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Annals of Medicine Dec 2023Trimethylamine N-oxide (TMAO) derived from gut microbiota causes kidney-heart damage in chronic kidney disease (CKD) patients. However, it is controversial whether CKD... (Meta-Analysis)
Meta-Analysis
Gut microbiota-derived trimethylamine N-oxide is associated with the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease: a systematic review and dose-response meta-analysis.
BACKGROUND
Trimethylamine N-oxide (TMAO) derived from gut microbiota causes kidney-heart damage in chronic kidney disease (CKD) patients. However, it is controversial whether CKD patients with higher TMAO are associated with a higher risk of death. We aimed to assess the correlation between circulating TMAO concentration and the risk of all-cause and cardiovascular death in CKD patients of different dialysis statuses and different races by dose-response analyses, and the underlying mechanisms were also explored by analyzing the correlations of TMAO with glomerular filtration rate (GFR) and inflammation.
METHOD
PubMed, Web of Science, and EMBASE were systematically searched up to 1 July 2022. A total of 21 studies involving 15,637 individuals were included. Stata 15.0 was used to perform the meta-analyses and dose-response analyses with extracted data. Subgroup analyses were conducted to recognize possible sources of heterogeneity.
RESULTS
The risk of all-cause mortality was increased in non-dialysis CKD patients (RR = 1.26, 95%CI = 1.03-1.54, = 0.028) and non-black dialysis patients (RR = 1.62, 95%CI = 1.19-2.22, = 0.002) with the highest circulating TMAO concentration, and the association was confirmed to be linear. In addition, an increased risk of cardiovascular mortality was also found in non-black dialysis patients with the highest circulating TMAO concentration (RR = 1.72, 95%CI = 1.19-2.47, = 0.004), likewise, a linear association was identified. However, for dialysis patients including blacks with high TMAO concentrations, there was no significant increase in either all-cause mortality (RR = 0.98, 95%CI = 0.94-1.03, = 0.542) or cardiovascular mortality (RR = 0.87, 95% CI = 0.65-1.17, = 0.362). Meanwhile, we verified strong correlations between TMAO and both GFR (= -0.49; 95% CI= -0.75, -0.24; < 0.001) and inflammatory markers ( = 0.43; 95% CI= 0.03, 0.84; = 0.036) in non-dialysis patients.
CONCLUSIONS
Increased circulating TMAO concentrations increase the risk of all-cause mortality in non-dialysis and non-black dialysis CKD patients. Moreover, elevated TMAO levels raise the cardiovascular mortality risk in non-black dialysis patients.Key messagesNon-dialysis and non-black dialysis CKD patients with higher circulating TMAO concentrations are associated with an increased risk of all-cause mortality.Non-black dialysis patients with higher concentrations of TMAO are associated with an increased risk of cardiovascular mortality.Circulating TMAO concentrations have a strong negative correlation with GFR and a positive correlation with inflammation biomarkers in non-dialysis CKD patients.
Topics: Humans; Cardiovascular Diseases; Gastrointestinal Microbiome; Inflammation; Renal Insufficiency, Chronic
PubMed: 37246850
DOI: 10.1080/07853890.2023.2215542 -
Frontiers in Pharmacology 2023is a core Chinese herbal medicine for the treatment of diabetes and diabetic nephropathy (DN). It has been used for the treatment of diabetes for over 1,000 years.... (Review)
Review
is a core Chinese herbal medicine for the treatment of diabetes and diabetic nephropathy (DN). It has been used for the treatment of diabetes for over 1,000 years. Catalpol is the main active compound in Rehmannia roots. Current evidence suggests that catalpol exhibits significant anti-diabetic bioactivity, and thus it has attracted increasing research attention for its potential use in treating DN. However, no studies have systematically evaluated these effects, and its mechanism of action remains unclear. This study aimed to evaluate the effects of catalpol on DN, as well as to summarize its possible mechanisms of action, in DN animal models. We included all DN-related animal studies with catalpol intervention. These studies were retrieved by searching eight databases from their dates of inception to July 2022. In addition, we evaluated the methodological quality of the included studies using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool. Furthermore, we calculated the weighted standard mean difference (SMD) with 95% confidence interval (CI) using the Review Manager 5.3 software and evaluated publication bias using the Stata (12.0) software. A total of 100 studies were retrieved, of which 12 that included 231 animals were finally included in this review. As compared to the control treatment, treatment with catalpol significantly improved renal function in DN animal models by restoring serum creatinine (Scr) ( = 0.0009) and blood urea nitrogen (BUN) ( < 0.00001) levels, reducing proteinuria ( < 0.00001) and fasting blood glucose (FBG) ( < 0.0001), improving kidney indices ( < 0.0001), and alleviating renal pathological changes in the animal models. In addition, it may elicit its effects by reducing inflammation and oxidative stress, improving podocyte apoptosis, regulating lipid metabolism, delaying renal fibrosis, and enhancing autophagy. The preliminary findings of this preclinical systematic review suggest that catalpol elicits significant protective effects against hyperglycemia-induced kidney injury. However, more high-quality studies need to be carried out in the future to overcome the methodological shortcomings identified in this review.
PubMed: 37621314
DOI: 10.3389/fphar.2023.1192694 -
Clinical Nutrition (Edinburgh, Scotland) Aug 2023Low-intake dehydration amongst older people, caused by insufficient fluid intake, is associated with mortality, multiple long-term health conditions and hospitalisation.... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Low-intake dehydration amongst older people, caused by insufficient fluid intake, is associated with mortality, multiple long-term health conditions and hospitalisation. The prevalence of low-intake dehydration in older adults, and which groups are most at-risk, is unclear. We conducted a high-quality systematic review and meta-analysis, implementing an innovative methodology, to establish the prevalence of low-intake dehydration in older people (PROSPERO registration: CRD42021241252).
METHOD
We systematically searched Medline (Ovid), Cochrane CENTRAL, Embase (Ovid), CINAHL and Proquest from inception until April 2023 and Nutrition and Food Sciences until March 2021. We included studies that assessed hydration status for non-hospitalised participants aged ≥65 years, by directly-measured serum/plasma osmolality, calculated serum/plasma osmolarity and/or 24-h oral fluid intake. Inclusion, data extraction and risk of bias assessment was carried out independently in duplicate.
RESULTS
From 11,077 titles and abstracts, we included 61 (22,398 participants), including 44 in quality-effects meta-analysis. Meta-analysis suggested that 24% (95% CI: 0.07, 0.46) of older people were dehydrated (assessed using directly-measured osmolality >300 mOsm/kg, the most reliable measure). Subgroup analyses indicated that both long-term care residents (34%, 95% CI: 0.09, 0.61) and community-dwelling older adults (19%, 95% CI: 0.00, 0.48) were highly likely to be dehydrated. Those with more pre-existing illnesses (37%, 95% CI: 0.14, 0.62) had higher low-intake dehydration prevalence than others (15%, 95% CI: 0.00, 0.43), and there was a non-significant suggestion that those with renal impairment (42%, 95% CI: 0.23, 0.61) were more likely to be dehydrated than others (23%, 95% CI: 0.03, 0.47), but there were no clear differences in prevalence by age, sex, functional, cognitive or diabetic status. GRADE quality of evidence was low as to the exact prevalence due to high levels of heterogeneity between studies.
CONCLUSION
Quality-effects meta-analysis estimated that a quarter of non-hospitalised older people were dehydrated. Widely varying prevalence rates in individual studies, from both long-term care and community groups, highlight that dehydration is preventable amongst older people.
IMPLICATIONS
One in every 4 older adults has low-intake dehydration. As dehydration is serious and prevalent, research is needed to better understand drinking behaviour and assess effectiveness of drinking interventions for older people.
Topics: Humans; Aged; Dehydration; Prevalence; Long-Term Care; Nutritional Status; Hospitalization
PubMed: 37330324
DOI: 10.1016/j.clnu.2023.06.010 -
Cureus Sep 2023Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug widely used as part of antiretroviral therapy (ART) to treat human immunodeficiency virus (HIV-1)... (Review)
Review
Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug widely used as part of antiretroviral therapy (ART) to treat human immunodeficiency virus (HIV-1) infection. Negative effects of tenofovir include impaired kidney function, especially with long-term use. In studies conducted among HIV-positive individuals, we found evidence of extensive kidney damage associated with TDF use. Despite the therapeutic importance of this consequence, its continued use in ART regimens was not contraindicated. The therapeutic and long-term effects of TDF are a major concern. However, in countries or settings where resources are limited and renal function monitoring cannot be ensured, screening methods to detect ART-related renal failure are still supported by data. Therefore, it is safe to re-evaluate the use of TDF-based ART. However, adherence to guidelines may be hampered by insufficient laboratory testing in low- and middle-income countries. More research is also needed among people under 18 years of age and pregnant and breastfeeding mothers.
PubMed: 37872903
DOI: 10.7759/cureus.45787 -
Communications Medicine Oct 2023A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in...
BACKGROUND
A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy.
METHODS
We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review.
RESULTS
Here we show that the majority of included papers have methodological limitations precluding robust assessment of treatment effect heterogeneity. For SGLT2-inhibitors, multiple observational studies suggest lower renal function as a predictor of lesser glycaemic response, while markers of reduced insulin secretion predict lesser glycaemic response with GLP1-receptor agonists. For both therapies, multiple post-hoc analyses of randomized control trials (including trial meta-analysis) identify minimal clinically relevant treatment effect heterogeneity for cardiovascular and renal outcomes.
CONCLUSIONS
Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.
PubMed: 37794166
DOI: 10.1038/s43856-023-00359-w -
Diagnostics (Basel, Switzerland) Apr 2024: To evaluate the clinical usefulness of demographic data, fetal imaging findings and urinary analytes were used for predicting poor postnatal renal function in children... (Review)
Review
: To evaluate the clinical usefulness of demographic data, fetal imaging findings and urinary analytes were used for predicting poor postnatal renal function in children with congenital megacystis. : A systematic review was conducted in MEDLINE's electronic database from inception to December 2023 using various combinations of keywords such as "luto" [All Fields] OR "lower urinary tract obstruction" [All Fields] OR "urethral valves" [All Fields] OR "megacystis" [All Fields] OR "urethral atresia" [All Fields] OR "megalourethra" [All Fields] AND "prenatal ultrasound" [All Fields] OR "maternal ultrasound" [All Fields] OR "ob-stetric ultrasound" [All Fields] OR "anhydramnios" [All Fields] OR "oligohydramnios" [All Fields] OR "renal echogenicity" [All Fields] OR "biomarkers" [All Fields] OR "fetal urine" [All Fields] OR "amniotic fluid" [All Fields] OR "beta2 microglobulin" [All Fields] OR "osmolarity" [All Fields] OR "proteome" [All Fields] AND "outcomes" [All Fields] OR "prognosis" [All Fields] OR "staging" [All Fields] OR "prognostic factors" [All Fields] OR "predictors" [All Fields] OR "renal function" [All Fields] OR "kidney function" [All Fields] OR "renal failure" [All Fields]. Two reviewers independently selected the articles in which the accuracy of prenatal imaging findings and fetal urinary analytes were evaluated to predict postnatal renal function. : Out of the 727 articles analyzed, 20 met the selection criteria, including 1049 fetuses. Regarding fetal imaging findings, the predictive value of the amniotic fluid was investigated by 15 articles, the renal appearance by 11, bladder findings by 4, and ureteral dilatation by 2. The postnatal renal function showed a statistically significant relationship with the occurrence of oligo- or anhydramnion in four studies, with an abnormal echogenic/cystic renal cortical appearance in three studies. Single articles proved the statistical prognostic value of the amniotic fluid index, the renal parenchymal area, the apparent diffusion coefficient (ADC) measured on fetal diffusion-weighted MRI, and the lower urinary tract obstruction (LUTO) stage (based on bladder volume at referral and gestational age at the appearance of oligo- or anhydramnios). Regarding the predictive value of fetal urinary analytes, sodium and β2-microglobulin were the two most common urinary analytes investigated (n = 10 articles), followed by calcium (n = 6), chloride (n = 5), urinary osmolarity (n = 4), and total protein (n = 3). Phosphorus, glucose, creatinine, and urea were analyzed by two articles, and ammonium, potassium, N-Acetyl-l3-D-glucosaminidase, and microalbumin were investigated by one article. The majority of the studies (n = 8) failed to prove the prognostic value of fetal urinary analytes. However, two studies showed that a favorable urinary biochemistry profile (made up of sodium < 100 mg/dL; calcium < 8 mg/dL; osmolality < 200 mOsm/L; β2-microglobulin < 4 mg/L; total protein < 20 mg/dL) could predict good postnatal renal outcomes with statistical significance and urinary levels of β2-microglobulin were significantly higher in fetuses that developed an impaired renal function in childhood (10.9 ± 5.0 mg/L vs. 1.3 ± 0.2 mg/L, -value < 0.05). : Several demographic data, fetal imaging parameters, and urinary analytes have been shown to play a role in reliably triaging fetuses with megacystis for the risk of adverse postnatal renal outcomes. We believe that this systematic review can help clinicians for counseling parents on the prognoses of their infants and identifying the selected cases eligible for antenatal intervention.
PubMed: 38611669
DOI: 10.3390/diagnostics14070756 -
JACC. Advances Feb 2024Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM)-1 are renal biomarkers increasingly appreciated for their role in the...
BACKGROUND
Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM)-1 are renal biomarkers increasingly appreciated for their role in the risk stratification and prognostication of heart failure (HF) patients. However, very few have been adopted clinically, owing to the lack of consistency.
OBJECTIVES
The authors aimed to study the association between cystatin C, NGAL, and KIM-1 and outcomes, mortality, hospitalizations, and worsening renal function (WRF) in patients with acute and chronic HF.
METHODS
We included peer-reviewed English-language articles from PubMed and EMBASE published up to December 2021. We analyzed the above associations using random-effects meta-analysis. Publication bias was assessed using funnel plots.
RESULTS
Among 2,631 articles, 100 articles, including 45,428 patients, met the inclusion criteria. Top-tertile of serum cystatin C, when compared to the bottom-tertile, carried a higher pooled hazard ratio (pHR) for mortality (pHR: 1.59, 95% CI: 1.42-1.77) and for the composite outcome of mortality and HF hospitalizations (pHR: 1.49, 95% CI: 1.23-1.75). Top-tertile of serum NGAL had a higher hazard for mortality (pHR: 2.91, 95% CI: 1.49-5.67) and composite outcome (HR: 4.11, 95% CI: 2.69-6.30). Serum and urine NGAL were significantly associated with WRF, with pHRs of 2.40 (95% CI: 1.48-3.90) and 2.01 (95% CI: 1.21-3.35). Urine KIM-1 was significantly associated with WRF (pHR: 1.60, 95% CI: 1.24-2.07) but not with other outcomes. High heterogeneity was noted between studies without an obvious explanation based on meta-regression.
CONCLUSIONS
Serum cystatin C and serum NGAL are independent predictors of adverse outcomes in HF. Serum and urine NGAL are important predictors of WRF in HF.
PubMed: 38939376
DOI: 10.1016/j.jacadv.2023.100765 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal... (Review)
Review
INTRODUCTION
Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal is the ultimate goal of kidney transplantation, and is made possible by the induction of immunological tolerance. The purpose of this paper is to review the safety and efficacy of immune tolerance induction strategies in living-donor kidney transplantation, both chimerism-based and non-chimerism-based. The impact of these strategies on transplant outcomes, including acute rejection, allograft function and survival, cost, and immune monitoring, will also be discussed.
MATERIALS AND METHODS
Databases such as PubMed, Scopus, and Web of Science, as well as additional online resources such as EBSCO, were exhaustively searched. Adult living-donor kidney transplant recipients who developed chimerism-based tolerance after concurrent bone marrow or hematopoietic stem cell transplantation or those who received non-chimerism-based, non-hematopoietic cell therapy using mesenchymal stromal cells, dendritic cells, or regulatory T cells were studied between 2000 and 2021. Individual sources of evidence were evaluated critically, and the strength of evidence and risk of bias for each outcome of the transplant tolerance study were assessed.
RESULTS
From 28,173 citations, 245 studies were retrieved after suitable exclusion and duplicate removal. Of these, 22 studies (2 RCTs, 11 cohort studies, 6 case-control studies, and 3 case reports) explicitly related to both interventions (chimerism- and non-chimerism-based immune tolerance) were used in the final review process and were critically appraised. According to the findings, chimerism-based strategies fostered immunotolerance, allowing for the safe withdrawal of immunosuppressive medications. Cell-based therapy, on the other hand, frequently did not induce tolerance except for minimising immunosuppression. As a result, the rejection rates, renal allograft function, and survival rates could not be directly compared between these two groups. While chimerism-based tolerance protocols posed safety concerns due to myelosuppression, including infections and graft-versus-host disease, cell-based strategies lacked these adverse effects and were largely safe. There was a lack of direct comparisons between HLA-identical and HLA-disparate recipients, and the cost implications were not examined in several of the retrieved studies. Most studies reported successful immunosuppressive weaning lasting at least 3 years (ranging up to 11.4 years in some studies), particularly with chimerism-based therapy, while only a few investigators used immune surveillance techniques. The studies reviewed were often limited by selection, classification, ascertainment, performance, and attrition bias.
CONCLUSIONS
This review demonstrates that chimerism-based hematopoietic strategies induce immune tolerance, and a substantial number of patients are successfully weaned off immunosuppression. Despite the risk of complications associated with myelosuppression. Non-chimerism-based, non-hematopoietic cell protocols, on the other hand, have been proven to facilitate immunosuppression minimization but seldom elicit immunological tolerance. However, the results of this review must be interpreted with caution because of the non-randomised study design, potential confounding, and small sample size of the included studies. Further validation and refinement of tolerogenic protocols in accordance with local practice preferences is also warranted, with an emphasis on patient selection, cost ramifications, and immunological surveillance based on reliable tolerance assays.
Topics: Adult; Humans; Kidney Transplantation; Living Donors; Immune Tolerance; Hematopoietic Stem Cell Transplantation; Transplantation, Homologous; Transplantation Tolerance
PubMed: 37709652
DOI: 10.1016/j.trre.2023.100792 -
European Journal of Cardio-thoracic... Oct 2023Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize... (Review)
Review
OBJECTIVES
Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize the current evidence and provide literature-based recommendations for the management of patients on DOACs in the perioperative phase.
METHODS
A general literature review was conducted on the pharmacology of DOACs and for recommendations on the management of cardiac surgical patients on DOACs. Additionally, we performed a systematic review for studies on the use of direct DOAC reversal agents in the emergency cardiac surgical setting.
RESULTS
When surgery is elective, the DOAC cessation strategy is relatively straightforward and should be adapted to the renal function. The same approach applies to urgent cases, but additional DOAC activity drug level monitoring tests may be useful. In emergency cases, idarucizumab can be safely administered to patients on dabigatran in any of the perioperative phases. However, andexanet alfa, which is not registered for perioperative use, should not be administered in the preoperative phase to reverse the effect of factor Xa inhibitors, as it may induce temporary heparin resistance. Finally, the administration of (activated) prothrombin complex concentrate may be considered in all patients on DOACs, and such concentrates are generally readily available.
CONCLUSIONS
DOACs offer several advantages over vitamin K antagonists, but care must be taken in patients undergoing cardiac surgery. Although elective and urgent cases can be managed relatively straightforwardly, the management of emergency cases requires particular attention.
Topics: Humans; Administration, Oral; Anticoagulants; Cardiac Surgical Procedures; Dabigatran; Hemorrhage; Heparin
PubMed: 37812245
DOI: 10.1093/ejcts/ezad340 -
BMC Cancer Nov 2023In muscle-invasive bladder cancer (MIBC), neoadjuvant chemotherapy (NAC) combined with radical cystectomy (RC) is critical in reducing disease recurrence, with GC... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In muscle-invasive bladder cancer (MIBC), neoadjuvant chemotherapy (NAC) combined with radical cystectomy (RC) is critical in reducing disease recurrence, with GC (gemcitabine and cisplatin) being one of the most commonly used NACs. Different GC schedules have been used, but the best neoadjuvant regimen is still unknown. The clinical outcomes of 3 and 4 cycles of neoadjuvant GC are compared in this systematic review and meta-analysis to determine which is best for patients with MIBC.
METHODS
We searched PubMed, Embase, Web of Science, Cochrane Library, CBM, CNKI, WAN FANG DATA, and meeting abstracts to identify relevant studies up to March 2023. Studies that compared 3 and 4 cycles of neoadjuvant GC for MIBC were included. The primary outcomes were pCR, pDS, OS, and CSS. The secondary outcome was recurrence and SAEs.
RESULTS
A total of 3 studies, with 1091 patients, were included in the final analysis. Patients that received 4 cycles of GC had a higher pCR (OR = 0.66; 95% CI, 0.50-0.87; p = 0.003) and pDS (OR = 0.63; 95% CI, 0.48-0.84; p = 0.002) than those who received 3 cycles. Regarding recurrence rate (OR = 1.23; 95% CI, 0.91-1.65; p = 0.18), there were no appreciable differences between the 3 and 4 cycles of GC. Survival parameters such as OS (HR, 1.35; 95% CI, 0.86-2.12; p = 0.19) and CSS (HR, 1.06; 95% CI, 0.82-1.38; p = 0.20) were similar. Only one trial reported on the outcomes of SAEs. And there were no statistically significant differences in thrombocytopenia, infection rate, neutropenic fever, anemia, or decreased renal function between patients. The neutropenia of patients was statistically different (OR = 0.72; 95% CI, 0.52-0.99; p = 0.04).
CONCLUSION
The 4-cycle GC regimen was superior to the 3-cycle regimen in only the pCR and pDS results. Survival and recurrence rates were similar between the two regimens. In both treatment regimes, the toxicity profile was manageable. However, due to the inherent drawbacks of retrospective research, this should be regarded with caution.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cystectomy; Gemcitabine; Muscles; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Retrospective Studies; Urinary Bladder Neoplasms
PubMed: 37932689
DOI: 10.1186/s12885-023-11572-0