Creatinine Levels Research Articles

The effect of TSH on kidney function

Background: The thyroid gland plays a vital role in the regulation of many physiological processes, including kidney function. Aim: The purpose of this study was to investigate the relationship between thyroid-stimulating hormone (TSH) and kidney function in male and female patients with hyperthyroidism, as well as in healthy control subjects. Method: A total of 60 participants from Najaf city, Iraq, were included in the study. This included 10 male and 10 female control subjects, as well as 20 male and 20 female patients with hyperthyroidism. Blood samples were collected from all participants and analyzed for TSH, urea, and creatinine levels. Result: The results showed a significant increase in TSH levels in both male and female patients with hyperthyroidism compared to control subjects. Urea levels were also significantly higher in hyperthyroidism patients compared to controls, while creatinine levels were not significantly different. In addition, there was a significant difference in the effects of TSH on kidney function between male and female patients with hyperthyroidism. Female patients with hyperthyroidism had significantly higher levels of urea and lower levels of creatinine compared to male patients with hyperthyroidism. These findings suggest a direct effect of TSH on kidney function and highlight the need for regular monitoring of kidney function in individuals with hyperthyroidism, particularly women. Further research is needed to fully understand the mechanisms behind the gender differences observed in this study and to develop targeted interventions for both men and women with thyroid disorders. Conclusion: our study provides valuable insights into the relationship between TSH and kidney function and highlights the need for multidisciplinary care and targeted interventions for individuals with thyroid disorders to prevent or minimize the risk of kidney dysfunction.

Analysis of Nutritional Status, Body Composition, and Creatinine Levels in Hemodialysis Patients at Ibnu Sina Yw-Umi Hospital Makassar

Hemodialysis is an essential therapy for managing chronic kidney failure, helping to maintain homeostasis by removing excess fluids, solutes, and toxins from the body. The global increase in the prevalence of chronic kidney disease (CKD) has led to a rising demand for hemodialysis. This study aims to analyze the relationship between nutritional status, body composition, and creatinine levels in hemodialysis patients at Ibnu Sina YW-UMI Makassar Hospital. Using an observational cross-sectional design, the study involved 16 patients whose body mass index (BMI), muscle mass, fat mass, total body fluid, and visceral fat were measured before and after dialysis. The results revealed significant changes in nutritional status, body composition, and creatinine levels pre- and post-hemodialysis, analyzed through paired T-tests at a 0.05 confidence level. Most patients were male, aged over 45, with normal nutritional status but abnormal creatinine levels. Body composition analysis showed significant differences in muscle mass, fat mass, total body fluid, and visceral fat before and after hemodialysis, with patients with higher muscle mass tending to have elevated creatinine levels. This study emphasizes the importance of monitoring body composition and creatinine levels to support the health of hemodialysis patients and highlights the need for personalized nutritional and therapeutic interventions in CKD care. Further research is needed to explore the long-term impacts of hemodialysis on nutritional status and kidney function.

Residual congestion in acute decompensated heart failure: A novel approach through microvascular imaging of renal circulation

Abstract Background In patients admitted for acute decompensated heart failure (ADHF), residual congestion at discharge is associated with adverse clinical outcomes. Traditionally, the extent of congestion has been inferred from central venous pressure, but it has also been highlighted that this is insufficient for a comprehensive evaluation of residual congestion. On the other hand, renal congestion is an important finding of organ congestion, and Superb Microvascular Imaging (SMI), a technique that reveals minute flow details, is promising for assessing renal circulation. We hypothesized that in patients with ADHF, assessment of renal circulation using SMI may be superior to conventional methods in assessing residual congestion. Methods In this prospective study, we enrolled 45 consecutive patients admitted with ADHF. We performed comprehensive evaluations including blood tests, echocardiography, and renal ultrasonography using SMI. The vascular index (VI), as measured by SMI, was calculated as the percentage of blood flow signal area in the region of interest. Subsequently, we calculated the intra-renal perfusion index (IRPI), representing cyclic variation in VI, as (maximum VI - minimum VI) within one cardiac cycle, divided by the maximum VI (Figure). Brain Natriuretic Peptide (BNP) levels were utilized to evaluate the state of decongestion. Results At discharge, the mean IRPI was 0.61±0.04, while the median BNP levels were 204.9 pg/ml (interquartile range: 102.7, 428.2). Patients exhibiting elevated log BNP levels at discharge (>2.31, based on median value) displayed significantly higher IRPI values [0.61(0.49, 0.86) vs 0.53(0.35, 0.59), p=0.02] and were older (80.8±8.5 vs 70.3±14.9 years, p=0.010). However, no significant differences were observed regarding laboratory parameters including hematocrit and creatinine levels, as well as echocardiographic parameters such as ejection fraction, E/e' ratio, and estimated right atrial pressure (RAP). Moreover, at discharge, creatinine levels (p=0.56) and estimated RAP (p=0.06) exhibited no significant correlation with IRPI. Conclusion Renal circulation evaluated by SMI may serve as a useful indicator of the extent of residual congestion at discharge compared to blood tests and echocardiographic estimates of right atrial pressure in patients admitted for ADHF.

Characteristics of fatal COVID-19 among pregnant women admitted to hospitals in Kazakhstan

Abstract Background The factors contributing to the fatal outcome of COVID-19 in pregnant women remain not entirely clear. We compared the prevalence rates of comorbidities and laboratory test results in pregnant survivors and non-survivors. Methods This retrospective study relied on clinical and laboratory data obtained from medical records of pregnant women with COVID-19 admitted to three hospitals of the Republic of Kazakhstan from 16.07.2021 to 31.01.2022. Overall, we obtained data on 157 pregnant women with COVID-19, of whom 95.9 % survived and 4.1 % died in the hospitals. Results Arterial hypertension was present in 50% of non-survivors vs. 7.9% of survivors (P = 0.001), diabetes mellitus was diagnosed in 16.7% of non-survivors vs. 2.3% of survivors (P = 0.044), and the rate of hyperglycemia was 40% and 7.2%, respectively (P = 0.009). Heart rhythm disturbance was present in 50% of non-survivors vs. 6.4% of survivors (P < 0.001), and already at the time of admission to the hospital, the non-survivors had significantly higher heart and respiratory rates. Laboratory tests showed that non-survivors had higher erythrocytes sedimentation rate, C-reactive protein, leukocyte count, and D-dimer levels (P = 0.001, P < 0.001, P = 0.038, P = 0.014, respectively). The creatinine level was within the normal range in both study groups, but it was relatively higher in the deceased pregnant women (71.3; IQR: 66-251.75) vs. 52; IQR: 43-63; P = 0.001). Finally, a higher proportion of those who died presented with abnormal chest CT as compared with the survivors (33.3% vs. 4.2%, P < 0.001). Conclusions The deceased had a higher rate of comorbidities. Given the vulnerability of pregnant women to COVID-19, it is essential to plan a prospective study to provide insights into the factors that contribute to severe COVID-19 outcomes in pregnant women. Key messages • Determining risk factors for fatal COVID-19 is crucial for effective medical care of pregnant women. • Identifying potential risk factors of fatal COVID-19 among pregnant women could help inform public health policies and clinical guidelines.

Adverse cardiovascular outcomes due to potential drug-drug interactions in statin therapy: a population-based study

Abstract Background Statins have been proven to reduce morbidity and mortality in patients with known atherosclerotic cardiovascular disease (ASCVD) and in primary prevention. Given their unique role in ASCVD, concomitant use of statins and other medications are inevitable. Our clinicians’ duty is to identify clinically important drug-drug interactions (DDI) with statins and to minimize potential life-threatening adverse drug reactions. Purpose To understand the clinical relevance of statin related DDI, we aimed to analyse the prevalence and level of severity of potential statin DDI in a real-world territory-wide population-based study. Methods We retrospectively analysed 95278 patients (mean age 64.3±11.4, female 45.0%) prescribed simvastatin (N=56111, 59%), atorvastatin (N=33902, 36%), or rosuvastatin (N=5265, 5%) from 2013-2022 among 16 public hospitals. Covariates were balanced with 1:1 propensity score matching for patients with and without potential DDI, resulting in 35907 patients in each arm. A composite 4-point MACE (major adverse cardiovascular events) was used as the primary outcome, which included coronary revascularisation, stroke, myocardial infarction (MI), and cardiovascular-related death (CV death). Cox proportional-hazard model with competing risk regression was performed to estimate adjusted hazards ratio (aHR) with corresponding 95% confidence intervals (CI). Secondary analyses would be focusing on adverse drug reactions in these three different statin subgroups. Results At 1-year follow up, subjects with potential statin related DDI have higher propensities of deranged liver function (ALT>=3x ULN, 4.9% vs 3.4%; p<0.001), elevated creatine kinase (CK>=5x ULN, 0.9% vs 0.5%, p<0.001) and deranged renal function (creatinine level >=2X ULN, 0.3% vs 0.2%, p<0.001) than non-DDI group. At 5-year follow up, the statin DDI group had higher incidences of MI (2.9% vs 1.9%, p<0.01), stroke (4.0% vs 2.3%, p<0.001) and CV death (1.7 % vs 1.5%, p=0.038). Potential DDI had most significant effect seen on simvastatin compared to other statins. Simvastatin DDI cohort had strong association with subsequent coronary vascularization (aHR 1.41, 95% CI 1.21–1.64, p<0.005), MI (aHR 1.66, 95% CI 1.46–1.88, p<0.005), stroke (aHR 1.95, 95% CI 1.76–2.16, p<0.005), and CV-related death (aHR 1.18, 95% 1.00–1.38, p=0.05) as compared to control. Atorvastatin DDI cohort was associated with higher rates of MI (aHR 1.81, 95% CI 1.54–2.12, p<0.005) and stroke (aHR 1.64, 95% CI 0.39–1.94, p<0.005) than control. Rosuvastatin DDI cohort was weakly associated with higher rates of MI (aHR 1.75, 95% CI 1.02–3.01, p=0.04). Conclusion Potential statin related drug-drug interactions are prevalent and were associated with major adverse cardiovascular events. Our real-world data demonstrated that simvastatin related drug-drug interaction pose a significant threat to our patients with association with CV death, myocardial infarction, stroke and future coronary revascularization.4-point MACE

Safety and efficacy of initiation SGLT in heart failure with a reduced left ventricular ejection fraction and chronic kidney disease on top of standard therapy with ARNI or ACE-i

Abstract Quadruple therapy remains underused in cases of heart failure with a reduced ejection fraction (HFrEF). Among eligible patients most of them take ACE-i/ARB and B-blockers, less MRAs and ARNI. There are many questions of adding new foundational drugs, especially in the case of coexisting of HFrEF and chronic kidney disease (CKD). The aim was to compare the safety and effectiveness of initiation SGLT in patients (P) with HFrEF and CKD on standard therapy with ARNI or ACE-I. Methods we identified 54 symptomatic P with HFrEF (EF≤40%) and CKD 3 (eGFR between 30 and 60 ml/min) on standard therapy (ACE-I or ARNI, B-blockers, MRAs). All P were divided into 2 groups: group 1- 26 P on ARNI, B-blockers, MRAs; group 2- 28 P on ACE-I, B-blockers, MRAs. All P started on dapagliflozin (D) with a dose of 10 mg daily. The potassium (K), creatinine levels, eGFR, clinic BP were estimated at baseline and at weeks 1, 2, 4, 6, 8, 12. At baseline and at weeks 4, 12 NT-proBNP, urine albumin-to-creatinine ratio (UCAR) were estimated and P underwent 24-hour BP measurements. Results At week 1 after initiation of D a mean eGFR deсreased not significant in both group. At week 2 in group 1 mean eGFR decreased by 1,9±1.1 ml/min/1.73m2, P<.05 and group 2-2,5±1.9 ml/min/1.73m2, P<.05. At week 4 in both groups mean eGFR deсreased significantly, but in group 2 the decline of eGFR was more pronounced (-2,4±2.6 ml/min/1.73m2 vs.-3,3±2.5 ml/min/1.73m2, P=.04), with not significant decreasing to 6, 8, 12 weeks. At week 1mean K changed not significantly after start of therapy in both groups. At week 4 in group 1mean K deсreased significantly from 4.97±0.6 to 4.63±0.57 mEq/l (P<.05), in group 2 K deсreased not significant. At week 4 in group 1 was a greater reduction NT-proBNP than in group 2 (-234±42 vs. -143±32 ng/L, P<.05). At week 12 in both groups a significant decrease NT-proBNP were observed, but in group 1 more pronounced (-865±89 ng/L and -573±78 ng/L, (P<.01; P<.05 respectively). UCAR was also reduced significantly in both groups, but in group 1 more pronounced (P<.01; P<.05 respectively). In group 1, there were more cases of symptomatic hypotension (10 vs. 8, P<.05) and greater decrease mean BP than in group 2 (P<.05), but it didn’t result in a withdrew. In return, maen doses diuretics were carefully decreased in both groups. At baseline in patients with HFrEF was an inverse correlation between GFR and NT-proBNP level (r=−0.328, P<.05). By linear regression analysis the eGFR was associated with NT-proBNP change (P<.05). Conclusion In patients with HFrEF and CKD, adding SGLT to standard therapy with ARNI, B-blockers, MRAs were paralleled by marked improvements in the neurohumoral profile by significantly reduced NT-proBNP compared with ACE-I, B-blockers, MRAs. SGLT initiation caused an early drop in eGFR, but in group ARNI the decline of eGFR was less pronounced with greater reduction in the albuminuria and was accompanied by decreased potassium level.

Acute kidney injury after catheter ablation of atrial fibrillation: comparison between different energy sources

Abstract Introduction Pulsed field ablation (PFA) is an innovative technology recently adopted for the treatment of atrial fibrillation (AF). Preclinical and clinical studies have reported a reassuring safety profile, because of its tissue specific effect, sparing adjacent tissues. However, two cases of acute kidney injury (AKI) secondary to hemolysis after PFA have recently been reported. Purpose To compare the incidence of AKI and hemolysis after catheter ablation of AF using radiofrequency energy (RFA), cryo-balloon energy (CBA) and PFA using a pentaspline catheter. Method Patients undergoing catheter ablation of AF were consecutively enrolled in a prospective registry in a tertiary referral center between April 2010 and January 2024. Blood samples including renal parameters and hemolysis indicators were obtained prior to the procedure and the day after the procedure. AKI was defined as an increase in serum creatinine by 26.5 µmol/L within up to 10 days after the procedure . Results A total of 2602 patients (median age 64 years, 29.4% female) underwent catheter ablation for AF. 1707 (66.4%) were treated with RFA, 557 (21.7%) using CBA and 306 (11.9%) using PFA. Median net duration of ablation was 1669 (IQR 1207, 2164) seconds for RFA, 1046 (IQR 840, 1451) seconds for CBA and, 80 (IQR 48, 85) seconds (32 (IQR 19, 34) applications) for PFA. AKI was found in 21 (0.012%), 1 (0.002%) and 1 (0.003%) patients treated with RFA, CBA and PFA, respectively, p=0.245. The case with AKI after PFA received a total of 86 PFA applications. There was a significant positive correlation for the RFA group between the ablation duration and the creatinine level after the procedure, while there was no positive correlation for the CBA and PFA group (Figure). At least one hemolysis indicator (Bilirubin, LDH or Urea levels) was elevated the day after the procedure in 53.1%, 50.1% and 46.5% in the RFA, CBA and PFA group, respectively, p=0.12. Conclusion AKI appears to be very rare after PFA and comparable to thermal energy forms. Hemolysis does not seem to be dependent on the used energy source for pulmonary vein isolation. Minimal hemolysis occurs when PFA is applied as recommended by the manufacturer.Graphical Abstract

Prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in patients admitted with acute heart failure

Abstract Introduction The inflammatory marker, soluble urokinase plasminogen activator receptor (suPAR), has emerged as a promising prognostic biomarker of heart failure (HF). Higher levels of suPAR in plasma are indicative of hospital readmissions and mortality. Currently little is known about suPAR-values upon admission in patients with acute heart failure (AHF). Purpose This study investigates the prevalence of elevated suPAR and prognostic value in patients hospitalized with AHF. Methods In this prospective cohort study, all patients ≥ 18 years old admitted at the Emergency Department at a large University Hospital in Denmark, were consecutively included from March 10, 2020, to March 31, 2022. The follow-up period was 365 days. The biomarker suPAR was measured in all patients upon admission (median time from admission to suPAR measurement was two hours (IQR 3: 3,9-6,9)). Patient data was extracted from the electronic patient record system, and a cardiologist adjudicated whether the patients had AHF. Patients were stratified according to validated cut-off values of suPAR above or below 6 ng/mL. Kaplan-Meier survival analysis and Cox Regression were used to assess the association between suPAR levels and one-year mortality outcomes. Results A total of 408 (5%) AHF patients, from a total population of 6,715, were included in the study. 40 patients were excluded due to missing suPAR-values and the final analysis comprised of 368 AHF patients. Among AHF patients upon admission, the mean suPAR value was 6.2 ng/mL (standard deviation [SD] = 4.8 ng/mL), and non-AHF patients had a mean value of 4.5 ng/mL (SD = 3.1 ng/mL). A suPAR level above 6 ng/mL was significantly associated with mortality (figure 1), log-rank test p-value < 0.0001. Furthermore, Cox regression analysis demonstrated that elevated suPAR levels were independently associated with increased risk of mortality with a hazard ratio (HR): 2.09 (95% CI: 1.59-2.90), p-value < 0.001 after adjusting for potential confounders: age, sex, atrial fibrillation, Chronic Obstructive Pulmonary Disease, and Creatinine levels. Conclusion The inflammatory biomarker suPAR measured upon hospital admission in AHF patients is significantly associated with one-year mortality in patients admitted with AHF. The potential of suPAR as a valuable prognostic marker in AHF is offering clinicians a tool to identify high-risk patients and tailor management strategies, accordingly, thereby improving patient outcomes.Figure 1 - 1 year mortality

Blood urea monitoring in heart failure patients - an important predictor of mortality

Abstract Background Recent ESC position statement regarding worsening renal failure recommends the use of blood urea monitoring of patients with heart failure with reduced ejection fraction (HFrEF). Although both serum creatinine and blood urea nitrogen are markers for renal dysfunction, blood urea nitrogen levels are also affected by reabsorption in the renal tubules, a process modulated by renin-angiotensin-aldosterone activity, sympathetic nervous activity and arginine-vasopressin activity. Thus, neurohormonal activity is reflected in the BUN/creatinine ratio (bUCR) which effectively ‘normalizes’ BUN for the degree of renal dysfunction, as measured by the creatinine level. Previous studies have demonstrated increased mortality at bUCR >100mmol/l. however, most of the prognostic data has come from patients admitted with acute heart failure. The use of bUCR in patients with chronic HFrHF receiving intensive titration of guideline directed medical therapy (GDMT) has not been studied. Purpose To identify the extent of blood urea monitoring in primary care in HFrEF and whether bUCR remains a significant prognostic indicator despite intensive GDMT. Methods We analysed the electronic health records of all patients referred to the Heart Failure Nurse Service (HFNS) in an NHS population approx. 400,000 in 2022. Inclusion criteria consists of patients with symptomatic heart failure NYHA II-IV with echocardiogram demonstrating HFrEF. Patients were segregated into two cohorts, with a urea/creatinine ratio greater or less than 100mmol/l and analysed. Results Data from 338 patients [mean age 72.3 ± 15.6 years; 218 (64.5%) males; 143 (42.3%) ischaemic cardiomyopathy; 141 (41.7%) AF; 49 (14.5%)] were analysed. Of these, 112 (33.1%) had chronic kidney disease (CKD) with eGFR <60 ml/min/1.73m2 at the time of HF diagnosis and 181 (53.6%) had CKD on discharge from the HFNS. During follow-up, 132 (39%) had further admission with HF and 76 (22.5%) died. Sixty-eight (20.1%) patients did not have blood urea checked despite the availability of serum creatinine. While an eGFR < 60 ml/min/1.73m2 at discharge was associated with a twofold increased risk of death (OR 2.4, 95% CI 1.1-5.3, p=0.029), a bUCR > 100mmol/l at discharge was associated with a four-times greater risk of death (OR 4.2, 95% CI 2.2-7.9, p <0.001). Conclusion Blood urea/creatinine ratio is an important predictor of outcome and can be utilised to help identify at-risk patients with HFrEF despite intensive GDMT.Survival from diagnosis bUCR

Sex differences in patients with acute myocardial infarction under 65 years of age: a Spanish cohort

Abstract Background Myocardial infarction (MI) clinical presentation and prognosis usually vary between men and women. Studying different age groups may be of interest. Aim Compare clinical characteristics and prognosis between men and women under 65 years old (y/o) with MI. Methods observational prospective study, including all patients admitted for MI between 2016 and 2023. Median follow-up was 43months[20-71]. Results Out of a total of 1064 patients, 436 were younger than 65 y/o (98 were women and 338 were men). The median age was similar in both sexes: 53.4[41-65] vs 54.2[43-65], p=0.24. A higher percentage of men were married (76.6 vs 59.2%, p<0.01), while a greater proportion of women were widowed (7.9 vs 1.3%, p<0.01). Men showed higher rates of permanent employment (71.4vs54.9%, p=0.01) and night shifts (58vs26.1%, p<0.01), whereas women had a higher unemployment rate (26.8vs15.2%, p=0.03) and reported higher levels of stress (70.3 vs 42.4%, p<0.01). The percentage of smokers was similar in both sexes (84.6% in men vs 75.8% in women, p=0.06), but there were more cocaine users in the male group (10.8vs1.4%, p=0.01). Women had a higher prevalence of autoimmune diseases (20.4 vs 6.2%, p<0.01), allergies (17.3 vs 5.6%, p<0.01), psychiatric illnesses (25.8 vs 9.9%, p<0.01), and migraines (15.6 vs 1.8%, p<0.01). Men had more history of previous coronary angioplasty (9.5 vs 3.1%, p=0.05). At admission, men presented with higher levels of creatine kinase (1175.2±1490.1 vs 766.5±1084.5 U/L, p=0.02), haemoglobin (15.2±1.6 vs 14±1.4 g/dl, p<0.01) and serum creatinine (1.2±1.4 vs 0.8±0.5 mg/dl, p<0.01), while women exhibited higher cholesterol levels (186.5±51.6 vs 174.9±44.5 mg/dl, p=0.03). Coronary dissection and myocardial infarction with non-obstructive coronary arteries were more frequent in women (14.3 vs 2.1%, p<0.01 and 27.6 vs 11.5%, p<0.01, respectively). Women also underwent additional tests at a higher rate, such as cardiac magnetic resonance (14.3 vs 4%, p<0.01) and vasospasm test (7.6vs1.9%, p=0.02). During hospitalization, men underwent drug-eluting stent implantation more frequently (66.7vs23.8%, p<0.01). At discharge, they were more likely to receive antiplateles (93.7vs84.5%, p<0.01), beta-blockers (81.7vs.71.1%, p=0.03), angiotensin-converting enzyme inhibitors (63.2vs49.5%, p=0.02) and statins (96.4vs84.5%, p<0.01). The rest of variables, which showed no significant differences, are in Table 1. Prognosis was similar in both sexes: death from any cause (HR 0.7, 95%CI[0.1-3.4]), cardiovascular readmission (HR 1.2, 95%CI[0.5-2.7]), reinfarction (HR 1.9, 95%CI[0.3-10.3]), stroke (HR 1, 95%CI[0.1-11.9]). Conclusion The clinical profile of men and women with MI is clearly different. The investigation into the underlying mechanisms of MI occasionally necessitates more extensive testing in women. Additionally, the treatment plans at discharge diverge between the two genders. Nevertheless, the prognosis appears to be similar for both sexes.

Efficacy and safety of ambulatory, weekly, high-intensity intravenous diuretic strategy for congestion-refractory heart failure patients: insights from the DEA-HF prospective randomized clinical trial

Abstract Background Congestion and volume overload are strongly associated with low quality of life and pose a significant risk for both rehospitalization and mortality in heart failure (HF) patients. Despite the widespread use of diuretics in HF, the use of weekly, intravenous (IV), high-intensity diuretic treatment has not been prospectively studied in the setting of ambulatory congestion-refractory patients. Purpose To assess the efficacy and safety of weekly high-intensity diuresis regimens in a practical setting of ambulatory day care for chronically congested HF patients. Methods We performed a sub-analysis on data from a prospective, randomized, cross-over controlled study (DEA-HF) originally designed to compare diuresis regimens in the setting of an HF ambulatory daycare unit who had signs of congestion or volume overload despite adherence to guideline-directed medical therapy. Each patient received three different IV diuretic regimens, in one of six randomized sequences: IV furosemide 250mg; IV furosemide 250mg + oral metolazone 5mg; and IV furosemide 250mg + IV acetazolamide 500mg. All regimens given on the same chronological week were pooled, and diuresis efficacy was assessed by measuring excreted urine volume and sodium weight 6 hours post treatment initiation. Additional assessment at one week post each treatment included serum levels of NT-ProBNP, body weight and creatinine as well as congestion score based on the presence of ascites, pleural effusion and pedal edema. Statistical analysis was based on linear mixed models while accounting for the random effect of patient identity. Results A total of 42 patients were recruited. The mean age was 72±9 years, twenty-one subjects (50%) had LVEF ≥ 50%. 74% of patients were NYHA III class. All patients were on contemporary guidelines-directed HF therapy. Analysis of excreted sodium weight and urine volume revealed values of 4202.1±180.1 mg (Mean±SEM) and 1.77±0.07 liter per visit, respectively. No significant differences in efficacy were detected among treatments given in consecutive weeks (P= 0.80 and 0.69 for differences in sodium weight and urine volume, respectively). After 4 weeks, log(NT-ProBNP) was significantly decreased (P=0.044), accompanied by a significant decrease of 2.4±0.62 kg in body weight (P=0.0004) and of 0.92±0.44 points in congestion score (P=0.037). Serum creatinine level was only slightly increased by 0.19±0.04 mg/dl (P=0.0001), demonstrating the overall safety of the high-intensity diuresis strategy. Conclusions In ambulatory, congestion refractory HF patients a strategy based on high-intensity, weekly diuresis therapy was safe and effective for three consecutive weeks. The natriuresis response to the treatments was maintained, NT-ProBNP levels and congestion score were decreased. The strategy may be instrumental for ambulatory HF patients that require diuretic therapy intensification and may allow to prevent hospitalization.

Association of thyroid hormones with the severity of chronic kidney disease: a cross-sectional observational study at Tabuk, Saudi Arabia

Background The interplay between chronic kidney disease (CKD) and thyroid dysfunction is becoming more evident in the biomedical community. However, the intricacies of their relationship warrant deeper investigation to understand the clinical implications fully. Objective This study aims to systematically evaluate the correlation between thyroid hormone levels, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4), and markers of renal disease severity. These markers include serum creatinine, urea, and parathyroid hormone (PTH) levels in individuals diagnosed with CK). Methods We conducted a cross-sectional observational study involving a cohort of 86 participants with CKD recruited from the renal clinic at King Fahad Hospital in Tabuk. Biochemical parameters, encompassing plasma electrolytes and thyroid hormone concentrations, were quantitatively assessed. These measurements were performed with the aid of a Roche Cobas E411 analyzer. The Pearson correlation coefficient was employed to delineate the strength and direction of the associations between the thyroid function markers and renal disease indicators. Results The statistical analysis highlighted a generally weak correlation between the concentrations of thyroid hormones and the indicators of renal disease severity, with Pearson correlation coefficients between −0.319 and 0.815. Critically, no significant correlation was found between creatinine and thyroid hormones (TSH, T3, T4), nor was any substantial correlation between urea and thyroid hormones. Conversely, a robust positive correlation was noted between the levels of parathyroid hormone and serum creatinine (r = 0.718, p < 0.001). Conclusion The data suggests that thyroid hormone levels have a minimal correlation with the severity of renal disease markers. In contrast, the pronounced correlation between PTH and creatinine underscores the importance of considering PTH as a significant factor in managing and therapeutic intervention of CKD complications. These initial findings catalyze further research to thoroughly investigate the pathophysiological relationships and potential therapeutic targets concerning thyroid dysfunction in patients with renal impairment.

Factors associated with 30-day mortality in patients receiving mechanical circulatory support for cardiogenic shock

Abstract Introduction Mechanical circulatory support (MCS) is often deployed in patients with refractory cardiogenic shock complicating acute myocardial infarction (AMI-CS). Nevertheless, the mortality rate in these patients remains utterly high, around 50%. Purpose The aim of this study was to identify patient characteristics associated with 30-day mortality in patients receiving MCS for AMI-CS. Methods In the Netherlands, all patients undergoing percutaneous coronary intervention (PCI) are prospectively entered in the Netherlands Heart Registration (NHR). Additional data were retrieved for all CS patients between 2017-2021 in 14 Dutch hospitals, including MCS usage. Survivors and non-survivors amongst MCS treated patients were compared to identify patient characteristics associated with 30-day mortality. In addition, multivariate logistic regression analysis on imputed data was performed to quantify these associations in adjustment for confounders. Results MCS was deployed in 516 (23.3%) of all AMI-CS patients. MCS patients had a mean age of 64.2 (± 12.5) years and 74.6% were male. An intra-aortic balloon pump (IABP) was used in 49.0% of the patients. Impella, extracorporeal membrane oxygenation (ECMO) and multiple devices were used in 18.2%, 13.2% and 18.4% respectively. The overall 30-day mortality rate was 55.0%. At baseline, MCS survivors were younger (62.8 vs 65.2, p=0.03), had diabetes less often (18.4 vs. 28.0, p=0.02), and presented with a higher mean arterial pressure (MAP) (77.9 vs. 71.7, p<0.01). An out-of-hospital cardiac arrest (OHCA) preceded in 34.3% of the survivors versus 42.0% of the non-survivors (p=0.09). Survivors also had lower admission levels of lactate (5.0 vs. 7.8, p<0.01), glucose (12.1 vs. 15.2, p<0.01) and creatinine (94 vs. 115, p<0.01). Multivessel disease (MVD) was present less frequently in survivors compared to non-survivors (62.1% vs. 74.2%, p<0.01). In-hospital cardiac arrest (IHCA) occurred less often in survivors both prior to PCI (8.2% vs. 18.0%, p<0.01) and during PCI (22.8% vs. 34.6%, p<0.01). After multivariate logistic regression, higher age (OR 1.04, 95%CI: 1.02-1.05), resuscitation prior to (OR 2.11, 95 %CI: 1.09-4.09) or during PCI (OR 1.58, 95% CI: 1.01-2.47) and the presence of MVD (OR 2.07, 95% CI: 1.32-3.25) were independently associated with 30-day mortality in AMI-CS patients who received MCS. Conclusion In AMI-CS patients who received MCS, older age, the occurrence of an IHCA prior to or during PCI, and the presence of MVD were independently associated with an increased 30-day mortality.Figure 1.Table 1.

UGT1A1 and BLVRA allele and genotype variants in neonatal patients with hyperbilirubinemia in southern China

We explore the allele and genotype distribution of UGT1A1 and BLVRA variants in individuals affected by neonatal hyperbilirubinemia in southern China. Blood specimens were collected from 240 neonates: 126 cases of hyperbilirubinemia and 114 healthy controls. Serum levels of total protein, albumin, bilirubin (total and direct), urea nitrogen, creatinine, and other biochemical parameters were quantified using a biochemical analyzer. Nine UGT1A1 and five BLVRA genetic variants were genotyped using flight time mass spectrometry. The allele and genotype frequencies of these variants and their associations with neonatal hyperbilirubinemia were analyzed. The genotype frequencies of CC and CG for the UGT1A1 variant rs11888492 in the hyperbilirubinemia group were 90.48% and 9.52%, respectively (P = 0.001), in comparison with the control group. The C and G allele frequencies of rs11888492 in the hyperbilirubinemia group were 95.24% and 4.76%, respectively (P = 0.023). Similarly, in the hyperbilirubinemia group, the genotype frequencies for the UGT1A1 variant rs4148325 were 90.48% CC, 8.73% CT, and 0.79% TT (P = 0.001), with corresponding allele frequencies of 94.84% for C and 5.16% for T (P = 0.002). No notable distinctions were detected for other variants. Newborns carrying the CC genotype of rs11888492 exhibited higher total bilirubin (TBIL) levels than those carrying the GG genotype (P = 0.034), whereas newborns carrying the CC genotype of rs4148325 displayed higher TBIL levels than those carrying the CT genotype (P = 0.003). The presence of the G allele at rs11888492 was found to be significantly correlated with a decreased likelihood of developing neonatal hyperbilirubinemia (odds ratio [OR]: 0.363; 95% confidence interval [CI] 0.169–0.777). Furthermore, a substantial reduction in the risk of neonatal hyperbilirubinemia associated with the CT genotype of rs4148325 were revealed (OR = 0.242; 95% CI 0.102–0.574). Additionally, an inverse relationship was identified between TBIL concentration and the quantity of genetic variants. The UGT1A1 variants rs11888492 and rs4148325 are strongly associated with neonatal hyperbilirubinemia in southern China.

Nephroprotective role of resveratrol in renal ischemia-reperfusion injury: a preclinical study in Sprague-Dawley rats

Abstract Background Renal ischemia-reperfusion injury (IRI) is a significant contributor to renal dysfunction, acute kidney injury (AKI), and associated morbidity and mortality. Resveratrol, a polyphenol and phytoalexin, is known for its anti-inflammatory, antioxidant, and anti-cancer properties. This study investigates the nephroprotective potential of resveratrol in a rat model of renal IRI. Materials and methods Twenty-eight male Sprague-Dawley rats were divided into four groups: Sham, IRI, DMSO, and Resveratrol. The Sham group underwent identical procedures without renal pedicle clamping, while the IRI group experienced 30 min of ischemia followed by 2 h of reperfusion. The DMSO group received dimethyl sulfoxide (DMSO) intraperitoneally 30 min before ischemia, and the Resveratrol group received 30 mg/kg resveratrol intraperitoneally 30 min before ischemia. Biochemical parameters (Urea, creatinine, IL-1β, NF-κβ, SOD, GSH, Bcl-2, and caspase-3) and histopathological changes were assessed. Results IRI caused a substantial increase in serum creatinine, Urea, IL-1β, NF-κβ, and caspase-3 levels, while simultaneously decreasing SOD, GSH, and Bcl-2 levels. Resveratrol treatment mitigated these effects by lowering inflammatory and apoptotic markers, enhancing antioxidant defenses, and improving histological outcomes. Conclusion Resveratrol demonstrates significant nephroprotective effects in renal IRI, primarily through its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Comparative analysis of multi-organ failure trajectories reflected by the MELD-3.0 following heart transplantation and heartmate 3 implantation

Abstract Background Multi-organ failure (MOF) frequently complicates advanced heart failure (HF), substantially impacting patient prognosis. The Model of End-Stage Liver Disease 3.0 (MELD-3.0) scale, encompassing liver and kidney function parameters, is a valuable tool for assessing the severity of organ dysfunction. Purpose This study aims to elucidate the trajectory of MOF in individuals undergoing either heart transplantation (HTx) or left ventricular assist device (LVAD) - HeartMate 3 implantation, utilizing the MELD-3.0 scale, over a 1-year follow-up period. Methods A comprehensive analysis was conducted, examining data from 1 month preceding to 1 year subsequent to the HTx or LVAD implantation. The MELD-3.0 score was calculated using the average values of international normalized ratio, bilirubin, creatinine, sodium, and albumin levels during this timeframe. Comparative assessments of the average MELD-3.0 scores were performed between the HTx and LVAD groups at 1 month pre-procedure, as well as at 1 week, 1 month, 3 months, 6 months, and 1 year post-procedure. Results The analysis included 107 patients undergoing HTx and 31 patients undergoing HMi, with a median age of 54 years (47-62), 85% were male. There was no difference in MELD-3.0 between HTx and LVAD patients in the pre-procedure period: 12.3 (7.3-15.9) vs 13.1 (7.7-16.6), p=0.95. There was also no difference in MELD-3.0 at 1 week and 1 month post-procedure. However, in the 3rd month, the difference gained statistical significance: 7.3 (4.6-9.4) vs 13.8 (11.5-19.7), p<0.01 and continued to be significant in the next follow-ups: 12-month 5.4 (3.1-10.2) vs 11.1 (6.7—15.1), p<0.01, comparing respectively HTx vs LVAD. In both groups of patients, a significant decrease in MELD-3.0 score from 3-month follow-up when compared to 1 month preceding the procedure was observed. Within 12 months post-procedure, 30 patients (22%) died (19 in HTx group and 11 in LVAD group), 8 LVAD patients (26%) had HTx. Conclusion The utilization of the MELD-3.0 scale reveals significant differences in the trajectory of multi-organ failure between HTx and LVAD patients. Both forms of advanced HF therapy result in an improvement of liver and kidney condition, while HTx patients' benefits are larger and last longer, highlighting the distinct impacts of this intervention on organ function.MELD 3.0 score in time

The influence of the daily salt-intake on the antihypertensive action and atrial natriuretic peptide level in patietns with angiotensin receptor neprilysin inhibition

Abstract Background The angiotensin receptor–neprilysin inhibitor (ARNI) is a drug which acts through angiotensin receptor blocking effect and the increase in atrail natriuretic peptide (ANP) through neprilysin inhibitor in hypertension (HT). These combined effects result in a reduced risk of hospitalization for heart failure or death from cardiovascular causes. ANP is also known for its various cardioprotective effects including vasodilator and natriuretic action. Acording to Guyton's pressure-natriuresis curve, the efficacy of angiotensin receptor blocker drugs is diminished in HT cases with high daily salt inatke. However, whether the effect of ARNI on HT is attenuated in patients with high daily salt intake remains unclear. Purpose The present study investigated the influence of a daily salt intake on the antihypertensive action and ANP level in patients with ARNI. Methods Fourty-four consecutive essential HT patients on ARNI were enrolled. Blood pressure and ANP level were measured at baseline (before taking ARNI) and 3 weeks later. ARNI (200mg) was prescribed and maintained during the study. In addtion, the daily salt intake was calculated using creatinine and natrium levels in urine, age, and body weight according to Japanese hypertensive guideline at baseline and 3 weeks later. Results The average age was 70±8 years old. About 50% (N=23) was male. The mean sytolic and diastolic blood pressure was 148±14mmHg and 89±10mmHg, respectively. The mean daily salt intake was 9.5±2.2 g/day at baseline. The mean ANP level was 529±300pg/ml. At follow up (3 weeks later), the mean systolic and diastolic blood pressure significanly went down to 132± 18 mmHg and 70± 9 mmHg, respectively (p=0.03). ANP level also increased from 529±300pg/ml to 793±580pg/ml. However, the mean daily salt intake was almost same as the baseline at 9.4±3.2 g/day. The patients were divided into 2 groups; high daily salt intake (N=20 with mean daily salt intake 10.5±1.7g/day)) and low daily salt intake (N=24 with 8.4±3.1g/day) groups compared to the baseline. The absolute and percentage changes in systolic blood pressure were almost same in the high and low daily salt intake groups (-12.7±15.8mmHg vs -13.7±14.2mmHg, p=0.75; -5.8±6.5% vs.-7.0±9.6%, p=0.58, respectively). However, the change rate in ANP level was significantly higer in the high daily salt intake group than in the low daily salt intake group (155±63 vs. 12±16%, p=0.01). Conclusion ARNI demonstrates effectiveness in lowering the blood pressure even in patients with higher salt intake, unlike angiotensin receptor blocker. In cases with high salt intake, the notable increase in ANP levels may contribute to decreasing blood pressure through vasodilator and natriuretic action.

Long-term outcomes of heart re-transplantation from HCV-viremic donors based on UNOS registry

Abstract Background The use of hepatitis C virus (HCV) viremic donors increased the heart donor pool, and reduced waitlist time and mortality among first-time single-organ heart transplant (HT) candidates without compromising their post-transplant survival. The outcomes of heart re-transplantation (re-HT) with the use of HCV-viremic donor grafts have not been investigated. Methods Using the United Network of Organ Sharing (UNOS) Registry we analyzed all adult patients who underwent single-organ heart re-HT in the United States between January 1, 2016, and December 31, 2022. HCV-viremic donors were defined by a positive nucleic acid amplification test (NAT+). Graft survival rates between HCV-viremic and HCV-non-viremic donor graft recipients were compared using a log rank test. Results During the study period, of 18,259 HTs performed, 427 (2.3%) constituted single-organ heart re-transplantations. Recipients of NAT+ grafts (n=19) compared to NAT- grafts (n=408) were more often male (84.2% vs 61.3%, p=0.04). Otherwise, there were no significant differences between the two groups in age, ethnicity, BMI, blood type, history of diabetes rates or stroke, creatinine or bilirubin levels, reason for re-HT, hemodynamics, use of mechanical circulatory support, and waitlist time. Ischemic time, frequency of female donors, HLA, ABO, CMV mismatch rates, and calculated panel reactive antibodies levels were comparable across the two groups. There were no significant differences in demographics or comorbidities rates between HCV-viremic and HCV-non-viremic donors apart from the cause of death. Among the donors of HCV-viremic grafts brain anoxia was reported more often (89.5%) than among HCV-non-viremic donors (40%), p <0.01. Rates of acute rejection treated in the first year after re-HT were comparable across the two groups. Over a mean follow-up of 3.0±2.1 and 3.3±1.8 years after re-HT from NAT- and NAT+ organ donors, respectively, graft survival rate at 1 year was 82% vs. 95% (p=0.3) and at 3 years 79% vs. 89%, respectively (p=0.6) (Figure). Conclusion Graft survival rates at 1 and 3 years post-heart re-HT in adult recipients of HCV-viremic donor grafts were comparable to those of recipients of HCV-non-viremic donor grafts. The current study provides compelling preliminary evidence that HCV-viremic donors constitute a viable donor pool for patients in need of heart re-transplantation.

Unveiling the prognostic journey: renal function trajectories in 'de novo' heart failure with reduced ejection fraction - insights from a cohort study and their impact on patient outcomes

Abstract Background HFrEF poses significant clinical challenges globally. Renal dysfunction frequently coexists with HF, exacerbating prognosis. However, the dynamic trajectory of renal function in 'de novo' HFrEF patients and its prognostic implications remain understudied. Methods We conducted a prospective cohort study involving 370 'de novo' HFrEF patients. Renal function was initially assessed upon admission and re-evaluated at the end of the titration period. The CKD-EPI formula was used for renal function assessment. Patients were followed up for a median of 15 months. Statistical analyses were performed to evaluate predictors of adverse outcomes. Results Baseline renal function significantly influenced outcomes, with eGFR < 45 ml/min associated with higher mortality and heart failure readmissions. Among patients with available renal function data at discharge (n=354), 87 (24.6%) had eGFR < 45 ml/min, while 267 (72.2%) ≥ 45 ml/min. Patients with eGFR < 45 ml/min exhibited older age, higher prevalence of comorbidities, lower haemoglobin levels, and higher creatinine and NT-proBNP levels, both at admission and discharge. Furthermore, they were less likely to receive certain heart failure medications at discharge. During follow-up, 46 deaths (13.0%) and 105 events of combined all-cause death and readmission due to heart failure (29.6%) occurred. Patients with eGFR ≥ 45 ml/min exhibited a lower overall mortality (HR: 0.29, p < 0.001) and all-cause death and heart failure readmissions (HR: 0.32, p < 0.001) both in univariate and multivariate analysis (HR: 0.63, p = 0.028 for mortality; HR: 0.53, p = 0.038 for combined endpoint). See Figure 1. Among patients with available renal function data at follow-up (n=304), 240 (78.9%) had eGFR ≥ 45 ml/min (stabilization or improvement), and 64 (21.1%) had eGFR < 45 ml/min (deterioration or previously < 45 ml/min). Patients with eGFR < 45 ml/min at follow-up exhibited older age, lower BMI, higher prevalence of comorbidities, lower haemoglobin levels, and higher NTproBNP levels at admission and discharge. They were also less likely to receive certain crucial heart failure medications at discharge and follow-up (Table 1). During follow-up, 31 deaths (10.1%) and 87 events of combined death and readmission due to heart failure (38.6%) occurred. In univariate analysis, patients with eGFR ≥ 45 ml/min exhibited a lower overall mortality (HR: 0.27, p < 0.001) and admissions (HR: 0.30, p < 0.001), which remained significant in multivariate analysis (HR: 0.43, p = 0.048 for mortality; HR: 46, p = 0.014 for admissions). See Figure 1. Conclusion Our findings underscore the importance of integrated heart-kidney care in 'de novo' HFrEF patients. Continuous monitoring of renal function and interventions to prevent deterioration are crucial for optimizing outcomes. Further research is needed to validate these findings and explore targeted therapeutic strategies for renal protection in HFrEF.

Nomogram-based prediction of MACE in older adults with STEMI

Abstract Introduction Despite the significant progress made in diagnosing and treating patients with ST elevation myocardial infarction (STEMI), high-risk subgroups such as older adults (those over 65 years-old) still face considerable residual risk of major adverse cardiovascular events (MACE) following treatment for their index event. Thus, it is crucial to create accurate, validated, and actionable tools to stratify patients according to their risk of MACE after admission for STEMI. Purpose Utilizing clinical data obtained from a registry of patients diagnosed with STEMI, this study aims to develop a nomogram that can reliably predict the likelihood of MACE incidence. Methods Using a large electronic single-center registry, all consecutive patients with STEMI, undergoing primary percutaneous coronary intervention (PCI), and aged 65 and above were identified. Demographic, laboratory, clinical and intra-procedural variables were examined. Univariate and multivariate logistic regression analyses were utilized to identify those factors which were independently associated with MACE incidence in the post PCI follow-up period. A nomogram was developed in a training set, and performance metrics such as receiver operating curves (ROC), calibration plots, and decision curve analysis were used for validation in a testing set. Analyses were performed using tidyverse and rms packages in R programming language. Results 1946 patients were included in the study and split into 70% training and 30% testing sets. Both groups were similar in terms of baseline demographic and clinical characteristics. Mean follow-up period was 17 months. Total MACE incidence in the post PCI follow-up period was 18%. Thirty-eight factors with limited missing information (<5%) were examined for their relationship with MACE incidence and after performing univariate and multivariate analysis 8 were selected for construction of the nomogram: left-ventricular ejection fraction (LVEF), serum creatinine, hemoglobin and fasting blood glucose levels, presence of valvular heart disease, post PCI TIMI flow grade, diameter of the stent placed in the culprit lesion, and presence of shock in the post PCI setting. The area under the curve (AUC) for MACE prediction in post PCI follow-up period showed acceptable discrimination (c-statistic=73%, 95%CI 71.2% to 76.3%). Calibration plots demonstrated that the nomogram model was well-calibrated, and its predictions were closely aligned with observed outcomes. Additionally, decision curve analysis indicated that the model exhibited strong discriminatory ability in predicting MACE. Conclusions A nomogram developed using a combination of laboratory, clinical, and procedural parameters reliably predicts future risk for MACE in older adults following STEMI. Future implementation of this model may identify the highest risk individuals to target more aggressive preventive efforts in a vulnerable cohort of patients.Plot 1Plot 2