Effects of osteoporosis medications on bone fracture in patients with chronic kidney disease.

PURPOSE OF THE STUDY: The risk of bone fracture is high in patients with chronic kidney disease (CKD), and aggressive treatment to reduce fragility fracture risk is the major strategy. However, the outcomes of osteoporosis medications in patients with CKD remain unclear. STUDY DESIGN: Patients with stage 3-5 CKD during 2011-2019 were enrolled. Patients were divided into two groups based on receiving osteoporosis medications (bisphosphonates, raloxifene, teriparatide or denosumab) or not. Two groups were matched at a 1:1 ratio by using propensity scores. The outcomes of interest were bone fractures, cardiovascular (CV) events and all-cause mortality. Cox proportional hazard regression models were applied to identify the risk factors. Additional stratified analyses by cumulative dose, treatment length and menopause condition were performed. RESULTS AND CONCLUSIONS: 67 650 patients were included. After propensity score matching, 1654 patients were included in the study and control group, respectively. The mean age was 70.2±12.4 years, and 32.0% of patients were men. After a mean follow-up of 3.9 years, the incidence rates of bone fracture, CV events and all-cause mortality were 2.0, 1.7 and 6.5 per 1000 person-months, respectively. Multivariate analysis results showed that osteoporosis medications reduced the risk of CV events (HR, 0.35; 95% CI, 0.18 to 0.71; p = 0.004), but did not alleviate the risks of bone fracture (HR, 1.48; 95% CI, 0.73 to 2.98; p = 0.28) and all-cause mortality (HR, 0.93; 95% CI, 0.67 to 1.28; p = 0.65). Stratified analysis showed that bisphosphonates users have most benefits in the reduction of CV events (HR, 0.26; 95% CI, 0.11 to 0.64; p = 0.003). In conclusion, osteoporosis medications did not reduce the risk of bone fractures, or mortality, but improved CV outcomes in patients with CKD.

Economic Analysis of a Ketoanalogue-Supplemented Very Low-Protein Diet in Patients With Chronic Kidney Disease in Taiwan and Thailand.

OBJECTIVE: A vegetarian very low-protein diet (VLPD) supplemented with ketoanalogues of essential amino acids Ketoanalogue-supplemented very low-protein diet (sVLPD) delays dialysis initiation in patients with chronic kidney disease (CKD). In this cost-effectiveness analysis, we compare an sVLPD with a conventional low-protein diet (LPD) in patients with CKD stage 4-5 using data from Taiwan and Thailand. DESIGN AND METHODS: A Markov model simulated health outcomes and care costs in patients receiving an sVLPD (0.3-0.4 g/kg-day, vegetarian diet) supplemented with ketoanalogues (1 tablet/5 kg-day) or an LPD (0.6 g/kg-day, mixed proteins). Health state transition probability and resource cost inputs were based on published literature and local sources, respectively. RESULTS: An sVLPD increased survival and quality-adjusted life years (QALYs) at a lower cost than an LPD. Total cost of care in Taiwan was 2,262,592.30 New Taiwan dollars (NTD) (68,059.35 EUR) with an LPD and 1,096,938.20 NTD (32,996.18 EUR) with an sVLPD (difference -1,165,654.10 NTD; -35,063.17 EUR). Total cost of care in Thailand was 500,731.09 Thai baht (THB) (14,584.12 EUR) with an LPD and 421,019.22 THB (12,262.46 EUR) with an sVLPD (difference -79,711.86 THB; -2,321.66 EUR). CONCLUSION: A ketoanalogue-supplemented vegetarian sVLPD increased QALYs and lowered lifetime care costs versus an LPD in patients with predialysis CKD in Taiwan and Thailand. These data, together with the new KDOQI Guidelines for nutrition in CKD, support dietary intervention using ketoanalogue-supplemented vegetarian sVLPDs to prevent CKD progression and postpone dialysis as a cost-effective approach, with beneficial effects for patients and health care providers.

Effects of osteoporosis medications on bone fracture in patients with chronic kidney disease.

PURPOSE OF THE STUDY: The risk of bone fracture is high in patients with chronic kidney disease (CKD), and aggressive treatment to reduce fragility fracture risk is the major strategy. However, the outcomes of osteoporosis medications in patients with CKD remain unclear. STUDY DESIGN: Patients with stage 3-5 CKD during 2011-2019 were enrolled. Patients were divided into two groups based on receiving osteoporosis medications (bisphosphonates, raloxifene, teriparatide or denosumab) or not. Two groups were matched at a 1:1 ratio by using propensity scores. The outcomes of interest were bone fractures, cardiovascular (CV) events and all-cause mortality. Cox proportional hazard regression models were applied to identify the risk factors. Additional stratified analyses by cumulative dose, treatment length and menopause condition were performed. RESULTS AND CONCLUSIONS: 67 650 patients were included. After propensity score matching, 1654 patients were included in the study and control group, respectively. The mean age was 70.2±12.4 years, and 32.0% of patients were men. After a mean follow-up of 3.9 years, the incidence rates of bone fracture, CV events and all-cause mortality were 2.0, 1.7 and 6.5 per 1000 person-months, respectively. Multivariate analysis results showed that osteoporosis medications reduced the risk of CV events (HR, 0.35; 95% CI, 0.18 to 0.71; p = 0.004), but did not alleviate the risks of bone fracture (HR, 1.48; 95% CI, 0.73 to 2.98; p = 0.28) and all-cause mortality (HR, 0.93; 95% CI, 0.67 to 1.28; p = 0.65). Stratified analysis showed that bisphosphonates users have most benefits in the reduction of CV events (HR, 0.26; 95% CI, 0.11 to 0.64; p = 0.003). In conclusion, osteoporosis medications did not reduce the risk of bone fractures, or mortality, but improved CV outcomes in patients with CKD.

Clinical characteristics and outcomes of patients requiring incident dialysis in Taiwan.

BACKGROUND: Despite having a well-established pre-end-stage kidney disease (pre-ESKD) care program, Taiwan has a high incidence of ESKD. Unrecovered incident dialysis may lead to the maintenance of dialysis. Contrast medium (CM) or general anesthesia (GA) may also induce dialysis. We aimed to examine the trends for incident dialysis, use of CM or GA, and its long-term trajectory outcomes. METHODS: Patients who received at least one dialysis intervention between 2010 and 2017 were identified using the National Health Insurance Research Database. We collected information on age, sex, comorbidities, causes of dialysis in outpatient or inpatient settings, use of CM or GA or pre-ESKD program enrolment before incident dialysis, and trajectory outcomes. RESULTS: Incident dialysis occurred more frequently in elderly inpatients with infectious diseases or previous chronic kidney disease (CKD). The number of patients who had a pre-ESKD care plan before incident dialysis increased from 25% in 2010 to 41% in 2017 (P < 0.001). In general, CM or GA exposure related with a higher mortality rate. Over the five-year longitudinal follow-up, patients without a history of CKD had a higher mortality rate than those with a history of CKD. CONCLUSION: Enrolment in the pre-ESKD care program increased, and inpatient incident dialysis decreased. The long-term survival of patients with CKD was higher than that of non-CKD patients after incident dialysis. CM or GA exposure appears to be related to dialysis-induced mortality, and further investigations are warranted.

The modulating effect of dietary protein intake on mortality in long-term hemodialysis patients: A nationwide population-based study.

AIMS OF THE STUDY: A high prevalence of protein-energy wasting and malnutrition among uremic patients is associated with an increase in morbidity and mortality. We aimed to investigate the modulating effect of daily dietary protein intake (DPI) evaluated by normalised protein catabolic rate (nPCR) on mortality in long-term haemodialysis (HD) patient from a nationwide population-based study. METHODS USED TO CONDUCT THE STUDY: By Taiwan Renal Registry Data System between 2005 and 2012, we divided the long-term HD patients into average nPCR < 1.2 and nPCR ≥ 1.2 groups according to the current guideline. The relation of nPCR with three-year all-cause and cardiovascular (CV) mortality were evaluated. The cox regression method for predicted mortality by nPCR was used. RESULTS OF THE STUDY: Among 88 330 HD patients, 58 122 (65.8%) patients were in average nPCR < 1.2 group and 30 208 (34.2%) in average nPCR ≥ 1.2 group. Both all-cause and cardiovascular (CV) mortality risks were increased in nPCR < 1.2 group after adjusting for demographics and laboratories cofactors in our multivariate cox regression model. Patients with nPCR < 1.2 and albumin ≥ 3.7 had a higher adjusted hazard ratio (aHR) for all-cause and CV mortality (1.16 [95% confidence interval (CI): 1.07-1.25, P < .001]; 1.15 [95% CI: 1.02-1.31, P = .03], respectively), compared with the reference group with nPCR ≥ 1.2 and albumin ≥ 3.7. Interestingly, there was no difference in mortality risk between low DPI subgroup (nPCR < 1.2 and Alb < 3.7) and the reference group (nPCR ≥ 1.2 and Alb < 3.7). Further stratification analysis revealed that low DPI subgroup (nPCR < 1.2, Alb ≥ 3.7 and TC ≥ 150) had an increased risk of both all-cause and CV mortality (aHR 1.14 [95% CI: 1.04-1.25, P = .005]; aHR 1.17 [95% CI: 1.02-1.35, P = .026], respectively). CONCLUSIONS DRAWN FROM THE STUDY: Low DPI (as presented by nPCR) independently correlated with all-cause and CV mortality among HD patients. Mortality risks were higher in low DPI patients even with normoalbuminaemia and non-hypocholesterolaemia. Further investigations on the importance of increasing DPI in HD patients is warranted.

Quantitative determination of human IgA subclasses and their Fc-glycosylation patterns in plasma by using a peptide analogue internal standard and ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry.

RATIONALE: Glycosylation on immunoglobulins is important for the immune function. In this study, we developed and validated a method for the absolute quantification of IgA subclasses and relative quantification of IgA-Fc glycopeptides by using affinity purification and ultrahigh-performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS). Only micro-volumes of plasma were required from each sample and we also applied the method to discover IgA and IgA-glycopeptide profiles in patients with chronic kidney diseases and IgA nephropathy. METHODS: Peptide M affinity beads were used to purify IgA, and a cost-effective peptide analogue was added as internal standard. With an efficient on-bead digestion process, purified samples were analyzed by UHPLC/MS/MS in multiple reaction monitoring mode. RESULTS: Correlation coefficients were greater than 0.999 for the IgA1 and IgA2 calibration curves and greater than 0.994 for glycopeptide regression curves. Intraday and interday precisions for IgA1 and IgA2 were <1.6% and <5.1% RSD, respectively. Intraday and interday accuracies ranged from 102.6 to 114.9% and 103.5 to 113.5% for IgA1 and IgA2, respectively. Stabilities of IgA1 and IgA2 at -80°C for 7 to 15 days ranged from 96.0 to 109.4%, respectively. The Pearson's correlation coefficient was 0.916 when comparing the IgA quantification results of the 30 clinical samples by using ELISAs and the developed UHPLC/MS/MS method. Compared with healthy controls, IgA and IgA-glycopeptides showed different profiles in patients with chronic kidney diseases and IgA nephropathy. CONCLUSIONS: The developed method showed good validation results, and the absolute quantification results of IgA correlated with those from ELISA. The pilot application study showed that IgA and IgA-glycopeptides can be potential biomarker candidates for kidney diseases, and more clinical sample applications are worth investigating.

Nifedipine Upregulates ATF6-α, Caspases -12, -3, and -7 Implicating Lipotoxicity-Associated Renal ER Stress.

Nifedipine (NF) is reported to have many beneficial effects in antihypertensive therapy. Recently, we found that NF induced lipid accumulation in renal tubular cells. Palmitic acid-induced renal lipotoxicity was found to be partially mediated by endoplasmic reticular (ER) stress, while it can also be elicited by NF in kidney cells; we examined the induction of suspected pathways in both in vitro and in vivo models. NRK52E cells cultured in high-glucose medium were treated with NF (30 µM) for 24-48 h. ER stress-induced lipotoxicity was explored by staining with thioflavin T and Nile red, transmission electron microscopy, terminal uridine nick-end labeling, and Western blotting. ER stress was also investigated in rats with induced chronic kidney disease (CKD) fed NF for four weeks. NF induced the production of unfolded protein aggregates, resulting in ER stress, as evidenced by the upregulation of glucose-regulated protein, 78 kDa (GRP78), activating transcription factor 6α (ATF6α), C/EBP-homologous protein (CHOP), and caspases-12, -3, and -7. In vitro early apoptosis was more predominant than late apoptosis. Most importantly, ATF6α was confirmed to play a unique role in NF-induced ER stress in both models. CKD patients with hypertension should not undergo NF therapy. In cases where it is required, alleviation of ER stress should be considered to avoid further damaging the kidneys.

Nifedipine Exacerbates Lipogenesis in the Kidney via KIM-1, CD36, and SREBP Upregulation: Implications from an Animal Model for Human Study.

Dysregulation of fatty acid oxidation and accumulation of fatty acids can cause kidney injury. Nifedipine modulates lipogenesis-related transcriptional factor SREBP-1/2 in proximal tubular cells by inhibiting the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway in vitro. However, the mechanisms by which nifedipine (NF) modulates lipotoxicity in vivo are unclear. Here, we examined the effect of NF in a doxorubicin (DR)-induced kidney injury rat model. Twenty-four Sprague-Dawley rats were divided into control, DR, DR+NF, and high-fat diet (HFD) groups. The DR, DR+NF, and HFD groups showed hypertension and proteinuria. Western blotting and immunohistochemical analysis showed that NF significantly induced TNF-α, CD36, SREBP-1/2, and acetyl-CoA carboxylase expression and renal fibrosis, and reduced fatty acid synthase and AMPK compared to other groups (p < 0.05). Additionally, 18 patients with chronic kidney disease (CKD) who received renal transplants were enrolled to examine their graft fibrosis and lipid contents via transient elastography. Low-density lipoprotein levels in patients with CKD strongly correlated with lipid contents and fibrosis in grafted kidneys (p < 0.05). Thus, NF may initiate lipogenesis through the SREBP-1/2/AMPK pathway and lipid uptake by CD36 upregulation and aggravate renal fibrosis in vivo. Higher low-density lipoprotein levels may correlate with renal fibrosis and lipid accumulation in grafted kidneys of patients with CKD.

Different Effects of Iron Indices on Mortality in Patients With Autosomal Dominant Polycystic Kidney Disease After Long-Term Hemodialysis: A Nationwide Population-Based Study.

OBJECTIVE: Iron supplementation and erythropoietin stimulating agents (ESAs) are essential for maintaining hemoglobin levels in hemodialysis patients. However, patients with autosomal-dominant polycystic kidney disease (PKD) have higher endogenous erythropoietin levels, so their recommended iron indices for hemodialysis patients may differ. This study evaluated iron profiles, including ferritin levels and transferrin saturation (TSAT) to identify factors affecting mortality in patients on dialysis, and those associated with mortality in patients with and without PKD. DESIGN: This cohort study from the Taiwan Renal Registry Data System stratified mortality risk by the presence of PKD recorded as the underlying disease. SUBJECTS: We enrolled 1346 hemodialysis patients with PKD and 82,873 hemodialysis patients without PKD. MAIN OUTCOME MEASURE: The primary outcome was 3-year all-cause mortality. Predictors included time-averaged and baseline serum ferritin levels and TSAT. Multivariate Cox regression analysis adjusting for age, comorbidities, and relevant laboratory parameters was used to estimate the all-cause hazard ratios (HRs) for mortality. RESULTS: The mean ages of patients with and without PKD were 56.2±13.2 and 61.7±13.5 years and the median follow-up time was 37 (15-76) months. The adjusted mortality risks for time-averaged ferritin levels >800 ng/mL (HR=1.52; 95% confidence interval: 1.40-1.65) or TSAT levels >50% (HR=1.46; 95% confidence interval: 1.30-1.65) were significantly higher among patients without PKD than those for patients with normal iron indices. However, a U-shaped curve of mortality against ferritin/TSAT levels was not observed in patients with PKD. In the sensitivity test, there was no difference among PKD patients who underwent regular ESA therapy and those who did not. CONCLUSION: Iron indices have different effects on mortality among patients with and without PKD. Iron supplementation, recommended serum ferritin levels, or TSAT should be monitored in hemodialysis patients, especially those without PKD. Clinicians should consider treating anemia in hemodialysis patients individually, especially in PKD.

Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway.

Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca2+ is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.

Kidney Cancer Linked to Chronic Hepatitis in the Asia-Pacific: A Population-Based Analysis.

BACKGROUND: The association of renal cancer with viral hepatitis infection remains unclear. Using an insurance data set, this population-based case-control study evaluated the association of renal cancer with chronic hepatitis virus infection in an endemic area of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. METHODS: We enrolled 17,747 patients with renal cancer during the period from 2000 to 2011 from the National Health Insurance Research Database of Taiwan. The control group comprised 35,494 randomly selected people without renal cancer matched by age and gender to the patients in the study group. ORs were calculated to assess the association of chronic hepatitis virus infection with renal cancer by using logistic regression analysis. RESULTS: Renal cancer was associated with HBV and HCV infection (OR 1.38, 95% CI 1.24-1.54; OR 1.24, 95% CI 1.07-1.44, respectively). An analysis stratified by gender and age revealed that young male HBV carriers had a higher risk of renal cancer compared with men without viral hepatitis (age <55 years: OR 1.94, 95% CI 1.57-2.39; 55≤ age <64 years: OR 1.40, 95% CI 1.05-1.86). Male HCV-infected patients aged <55 years (OR 1.90, 95% CI 1.11-3.26) and female HCV carriers aged between 55 and 64 years (OR 1.59, 95% CI 1.00-2.53) had a significantly higher risk of renal cancer compared with their counterparts. CONCLUSIONS: Renal cancer is significantly associated with chronic hepatitis infection, particularly in younger HBV-infected men.

Intestinal goblet cell carcinoid presenting with recurrent sterile peritonitis in a patient on peritoneal dialysis: a case report.

BACKGROUND: Goblet cell carcinoid is a rare variant of appendiceal carcinoid with mixed endocrine and exocrine features. The most common symptom and signs are abdominal pain, acute appendicitis and palpable mass. Additionally, abdominal pain is common in patient on peritoneal dialysis, which may confound the diagnosis in such patient. CASE PRESENTATION: We report a 71- years- old woman on peritoneal dialysis that experienced several episodes of abdominal cramping pain and sterile peritonitis. She had one episode of severe pain and underwent an appendectomy for suspicion of appendicitis. Goblet cell carcinoid was diagnosed. She had no further abdominal pain after she received appendectomy. CONCLUSIONS: Malignant dialysate was rarely reported in patient with peritoneal dialysis. However, goblet cell carcinoid can initially present with acute appendicitis, chronic intermittent abdominal pain and mimicking peritonitis. In systemically reviewing the literature, this is the first case report of sterile peritonitis with peritoneal dialysis caused by goblet cell carcinoid.

Different effect of hypercholesterolemia on mortality in hemodialysis patients based on coronary artery disease or myocardial infarction.

BACKGROUND: Studies on the association of total cholesterol (TC) levels and mortality in hemodialysis (HD) patients demonstrated conflicting results. The differenct effect of Hypercholesterolemia on HD patients based on the presence of myocardial infarction (MI) or coronary artery disease (CAD) is unknown. METHODS: We analyzed data from the Taiwan Renal Registry Data System (TWRDS) between 2005 and 2012. Patients were divided into MI/CAD or non-MI/CAD group. The primary outcome was three-year mortality. The association between primary outcome and first year average TC and effect of change in cholesterol level between the first and third year of dialysis were explored. RESULTS: Of 90,795 HD patients, 77,762 (85.6%) patients were assigned to non-MI/CAD group and 13,033 (14.4%) to the MI/CAD group. In the non-MI/CAD subjects, both TC > 250 mg/dL and < 150 mg/dL were associated with increased risk of mortality (adjusted hazard ratio [HR]; 95% confidence interval [CI]: 1.27; 1.17-1.37 and 1.14; 1.11-1.18) compared to the reference (TC: 150-200 mg/dL). In the MI/CAD patients, only TC < 150 mg/dL had increased risk (HR; 95% CI: 1.15; 1.08-1.24). In addition, patients of the non-MI/CAD group with highest level of TC (>250 mg/dL) in both first and third year of dialysis had a 64% increased risk for mortality (HR: 1.64, 95% CI: 1.51-1.80). CONCLUSION: In this nationwide hemodialysis cohort, hypercholesterolemia was associated with increased mortality in HD patients without MI/CAD. Further investigation on primary prevention of CAD with statin is warranted.

Arterial Stiffness Index and Coronary Artery Plaques in Patients with Subclinical Coronary Atherosclerosis.

BACKGROUND: Arterial stiffness is a physiologic quantitative value used to measure arterial compliance. It is predictive of coronary atherosclerosis in patients with intermediate to high cardiovascular risk. However, a correlation between arterial stiffness and subclinical coronary atherosclerosis has yet to be established. Therefore, the purpose of this study was to evaluate arterial stiffness using an arterial stiffness index (ASI) and investigate its association with coronary artery plaque in patients with subclinical coronary atherosclerosis. METHODS: Our study enrolled 156 consecutive subjects who underwent health screening using a 64-slice cardiac computed tomography angiography (CCTA). Their arterial stiffness index was assessed noninvasively by CardioVision(®) MS-2000. The atheroma on the coronary vessel walls was analyzed. RESULTS: Of the 156 patients, 53 displayed at least one > 50% stenotic lesion over the coronary arteries in CCTA images. The patients with at least one > 50% coronary stenotic plaque were older and had higher systolic blood pressure and ASI values than patients without > 50% coronary stenotic plaque. After dividing the study population into 2 groups by those patients over and under 50 years of age, the ASI positively correlated with the presentation of at least one > 50% coronary stenotic plaque in patients aged ≥ 50 years (odds ratio = 1.02, 95% confidence interval: 1.00-1.04, p = 0.03). CONCLUSIONS: The ASI could play a role in risk stratification systems for coronary artery disease in patients with subclinical coronary atherosclerosis, and is a useful clinical marker for the correlation of early coronary plaque. KEY WORDS: Arterial stiffness; Arterial stiffness index; Atherosclerosis; Coronary artery plaque.

Risk factors for AKI or mortality and long-term follow-up in COVID-19 infected patients in the era nefore vaccination.

BACKGROUND: Acute kidney injury (AKI) is a severe complication of coronavirus disease 2019 (COVID-19) and is associated with a higher risk of mortality. Understanding the risk factors contributing to COVID-19-related AKI and mortality before vaccination is important for the initiation of preventative measures and early treatment strategies. METHODS: This study included patients aged ≥18 years diagnosed with COVID-19 through polymerase chain reaction from May 2020 to July 2021, admitted in three local hospitals in Taiwan, with an extended follow-up until June 30, 2022. A median follow-up period of 250 days was used to assess AKI development and mortality. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. Multivariate Cox regression analysis of AKI and mortality-related risk factors was performed. RESULTS: Of the 720 hospitalized patients with COVID-19, 90 (22%) developed AKI. Moreover, 80%, 10.1%, and 8.9% of the patients had stage 1, 2, and 3 AKI, respectively. Patients with stage 1-3 AKI had significantly lower survival rates than those without AKI (p = 0.0012). The mean duration of post-admission AKI occurrence was 9.50 ± 11.32 days. Older age, hypoalbuminemia, and higher D-dimer and ferritin levels were associated with COVID-19 mortality. In COVID-19 AKI, in addition to older age and high D-dimer and ferritin levels, chronic kidney disease emerged as an independent risk factor. CONCLUSION: COVID-19-related AKI develops early, exhibits a temporal association with respiratory failure, and is linked to an unfavorable prognosis. The mortality rate increased according to the AKI stage (p = 0.0012). Age; albumin, D-dimer, and ferritin levels; and the underlying chronic kidney disease status upon admission are crucial factors for predicting AKI development, which increases the mortality risk. Monitoring the renal function not only within 10 days of COVID-19 onset, but also within one month after the disease onset.

Determinants of the creatinine clearance to glomerular filtration rate ratio in patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Creatinine secretion, as quantified by the ratio of creatinine clearance (CrCl) to glomerular filtration rate (GFR), may introduce another source of error when using serum creatinine concentration to estimate GFR. Few studies have examined determinants of the CrCl/GFR ratio. We sought to study whether higher levels of albuminuria would be associated with higher, and being non-Hispanic black with lower, CrCl/GFR ratio. METHODS: We did a cross-sectional analysis of 1342 patients with chronic kidney disease from the Chronic Renal Insufficiency Cohort (CRIC) who had baseline measure of iothalamate GFR (iGFR) and 24-hour urine collections. Our predictors included urine albumin as determined from 24-hour urine collections (categorized as: <30, 30-299, 300-2999 and ≥3000 mg), and race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic). Our outcome was CrCl/iGFR ratio, a measure of creatinine secretion. RESULTS: Mean iGFR was 48.0 ± 19.9 mL/min/1.73 m², median albuminuria was 84 mg per day, and 36.8% of the study participants were non-Hispanic black. Mean CrCl/iGFR ratio was 1.19 ± 0.48. There was no association between the CrCl/iGFR ratio and urine albumin (coefficient 0.11 [95% CI-0.01-0.22] for higest verus lowest levels of albuminuria, p = 0.07). Also, there was no association between race/ethnicity and CrCl/iGFR ratio (coefficient for non-Hispanic blacks was-0.03 [95% CI-0.09-0.03] compared with whites, p = 0.38). CONCLUSIONS: Contrary to what had been suggested by prior smaller studies, CrCl/GFR ratio does not vary with degree of proteinuria or race/ethnicity. The ratio is also closer to 1.0 than reported by several frequently cited reports in the literature.

Currently Used Methods to Evaluate the Efficacy of Therapeutic Drugs and Kidney Safety.

Kidney diseases with kidney failure or damage, such as chronic kidney disease (CKD) and acute kidney injury (AKI), are common clinical problems worldwide and have rapidly increased in prevalence, affecting millions of people in recent decades. A series of novel diagnostic or predictive biomarkers have been discovered over the past decade, enhancing the investigation of renal dysfunction in preclinical studies and clinical risk assessment for humans. Since multiple causes lead to renal failure, animal studies have been extensively used to identify specific disease biomarkers for understanding the potential targets and nephropathy events in therapeutic insights into disease progression. Mice are the most commonly used model to investigate the mechanism of human nephropathy, and the current alternative methods, including in vitro and in silico models, can offer quicker, cheaper, and more effective methods to avoid or reduce the unethical procedures of animal usage. This review provides modern approaches, including animal and nonanimal assays, that can be applied to study chronic nonclinical safety. These specific situations could be utilized in nonclinical or clinical drug development to provide information on kidney disease.

Comparison of Humoral Antibody Responses and Seroconversion Rates between Two Homologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination in Patients Undergoing Maintenance Hemodialysis.

BACKGROUND: Hemodialysis patients are at an increased risk of SARS-CoV-2 infection and are excluded from preauthorization COVID-19 vaccine trials; therefore, their immunogenicity is uncertain. METHODS: To compare the antibody responses to homologous ChAdOx1 and mRNA-1273 SARS-CoV-2 vaccination in hemodialysis patients, 103 age- and sex-matched hemodialysis patients with two homologous prime-boost vaccinations were recruited to detect anti-receptor-binding domain (RBD) IgG levels and seroconversion rates (SCRs) 14 days after a prime dose (PD14), before and 28 days after a boost dose (pre-BD0 and BD28). RESULTS: Both mRNA-1273 and ChAdOx1 vaccinations elicited immunogenicity in study subjects, and the former induced higher anti-RBD IgG levels than the latter. The SCRs of both groups increased over time and varied widely from 1.82% to 97.92%, and were significantly different at PD14 and pre-BD0 regardless of different thresholds. At BD28, the SCRs of the ChAdOx1 group and the mRNA-1273 group were comparable using a threshold ≥ 7.1 BAU/mL (93.96% vs. 97.92%) and a threshold ≥ 17 BAU/mL (92.73% vs. 97.92%), respectively, but they were significantly different using a threshold ≥ 20.2% of convalescent serum anti-RBD levels (52.73% vs. 95.83%). The seroconversion (≥20.2% of convalescent level) at BD28 was associated with mRNA-1273 vaccination after being adjusted for age, sex, body mass index, and the presence of solicited reactogenicity after a prime vaccination. CONCLUSION: Our prospective, observational cohort indicates that a full prime-boost mRNA-1273 vaccination is likely to provide higher immune protection in hemodialysis patients compared to ChAdOx1, and this population with a prime-boost ChAdOx1 vaccination should be prioritized for a third dose.

Label-Free, Portable, and Color-Indicating Cholesteric Liquid Crystal Test Kit for Acute Myocardial Infarction by Spectral Analysis and Naked-Eye Observation.

The early diagnosis of acute myocardial infarction is difficult in patients with nondiagnostic characteristics. Acute myocardial infarction with chest pain is associated with increased mortality. This study developed a portable test kit based on cholesteric liquid crystals (CLCs) for the rapid detection of AMI through eye observation at home. The test kit was established on dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride-coated substrates covered by a CLC-binding antibody. Cardiac troponin I (cTnI) is a major biomarker of myocardial cellular injury in human blood. The data showed that the concentration of cTnI was related to light transmittance in a positive way. The proposed CLC test kit can be operated with a smartphone; therefore, it has high potential for use as a point-of-care device for home testing. Moreover, the CLC test kit is an effective and innovative device for the rapid testing of acute myocardial infarction-related diseases through eye observation, spectrometer, or even smartphone applications.

The Effect of Statin on Anemia in Patients with Chronic Kidney Disease and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

Although erythropoietin-stimulating agents are effective in treating anemia in patients with end-stage kidney disease (ESKD) undergoing hemodialysis, some ESKD patients, especially those with inflammation, continue to suffer from anemia. Statin, an inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase with lipid-lowering effects, may have a pleiotropic effect in reducing inflammation, and thus increase hemoglobin (Hb) level. We searched the PubMed, Embase, and Cochrane databases for relevant studies. The population of interest comprised advanced chronic kidney disease (CKD) patients and ESKD patients receiving hemodialysis with statin treatment. The included study designs were randomized control trial/cohort study/pre-post observational study, and outcomes of interest were Hb, erythropoietin resistance index (ERI) and ferritin. PRISMA 2020 guidelines were followed, and risk of bias (RoB) was assessed using the RoB 2.0 tool in randomized controlled trials, and the Newcastle-Ottawa scale (NOS) in cohort studies. We eventually included ten studies (5258 participants), comprising three randomized controlled trials and seven cohort studies. Overall, Hb increased by 0.84 g/dL (95% confidence interval [CI]: -0.02 to 1.70) in all groups using statins, including single-arm cohorts, and by 0.72 g/dL (95% CI: -0.02 to 1.46) in studies with placebo control. Hb levels were higher in the study group than in the control group, with a mean difference of 0.18 g/dL (95% CI: 0.04-0.32) at baseline and 1.0 g/dL (95% CI: 0.13-1.87) at the endpoint. Ferritin increased by 9.97 ng/mL (95% CI: -5.36 to 25.29) in the study group and decreased by 34.01 ng/mL (95% CI: -148.16 to 80.14) in the control group; ferritin fluctuation was higher in the control group. In conclusion, statin may improve renal anemia in ESKD patients receiving hemodialysis and regular erythropoietin-stimulating agents. Future studies with more rigorous methodology and larger sample size study should be performed to confirm this beneficial effect.