The role of interleukin-20 and vascular endothelial growth factor-A biomarkers in the detection of renal impairment in patients with multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a malignant incurable disease characterized by monoclonal plasma cell increase associated with renal impairment. Evaluation of neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), hemoglobin/red cell distribution width (HB/RDW), interleukin-20 (IL-20), and vascular endothelial growth factor-A (VEGFA) in patients with MM (with or without renal impairment) as prognostic and severity indicators. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted on sixty MM patients with renal impairment, sixty MM patients without renal impairment, and sixty subjects (control group). Complete blood count, IL-20 immunoassay, and gene expression of IL-20, and VEGFA were evaluated. RESULTS: Higher levels of NLR, MLR, and IL-20, and moreover lower levels of PLR, HB/RDW, as well as upregulation of IL-20, and VEGFA gene expression were detected in MM patients, especially those with renal impairment. Receiver operating characteristic curves analysis of NLR, MLR, PLR, and IL-20 showed high sensitivity and specificity in the diagnosis of MM and disease stages. CONCLUSIONS: NLR, MLR, PLR, HB/RDW, IL-20, and VEGFA may be implicated in the inflammatory process of MM and renal impairment pathogenesis. NLR, MLR, and IL-20 can be used as prognostic markers in MM stages.

Carfilzomib­Induced Thrombotic Microangiopathy­Two Case Reports.

BACKGROUND: Thrombotic microangiopathy (TMA) is a pathological syndrome characterized by a combination of three key features: microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and organ damage, primarily affecting the kidneys. There are several drugs known to have a definite or probable causal association with TMA, and carfilzomib, a second-generation irreversible proteasome inhibitor (PI), approved for the treatment of multiple myeloma (MM), is one of them. In the medical literature, there have been a growing number of reports describing this serious adverse event occurring in MM patients. The precise mechanisms underlying the development of PI-induced TMA are not yet fully understood. Significant improvements in both renal and hematological aspects have been documented following the administration of eculizumab. RECENT FINDINGS: In this report, we present two cases of MM patients who developed TMA while undergoing carfilzomib therapy. These cases were successfully treated at the Haematology Unit, Careggi Hospital in Florence. In our cases as well, the introduction of eculizumab resulted in rapid enhancements in renal function and platelet count, ultimately leading to the discontinuation of hemodialysis after 4 and 2 weeks, respectively. DISCUSSION AND CONCLUSION: We assessed 91 patients who received carfilzomib-based therapies at our Haematology Department, during which we identified two cases of DITMA (2.2% incidence). Additionally, we conducted a literature review and discovered a total of 75 documented cases of carfilzomib-induced TMA. Our experience aligns with the cases reported in literature: this adverse event can manifest at any point during treatment, regardless of the specific drug combinations used alongside carfilzomib. The initial and most crucial step in its management involves discontinuing carfilzomib therapy; therefore, recognizing TMA in a timely manner is of utmost importance. Eculizumab could play a role in improving and expediting the resolution of this potentially fatal adverse event, but further studies are needed. In a MM patient receiving carfilzomib, presenting with anemia, thrombocytopenia, and impaired renal function, a carfilzomib-induced TMA should be suspected in order to discontinue the causative agent.

Apixaban trough concentrations in atrial fibrillation patients with reduced renal function.

INTRODUCTION: The direct factor Xa inhibitor apixaban is partially eliminated by the kidneys but is still prescribed at fixed doses without therapeutic drug monitoring across varying levels of renal function. If apixaban accumulates due to renal impairment, this may translate into safety concerns, e.g. the risk for bleeding. The purpose of this study was to measure apixaban trough concentrations in patients with different stages of renal function/renal impairment. METHODS: Apixaban trough concentrations were measured using LC-MS/MS in patients with atrial fibrillation, having normal renal function (apixaban 5 mg BID, n=39), moderate renal impairment (apixaban 5 mg BID, n=40) and severe renal impairment (apixaban 2.5 mg BID, n=6). The median (min-max) relative eGFR values were 84.8 (71.7-111.4), 51.4 (31.3-67.2) and 23.0 (21.9-28.4) mL/min/1.73 m², in the three groups, respectively. RESULTS: Patients with moderate renal impairment had significantly higher apixaban trough concentrations than patients with normal renal function. The median (min-max) trough concentrations were 59.8 ng/mL (15.5-170.9) for normal renal function, 128.9 ng/mL (41.4-295.4) for moderate renal impairment and 81.7 ng/mL (61.8-109.0) for severe renal impairment. The trough concentrations correlated significantly with renal function measured as relative/absolute eGFR creatinine/cystatin C. CONCLUSIONS: The standard dosing regimen of 5 mg apixaban BID renders exposure that is roughly twice as high in patients with moderately reduced renal function compared to patients with normal renal function. We suggest that patients with moderately reduced renal function ought to be monitored. Possibly, a dose reduction may be considered to achieve similar exposure as in patients with normal renal function.

Role of Urinary Matrix Metalloproteinase-7 (MMP-7) as an Early Marker of Renal Dysfunction in Diabetic Individuals: A Cross-Sectional Study.

BACKGROUND AND OBJECTIVES: The matrix metalloproteinase 7 (MMP-7) level gets heightened in the urine samples of diabetic individuals with impaired renal function. Renal biopsy is seldom offered because of its invasive nature. These concerns spurred the investigation of relationships between urine MMP-7 levels and the renal function of diabetic individuals. Studies exploring this aspect are scarce. We aimed to evaluate the glycemic and renal parameters of female and male individuals with or without type 2 diabetes mellitus (T2DM) or kidney disease. We also assessed the correlation of urine MMP-7 with various parameters. METHODS: This prospective, analytical, cross-sectional study was conducted at Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar, India, from February 2020 to January 2023. Female and male individuals 18-85 years of age diagnosed with either T2DM, hypertension, or kidney disease were assessed for their glycemic indices and renal parameters. Those with both renal disease and T2DM were placed in group A. The diabetic individuals without kidney disease constituted group B. People in group C had neither kidney disease nor T2DM. Patients in group D had kidney disease but were not diabetics. The parameters of the male and female participants in each of the four groups were assessed and compared, including: age, body mass index (BMI), fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), serum urea, serum creatinine, estimated glomerular filtration rate (eGFR), urine albumin, urine creatinine, urine albumin-creatinine ratio (ACR), serum sodium, serum potassium, and urine MMP-7 levels. Furthermore, we correlated urine MMP-7 with all these traits. We used R software (version 4.4.0, Vienna, Austria) for data analysis. RESULTS: Two hundred eighty-seven (87.5%) of the 328 individuals we screened were eligible. Of them, group A had the maximum number (94) of participants, followed by B (75), C (65), and D (53). Males comprised 60.3% (n = 173) of the study population. The median age of the participants was 52.0 (44.0-61.1) years. The intergroup variations were statistically significant (p < 0.001) owing to their glycemic status and renal function. The gender-basis comparison of FBS and HbA1c yielded non-significant differences. On the contrary, assessment of the renal parameters revealed significant differences (p < 0.001) between females and males. The study population had a median urine MMP-7 level of 19.9 (1.1-50.5) µg/L. Significant associations with urine MMP-7 were found with serum creatinine (r = 0.91, p < 0.001), urine ACR (r = 0.86, p < 0.001), and eGFR (r = -0.84, p < 0.001). CONCLUSION: Our study portrayed that male diabetics, in comparison to female diabetics, had greater levels of urine ACR, urine MMP-7, eGFR, and serum creatinine. Moreover, urine ACR, eGFR, and serum creatinine strongly correlated with the urine MMP-7 level.

VEPTP inhibition with an extracellular domain targeting antibody did not restore albuminuria in a mouse model of diabetic kidney disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. DKD is a heterogeneous disease with complex pathophysiology where early endothelial dysfunction is associated with disease progression. The Tie2 receptor and Angiopoietin 1 and 2 ligands are critical for maintaining endothelial cell permeability and integrity. Tie2 signaling is negatively regulated by the endothelial specific transmembrane receptor Vascular Endothelial Protein Tyrosine Phosphatase (VEPTP). Genetic deletion of VEPTP protects from hypertension and diabetes induced renal injury in a mouse model of DKD. Here, we show that VEPTP inhibition with an extracellular domain targeting VEPTP antibody induced Tie2 phosphorylation and improved VEGF-A induced vascular permeability both in vitro and in vivo. Treatment with the VEPTP blocking antibody decreased the renal expression of endothelial activation markers (Angpt2, Edn1, and Icam1) but failed to improve kidney function in db/db uninephrectomized ReninAAV DKD mice.

Predictive value of fine fibrillatory wave for declining eGFR in patients with persistent atrial fibrillation: Long-term follow-up study.

BACKGROUND: Renal dysfunction has been identified as a risk factor for both stroke and bleeding events in atrial fibrillation (AF) patients, yet the mechanisms remain unclear. We examines the connection between fine fibrillatory wave and estimated glomerular filtration rate (eGFR) decline, alongside chronic kidney disease (CKD). METHODS: Persistent AF patients admitted to Jinan University's First Affiliated Hospital from January 2019 to June 2023 were enrolled. Kaplan-Meier analysis explored kidney endpoints for coarse and fine fibrillatory wave. A multivariate Cox model estimated adjusted hazard ratios (HR) and 95 % confidence intervals (95 % CI) to determine the correlation between fine fibrillatory wave and eGFR decline, as well as CKD. RESULTS: Of the 3521 AF patients, 229 were ultimately included in the analysis of this study. The median age of these patients was 75 years, with 58 % being male. The median follow-up time was 23 months, and the mean eGFR was 70 ± 19 mL/min/1.73 m2. Multivariate COX regression analysis revealed fine fibrillatory wave (HR = 8.311, 95 % CI 3.418-20.211, p < 0.001) as an independent risk factor associated with a ≥ 30 % decline in eGFR. Among 166 AF patients with eGFR >60 mL/min/1.73 m2, 40 cases (24 %) experienced a decline to <60 mL/min/1.73 m2. In comparison to coarse fibrillatory wave, the risk of fine fibrillatory wave causing eGFR decline to <60 mL/min/1.73 m2 was approximately 4.6 times higher (HR = 4.645, 95 % CI 2.127-10.142, p<0.001). CONCLUSIONS: Fine fibrillatory wave was independently associated with the risk of eGFR decline ≥30 % and eGFR decline to <60 mL/min/1.73 m2.

Impact of multiple comorbidities on long-term mortality in older patients following transcatheter aortic valve replacement.

Background: Older candidates for transcatheter aortic valve replacement (TAVR) frequently present with both cardiac and noncardiac comorbidities. There are few risk scores that evaluate a wide range of comorbidities. Methods: Patients who underwent TAVR for severe aortic stenosis were retrospectively evaluated. A new prediction model (Cardiac and nonCardiac Comorbidities risk score: 3C score) was determined based on coefficient in the multivariate Cox regression analysis for two-year all-cause mortality. C-statistics were assessed to compare the predictive abilities of the 3C score, the Charlson Comorbidities Index (CCI) score, the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II, and the Model for End-stage Liver Disease eXcluding International normalized ratio (MELD-XI) score. Results: The present study included 226 patients (age, 86 ± 5 years; males, 38 %). The values of the CCI score, EuroSCORE II, and MELD-XI score were 2 (1-3), 3.36 (2.12-4.58), and 5.35 (3.05-8.55), respectively. Multivariate Cox regression analysis identified two cardiac (left ventricular ejection fraction [LVEF] <40 % [2 points]; pulmonary hypertension [1 point]) and three noncardiac comorbidities (hepatobiliary system impairment [3 points]; estimated glomerular filtration rate <30 ml/min/1.73 m2 [1 point]; cachexia [1 point]). The C-statistics of the 3C score, EuroSCORE II, MELD-XI score, and CCI score were 0.767 (0.666-0.867), 0.610 (0.491-0.729), 0.580 (0.465-0.696), and 0.476 (0.356-0.596), respectively (p < 0.001). Conclusions: Among cardiac and noncardiac comorbidities, special attention should be given to hepatobiliary system impairment and reduced LVEF in older patients following TAVR. The 3C score may contribute to the risk stratification.

A Novel Formulation of Ketorolac Tromethamine (NTM-001) in Continuous Infusion in Adults with and without Renal Impairment: A Randomized Controlled Pharmacologic Study.

INTRODUCTION: There is a medical need for a safe, effective nonopioid postoperative analgesic for older subjects, including those with mild to moderate renal impairment. METHODS: Participants (≥ 65 years) were stratified by no, mild, or moderate renal impairment defined as creatinine clearance 60-89 mL/min for mild and 30-59 mL/min for moderate. Subjects were randomized to receive a loading dose of 6.25 mg of ketorolac tromethamine drug candidate NTM-001 followed by a 1.75 mg/h continuous intravenous (IV) infusion over 24 h or an IV bolus injection of ketorolac tromethamine (KETO-BOLUS) of 15 mg every 6 h. There were four treatment periods of 24 h for each subject with a minimum 7-day washout between them. This was a crossover study so subjects served as their own controls. Blood drawn from the subjects was used to plot concentration-time profiles against target profiles. Adverse events were monitored. RESULTS: Thirty-nine subjects enrolled. Concentration-time profiles showed low intersubject variability. Model-predicted curves for those with renal impairment closely matched observed plasma concentrations. Continuous infusion maintained higher mean plasma concentrations than the bolus regimen. No serious or unexpected adverse events were observed. No deaths occurred. CONCLUSIONS: NTM-001 was considered safe and well tolerated in this population of participants ≥ 65 years, including in those with mild or moderate renal impairment. There were fewer adverse events in the continuous infusion group. The predictable pharmacologic properties and blood concentration levels suggest that continuous IV infusion of ketorolac can be used as an effective postoperative pain reliever in older subjects.

Controlling postoperative pain can lead to faster recovery. Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID), like ibuprofen and naproxen, that can be as effective as morphine without the same risks. In hospitals, ketorolac is usually administered intravenously (IV) either continuously or as a bolus injection. A bolus of ketorolac may result in adverse gastrointestinal side effects. In this study, a new formulation of ketorolac tromethamine, NTM-001, was administered IV as a continuous 24 h infusion compared to IV boluses of ketorolac tromethamine every 6 h in volunteers. Volunteers were older (≥ 65 years) and had no, mild, or moderate kidney dysfunction. One randomized group received a starting IV dose of 6.26 mg followed by a continuous IV infusion of 1.75 mg/h of over 24 h. The other group received single NTM-001 IV bolus injections of ketorolac tromethamine 15 mg every 6 h over 24 h (4 doses, 60 mg) over the 24 h. After completing the first study, subjects waited at least a week and then switched groups, giving the study a crossover design so it could be observed how each subject responded to both regimens. Blood drawn from the subjects was tested for standard pharmacokinetic (PK) parameters. The data show that blood concentrations of NTM-001 can be reliably predicted. Side effects were mild and the continuous infusion reduced side effects. No unexpected adverse events occurred. These data show that NTM-001 can be used safely in older individuals, including those with mild or moderate kidney impairment.

Albumin-to-Globulin Ratio Combined with Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor in Multiple Myeloma with Renal Impairment.

Background: The albumin-to-globulin ratio (AGR) and neutrophil-to-lymphocyte ratio (NLR) have been recently regarded as promising prognostic factors in various malignancies. The present study investigated the prognostic value of combining the AGR and NLR (ANS) for risk assessments in multiple myeloma (MM) with renal impairment (RI). Methods: From 2011 to 2018, 79 patients with MM and RI were enrolled in this study. Receiver operating curves (ROCs) were constructed to determine optimal AGR and NLR thresholds for predicting overall survival (OS) and progression-free survival (PFS) during follow up. The prognostic values of AGR, NLR, and ANS were evaluated with Cox regression and Kaplan-Meier methods. We also created a predictive nomogram for prognostic evaluations of OS and PFS, and the predictive accuracy was assessed with a concordance index (c-index). Results: The ROC curves analyses showed that the optimal cut-off levels were 2.27 for NLR and 1.57 for AGR. A high NLR and a high ANS were significantly associated with worse OS and PFS. However, a high NLR combined with a low AGR was associated with worse OS. Multivariate analyses demonstrated that both the NLR and ANS were independent predictors for both OS and PFS and that a low AGR was an independent predictor of a reduced OS. The nomogram accurately predicted OS (c-index: 0.785) and PFS (c-index: 0.786) in patients with MM and RI. Conclusion: ANS may serve as a potential prognostic biomarker in patients with MM and RI. The proposed nomograms may facilitate prognostic predictions for patients with MM and RI.

Prognosis of concurrent renal impairment at diagnosis of multiple myeloma: a systematic review.

BACKGROUND: Multiple myeloma is a malignant tumour of the blood in which abnormal proliferation of plasma cells leads to bone destruction, renal impairment, anaemia, and hypercalcaemia. Renal impairment caused by multiple myeloma is a common and serious condition; however, the prognosis of multiple myeloma at the time of diagnosis remains unclear. METHOD: We conducted searches for literature in PubMed, Web of Science, Cochrane, Embase, CNKI, Wanfang, and VIP databases up to 30 April 2023. Progression-free survival and overall survival with and without renal impairment at the time of multiple myeloma diagnosis were compared, and prognostic indicators were analysed. RESULTS: Six studies were finally included. Among patients with multiple myeloma, 319 had renal impairment, and 1166 had no renal impairment. Compared to the control group, no significant difference was observed in overall or progression-free survival in patients with multiple myeloma complicated with renal impairment. CONCLUSION: The limited low-quality evidence available does not support an association between prognosis and multiple myeloma complicated by kidney injury.

Characterization of renal damage in Wilson's disease-Detailed analysis of 20 Chinese cases.

OBJECTIVE: Copper metabolism disorder disease is thought to contribute to renal symptoms in Wilson's disease (WD). Nonetheless, there remains limited knowledge regarding the precise characteristics of renal damage in individuals with Wilson's disease, encompassing clinical presentations, biochemical indicators, imaging findings, and renal histopathological alterations. METHODS: In this study, 20 patients diagnosed with Wilson's disease and renal involvement were enrolled in our hospital. These patients met the validated European criteria for Wilson's disease, and those with primary kidney disease or secondary renal damage caused by other underlying conditions were excluded. The baseline data of patients were collected. Various biochemical and hematological parameters were monitored. Biochemical examinations were measured using an automatic biochemistry analyzer, blood routines were tested by flow cytometry analysis, 24-h urine copper was tested by atomic absorption spectrophotometer. Besides, CER was measured by turbidimetric immunoassay with a Hitachi 7020 automatic biochemical analyzer (the intraplate and interplate coefficients of variation were 2.7% and 5.13% respectively). Copper oxidase was tested by colorimetric method using p-phenylenediamine hydrochloride (the intraplate and interplate coefficients of variation were both <10%). Diagnostic criteria for Wilson's disease and kidney damage were established based on the European Association for the Study of the Liver (EASL) and CKD Epidemiology Collaboration guidelines, respectively. Statistical analysis was carried out using t-tests and χ2 tests in SPSS 22.0 software. Significant differences were considered when P<0.05. RESULTS: In those patients with Wilson's disease-related renal damage, edema, gross hematuria, oliguria, and lumbar pain were present in most patients. Microscopic haematuria and proteinuria were also observed in 19 patients. Compared to patients without renal involvement, those with renal complications exhibited a significant increase in white blood cell (WBC) and neutrophil counts (P<0.05). Additionally, patients with renal damage showed a noteworthy rise in both diastolic and systolic blood pressure, along with a significant reduction in hemoglobin levels (P<0.05). Color Doppler ultrasound results revealed diffuse lesions in both kidneys in 12 patients, renal cysts were identified in 5 patients, and 2 patients exhibited abnormal renal blood flow signals. Meanwhile, varying degrees of IgA, IgM, IgG-based immunoglobulins, complement C3 and C1q deposition in the glomerular mesangial area were detected by immunofluorescence. Furthermore, renal puncture biopsy results revealed a spectrum of findings, including minimal change nephrosis in 1 case, IgA nephropathy in 3 cases, atypical membranous proliferative nephropathy in 2 cases, and focal segmental glomerulosclerosis in 1 case. CONCLUSION: This study comprehensively elucidates the distinct attributes of renal damage related to Wilson's disease, while also speculating that renal dysfunction in Wilson's disease could be linked to immune complex deposition. Depending on the underlying pathogenesis, kidney injury associated with Wilson's disease can be classified as primary or secondary. To slow down the progression of renal impairment, it is essential to undergo a renal biopsy pathological examination as early as possible to clarify the type of impairment and take the appropriate treatment.

Safety and effectiveness of remdesivir in hospitalized patients with COVID-19 and severe renal impairment: experience at a large medical center.

BACKGROUND: Literature on the safety of remdesivir in hospitalized COVID-19 patients with severe renal impairment is limited. We aimed to investigate the safety and effectiveness of remdesivir in this population. METHODS: We conducted a retrospective cohort study of adult hospitalized COVID-19 patients who received remdesivir between April 2022 and October 2022. Outcomes were compared between estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and ≥30 mL/min/1.73 m2 groups. The primary safety outcomes were acute kidney injury (AKI) and bradycardia, while the primary effectiveness outcomes included mortality in COVID-19-dedicated wards and hospital mortality. Secondary outcomes included laboratory changes, disease progression, and recovery time. RESULTS: A total of 1,343 patients were recruited, with 307 (22.9%) in the eGFR <30 group and 1,036 (77.1%) in the eGFR ≥30 group. Patients with an eGFR <30 had higher risks of AKI (adjusted hazard ratio [aHR] 2.92, 95% CI 1.93-4.44) and hospital mortality (aHR 1.47, 95% CI 1.06-2.05) but had comparable risks of bradycardia (aHR 1.15, 95% CI 0.85-1.56) and mortality in dedicated wards (aHR 1.43, 95% CI 0.90-2.28) than patients with an eGFR ≥30. Risk of disease progression was higher in the eGFR <30 group (adjusted odds ratio 1.62, 95% CI 1.16-2.26). No difference between the two groups in laboratory changes and recovery time. CONCLUSIONS: Hospitalized COVID-19 patients receiving remdesivir with severe renal impairment had an increased risk of AKI, hospital mortality, and COVID-19 disease progression compared to patients without severe renal impairment.

Urinary Insulin-Like Growth Factor-Binding Protein 7 (IGFBp7), Urinary Tissue Inhibitor of Matrix Metalloproteinase 2 (TIMP2), and Serum Transgelin as Novel Biomarkers of Kidney Injury in Multiple Myeloma.

Renal dysfunction is a common complication of MM and is associated with poor prognosis, particularly when progressive. Early identification of renal dysfunction is essential for prompt treatment for disease control and restoration of renal function. Urinary insulin-like growth factor-binding protein 7 (IGFBP-7), urinary tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and serum transgelin levels were measured using enzyme-linked immunosorbent assays and evaluated as biomarkers for the prediction of renal impairment in patients with multiple myeloma. U IGFBP-7/creatinine ratio, U TIMP2/creatinine ratio, and serum transgelin levels were higher in patients with MM than healthy controls, and predicted renal insufficiency in MM. Serum transgelin, urinary IGFBp7, and TIMP2 levels may have utility as biomarkers of renal tubular injury and predict future renal impairment in patients with MM.

Clinical Efficacy and Safety of Low-Dose Pemafibrate in Patients With Severe Renal Impairment: A Retrospective Study.

BACKGROUND: The management of hypertriglyceridemia in patients with chronic kidney disease (CKD) is important. Pemafibrate, a novel selective peroxisome proliferator-activated receptor-alpha modulator with less toxic effects on liver and kidney function than those of other fibrates, has recently been approved for the treatment of patients with an estimated glomerular filtration rate (eGFR) lower than 30 mL/min/1.73 m2. However, the efficacy and safety of pemafibrate in patients with severe renal impairment have not yet been established. METHODS: This single-center, retrospective observational study included 12 outpatients with CKD and hypertriglyceridemia, who were newly started on low-dose pemafibrate (0.1 mg/day) treatment between December 2021 and May 2023 and whose eGFRs were less than 30 mL/min/1.73 m2 at baseline. Blood samples were collected before and at 12 weeks after pemafibrate treatment. RESULTS: After 12 weeks of treatment, the serum triglyceride level was significantly decreased, whereas the high-density lipoprotein cholesterol level was significantly increased. The serum alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and uric acid levels were also significantly decreased, without worsening of the eGFR and serum creatinine levels. In the subgroup analysis, there were no significant differences in the changes in clinical parameters regardless of statin use and CKD stage at baseline. CONCLUSIONS: Low-dose pemafibrate administration in patients with severe renal impairment resulted in significant improvements in triglyceride, high-density lipoprotein cholesterol, and serum uric acid levels, and liver function, without adverse events.

Clinical outcomes and safety of remdesivir in hospitalized individuals with COVID-19, with or without severe renal impairment.

BACKGROUND: The use of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal impairment has been approved; however, limited clinical data exist. Accordingly, we aimed to compare outcomes and adverse events associated with remdesivir in hospitalized patients with COVID-19, with and without severe renal impairment. METHODS: Hospitalized patients with COVID-19 undergoing a 5-day remdesivir course at Taipei Veterans General Hospital from April 1 to July 31, 2022, were enrolled. Comparative analysis of outcomes and safety between patients with or without severe renal impairment (estimated glomerular filtration rate of < 30 mL/min per 1.73 m2) were conducted. Prognostic factors associated with 28-day mortality in patients with severe renal impairment were investigated using logistic regression analysis. RESULTS: A total of 671 hospitalized patients, including 132 patients with severe renal impairment, who received a 5-day course of remdesivir were analyzed. The 28-day mortality was higher in patients with severe renal impairment than in patients without severe renal impairment (15.2% vs. 7.8%). The proportion of patients with acute kidney injury (AKI) and deteriorated liver function after completing remdesivir therapy was similar between the patients with and without severe renal impairment, and the recovery rate of AKI was similar in both groups. The sequential organ failure assessment score was an independent factor associated with 28-day mortality in patients with severe renal impairment. CONCLUSIONS: Remdesivir was well-tolerated in hospitalized patients with COVID-19, regardless of renal function. Our findings support the recent recommendation to administer remdesivir in patients with severe renal impairment.

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation.

CONTEXT: Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation. OBJECTIVE AND METHODS: Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73 m2; CKDG3a/b; n = 35) or normal renal function (eGFR >90 ml/min/1.73 m2; CKDG1; n = 35) received 12,000, 24,000 or 48,000 IU D3/month for 1 year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression. RESULTS: Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNFα were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNFα significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR. CONCLUSION: Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.

Increased risk of hypocalcemia with decreased kidney function in patients prescribed bisphosphonates based on real-world data from the MID-NET® in Japan: a new-user cohort study.

BACKGROUND: In the post-marketing stage, cases of hypocalcemia associated with bisphosphonate preparations (BPs) have been reported in patients with decreased kidney function, despite warning against use of BPs in such patients in the package insert (PI) of Japan. The purpose of this study was to investigate the safety of BPs in patients with decreased kidney function. METHODS: The cohort study was conducted in patients with osteoporosis and newly prescribed bisphosphonate utilizing real-world data from MID-NET® in Japan. The adjusted hazard ratios (aHRs) for hypocalcemia (a corrected serum Ca level < 8.00 mg/dL) relative to the normal group were calculated in each decreased kidney function group (mild, moderate or severe group). RESULTS: A total of 14,551 patients were included in the analysis, comprising 2,601 (17.88%) with normal (eGFR ≥ 90 mL/min/1.73m2), 7,613 (52.32%) with mild (60 ≤ eGFR < 90 mL/min/1.73m2), 3,919 (26.93%) with moderate (30 ≤ eGFR < 60 mL/min/1.73m2), and 418 (2.87%) with severe kidney function (eGFR < 30 mL/min/1.73m2). The aHRs (95% confidence interval) for hypocalcemia were 1.85 (0.75-4.57), 2.30 (0.86-6.21), and 22.74 (8.37-61.78) in the mild, moderate, and severe groups, respectively. The increased risk of hypocalcemia depending on kidney function was also observed even when calculating the aHR for each specific BP such as alendronate sodium hydrate, minodronic acid hydrate, and sodium risedronate hydrate. Furthermore, similar results were obtained in the sensitivity analysis by altering the outcome definition to a 20% or more reduction in corrected serum Ca level from the baseline, as well as when focusing on patients with more than one laboratory test result per 30 days during the follow-up period. CONCLUSIONS: These findings suggest that the risk of hypocalcemia during BP prescription is higher in patients with decreased kidney function, particularly those with severely decreased kidney function. The quantitative real-world evidence on the safety risk of BPs obtained in this study has led to the PI revision describing a relationship between hypocalcemia risk and decreased kidney function as a regulatory action in Japan and will contribute to promoting the proper use of BPs with appropriate risk management in clinical practice.

Real-World Registry on the Pharmacotherapy of Multiple Myeloma and Associated Renal and Pulmonary Impairments in the Greater Gulf Region: Protocol for a Retrospective Real-World Data Study.

BACKGROUND: Multiple myeloma (MM) is the second-most common cancer among hematological malignancies. Patients with active disease may experience several comorbidities, including renal insufficiency and asthma, which may lead to treatment failure. The treatment of relapsed or refractory MM (RRMM) has been associated with multiple factors, causing a decline in progression-free survival as well as overall survival with subsequent lines of therapy. Data about the characteristics of this group of patients in the Greater Gulf region are lacking. OBJECTIVE: The primary objective of this study is to describe the disease characteristics and various treatment approaches or regimens used in the management of patients with RRMM in the Greater Gulf region. METHODS: We will conduct a regional, retrospective study collecting real-world and epidemiological data on patients with MM in countries of the Greater Gulf region. Medical records will be used to obtain the required data. Around 150 to 170 patients' records are planned to be retrospectively reviewed over 6 months without any cross-sectional or prospective intervention. Cases will be collected from Saudi Arabia, the United Arab Emirates, Kuwait, Oman, and Qatar. Descriptive as well as analytical statistics will be performed on the extracted data. The calculated sample size will allow us to estimate the percentages of RRMM cases with acceptable precision while complying with the challenges in light of data scarcity. We will obtain a comprehensive description of the demographic profile of patients with MM; treatment outcomes; the proportion of patients with MM with renal impairment and asthma, chronic obstructive pulmonary disease, or both at the time of diagnosis and any subsequent point; and data related to treatment lines, regimens, and MM-associated morbidities. RESULTS: Patient medical records were reviewed between June 2022 and January 2023 for eligibility and data extraction. A total of 148 patients were eligible for study inclusion, of whom 64.2% (n=95) were male and 35.8% (n=53) were female. The study is currently in its final stages of data analysis. The final manuscript is expected to be published in 2024. CONCLUSIONS: Although MM is a predominant hematological disease, data on its prevalence and patients' characteristics in the Greater Gulf region are scarce. Therefore, this study will give us real-world insights into disease characteristics and various management approaches of patients with MM in the Greater Gulf region. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49861.

Ablation of Kidney Tumors in Patients with Substantial Kidney Impairment: Current Status.

PURPOSE OF REVIEW: To review the current status of kidney tumor ablation in patients with substantial kidney impairment. RECENT FINDINGS: Few reports of kidney tumor ablation in such patients have recently been published. The reported prevalence of patients with stage 4 or 5 chronic kidney disease (CKD) among patients undergoing ablation is 2.0%-10%. In patients with stage 4 or 5 CKD, local tumor control rates were 88%-100%. The effect of ablation on CKD stage is unclear, and the observed deteriorations in kidney function are consistent with both the effect of cryoablation and the natural course of advanced CKD. According to guidelines, active surveillance may be selected. The goals of treatment are complete tumor removal and maintenance of kidney function, both of which can be met by ablation. Given the limited treatment options, ablation may play a pivotal role in the management of patients with advanced CKD.