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Medicine Feb 2024In China, Salvia miltiorrhiza and ligustrazine (SML) injection are widely used as adjunctive therapy for patients with diabetic kidney disease (DKD). However, different... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In China, Salvia miltiorrhiza and ligustrazine (SML) injection are widely used as adjunctive therapy for patients with diabetic kidney disease (DKD). However, different studies have reported conflicting results. Therefore, a systematic review and meta-analysis are necessary to assess the efficacy and safety of SML injection for the treatment of DKD.
METHODS
We searched 6 electronic literature databases comparing randomized controlled trials (RCTs) of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), SML injection in combination with ACEIs/ARBs that were conducted from inception until September 5, 2023. Two reviewers extracted data and independently assessed the risk of bias. Using the Cochrane Risk of Bias Tool for Risk Assessment. Mean differences (MD) were combined with random-effects models and the corresponding 95% confidence intervals (CI) were reported. Review Manager 5.4 software was used for meta-analysis. Stata 17.0 software was used for sensitivity analysis and Egger test.
RESULTS
The combined results show that the use of SML injection along with ACEI/ARB led to better outcomes than the use of controls in terms of enhancing recovery: renal function: Serum creatinine (MD = -14.69, 95% CI (-19.38, -10.00)), Blood urea nitrogen (MD = -1.23, 95% CI (-1.72, -0.74)), Urinary β2-microglobulin (MD = -4.58, 95% CI (-7.72, -1.44)); urinary protein: Urinary albumin excretion rate (MD = -45.74, 95% CI (-58.92, -32.56)), Urine albumin-creatinine ratio (MD = -11.93, 95% CI (-13.89, -9.96)), 24-h urine proteinuria (MD = -0.59, 95% CI (-0.86, -0.32)), Urine microalbumin (MD = -13.50, 95% CI (-20.18, -6.83)). Additionally, adjuvant therapy with SML injection enhanced results in blood glucose, blood pressure, lipids, and inflammatory responses, and no significant variations in adverse events were discovered between the 2 groups.
CONCLUSIONS
In patients with DKD, combining SML injection with ACEI/ARB improves renal function, renal proteinuria, hyperglycemia, blood pressure, dyslipidemia, and inflammatory response.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Salvia miltiorrhiza; Proteinuria; Albumins; Angiotensin Receptor Antagonists; Diabetes Mellitus; Pyrazines
PubMed: 38394516
DOI: 10.1097/MD.0000000000035853 -
Canadian Journal of Kidney Health and... 2023Type 2 diabetes (T2D) and kidney disease are risk factors for vitamin D deficiency. Native forms of vitamin D have a lower risk of hypercalcemia than calcitriol, the...
BACKGROUND
Type 2 diabetes (T2D) and kidney disease are risk factors for vitamin D deficiency. Native forms of vitamin D have a lower risk of hypercalcemia than calcitriol, the active hormone. The enzyme responsible for activating native vitamin D is now known to be expressed throughout the body; therefore, native vitamin D may have clinically relevant effects in many body systems.
OBJECTIVE
The objective of this systematic review was to examine the effect of native vitamin D supplementation on clinical outcomes and surrogate laboratory measures in patients with T2D and diabetic kidney disease (DKD).
DESIGN
Systematic review.
SETTING
Randomized controlled trials (RCTs) conducted in any country.
PATIENTS
Adults with T2D and DKD receiving supplementation with any form of native vitamin D (eg, ergocalciferol, cholecalciferol, calcifediol).
MEASUREMENTS
Clinical outcomes and surrogate clinical and laboratory measures reported in each of the trials were included in this review.
METHODS
The following databases were searched from inception to January 31, 2023: Embase, MEDLINE, Cochrane CENTRAL, Web of Science, ProQuest Dissertations and Theses, and medRxiv. Only RCTs examining supplementation with a native vitamin D form with a control or placebo comparison group were included. We excluded studies reporting only vitamin D status or mineral metabolism parameters, without any other outcomes of clinical relevance or surrogate laboratory measures. Study quality was evaluated using the Cochrane risk-of-bias tool (RoB2). Results were synthesized in summary tables for each type of outcome with the values from the original studies displayed.
RESULTS
Nine publications were included, corresponding to 5 separate RCTs (377 participants total). Mean age ranged from 40 to 63. All trials administered vitamin D. Intervention groups experienced improvements in vitamin D status and a reduction in proteinuria in 4 of the 5 included RCTs. There was a decrease in low-density lipoprotein and total cholesterol in the 2 trials in which they were measured. Improvements in bone mass, flow-mediated dilation, and inflammation were also reported, but each was only measured in 1 RCT. Effects on glucose metabolism, high-density lipoprotein, triglycerides, blood pressure, oxidative stress, and kidney function were mixed. No serious adverse effects were reported.
LIMITATIONS
Limitations include the small number of RCTs and lack of information on the use of drugs that affect measured outcomes (eg, proteinuria-lowering renin-angiotensin-aldosterone system inhibitors and lipid-lowering medication) in most studies. Our study is also limited by the absence of a prestudy protocol and registration.
CONCLUSIONS
Native vitamin D is a safe treatment that improves vitamin D status in patients with DKD. Vitamin D may modify proteinuria and lipid metabolism in DKD, but further well-designed trials that include well-established treatments are necessary. Overall, there is limited evidence for beneficial pleiotropic effects of vitamin D in patients with DKD.
PubMed: 38033482
DOI: 10.1177/20543581231212039 -
Cureus Apr 2024Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is an immune-mediated kidney disease characterized by the inflammation of small blood... (Review)
Review
Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is an immune-mediated kidney disease characterized by the inflammation of small blood vessels in the kidney, leading to renal impairment and potentially irreversible damage. Concerns have been raised over the reports of myeloperoxidase/perinuclear (MPO/p) ANCA GN following the coronavirus disease 2019 (COVID-19) vaccination. Our study provides a comprehensive insight into perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) GN after COVID-19 vaccination. We conducted a comprehensive literature search on PubMed, Cochrane Library, and EMBASE using the Medical Subject Headings (MeSH) terms related to "covid-19 vaccine," "glomerulonephritis," "p-ANCA," and "MPO-ANCA" up to March 5, 2024, to include cases of p-ANCA-associated GN following COVID-19 vaccination. Of the 4,102 articles, we included 29, reporting 35 patients demonstrating COVID-19 vaccine-induced p-ANCA GN, with 23 (65.7%) females and a median age of 69 years (mean ± SD = 63.22 ± 16). Twenty-six (74.28%) patients received the mRNA vaccine (Pfizer = 19, Moderna = 7). Seventeen (48.57%) patients presented with p-ANCA GN after the second dose of the COVID-19 vaccine, with a median gap of 19 days (1-84 days). Constitutional symptoms (54.28%) and acute kidney injury (42.85%) were the most reported initial presentations, and elevated serum creatinine (mean peak serum creatinine = 4.98 ± 5.02 mg/dL), hematuria, and proteinuria were the laboratory findings. MPO/p-ANCA was positive in 31 (88.6%) patients. All patients underwent renal biopsy, and crescentic GN was the most common finding among 27 (77.14%) patients. Management of p-ANCA GN included steroids in 30 (85.71%) patients, followed by rituximab (28.57%), and plasmapheresis (22.86%). Most patients responded well to treatment, with complete remission in 29 (82.86%) and relapse in four (11.42%) patients. Two patients did not achieve remission and became dialysis dependent. ANCA-associated GN is a rare and life-threatening complication of the COVID-19 vaccine, necessitating urgent evaluation and management. COVID-19 vaccine-induced p-ANCA GN should be included in the differential diagnoses of patients presenting with kidney injury after vaccination.
PubMed: 38817489
DOI: 10.7759/cureus.59390 -
Cureus Feb 2024The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs)... (Review)
Review
The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs) are antibodies that target cytotoxic thymus (T) lymphocyte antigen-4 (CTLA-4) and its receptor. They function by stimulating T-cell activity against malignancies. Immune-related adverse events (irAEs) are a distinct class of inflammatory side effects that are specific to a given organ. Antineoplastic medications can impact any part of the kidney, leading to the development of proteinuria, hypertension, electrolyte abnormalities, glomerulonephritis, and both acute and chronic interstitial nephritis. We reviewed the scientific literature regarding kidney problems that can arise from chemotherapy and immunotherapy for neoplasms, such as various cancers, melanoma, non-small cell lung cancer, and colorectal cancer. We discussed the pathophysiology, associated risk factors, management, and safety measures for patients experiencing acute renal injury after a new immunotherapy medication treatment. Antineoplastic drugs have the potential to damage the renal tubules, glomeruli, parenchyma, and blood vessels, among other kidney tissues. This can result in a broad spectrum of complications, spanning from a rise in serum creatinine levels without symptoms to the development of acute kidney injury (AKI). The research examined a range of risk factors associated with acute kidney injury (AKI). These factors encompassed age, gender, preexisting medical conditions (such as diabetes, hypertension, and chronic kidney disease), and the medications that patients were taking at the beginning of the study, which included non-steroidal anti-inflammatory drugs, renin-angiotensin system inhibitors, allopurinol, diuretics, corticosteroids, and proton pump inhibitors. The data suggests that patients who were receiving baseline treatment with proton pump inhibitors (PPIs) or corticosteroids had a higher risk of mortality. This study serves as an illustration of the effective management of acute kidney injury and proteinuria linked to novel immunotherapy drugs like pembrolizumab. The approach involved the use of corticosteroids tailored to the patient's condition. Furthermore, it references the recommendations outlined in the Common Terminology Criteria for Adverse Events (CTCAE). Prompt recognition and effective management of these side effects are essential to optimizing outcomes for patients undergoing immunotherapy. Our results were refined and focused by utilizing Medical Subject Headings (MeSH) keywords in our search strategy. The MeSH keywords used were "renal side effects" OR "immunotherapy" OR "cancer treatment." The studies reviewed encompassed a total of 48,529 participants among the 21 studies examined.
PubMed: 38516472
DOI: 10.7759/cureus.54487 -
Liver Cancer Dec 2023The aim of the study was to investigate the incidence and spectrum of adverse events in unresectable hepatocellular carcinoma (HCC) patients treated with immune...
Adverse Events of Immune Checkpoint Inhibitor-Based Therapies for Unresectable Hepatocellular Carcinoma in Prospective Clinical Trials: A Systematic Review and Meta-Analysis.
BACKGROUND
The aim of the study was to investigate the incidence and spectrum of adverse events in unresectable hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs) or ICI-based combinations.
SUMMARY
The study protocol was prospectively registered on PROSPERO (CRD42022319255). We searched PubMed, EMBASE, and the Cochrane Library for published clinical trials from database inception to April 22, 2022. Studies that included at least one group of unresectable HCC patients treated with ICIs or ICI-based combinations and reported the incidence or spectrum of treatment-related adverse events (trAEs) or immune-related adverse events (irAEs) were eligible. The incidence and spectra of all-grade and grade ≥3 trAEs were the primary outcomes. The profiles of irAEs, the incidence of trAEs leading to treatment discontinuation, and treatment-related mortalities were additional outcomes. We applied random-effects models to pool the incidence and spectra of adverse events. Subgroup analyses and meta-regression were performed. The literature search identified 2,464 records. Twenty studies (4,146 participants with HCC) met the eligibility criteria. The pooled incidences of all-grade trAEs, grade ≥3 trAEs, all-grade irAEs, and grade ≥3 irAEs were 80.1% (95% CI: 73.8-85.2), 35.4% (95% CI: 27.2-44.6), 31.1% (95% CI: 21.0-43.5), and 6.6% (95% CI: 3.6-11.8), respectively. ICIs plus oral targeted agents (all-grade OR = 17.07, 95% CI: 6.05-48.16, < 0.001; grade ≥3 OR = 9.35, 95% CI: 4.53-19.29, < 0.001) and ICIs plus intravenous targeted agents (all-grade OR = 4.91, 95% CI: 1.80-13.42, = 0.003; grade ≥3 OR = 4.21, 95% CI: 1.42-12.48, = 0.012) were associated with increased trAEs compared with monotherapy. The all-grade trAEs with the highest pooled incidences were reactive capillary endothelial proliferation (49.2%, 95% CI: 26.3-72.3), neutropenia (34.6%, 95% CI: 17.1-57.5), and proteinuria (32.8%, 95% CI: 19.8-49.2). The grade ≥3 trAEs with the highest pooled incidences were hypertension (11.1%, 95% CI: 4.0-29.0), neutropenia (10.5%, 95% CI: 7.0-15.4), and increased aspartate aminotransferase (7.7%, 95% CI: 6.3-9.4). The pooled incidence of trAEs leading to treatment discontinuation was 8.0% (95% CI: 6.0-10.5), and the overall incidence of treatment-related mortalities was 1.1%.
KEY MESSAGES
This study comprehensively summarized the incidence and spectrum of trAEs in unresectable HCC patients receiving ICIs or ICI-based combinations in clinical trials. The results from this study will provide a useful reference to guide clinical practice.
PubMed: 38476294
DOI: 10.1159/000528698 -
European Journal of Preventive... Jan 2024Hypertensive pregnancy is associated with increased risks of developing a range of vascular disorders in later life. Understanding when hypertensive target organ damage...
AIMS
Hypertensive pregnancy is associated with increased risks of developing a range of vascular disorders in later life. Understanding when hypertensive target organ damage first emerges could guide optimal timing of preventive interventions. This review identifies evidence of hypertensive target organ damage across cardiac, vascular, cerebral, and renal systems at different time points from pregnancy to postpartum.
METHODS AND RESULTS
Systematic review of Ovid/MEDLINE, EMBASE, and ClinicalTrials.gov up to and including February 2023 including review of reference lists. Identified articles underwent evaluation via a synthesis without meta-analysis using a vote-counting approach based on direction of effect, regardless of statistical significance. Risk of bias was assessed for each outcome domain, and only higher quality studies were used for final analysis. From 7644 articles, 76 studies, including data from 1 742 698 pregnancies, were identified of high quality that reported either blood pressure trajectories or target organ damage during or after a hypertensive pregnancy. Left ventricular hypertrophy, white matter lesions, proteinuria, and retinal microvasculature changes were first evident in women during a hypertensive pregnancy. Cardiac, cerebral, and retinal changes were also reported in studies performed during the early and late post-partum period despite reduction in blood pressure early postpartum. Cognitive dysfunction was first reported late postpartum.
CONCLUSION
The majority of target organ damage reported during a hypertensive pregnancy remains evident throughout the early and late post-partum period despite variation in blood pressure. Early peri-partum strategies may be required to prevent or reverse target organ damage in women who have had a hypertensive pregnancy.
Topics: Female; Humans; Pregnancy; Postpartum Period; Hypertension, Pregnancy-Induced; Pregnancy Complications, Cardiovascular; Time Factors
PubMed: 37607255
DOI: 10.1093/eurjpc/zwad275 -
PloS One 2024The objective of this study was to evaluate the relationship between the platelet-to-lymphocyte ratio (PLR) and systemic lupus erythematosus (SLE). Additionally, the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to evaluate the relationship between the platelet-to-lymphocyte ratio (PLR) and systemic lupus erythematosus (SLE). Additionally, the study aimed to establish an association between PLR and SLE disease activity, specifically lupus nephritis (LN).
METHODS
We conducted a comprehensive search across Medline, Embase, and Cochrane databases to identify relevant articles. Subsequently, we performed meta-analyses to compare PLR between SLE patients and controls, as well as active and inactive SLE cases, along with LN and non-LN groups. Furthermore, a meta-analysis was conducted on correlation coefficients between PLR and various parameters in SLE patients, including the SLE Disease Activity Index (SLEDAI), C3, C4, anti-dsDNA, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).
RESULTS
In total, fifteen studies comprising 1,522 SLE patients and 1,424 controls were eligible for inclusion. The meta-analysis demonstrated a significant elevation of PLR in the SLE group compared to the control group (Standardized Mean Difference [SMD] = 0.604, 95% Confidence Interval [CI] = 0.299-0.909, p < 0.001). Upon stratification by ethnicity, an elevated PLR was observed in the SLE group among both Asian and Arab populations. Subgroup analysis based on sample size revealed consistently higher PLR in both small (n < 200) and large sample (n ≥ 200) SLE groups. Moreover, when considering disease activity, there was a noteworthy trend of increased PLR in the active disease group compared to the inactive group (SMD = 0.553, 95% CI = 0.000-1.106, p = 0.050). However, the meta-analysis did not demonstrate a significant distinction in PLR between the LN and non-LN groups. Notably, a positive association was established between PLR and SLEDAI (correlation coefficient = 0.325, 95% CI = 0.176-0.459, p < 0.001). Furthermore, PLR exhibited positive correlations with ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels.
CONCLUSIONS
The outcomes of this meta-analysis underscored the elevated PLR in SLE patients, suggesting its potential as a biomarker for gauging systemic inflammation in SLE. Additionally, PLR exhibited correlations with SLEDAI, as well as with key indicators such as ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels.
Topics: Humans; Lupus Erythematosus, Systemic; Biomarkers; Lymphocytes; Blood Platelets; Inflammation; Blood Sedimentation; Platelet Count; C-Reactive Protein; Lupus Nephritis; Lymphocyte Count
PubMed: 38753735
DOI: 10.1371/journal.pone.0303665 -
Cureus Jan 2024Idiopathic membranous nephropathy (IMN) with moderate risk or above was recommended to receive immunosuppressive therapy. We attempted to evaluate the optimal dose of... (Review)
Review
PURPOSE
Idiopathic membranous nephropathy (IMN) with moderate risk or above was recommended to receive immunosuppressive therapy. We attempted to evaluate the optimal dose of glucocorticoid when combined with evidence-proven effective immunosuppressants by network meta-analysis.
METHODS
A systematic review of the literature was conducted in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until January 2022. Randomized controlled trials (RCTs) in IMN limited to supportive care, glucocorticoids, cyclophosphamide, chlorambucil, calcineurin inhibitors (CNIs), and rituximab were screened.
RESULTS
Twenty-eight RCTs of 1,830 patients were included. Therapeutic regimens were divided as follows: moderate- to high-dose glucocorticoids plus CNIs (HMSCn), moderate- to high-dose glucocorticoids plus cyclophosphamide (HMSCt), moderate- to high-dose glucocorticoids plus chlorambucil (HMSCh), zero- to low-dose glucocorticoids plus CNIs (LNSCn), zero- to low-dose glucocorticoids plus cyclophosphamide (LNSCt), rituximab alone (R), glucocorticoids alone (SE), and supportive care alone (SP). Compared with SP, HMSCh (risk ratio [RR]: 1.77, 95% confidence interval [CI]: 1, 3.18), HMSCn (RR: 2.5, 95%CI: 1.25, 5.11), HMSCt (RR: 2.15, 95%CI: 1.29, 3.64), LNSCn (RR: 2.16, 95%CI: 1.25, 3.95), and R (RR: 2.07, 95%CI: 1, 4.39) had a higher probability of total remission rate, while HMSCn represented the highest probability depending on the surface under the cumulative ranking area (SUCRA) ranking values. Regarding infection, no significant difference was found between different doses of glucocorticoids plus the same immunosuppressant. HMSCn and HMSCt showed superiority in reducing 24-hour urine total protein compared with HMSCh, LNSCn, SE, and SP, while HMSCn seemed to be the most effective regimen through the ranking of SUCRA value.
CONCLUSION
Moderate- to high-dose glucocorticoids showed superiority in proteinuria remission when combined with CNIs in IMN, with no increasing risk of infection.
PubMed: 38333440
DOI: 10.7759/cureus.51936 -
Internal and Emergency Medicine Jan 2024Henoch-Schonlein purpura (HSP) is an IgA-mediated systemic small-vessel vasculitis (IgAV) that typically presents with a variable tetrad of symptoms. HSP if often...
BACKGROUND
Henoch-Schonlein purpura (HSP) is an IgA-mediated systemic small-vessel vasculitis (IgAV) that typically presents with a variable tetrad of symptoms. HSP if often preceded by respiratory tract infections, vaccinations, drugs or malignancies. During the recent COVID-19 pandemic multiples cases of HSP have been described after both infection and vaccination for SARS-CoV2. This study aims to perform a systematic review of literature and describe an additional complicated case of de-novo HSP appeared after the administration of the third dose of a mRNA-SARS-CoV2 vaccination.
METHODS
Electronic bibliographic research was performed to identify all the original reports describing cases of de-novo HSP or IgAV appeared after respiratory infection or vaccine administration for SARS-CoV2. We included all case series or case reports of patients who respected our inclusion and exclusion criteria.
RESULTS
Thirty-eight publications met our pre-defined inclusion criteria, for an overall number of 44 patients. All patients presented with palpable purpura variable associated with arthralgia, abdominal pain or renal involvement. Increased levels of inflammation markers, mild leukocytosis and elevated D-dimer were the most common laboratory findings. Up to 50% of patients presented proteinuria and/or hematuria. Almost all skin biopsies showed leukocytoclastic vasculitis, with IgA deposits at direct immunofluorescence in more than 50% of cases.
CONCLUSIONS
Our results suggest that the immune response elicited by SARS-CoV2 vaccine or infection could play a role in the development of HSP. Current research suggests a possible role of IgA in immune hyperactivation, highlighted by early seroconversion to IgA found in some COVID-19 patients who develop IgA vasculitis.
Topics: Humans; COVID-19; IgA Vasculitis; Immunoglobulin A; Pandemics; RNA, Viral; SARS-CoV-2; Vaccines
PubMed: 37500944
DOI: 10.1007/s11739-023-03366-w -
Clinical Nephrology Oct 2023Regular monitoring is required to ensure that patients who have, or are at risk of, chronic kidney disease (CKD) receive appropriate management. Guidelines recommend...
BACKGROUND
Regular monitoring is required to ensure that patients who have, or are at risk of, chronic kidney disease (CKD) receive appropriate management. Guidelines recommend regular testing of estimated glomerular filtration rate (GFR) and albuminuria. However, evidence suggests that albuminuria testing rates, specifically urine albumin-to-creatinine ratio (UACR), are suboptimal.
AIM
To assess published evidence relating to the drivers of non-adherence to albuminuria testing guidelines and the impact of not identifying CKD across the course of progression.
MATERIALS AND METHODS
A systematic review of five bibliographic databases was conducted, supplemented by hand searches of relevant conference abstracts.
RESULTS
One study was identified that reported drivers of non-adherence to albuminuria testing guidelines. The largest barrier was the perception that testing does not impact patient management. Thirteen studies were identified that evaluated the impact of not identifying CKD patients. All included studies analyzed the effect of not identifying worsening CKD severity leading to late referral (LR). 12/13 studies reported only on clinical impact, and 1/13 reported on clinical and economic impact. LR led to higher costs and worse outcomes than early referral, including higher rates of mortality and worsened kidney replacement therapy preparation.
CONCLUSION
This systematic review demonstrates a gap in evidence exploring the drivers of non-adherence to albuminuria testing guidelines and the impact of not identifying patients in the early stages of CKD. Guideline-recommended testing allows timely identification, referral, and treatment for patients with, or at risk of, CKD, providing the best chance of avoiding the worsened outcomes identified in this review.
Topics: Humans; Albuminuria; Dietary Supplements; Referral and Consultation; Renal Insufficiency, Chronic
PubMed: 37644841
DOI: 10.5414/CN111106