Determination of a vancomycin nephrotoxicity threshold and assessment of target attainment in hematology patients.

An area-under-the-curve (AUC24)-based approach is recommended to guide vancomycin therapeutic drug monitoring (TDM), yet trough concentrations are still commonly used despite associated risks. A definitive toxicity target is lacking, which is important for hematology patients who have a higher risk of nephrotoxicity. The aims were to (1) assess the impact of trough-based TDM on acute kidney injury (AKI) incidence, (2) establish a vancomycin nephrotoxicity threshold, and (3) evaluate the proportion of hematology patients achieving vancomycin therapeutic targets. Retrospective data was collected from 100 adult patients with a hematological malignancy or aplastic anemia who received vancomycin between April 2020 and January 2021. AKI occurrence was determined based on serum creatinine concentrations, and individual pharmacokinetic parameters were estimated using a Bayesian approach. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pharmacokinetic indices to predict AKI occurrence. The proportion of patients who achieved target vancomycin exposure was evaluated based on an AUC24/MIC ≥400 and the determined toxicity threshold. The incidence of AKI was 37%. ROC curve analysis indicated a maximum AUC24 of 644 mg.h/L over the treatment period was an important predictor of AKI. By Day 4 of treatment, 29% of treatment courses had supratherapeutic vancomycin exposure, with only 62% of courses achieving AUC24 targets. The identified toxicity threshold supports an AUC24 target range of 400-650 mg.h/L, assuming an MIC of 1 mg/L, to optimize vancomycin efficacy and minimize toxicity. This study highlights high rates of AKI in this population and emphasizes the importance of transitioning from trough-based TDM to an AUC-based approach to improve clinical outcomes.

Efficacy and Safety of Vildagliptin for Type 2 Diabetes in Patients With Diabetic Kidney Disease.

BACKGROUND/AIM: Vildagliptin is one of the dipeptidyl peptidase-4 (DPP-4) inhibitors that have been shown to improve hyperglycemia in clinical trials among patients with type 2 diabetes. However, few studies have examined the efficacy of vildagliptin in patients with diabetic kidney disease (DKD). PATIENTS AND METHODS: Eight patients with DKD received oral vildagliptin 50-100 mg/day. The duration of diabetes was 6.7±5.9 years and observation period was 23.6±9.8 months. Changes in fasting blood glucose, and hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), and urine protein-to-creatinine ratio (UPCR) were studied before and after the administration of vildagliptin. RESULTS: Vildagliptin treatment significantly decreased fasting blood glucose and HbA1c, compared to baseline (132±56 mg/dl, p=0.036, 6.0±0.3, p=0.041, respectively). UPCR tended to be decreased, albeit without statistical significance. However, eGFR was decreased after the administration of vildagliptin. No significant adverse effects were observed in all patients during the study. CONCLUSION: Although the sample size was limited and the observation period was brief, vildagliptin was found to be an effective and reasonably well-tolerated treatment for patients with DKD.

Urinary albumin creatinine ratio is associated with lipid profile.

Moderately elevated albuminuria (30-300 mg/g) is a marker of renal dysfunction and a risk factor of cardiovascular disease. Additionally, several recent studies have reported a relationship between moderately elevated albuminuria and triglyceride (TG) levels. Therefore, we aimed to evaluate the relationship between the urine albumin-to-creatinine ratio (UACR) and total cholesterol (TC), TG, and high-density lipoprotein C (HDL-C) levels. We analyzed data from 19,340 patients from the 2011-2014 and 2019-2020 from the Korea National Health and Nutrition Examination Surveys. Multivariate linear regression analysis showed that the UACR was positively associated with TC and TG levels and negatively associated with HDL-C levels in both Korean women and men. These results were reanalyzed according to the degree of proteinuria (normal, moderately elevated albuminuria, and severely elevated albuminuria (≥ 300 mg/g)). We found a positive relationship between UACR and TC and TG levels, but a negative association with HDL-C levels, except for TC (moderately elevated albuminuria) and HDL-C (moderately elevated albuminuria) in Korean men and TC (severely elevated albuminuria), TG (severely elevated albuminuria), and HDL-C (normal range albuminuria) in Korean women. The correlation between albuminuria and lipid profiles became more evident as albuminuria shift from normal to the severely elevated albuminuria. Thus our multivariate linear regression analysis showed that lipid profiles (TG, TC, and HDL-C levels) were associated with the UACR.

II Brazilian Society of Rheumatology consensus for lupus nephritis diagnosis and treatment.

OBJECTIVE: To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN). METHODS: Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion. RESULTS: All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy. CONCLUSION: This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.

[To what extent does the eGFR reflects renal function?] / In hoeverre weerspiegelt de eGFR de nierfunctie?

Glomerular filtration rate (GFR) serves as a marker for various renal functions. Different formulas are available to calculate an estimated GFR (eGFR), which are commonly based on serum creatinine, age, and sex. However, the eGFR merely reflects GFR under specific conditions. Due to the multitude of functions of the kidney, it is not possible to capture all aspects in one value. To diagnose renal diseases comprehensively, not only eGFR but also urine analysis and clinical context should be considered. Interpretation of eGFR for renal function monitoring requires careful consideration of factors such as (blood pressure) medication, diabetes, obesity, and pregnancy. Combining various laboratory parameters with a patient's clinical context provides an overview of the different functions of the kidney and its consequences for the patient.

[Estimating glomerular filtration rate]. / Het schatten van de glomerulaire filtratiesnelheid.

Almost all laboratories in The Netherlands report an estimated glomerular filtration rate (eGFR) whenever a value for plasma creatinine is requested. This formula is based on gender and age, besides the plasma creatinine concentration, and sometimes also a correction for race is applied. While this GFR reporting improved the recognition of chronic kidney disease, the formulas used have intrinsic limitations. Moreover, recently a novel formula that obviates the need for a correction factor for race has been proposed. In this article the strengths and weaknesses of plasma creatinine and formulas based on that are discussed, following ten frequently asked questions.

A lower eGFRcystatin C/eGFRcreatinine ratio is associated with greater cardiovascular risk (higher Framingham Risk Score) in Chinese patients with newly diagnosed type 2 diabetes mellitus.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients. Shrunken pore syndrome (SPS) is defined as eGFRcystatin C/eGFRcreatinine ratio <0.70 and predicts high CVD mortality. The Framingham Risk Score (FRS) is used to estimate an individual's 10-year CVD risk. This study investigated the association between FRS and eGFRcystatin C/eGFRcreatinine ratio in T2DM patients. METHODS: Patients aged 18-80 years who were newly diagnosed with T2DM were included in this retrospective study. Ordinal logistic regression analysis was used to investigate the association between risk factors of T2DM and FRS. A Generalized Linear Model was used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: There were 270 patients included in the study. Only 27 patients (10%) met the diagnostic criteria of SPS. Ordinal logistic regression analysis showed that SPS was not correlated with FRS risk (OR = 1.99, 95%CI = 0.94-4.23, p = 0.07), whereas eGFRcystatin C/eGFRcreatinine (OR = 0.86, 95%CI = 0.77-0.97, p = 0.01) showed a significant negative association with FRS risk. Compared with eGFRcystatin C/eGFRcreatinine>0.85, eGFRcystatin C/eGFRcreatinine≤0.85 increased FRS risk (OR = 1.95, 95%CI = 1.18-3.21, p < 0.01). After adjustment for confounding factors, increased eGFRcystatin C/eGFRcreatinine ratio was associated with decreased FRS risk when considered as a continuous variable (OR = 0.87, 95%CI = 0.77-0.99, p = 0.03). The FRS risk in patients with eGFRcystatin C/eGFRcreatinine≤0.85 is 1.86 times higher than that in patients with eGFRcystatin C/eGFRcreatinine>0.85 (OR = 1.86, 95%CI = 1.08-3.21, p = 0.03). CONCLUSIONS: In the current study, no significant association between SPS and FRS was identified. However, lower eGFRcystatin C/eGFRcreatinine and eGFRcystatin C/eGFRcreatinine≤0.85 were associated with a significantly increased CVD risk in T2DM.

Deciphering AKI in Burn Patients: Correlations between Clinical Clusters and Biomarkers.

Acute kidney injury (AKI) is a significant complication in burn patients, impacting outcomes substantially. This study explores the heterogeneity of AKI in burn patients by analyzing creatinine time-series data to identify distinct AKI clusters and evaluating routine biomarkers' predictive values. A retrospective cohort analysis was performed on 2608 adult burn patients admitted to Hangang Sacred Heart Hospital's Burn Intensive Care Unit (BICU) from July 2010 to December 2022. Patients were divided into four clusters based on creatinine trajectories, ranging from high-risk, severe cases to lower-risk, short-term care cases. Cluster A, characterized by high-risk, severe cases, showed the highest mortality and severity, with significant predictors being PT and TB. Cluster B, representing intermediate recovery cases, highlighted PT and albumin as useful predictors. Cluster C, a low-risk, high-resilience group, demonstrated predictive values for cystatin C and eGFR cys. Cluster D, comprising lower-risk, short-term care patients, indicated the importance of PT and lactate. Key biomarkers, including albumin, prothrombin time (PT), cystatin C, eGFR cys, and total bilirubin (TB), were identified as significant predictors of AKI development, varying across clusters. Diagnostic accuracy was assessed using area under the curve (AUC) metrics, reclassification metrics (NRI and IDI), and decision curve analysis. Cystatin C and eGFR cys consistently provided significant predictive value over creatinine, with AUC values significantly higher (p < 0.05) in each cluster. This study highlights the need for a tailored, biomarker-driven approach to AKI management in burn patients, advocating for the integration of diverse biomarkers in clinical practice to facilitate personalized treatment strategies. Future research should validate these biomarkers prospectively to confirm their clinical utility.

[Clinical Significance of Serum ADA Combined with GLB, CREA, ß2-MG and HGB in Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To investigate the role of serum adenosine deaminase (ADA) combined with globulin (GLB), creatinine (CREA), ß2-microglobulin (ß2-MG) and hemoglobin (HGB) in the initial screening of multiple myeloma (MM), in order to reduce missed diagnosis and misdiagnosis of MM. METHODS: A retrospective analysis was performed on 62 newly diagnosed multiple myeloma (NDMM) patients who were admitted to the Department of Hematology of the First Affiliated Hospital of Chengdu Medical College from April 2018 to December 2021, and 33 patients with benign hematologic diseases and 30 healthy subjects were selected as the control group. The expression of ADA in pan-cancer was analyzed using TCGA and GTEx databases. The general data and laboratory indicators of the subjects were collected, and the differences of ADA activity and other laboratory indicators in each group were compared. The relationship between serum ADA activity and clinical data of NDMM patients was analyzed. The changes of ADA activity before and after chemotherapy in NDMM patients and the differences of ADA activity in NDMM patients with different DS and ISS stages were compared. Multivariate logistic regression was used to analyze the risk factors of NDMM. The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of ADA and other laboratory indicators in MM. Bioinformatics method was used to analyze the co-expression networks and enrichment pathways of ADA. RESULTS: ADA level was significantly upregulated in tissues of 14 types of cancer in TCGA database, and ADA was highly expressed in 11 types of cancer in TCGA combined with GTEx databases. The serum levels of ADA, GLB, uric acid (UA), cystatin C (CysC) and ß2-MG in the NDMM group were significantly higher than those in benign hematologic disease group and healthy control group ( P < 0.05), while the levels of ALB and the value of albumin to globulin ratio (A∶G) in the NDMM group were significantly lower than those in the other two groups ( P < 0.001). There were significant differences in DS stage (P =0.036), ISS stage (P =0.019) and the levels of CREA (P =0.036), UA (P =0.034), ß2-MG (P =0.019) in NDMM patients with different ADA activity levels. After primary chemotherapy, ADA activity and ß2-MG concentration were decreased in NDMM patients ( P < 0.01). The comparison results of patients in different stages showed that ADA activity of patients in DS stage I+II was significantly lower than that of patients in DS stage III (P <0.05), and ADA activity of patiens in ISS stage I+II was significantly lower than that of patients in ISS stage III ( P < 0.01). Multivariate logistic regression analysis showed that increased GLB, increased ADA activity, increased CREA, increased ß2-MG and decreased HGB were independent risk factors for NDMM. The area under the curve (AUC) of ADA in the diagnosis of MM was 0.847, and the AUC of ADA combined with GLB, CREA, ß2-MG and HGB in the diagnosis of MM was 0.940. The results of co-expression network and enrichment pathway analysis showed that ADA bounded to 20 proteins and it was significantly associated with the metabolic pathways of purine, pyrimidine, nicotinate and nicotinamide. CONCLUSION: The detection of ADA activity in serum is of positive significance for the auxiliary diagnosis, therapeutic evaluation and monitoring the progress of NDMM patients. ADA combined with GLB, CREA, ß2-MG and HGB can improve the detection rate of MM, and reduce missed diagnosis and misdiagnosis to a certain extent.

Development of normal reference intervals for renal function in pregnancy: a secondary analysis of clinical trial data.

BACKGROUND: Due to its potential nephrotoxicity, screening for pre-existing renal function disorders has become a routine clinical assessment for initiating Tenofovir diphosphate fumarate (TDF)-containing antiretroviral treatment (ART) or pre-exposure prophylaxis (PrEP) in pregnant and non-pregnant adults. We aimed to establish reference values for commonly used markers of renal function in healthy pregnant women of African origin. METHODS: Pregnant women ≥18 years, not living with HIV, and at 14-28 weeks gestation were enrolled in a PrEP clinical trial in Durban, South Africa between September 2017 and December 2019. Women were monitored 4-weekly during pregnancy until six months postpartum. We measured maternal weight and serum creatinine (sCr) at each visit and calculated creatinine clearance (CrCl) rates using the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae. Reference ranges for sCr and CrCl by CG and MDRD calculations were derived from the mean ± 2SD of values for pregnancy and postdelivery. RESULTS: Between 14--and 40 weeks gestation, 249 African women not exposed to TDF-PrEP contributed a total of 1193 renal function values. Postdelivery, 207 of these women contributed to 800 renal function values. The normal reference range for sCr was 30-57 and 32-60 umol/l in the 2nd and 3rd trimesters of pregnancy. Normal reference ranges for CrCl using the MDRD calculation were 129-282 and 119-267 ml/min/1.73m2 for the 2nd and 3rd trimesters, respectively. Using the CG method of calculation, normal reference ranges for CrCl were 120-304 and 123-309 ml/min/1.73m2 for the 2nd and 3rd trimesters respectively. In comparison, the normal reference range for sCr, CrCl by MDRD and CG calculations postpartum was 40-77 umol/l, 92-201, and 90-238 ml/min/1.73m2, respectively. CONCLUSIONS: In African women, the Upper Limit of Normal (ULN) for sCr in pregnancy is approximately 20% lower than 6 months postnatally. Inversely, the Lower Limit of Normal (LLN) for CrCl using either MDRD or CG equation is approximately 35% higher than 6 months postnatally. We provide normal reference ranges for sCr and CrCl for both methods of calculation and appropriate for the 2nd and 3rd trimesters of pregnancy in African women.

Screening for pre-existing renal function disorders has become a routine clinical assessment for initiating TDF-containing antiretroviral treatment or pre-exposure prophylaxis in adults including pregnant women. Pregnancy inherently increases renal function, hence normal reference standards for non-pregnant adults cannot be used for pregnant women. In a secondary analysis of data from a healthy pregnant population not living with HIV who participated in a PrEP clinical trial, we established reference intervals for serum creatinine (sCr) concentration and creatinine clearance (CrCl) during pregnancy and postpartum in an African population. Using sCr and CrCl values for 249 healthy pregnant African women, we can confirm that the upper limit of normal for sCr in pregnancy is 20% lower than that for the 6-month postnatal period and recommend an upper limit of 57 umol/l and 60 umol/l in the second and third trimesters respectively to determine normal renal function in pregnant African women.We further determined the lower limit of normal for creatinine clearance using two methods of calculation, which was 35% higher than that of the postnatal period. Using the modification of diet in renal disease calculation, we recommend a lower limit of 129 and 119 ml/min/1.73m² for the second and third trimesters respectively. Using the Cockcroft­Gault calculation, we recommend a lower limit of 120 and 123 ml/min/1.73m² for the second and third trimesters respectively. Using current standard cut-off values estimated for adults may lead to underreporting of abnormal renal function in African pregnant women.

Plasma D-asparagine and the D/L-serine ratio reflect chronic kidney diseases in children regardless of physique.

Biomarkers that accurately reflect renal function are essential in management of chronic kidney diseases (CKD). However, in children, age/physique and medication often alter established renal biomarkers. We studied whether amino acid enantiomers in body fluids correlate with renal function and whether they are influenced by physique or steroid medication during development. We conducted a prospective study of children 2 to 18 years old with and without CKD. We analyzed associations of serine/asparagine enantiomers in body fluids with major biochemical parameters as well as physique. To study consequences of kidney dysfunction and steroids on serine/asparagine enantiomers, we generated juvenile mice with uninephrectomy, ischemic reperfusion injury, or dexamethasone treatment. We obtained samples from 27 children, of which 12 had CKD due to congenital (n = 7) and perinatal (n = 5) causes. Plasma D-asparagine and the D/L-serine ratio had robust, positive linear associations with serum creatinine and cystatin C, and detected CKD with high sensitivity and specificity, uninfluenced by body size or biochemical parameters. In the animal study, kidney dysfunction increased plasma D-asparagine and the D/L-serine ratio, but dexamethasone treatment did not. Thus, plasma D-asparagine and the D/L-serine ratio can be useful markers for renal function in children.

Late Kidney Injury After Admission to Intensive Care Unit for Acute Heart Failure.

Late kidney injury (LKI) in patients with acute heart failure (AHF) requiring intensive care is poorly understood.We analyzed 821 patients with AHF who required intensive care. We defined LKI based on the ratio of the creatinine level 1 year after admission for AHF to the baseline creatinine level. The patients were categorized into 4 groups based on this ratio: no-LKI (< 1.5, n = 509), Class R (risk; ≥ 1.5, n = 214), Class I (injury; ≥ 2.0, n = 78), and Class F (failure; ≥ 3.0, n = 20). Median follow-up after admission for AHF was 385 (346-426) days. Multivariate logistic regression analysis revealed that acute kidney injury (AKI) during hospitalization (Class R, odds ratio [OR]: 1.710, 95% confidence interval [CI]: 1.138-2.571, P = 0.010; Class I, OR: 6.744, 95% CI: 3.739-12.163, P < 0.001; and Class F, OR: 9.259, 95% CI: 4.078-18.400, P < 0.001) was independently associated with LKI. Multivariate Cox regression analysis showed that LKI was an independent predictor of 3-year all-cause death after final follow-up (hazard ratio: 1.545, 95% CI: 1.099-2.172, P = 0.012). The rate of all-cause death was significantly lower in the no-AKI/no-LKI group than in the no-AKI/LKI group (P = 0.048) and in the AKI/no-LKI group than in the AKI/LKI group (P = 0.017).The incidence of LKI was influenced by the presence of AKI during hospitalization, and was associated with poor outcomes within 3 years of final follow-up. In the absence of LKI, AKI during hospitalization for AHF was not associated with a poor outcome.

Urine multi-index intelligent detection based on polymer/paper hybrid microfluidic biochip for hyperuricemia monitoring.

Hyperuricemia (HUA) has gradually become a public health burden as an independent risk factor for a variety of chronic diseases. Herein, a user-friendly point-of-care (POC) detection system (namely "Smart-HUA-Monitor") based on smartphone-assisted paper-based microfluidic is proposed for colorimetric quantification of HUA urinary markers, including uric acid (UA), creatinine (CR) and pH. The detection limits of UA and CR were 0.0178 and 0.5983 mM, respectively, and the sensitivity of pH were 0.1. The method was successfully validated in artificial urine samples and 100 clinical samples. Bland-Altman plots showed a high consistency between µPAD and the testing instruments (HITACHI 7600 Automatic Analyzer, URIT-500B Urine Analyzer and AU5800B automatic biochemical analyzer) in hospital. Smart-HUA-Monitor provides an accurate quantitative, rapid, low-cost and reliable tool for the monitoring and early diagnosis of HUA urine indicators.

Relationship between proteinuria and changes in antepartum and postpartum choroidal thickness in patients with pre-eclampsia.

Pre-eclampsia (PE) is a hypertensive disorder characterised by systemic vascular resistance and endothelial dysfunction. It is known to influence choroidal thickness (CT). No previous studies have explored the antepartum and postpartum changes in CT with respect to the protein-creatinine ratio (PCR), a measure of proteinuria that is a clinical hallmark of PE. This study evaluated the correlations between antepartum and postpartum CT and the PCR in patients with PE. In this retrospective study, sixty-six eyes (66 patients) were analysed. The patients were divided into two groups according to the median PCR value (2.36 mg/mg): low PCR group (< 2.36 mg/mg) and high PCR group (≥ 2.36 mg/mg). Ophthalmologic clinical data were collected and assessed. We observed higher antepartum CT and higher mean arterial pressure in high PCR group than in low PCR group. Moreover, postpartum CT decreased significantly in high PCR group. In the multivariate analysis, CT changes were correlated with antepartum CT and antepartum PCR after logarithm transformation. In conclusion, a greater decrease in CT was observed in high PCR group than in low PCR group. Further, the antepartum PCR showed a correlation with the extent of CT reduction.

Patterns of kidney function and risk assessment in a nationwide laboratory database: the Brazilian CHECK-CKD study.

BACKGROUND: Chronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries. METHODS: A retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months. RESULTS: Out of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing. CONCLUSION: Our findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.

Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis. METHODS: PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software. RESULTS: A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (ß2-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or ß2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias. CONCLUSIONS: The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly used to treat diabetic neuropathy (DN) and Astragalus membranaceus components are known to improve DN symptoms.We aimed to establish the efficacy and safety of using Astragalus combined with RAAS inhibitors.Astragalus combined with RAAS inhibitors enhances the total effective rate of diabetic neuropathy response to treatment and reduces urinary protein excretion rate, serum creatinine, blood urea nitrogen and HbAlc.Sensitivity analysis affirms study stability, while publication bias was detected for total effective rate, serum creatinine, and 24 h urinary protein levels.

The role of sacubitril/valsartan in abnormal renal function patients combined with heart failure: a meta-analysis and systematic analysis.

AIMS: This study aimed to investigate the efficacy and safety of sacubitril/valsartan in abnormal renal function (eGFR < 60 ml/min/1.73m2) patients combined with heart failure based on randomized controlled trials (RCTs) and observational studies. METHODS: The Embase, PubMed and the Cochrane Library were searched for relevant studies from inception to December 2023. Dichotomous variables were described as event counts with the odds ratio (OR) and 95% confidence interval (CI) values. Continuous variables were expressed as mean standard deviation (SD) with 95% CIs. RESULTS: A total of 6 RCTs and 8 observational studies were included, involving 17335 eGFR below 60 ml/min/1.73m2 patients combined with heart failure. In terms of efficacy, we analyzed the incidence of cardiovascular events and found that sacubitril/valsartan significantly reduced the risk of cardiovascular death or heart failure hospitalization in chronic kidney disease (CKD) stages 3-5 patients with heart failure (OR: 0.65, 95%CI: 0.54-0.78). Moreover, sacubitril/valsartan prevented the serum creatinine elevation (OR: 0.81, 95%CI: 0.68-0.95), the eGFR decline (OR: 0.83, 95% CI: 0.73-0.95) and the development of end-stage renal disease in this population (OR:0.73, 95%CI:0.60-0.89). As for safety outcomes, we did not find that the rate of hyperkalemia (OR:1.31, 95%CI:0.79-2.17) and hypotension (OR:1.57, 95%CI:0.94-2.62) were increased in sacubitril/valsartan group among CKD stages 3-5 patients with heart failure. CONCLUSIONS: Our meta-analysis proves that sacubitril/valsartan has a favorable effect on cardiac function without obvious risk of adverse events in abnormal renal function patients combined with heart failure, indicating that sacubitril/valsartan has the potential to become perspective treatment for these patients.

Effect of 2 Years of Monthly Calcifediol Administration in Postmenopausal Women with Vitamin D Insufficiency.

BACKGROUND: We assessed the long-term (24 months) efficacy and safety of monthly calcifediol (0.266 mg) in the correction and maintenance of total 25(OH)D levels in postmenopausal women with basal values <30 ng/mL. METHODS: We initially enrolled 45 consecutive patients during the period September 2019-September 2020. After an initial visit, patients were instructed to return at 3, 6, 9, 12 and 24 months for measuring serum total 25(OH)D, ionised calcium, creatinine and isoenzyme of alkaline phosphatase (bALP). Here, we report only the per-protocol analysis, because the COVID-19 pandemic precluded adherence to the scheduled visits for some patients. RESULTS: The patients' mean age was 62.4 ± 9.0 years. Mean basal 25(OH)D levels were 20.5 ± 5.3 ng/mL. There was a continuous increase of mean 25(OH)D values (p for trend < 0.001). However, mean values at month 24 (36.7 ± 15.9) were not significantly different in respect to values at month 12 (41.2 ± 11.18). At 24 months, only 1 out 19 patients had a value <20 ng/mL. There was a significant decrease with time of mean values of bALP (p < 0.0216), with no significant changes between 12 and 24 months. No significant changes were observed as far as ionised calcium or creatinine were concerned. CONCLUSIONS: The long-term administration of calcifediol maintains stable and sustained 25(OH)D concentrations, with no safety concerns.

Creatine homeostasis and the kidney: comparison between kidney transplant recipients and healthy controls.

Creatine is a natural nitrogenous organic acid that is integral to energy metabolism and crucial for proper cell functioning. The kidneys are involved in the first step of creatine production. With kidney transplantation being the gold-standard treatment for end-stage kidney disease, kidney transplant recipients (KTR) may be at risk of impaired creatine synthesis. We aimed to compare creatine homeostasis between KTR and controls. Plasma and urine concentrations of arginine, glycine, guanidinoacetate, creatine and creatinine were measured in 553 KTR and 168 healthy controls. Creatine intake was assessed using food frequency questionnaires. Iothalamate-measured GFR data were available in subsets of 157 KTR and 167 controls. KTR and controls had comparable body weight, height and creatine intake (all P > 0.05). However, the total creatine pool was 14% lower in KTR as compared to controls (651 ± 178 vs. 753 ± 239 mmol, P < 0.001). The endogenous creatine synthesis rate was 22% lower in KTR as compared to controls (7.8 ± 3.0 vs. 10.0 ± 4.1 mmol per day, P < 0.001). Despite lower GFR, the plasma guanidinoacetate and creatine concentrations were 21% and 41% lower in KTR as compared to controls (both P < 0.001). Urinary excretion of guanidinoacetate and creatine were 66% and 59% lower in KTR as compared to controls (both P < 0.001). In KTR, but not in controls, a higher measured GFR was associated with a higher endogenous creatine synthesis rate (std. beta: 0.21, 95% CI: 0.08; 0.33; P = 0.002), as well as a higher total creatine pool (std. beta: 0.22, 95% CI: 0.11; 0.33; P < 0.001). These associations were fully mediated (93% and 95%; P < 0.001) by urinary guanidinoacetate excretion which is consistent with production of the creatine precursor guanidinoacetate as rate-limiting factor. Our findings highlight that KTR have a disturbed creatine homeostasis as compared to controls. Given the direct relationship of measured GFR with endogenous creatine synthesis rate and the total creatine pool, creatine supplementation might be beneficial in KTR with low kidney function.Trial registration ID: NCT02811835.Trial registration URL: https://clinicaltrials.gov/ct2/show/NCT02811835 .