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International Journal of Cardiology Aug 2023Cardiometabolic index (CMI) is recently considered to have certain significance in the screening of diabetes, atherosclerosis, and renal dysfunction. Therefore, this...
PURPOSE
Cardiometabolic index (CMI) is recently considered to have certain significance in the screening of diabetes, atherosclerosis, and renal dysfunction. Therefore, this study intends to explore the relationship between CMI and the risk of albuminuria.
METHODS
This is a cross-sectional study involving 2732 elderly people (age ≥ 60). The research data are from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Calculate CMI index: Triglyceride (TG) (mmol/L)/ High density lipid-cholesterol (HDLC) (mmol/L) × WHtR.
RESULTS
The CMI level in microalbuminuria group was significantly higher than that in normal albuminuria group (P < 0.05 or P < 0.01), whether in the general population or in diabetes and hypertensive population respectively. The proportion of abnormal microalbuminuria increased gradually with the increase of CMI tertile interval (P < 0.01). Correlation analysis showed that CMI was positively correlated with urinary albumin-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine (Scr), and negatively correlated with estimated glomerular filtration rate (eGFR). With the occurrence of albuminuria as the dependent variable, weighted logistic regression analysis showed that CMI was an independent risk factor for microalbuminuria. Weighted smooth curve fitting showed that CMI index was linearly related to the risk of microalbuminuria. Subgroup analysis and interaction test showed that they participated in this positive correlation.
CONCLUSIONS
Obviously, CMI is independently associated with microalbuminuria, suggesting that CMI, a simple indicator, can be used for risk assessment of microalbuminuria, especially in diabetes patients.
Topics: Aged; Humans; Nutrition Surveys; Albuminuria; Cross-Sectional Studies; Hypertension; Diabetes Mellitus; Albumins; Kidney
PubMed: 37059309
DOI: 10.1016/j.ijcard.2023.04.017 -
Clinical Journal of the American... Apr 2024IgA nephropathy is the most common primary GN. Clinical features of IgA nephropathy include proteinuria, which is the strongest known surrogate of progression to kidney... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
IgA nephropathy is the most common primary GN. Clinical features of IgA nephropathy include proteinuria, which is the strongest known surrogate of progression to kidney failure. Complement pathway activation is a critical driver of inflammation and tissue injury in IgA nephropathy. Cemdisiran is an investigational RNA interference therapeutic that suppresses hepatic production of complement component 5 (C5), thereby potentially reducing proteinuria in IgA nephropathy. We evaluated the efficacy and safety of cemdisiran in adult patients with IgA nephropathy at high risk of kidney disease progression.
METHODS
In this phase 2, 36-week, double-blind study, adult patients with IgA nephropathy and urine protein ≥1 g/24 hours were randomized (2:1) to subcutaneous cemdisiran 600 mg or placebo every 4 weeks in combination with the standard of care. The primary end point was percentage change from baseline at week 32 in urine protein-to-creatinine ratio (UPCR) measured by 24-hour urine collection. Additional end points included change from baseline in UPCR measured by spot urine, serum C5 level, and safety assessments.
RESULTS
Thirty-one patients were randomized (cemdisiran, N =22; placebo, N =9). Cemdisiran-treated patients had a placebo-adjusted geometric mean change in 24-hour UPCR of -37.4% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.69 [0.10]) at week 32. Spot UPCR was consistent with 24-hour UPCR placebo-adjusted change of -45.8% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.73 [0.11]). Mean (SD) change in serum C5 level from baseline at week 32 was -98.7% (1.2) with cemdisiran and 25.2% (57.7) with placebo. Over 36 weeks, most adverse events were mild or moderate and transient; the most common adverse event after cemdisiran treatment was injection-site reaction (41%).
CONCLUSIONS
These findings indicate that treatment with cemdisiran resulted in a reduction of proteinuria at week 32 and was well tolerated.
Topics: Adult; Humans; Glomerulonephritis, IGA; Glomerular Filtration Rate; Proteinuria; Kidney Function Tests; Double-Blind Method
PubMed: 38214599
DOI: 10.2215/CJN.0000000000000384 -
Clinical Journal of the American... Sep 2023Dasatinib has been associated with nephrotoxicity. We sought to examine the incidence of proteinuria on dasatinib and determine potential risk factors that may increase...
BACKGROUND
Dasatinib has been associated with nephrotoxicity. We sought to examine the incidence of proteinuria on dasatinib and determine potential risk factors that may increase dasatinib-associated glomerular injury.
METHODS
We examined glomerular injury through urine albumin-creatinine ratio (UACR) in 82 patients with chronic myelogenous leukemia who were on tyrosine-kinase inhibitor therapy for at least 90 days. t tests were used to compare mean differences in UACR, while regression analysis was used to assess the effects of drug parameters on proteinuria development while on dasatinib. We assayed plasma dasatinib pharmacokinetics using tandem mass spectroscopy and further described a case study of a patient who experienced nephrotic-range proteinuria while on dasatinib.
RESULTS
Participants treated with dasatinib ( n =32) had significantly higher UACR levels (median 28.0 mg/g; interquartile range, 11.5-119.5) than participants treated with other tyrosine-kinase inhibitors ( n =50; median 15.0 mg/g; interquartile range, 8.0-35.0; P < 0.001). In total, 10% of dasatinib users exhibited severely increased albuminuria (UACR >300 mg/g) versus zero in other tyrosine-kinase inhibitors. Average steady-state concentrations of dasatinib were positively correlated with UACR ( ρ =0.54, P = 0.03) and duration of treatment ( P = 0.003). There were no associations with elevated BP or other confounding factors. In the case study, kidney biopsy revealed global glomerular damage with diffuse foot process effacement that recovered on termination of dasatinib treatment.
CONCLUSIONS
Exposure to dasatinib was associated with a significant chance of developing proteinuria compared with other similar tyrosine-kinase inhibitors. Dasatinib plasma concentration significantly correlated with higher risk of developing proteinuria while receiving dasatinib.
PODCAST
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_09_08_CJN0000000000000219.mp3.
Topics: Humans; Dasatinib; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Proteinuria; Albuminuria; Tyrosine
PubMed: 37382967
DOI: 10.2215/CJN.0000000000000219 -
Prilozi (Makedonska Akademija Na... Jul 2023Even though nephrology has made much progress, reducing the progression of the chronic kidney disease remains, in fact, one of the biggest challenges. Long before the... (Review)
Review
Even though nephrology has made much progress, reducing the progression of the chronic kidney disease remains, in fact, one of the biggest challenges. Long before the renal replacement therapy (RRT), it was known that limiting the protein could help almost all uremia symptoms. Although it was proposed as early as the 1960s, it only became widely used in the 1980s. By lowering the urea and other nitrogen wastes and lowering the metabolic acidosis, oxidative stress, and insulin resistance, limiting the amount of protein in your diet can help improve uremic symptoms. Also, limiting the protein in the diet positively controls the cardiovascular complications, including the arterial blood pressure and proteinuria reduction, which are risk factors for CKD progression. This mini-review examines the impact of protein restriction on the possibility of slowing CKD progression in depth.
Topics: Humans; Diet, Protein-Restricted; Renal Insufficiency, Chronic; Proteinuria; Renal Replacement Therapy; Risk Factors; Disease Progression; Kidney Failure, Chronic
PubMed: 37453111
DOI: 10.2478/prilozi-2023-0025 -
Journal of the American Society of... Oct 2023Among patients with CKD, optimal use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers after AKI is uncertain. Despite these medications'...
SIGNIFICANCE STATEMENT
Among patients with CKD, optimal use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers after AKI is uncertain. Despite these medications' ability to reduce risk of mortality and other adverse outcomes, there is concern that ACEi/ARB use may delay recovery of kidney function or precipitate recurrent AKI. Prior studies have provided conflicting data regarding the optimal timing of these medications after AKI and have not addressed the role of kidney recovery in determining appropriate timing. This study in US Veterans with diabetes mellitus and proteinuria demonstrated an association between ACEi/ARB use and lower mortality. This association was more pronounced with earlier post-AKI ACEi/ARB use and was not meaningfully affected by initiating ACEis/ARBs before versus after recovery from AKI.
BACKGROUND
Optimal use of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) after AKI is uncertain.
METHODS
Using data derived from electronic medical records, we sought to estimate the association between ACEi/ARB use after AKI and mortality in US military Veterans with indications for such treatment (diabetes and proteinuria) while accounting for AKI recovery. We used ACEi/ARB treatment after hospitalization with AKI (defined as serum creatinine ≥50% above baseline concentration) as a time-varying exposure in Cox models. The outcome was all-cause mortality. Recovery was defined as return to ≤110% of baseline creatinine. A secondary analysis focused on ACEi/ARB use relative to AKI recovery (before versus after).
RESULTS
Among 54,735 Veterans with AKI, 31,146 deaths occurred over a median follow-up period of 2.3 years. Approximately 57% received an ACEi/ARB <3 months after hospitalization. In multivariate analysis with time-varying recovery, post-AKI ACEi/ARB use was associated with lower risk of mortality (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI], 0.72 to 0.77). The association between ACEi/ARB use and mortality varied over time, with lower mortality risk associated with earlier initiation ( P for interaction with time <0.001). In secondary analysis, compared with those with neither recovery nor ACEi/ARB use, risk of mortality was lower in those with recovery without ACEi/ARB use (aHR, 0.90; 95% CI, 0.87 to 0.94), those without recovery with ACEi/ARB use (aHR, 0.69; 95% CI, 0.66 to 0.72), and those with ACEi/ARB use after recovery (aHR, 0.70; 95% CI, 0.67 to 0.73).
CONCLUSIONS
This study demonstrated lower mortality associated with ACEi/ARB use in Veterans with diabetes, proteinuria, and AKI, regardless of recovery. Results favored earlier ACEi/ARB initiation.
Topics: Humans; Renin-Angiotensin System; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Veterans; Diabetic Nephropathies; Acute Kidney Injury; Proteinuria; Retrospective Studies; Diabetes Mellitus
PubMed: 37545022
DOI: 10.1681/ASN.0000000000000196 -
La Revue Du Praticien Sep 2023CHILDHOOD-ONSET SYSTEMIC LUPUS. Childhood-onset systemic lupus (SL) is a rare multifactorial autoimmune disease belonging to connectivitis. Clinical presentation is very...
CHILDHOOD-ONSET SYSTEMIC LUPUS. Childhood-onset systemic lupus (SL) is a rare multifactorial autoimmune disease belonging to connectivitis. Clinical presentation is very heterogeneous with multi-systemic involvement: skin, joint, renal, hematological, neuropsychiatric, pulmonary, cardiac among others. Renal involvement is particularly frequent and severe in children and must be checked ou on a regular basis by screening for proteinuria. Lab exams show the production of antibodies directed against the native double-stranded DNA, excessive production of type I interferon, consumption of complement is observed during periods of flare-up. There are rare forms of monogenic SL which must be evocated in case of early-onset, familial cases or when occurring in boys.
Topics: Child; Male; Humans; Autoimmune Diseases; Kidney; Proteinuria
PubMed: 37796271
DOI: No ID Found -
Journal of Renal Nutrition : the... Sep 2023Diabetes Mellitus is a highly prevalent condition in which Diabetes Mellitus type 2 is the most common. Diabetic Kidney Disease is one of the most relevant complications... (Review)
Review
Diabetes Mellitus is a highly prevalent condition in which Diabetes Mellitus type 2 is the most common. Diabetic Kidney Disease is one of the most relevant complications and affects approximately one-third of patients with Diabetes Mellitus. It is characterized by increased urinary protein excretion and a decrease in glomerular filtration rate, assessed by serum creatinine levels. Recent studies have shown that vitamin D levels are low in these patients. This study aimed to conduct a systematic review of the effects of vitamin D supplementation on proteinuria and creatinine, which are important markers for assessing the severity of kidney disease in patients with Diabetic Kidney Disease. PUBMED, EMBASE, and COCHRANE databases were consulted, Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were followed, and the COCHRANE toll for bias assessment was applied. Six papers were quantitative studies and fulfilled the inclusion criteria for this review. The results showed that vitamin D supplementation of 50,000 I.U./week for 8 weeks effectively reduced proteinuria and creatinine in patients with Diabetic Kidney Disease, particularly in patients with Diabetes Mellitus type 2. Vitamin D supplementation is beneficial for patients with Diabetic Kidney Disease by having essential effects on disease-related inflammatory markers, such as the reduction of proteinuria and creatinine. However, more clinical trials must be conducted to evaluate the intervention among more significant numbers of patients.
Topics: Humans; Diabetic Nephropathies; Creatinine; Vitamin D; Diabetes Mellitus, Type 2; Proteinuria; Dietary Supplements
PubMed: 37302723
DOI: 10.1053/j.jrn.2023.05.006 -
Clinical and Experimental Hypertension... Dec 2023Previous studies have demonstrated that the triglyceride-glucose (TyG) index is significantly associated with vascular damage. Albuminuria is a marker of...
BACKGROUND
Previous studies have demonstrated that the triglyceride-glucose (TyG) index is significantly associated with vascular damage. Albuminuria is a marker of hypertension-mediated organ damage (HMOD) and has been linked to a greater risk of cardiovascular disease (CVD). However, the association between the TyG index and albuminuria in patients with hypertension is not clear. This population research focused on subjects with hypertension to investigate the association between an elevated TyG index and albuminuria.
METHODS
From September 2019 to November 2019, 789 hypertensive participants were involved in our research. Logistic regression models were performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for albuminuria according to the quartiles of the TyG index.
RESULTS
Multivariate logistic regression analysis revealed that the TyG index was significantly associated with albuminuria. Using the lowest TyG index quartile as the reference, the fully adjusted ORs (95% CIs) for albuminuria for TyG index quartile II, quartile III, and quartile IV were 1.90 (1.17-3.12), 1.81 (1.07-3.07), and 3.46 (2.06-5.91), respectively. The results in the subgroup analysis were similar to the main analyses except for the smokers. Restricted cubic spline curves based on logistic regression models evaluated the linear association between the TyG index and albuminuria (P for nonlinear = 0.831).
CONCLUSION
The TyG index was positively associated with albuminuria among hypertensive participants.
Topics: Humans; Albuminuria; Hypertension; Cardiovascular Diseases; Glucose; Triglycerides; Blood Glucose; Risk Factors; Biomarkers
PubMed: 36540929
DOI: 10.1080/10641963.2022.2150204 -
American Journal of Physiology. Renal... Dec 2023The discovery of zinc fingers and homeoboxes (ZHX) transcriptional factors and the upregulation of hyposialylated angiopoietin-like 4 (ANGPTL4) in podocytes have been... (Review)
Review
The discovery of zinc fingers and homeoboxes (ZHX) transcriptional factors and the upregulation of hyposialylated angiopoietin-like 4 (ANGPTL4) in podocytes have been crucial in explaining the cardinal manifestations of human minimal change nephrotic syndrome (MCNS). Recently, uncovered genomic defects upstream of induce a hypomorph state that makes podocytes inherently susceptible to mild cytokine storms resulting from a common cold. In hypomorph podocytes, ZHX proteins are redistributed away from normal transmembrane partners like aminopeptidase A (APA) toward alternative binding partners like IL-4Rα. During disease relapse, high plasma soluble IL-4Rα (sIL-4Rα) associated with chronic atopy complements the cytokine milieu of a common cold to displace ZHX1 from podocyte transmembrane IL-4Rα toward the podocyte nucleus. Nuclear ZHX1 induces severe upregulation of , resulting in incomplete sialylation of part of the ANGPTL4 protein, secretion of hyposialylated ANGPTL4, and hyposialylation-related injury in the glomerulus. This pattern of injury induces many of the classic manifestations of human minimal change disease (MCD), including massive and selective proteinuria, podocyte foot process effacement, and loss of glomerular basement membrane charge. Administration of glucocorticoids reduces upregulation, which reduces hyposialylation injury to improve the clinical phenotype. Improving sialylation of podocyte-secreted ANGPTL4 also reduces proteinuria and improves experimental MCD. Neutralizing circulating TNF-α, IL-6, or sIL-4Rα after the induction of the cytokine storm in hypomorph mice reduces albuminuria, suggesting potential new therapeutic targets for clinical trials to prevent MCD relapse. These studies collectively lay to rest prior suggestions of a role of single cytokines or soluble proteins in triggering MCD relapse.
Topics: Mice; Humans; Animals; Nephrosis, Lipoid; Podocytes; Common Cold; Proteinuria; Glomerular Basement Membrane; Recurrence; Nephrotic Syndrome; Transcription Factors; Homeodomain Proteins
PubMed: 37795536
DOI: 10.1152/ajprenal.00219.2023 -
The Cochrane Database of Systematic... Feb 2024IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years. Non-immunosuppressive treatment has become a mainstay in the management of IgAN by improving blood pressure (BP) management, decreasing proteinuria, and avoiding the risks of long-term immunosuppressive management. Due to the slowly progressive nature of the disease, clinical trials are often underpowered, and conflicting information about management with non-immunosuppressive treatment is common. This is an update of a Cochrane review, first published in 2011.
OBJECTIVES
To assess the benefits and harms of non-immunosuppressive treatment for treating IgAN in adults and children. We aimed to examine all non-immunosuppressive therapies (e.g. anticoagulants, antihypertensives, dietary restriction and supplementation, tonsillectomy, and herbal medicines) in the management of IgAN.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to December 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included.
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed search results, extracted data and assessed study quality. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using random-effects meta-analysis. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
This review includes 80 studies (4856 participants), of which 24 new studies (2018 participants) were included in this review update. The risk of bias within the included studies was mostly high or unclear for many of the assessed methodological domains, with poor reporting of important key clinical trial methods in most studies. Antihypertensive therapies were the most examined non-immunosuppressive therapy (37 studies, 1799 participants). Compared to placebo or no treatment, renin-angiotensin system (RAS) inhibition probably decreases proteinuria (3 studies, 199 participants: MD - 0.71 g/24 h, 95% CI -1.04 to -0.39; moderate certainty evidence) but may result in little or no difference to kidney failure or doubling of serum creatinine (SCr), or complete remission of proteinuria (low certainty evidence). Death, remission of haematuria, relapse of proteinuria or > 50% increase in SCr were not reported. Compared to symptomatic treatment, RAS inhibition (3 studies, 168 participants) probably decreases proteinuria (MD -1.16 g/24 h, 95% CI -1.52 to -0.81) and SCr (MD -9.37 µmol/L, 95% CI -71.95 to -6.80) and probably increases creatinine clearance (2 studies, 127 participants: MD 23.26 mL/min, 95% CI 10.40 to 36.12) (all moderate certainty evidence); however, the risk of kidney failure is uncertain (1 study, 34 participants: RR 0.20, 95% CI 0.01 to 3.88; very low certainty evidence). Death, remission of proteinuria or haematuria, or relapse of proteinuria were not reported. The risk of adverse events may be no different with RAS inhibition compared to either placebo or symptomatic treatment (low certainty evidence). In low certainty evidence, tonsillectomy in people with IgAN in addition to standard care may increase remission of proteinuria compared to standard care alone (2 studies, 143 participants: RR 1.90, 95% CI 1.45 to 2.47) and remission of microscopic haematuria (2 studies, 143 participants: RR 1.93, 95% CI 1.47 to 2.53) and may decrease relapse of proteinuria (1 study, 73 participants: RR 0.70, 95% CI 0.57 to 0.85) and relapse of haematuria (1 study, 72 participants: RR 0.70, 95% CI 0.51 to 0.98). Death, kidney failure and a > 50% increase in SCr were not reported. These trials have only been conducted in Japanese people with IgAN, and the findings' generalisability is unclear. Anticoagulant therapy, fish oil, and traditional Chinese medicines exhibited small benefits to kidney function in patients with IgAN when compared to placebo or no treatment. However, compared to standard care, the kidney function benefits are no longer evident. Antimalarial therapy compared to placebo in one study reported an increase in a > 50% reduction of proteinuria (53 participants: RR 3.13 g/24 h, 95% CI 1.17 to 8.36; low certainty evidence). Although, there was uncertainty regarding adverse events from this study due to very few events.
AUTHORS' CONCLUSIONS
Available RCTs focused on a diverse range of interventions. They were few, small, and of insufficient duration to determine potential long-term benefits on important kidney and cardiovascular outcomes and harms of treatment. Antihypertensive agents appear to be the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The benefits of RAS inhibition appear to outweigh the harms in patients with IgAN. The certainty of the evidence of RCTs demonstrating a benefit of tonsillectomy to patients with Japanese patients with IgAN was low. In addition, these findings are inconsistent across observational studies in people with IgAN of other ethnicities; hence, tonsillectomy is not widely recommended, given the potential harm of therapy. The RCT evidence is insufficiently robust to demonstrate efficacy for the other non-immunosuppressive treatments evaluated here.
Topics: Humans; Antihypertensive Agents; East Asian People; Glomerulonephritis, IGA; Hematuria; Proteinuria; Recurrence; Renal Insufficiency
PubMed: 38299639
DOI: 10.1002/14651858.CD003962.pub3