered for chronic pain relief and treatment of opioid dependence. Concurrent with its increased consumption, toxicities and fatalities have... (Review)
Review
BACKGROUND
Methadone is commonly administered for chronic pain relief and treatment of opioid dependence. Concurrent with its increased consumption, toxicities and fatalities have increased. One of the adverse effects of opioid analgesics, including methadone, is that of nephrotoxicity. Opioids can have an effect on renal function through several different mechanisms.
METHODS
We searched common bibliographical databases for the terms methadone, toxicity, poisoning, kidney, renal, and nephrotoxicity and summarize our findings in this review.
RESULTS
Methadone can have both direct and indirect effects on the kidney. These effects include rhabdomyolysis (leading to acute kidney injury), volumetric changes, renal lipidosis and amyloidosis, kidney growth during pregnancy, and kidney transplant rejection.
CONCLUSION
Improved understanding of the effects of methadone on kidney function can promote safer and more confident use of the drug.
PubMed: 28018795
DOI: 10.1186/s40064-016-3757-1 -
Journal of Diabetes Research 2019Previous studies involving patients with diabetes have indicated that sarcopenia is related to renal function. The objective of the present study was to investigate the... (Meta-Analysis)
Meta-Analysis
Previous studies involving patients with diabetes have indicated that sarcopenia is related to renal function. The objective of the present study was to investigate the association between sarcopenia and urinary albumin level, urinary protein level, and estimated glomerular filtration rate (eGFR) in patients with diabetes. A meta-analysis of observational studies was conducted. A literature search was performed using MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov. Data were extracted from studies investigating the association between sarcopenia and urinary albumin level, urinary protein level, and eGFR and by calculating odds ratio (OR) and 95% confidence intervals (CIs). Statistical analysis was performed using a random-effects model to calculate pooled OR and 95% CI. Six studies (2662 patients) that met the criteria were included in the meta-analysis. Sarcopenia was significantly associated with urinary albumin level with a pooled OR of 2.11 (95% CI, 1.55-2.88; < 0.001). The pooled ORs of the associations between sarcopenia and urinary protein level and decreased eGFR were 1.82 (95% CI, 1.13-2.92; = 0.01) and 3.75 (95% CI, 1.24-11.41), respectively. Sarcopenia was significantly associated with urinary albumin level, urinary protein level, and decreased eGFR. However, further investigations are needed, including meta-analyses with a larger number of studies.
Topics: Albuminuria; Diabetes Mellitus; Diabetic Nephropathies; Glomerular Filtration Rate; Humans; Odds Ratio; Proteinuria; Sarcopenia
PubMed: 31828155
DOI: 10.1155/2019/1365189 -
Renal Failure Dec 2023The long-term mortality of kidney transplantation patients with atypical hemolytic uremic syndrome remains high, and the efficacy of the main treatment eculizumab is... (Meta-Analysis)
Meta-Analysis Review
New findings in preventing recurrence and improving renal function in AHUS patients after renal transplantation treated with eculizumab: a systemic review and meta-analyses.
BACKGROUND
The long-term mortality of kidney transplantation patients with atypical hemolytic uremic syndrome remains high, and the efficacy of the main treatment eculizumab is still controversial.
OBJECTIVE
A comprehensive systematic review and meta-analysis of clinical trials using eculizumab in renal transplant patients with atypical hemolytic uremic syndrome was conducted to evaluate the efficacy of this therapy and its impact on renal function.
METHODS
A comprehensive systematic search was conducted across multiple reputable databases, including Ovid (MEDLINE, EMBASE), PubMed, and the Cochrane Library (since database inception), to identify relevant studies exploring the use of eculizumab in patients with atypical hemolytic uremic kidney transplantation. Various renal function parameters, such as dialysis, rejection, glomerular filtration rate, serum creatinine, lactate dehydrogenase, and platelet count, along with patient relapse rates, were extracted and summarized using a combination of robust statistical methods, including fixed effects, random effects, and general inverse variance methods.
RESULT
Eighteen trials with 618 subjects were analyzed. Our analysis suggests that the use of eculizumab is associated with a reduced likelihood of AHUS recurrence (odds ratio (OR) = 0.05, 95% CI: 0.00-0.13), as well as a significant reduction in the need for dialysis (odds ratio (OR) = 0.13, 95% CI: 0.01-0.32). Additionally, eculizumab treatment led to lower serum creatinine levels (mean differences (MD) = 126.931μmoI/L, 95% CI: 115.572μmoI/L-138.290μmoI/L) and an improved glomerular filtration rate (mean differences (MD) = 59.571 ml/min, 95% CI: 57.876 ml/min-61.266 mL/min). Our results also indicate that the use of eculizumab reduces the likelihood of rejection (odds ratio (OR) = 0.09, 95% CI: 0.01-0.22). Furthermore, the drug was effective in improving platelet counts (×10∧9/L) (mean differences (MD) = 163.421, 95% CI: 46.998-279.844) and lactate dehydrogenase levels (mean differences (MD) = 336.608 U/L, 95% CI: 164.816 U/L-508.399 U/L).
CONCLUSIONS
Based on the meta-analysis, treatment with eculizumab can reduce dialysis rates and improve patients' quality of life by enhancing renal function.
Topics: Humans; Atypical Hemolytic Uremic Syndrome; Creatinine; Kidney; Kidney Transplantation; Lactate Dehydrogenases; Quality of Life; Recurrence
PubMed: 37563792
DOI: 10.1080/0886022X.2023.2231264