Higher Serum Creatinine Levels Research Articles

Effect of zinc supplementation on symptom reduction and length of hospital stay among pediatric patients with Coronavirus disease 2019 (COVID-19)

ObjectivesZinc is considered an essential multipurpose trace element because of its ability to act as a cofactor and signaling molecule. As reported in earlier studies of pediatric respiratory infection management, zinc exhibits potent immunoregulatory and antiviral properties, but its effects on pediatric patients with COVID-19 remain unknown. The aim of this study was to determine the extent to which zinc supplementation improves COVID-19 symptoms, length of hospitalization and, to determine how zinc supplementation impacts ICU admission, in-hospital mortality, need for ventilation, duration of ventilation, need for vasopressors, development of liver injury, or respiratory failure. MethodsPediatric patients younger than 18 years with confirmed COVID-19 infection during the study period (March 1, 2020, to December 31, 2021) were recruited for this retrospective cohort study. The study population was divided into two arms (zinc/no zinc supplementation as an adjunct to standard therapy). ResultsOf 169 hospitalized patients who were screened, 101 met the inclusion criteria. No statistically significant association was found between the administration of zinc as adjunctive therapy and symptom reduction, intensive care unit (ICU) admission, or mortality (p = 0.105; p = 0.941, and p = 0.073, respectively). However, zinc supplementation was associated with a statistically significant reduction in respiratory failure and length of hospitalization (p = 0.004 and p = 0.017, respectively), also, zinc administration was associated with elevated serum creatinine (p = 0.01*) ConclusionsAmong pediatric patients with COVID-19, zinc supplementation was associated with shorter hospital stay. However, there was no significant difference between the two groups in terms of symptom improvement, in-hospital mortality, or ICU admission. In addition, the study raises question about the possibility of kidney injury as indicated by high levels of serum creatinine.

A comparison of heart failure patients with reduced ejection fraction in the Moravian Midlands Registry with the LCZ696 patients in the Paradigm-HF trial.

There are limited data on real clinical practice in heart failure patients in the Czech Republic. We analysed the clinical parameters from the Moravian Midlands Registry (MMR) and compared them to LCZ696 patients in the Paradigm-HF trial. The Moravian Midlands Registry is a retrospective patient database from two outpatient cardiology centres in the Czech Republic. The Paradigm-HF is a large-scale prospective randomized multicentre trial with more than 8000 individuals with stabilized chronic heart failure. A retrospective analysis of heart failure with reduced ejection fraction patients from two outpatient cardiology centres in the Czech Republic from October 2016 to December 2019. Patients in the MMR were younger (60.5 ± 10.7 vs 63.8 ± 11.5 years, P<0.05), had a higher body mass index (30.3 ± 5.0 vs 28.1 ± 5.5, P<0.05) and higher serum creatinine level (101.9 ± 36.0 vs 99.9 ± 26.5 µmol/L, P<0.05). MMR patients had lower left ventricular ejection fraction (27.8 ± 6.9 vs 29.6 ± 6.1%, P<0.05). The serum N-terminal pro-B-type natriuretic peptide, [2563.5 (377-3536) vs 1631 (885-3154), was non significantly higher P=0.07]. Pharmacotherapy use differed for mineralocorticoid antagonist (91.4% in MMR vs 54.2% in Paradigm-HF), and digoxin (13.5% vs 29.2%). Beta-blocker use was similar (96.2% vs 93.1%) as was angiotensin-converting enzyme (ACE) inhibitors - (71.2% vs 78.0%) and angiotensin-receptor blockers - ARB (27.9% vs 22.2%). Dosages of the commonly used ACE inhibitors at the screening visit (Paradigm-HF) / before angiotensin receptor-neprilysin inhibitor administration (MMR) differed significantly only for ramipril (7.0 ± 3.1 mg vs 4.8 ± 2.9 mg, P<0.05), dosages of ARB were - losartan (67.1 ± 30.2 vs 39.6 ± 32.0 mg, P=0.09) and valsartan (181.5 ± 71.1 vs 130.9 ± 82.2 mg, P=0.07). There was a substantial difference in device-based therapy (ICD in 60.6%, CRT 25.9% in MMR vs 14.9% and 7.0% in Paradigm-HF). The differences between the groups for the majority of clinical parameters compared were minimal, except for younger age, higher body mass index and serum creatinine level and lower left ventricular ejection fraction and substantially lower dosage of administered ramipril prior to commencing sacubitril/valsartan therapy. There was a higher prevalence of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy (CRT) in the MMR group.

Clinical characteristics and prognosis of pulmonary renal syndrome in West China

Pulmonary renal syndrome (PRS) is a rare and life-threatening syndrome. Interstitial lung disease (ILD) has been recently considered another phenotype of lung dysfunction in patients with PRS, but there are very limited data. The characteristics of fifty PRS patients were retrospectively reviewed after a 3-year follow-up, and the differences between PRS patients whose lung dysfunction presented as diffuse alveolar hemorrhage (DAH group) and those with interstitial lung disease (ILD group) were also analyzed. The median age at diagnosis of PRS patients was 50.78 ± 17.88 years, and the main symptoms at disease onset were proteinuria (94.00%), hemoptysis (68.00%), dyspnea (32.00%) and fever (12.00%). DAH patients were younger and had significantly lower hemoglobin levels, a higher incidence of hemoptysis, and higher serum creatinine levels at onset than ILD patients. Univariate analyses of PRS patients showed that respiratory failure and the initiation of mechanical ventilation predicted patient death and that the initiation of hemodialysis and higher serum creatinine levels at onset predicted ESRD. Multivariate analyses showed that respiratory failure and anti-GBM antibody positivity could independently predict patient death. Survival analyses showed that 1- and 3-year patient survival rates and ESRD-free survival rate were not significantly different between the two groups. ILD was another important phenotype of lung dysfunction in patients with PRS. Poor outcomes were observed in PRS patients with ILD and in PRS patients with DAH.

Mucocutaneous Changes in End-Stage Renal Disease Under Regular Hemodialysis - A Cross-Sectional Study.

Patients with end-stage renal disease (ESRD) suffer from mucocutaneous changes that could significantly impair the quality of life. We aimed this study to assess the mucocutaneous changes in hemodialysis patients and to correlate the serum creatinine to these changes. Data were collected from the Hemodialysis Center at Benha University. A cross-sectional study design on 130 chronic kidney disease (CKD) patients (30-60 years old, 84 males, 46 females) undergoing hemodialysis. Oral examinations were done for these patients as per the modified World Health Organization oral health survey 2013 criteria. All the mucocutaneous changes were recorded then types, distribution, and frequencies were calculated and correlated to serum creatinine. Mucocutaneous abnormalities were present in 100% of the studied CKD sample. We observed that pallor (76.2%), xerostomia (70%), petechiae/purpura (49.2%), altered taste (49.2%), and lip pigmentation (40.8%) were the most prevalent mucocutaneous changes among the CKD patients undergoing hemodialysis. A strong association was detected between serum creatinine and the following: abnormal lip pigmentation and lichen planus. There is an association between lip pigmentation and lichen planus in CKD patients and the level of serum creatinine as the higher level of serum creatinine was found in the patients with abnormal lip pigmentation and the atrophic lichen planus patients.

Polymorphisms of CARD9 Gene Predict Disease Progression and Renal Survival of Immunoglobulin A Nephropathy

Introduction: A previous genome-wide association study has identified CARD9 (caspase recruitment domain family member 9) as a susceptibility gene for immunoglobulin A nephropathy (IgAN), which encodes an adapter protein and is related to mucosal immunity. This study aimed to investigate the association of CARD9 variants with the clinicopathological phenotypes and prognosis of IgAN. Methods: Eight single nucleotide polymorphisms within CARD9 were genotyped using Sequenom MassARRAY iPLEX for 986 IgAN patients in this study. Logistic and linear regression analyses adjusted for age and gender were performed to evaluate the effects of CARD9 gene polymorphisms on clinicopathological phenotypes. The Kaplan-Meier method and Cox proportional hazard models were applied to analyze the associations between genetic variants and renal survival. Results: The T allele of rs10747047 was strongly associated with higher levels of serum creatinine (p = 0.005) and lower levels of estimated glomerular filtration rate (p = 0.005). The rs10870149-G and rs10870077-C alleles were associated with elevated 24-h urine protein excretion (p = 0.041 and 0.022, respectively) and more serious segmental glomerulosclerosis lesions (p = 0.005 and 0.041, respectively) in IgAN patients. Carriers with the T allele of rs10781533 and the C allele of rs3812552 also presented with severe segmental glomerulosclerosis lesions (p = 0.001 and 0.010, respectively). Additionally, rs10747047-C and rs10870077-C alleles were independently related to the poor prognosis of IgAN patients after adjustments for covariates (TT vs. CC hazard ratio [HR] = 0.138, 95% confidence interval [95% CI] = 0.022–0.871, p = 0.035; GG vs. CC HR = 0.321, 95% CI = 0.123, 0.836, p = 0.020, respectively). Conclusion: CARD9 variants are associated with disease severity and rapid disease progression for IgAN in a Chinese Han population.

Böbrek Nakli Alıcılarında Düşme: Geleneksel Derleme

Kidney transplantation is the gold standard treatment for end stage renal disease. Despite the improvement in survival and quality of life, the prevalence of falls is higher in kidney transplant recipients. Factors that increase the risk for falls include female gender, older age, impaired balance control, lower ankle dorsiflexion muscle strength, high serum creatinine levels, and the use of antidiabetic medications. Functional limitations, fatigue, low cardio-respiratory fitness, changes in mineral metabolism lead to bone mineral disease in chronic kidney disease and can finally play an important role in occurrence of accidental falls in pre-transplantation period. Fractures without dislocations or head injury-related hemorrhages constitute a majority for the serious fall-related injury types. In addition to many factors such as cumulative dose of corticosteroids, younger age at transplantation, hyperparathyroidism, vitamin D deficiency and renal osteodystrophy, risk of falls also contribute to increased post-transplantation bone loss and fracture risk. Hip fractures requiring hospitalization in the post-kidney transplant period are associated with a higher risk of mortality. It is important to understand the underlying mechanisms for falls in kidney transplant recipients in order to prevent severe injuries including fractures and decrease healthcare costs. The awareness of healthcare professionals should be increased for falls in this specific population to design multidisciplinary therapeutic approaches including risk factor assessment, exercise programs and patient and caregiver education not only for kidney transplant recipients but also for the patients waiting on a transplantation list.

Effects of nonsurgical periodontal therapy on serum creatinine level in systemically healthy individuals with periodontitis: An interventional study.

Several studies have suggested a relationship between periodontitis and serum creatinine levels. Both low and high serum creatinine levels have been reported in individuals with periodontitis. The impact of periodontal therapy on serum creatinine levels has not been fully investigated yet. The aim of the study is to estimate the influence of nonsurgical periodontal therapy (NSPT) on serum creatinine levels in systemically healthy individuals with periodontitis at stage II and stage III with grade A and grade B. Sixty-eight systemically healthy individuals included in the study were divided into Group A (GA) (Periodontally healthy) and Group B (GB) (Periodontitis: stage II and III with grade A and grade B). Gingival index, sulcular bleeding index, probing pocket depth, clinical attachment level, body mass index, and serum creatinine levels were recorded at baseline for both GA and GB, 90 days after NSPT for GB only. Collected data were analyzed statistically. Serum creatinine levels in GB were significantly higher when compared with GA and serum creatinine levels in GB before and 90 days after NSPT were statistically insignificant. Serum creatinine levels were higher in individuals with periodontitis when compared with periodontally healthy individuals and NSPT has no considerable influence on the serum creatinine levels in individuals with periodontitis. Further studies are required to confirm these findings.

PS-R04-6: A CASE OF MALIGNANT NEPHROSCLEROSIS WITHDREW FROM TEMPORARY HEMODIALYS

In the Case of AKI (acute renal injury) due to malignant hypertension, appropriate BP (Blood Pressure) management is important and sometimes requires hemodialysis. Here we report a 49-year-old female patient with malignant hypertension, AKI and acute pulmonary edema. She presented with severe hypertension (BP213/150 mmHg), high serum creatinine level (Cr12.74 mg/dL), congestive heart in chest radiographic findings and nerve head edema (Scheie: H4S3). There were no findings associated with renal artery stenosis. She was diagnosed as AKI due to malignant hypertension. Nicardipine continuous intravenous infusion was carried out for BP control and temporary hemodialysis had begun almost simultaneously. On Day 5 of admission, she had received oral Ca blocker and low dose of ACE inhibitor (temocapril). BP level remained stable thereafter. Nevertheless, oliguric renal failure lasted for several weeks. On Day 10 of admission, we performed renal biopsy and confirmed onion-skin-like intimal thickening and luminal narrowing findings. These were corresponded to malignant nephrosclerosis, not to chronic nephritic syndrome. We continued 2 times per week hemodialysis using the indwelling catheter after discharge. Her daily urinary output increased substantially day by day (over 1000 ml/day) and her serum creatinine level became less and less around Cr 4.0 mg/dL. This case withdrew temporary hemodialysis over a period of five months conclusively. In some cases, renal dysfunction is improved slowly in the long-term course by appropriate BP management. Accordingly, it is necessary to evaluate the possibility whether or not withdrawing from hemodialysis in the cases of AKI due to malignant hypertension.

Serum Creatinine Levels Have Been Shown to Accurately Predict in-Hospital Mortality in Individuals who have Been Effectively Treated with PPCI

Objective: The purpose of this study was to assess the predictive value of serum creatinine for in-hospital mortality among patients who had acute coronary syndromes. Study Design: An observational study Place and Duration: This observational study was conducted at Department of Cardiology, Rashid Latif Medical College, Lahore and Nowshera Medical College, Nowshera, KPK in the duration from 1st May, 2022 to 31 October, 2022. Methods: Total 198 patients had acute coronary syndromes who underwent successful primary percutaneous coronary intervention (PCI) were included. Patients were aged between 25-80 years. After receiving written consent, we recorded the subjects' ages, sexes, BMIs, and diagnoses in detail. Within 12 hours of an AMI diagnosis, serum creatinine levels were taken. Patients were split into two groups based on their serum creatinine levels upon admission. There are two categories, those with high levels of serum creatinine (over 1.3 mg/dL) and those with normal levels (below 1.3 mg/dL). Life expectancy at death was measured at one year. All of the information was analyzed with SPSS 22.0. Results: There were majority 140 (70.7%) males and 58 (29.3%) females in this study. Mean age of the patients was 55.18±11.24 years and had mean BMI was 24.6±14.52 kg/m2. Mean serum urea level was 37.3±0.22 mg/dL. Diabetes found in 40 (20.2%) cases and frequency of hypertension was 82 (41.4%). Anterior myocardial infarction was found in 79 (39.9%) cases followed by Inferior MI in 73 (36.9%) cases and non-ST MI in 46 (23.2%) cases. Mean left ventricular ejection fraction (LVEF) was 45±7.17 %. We found elevated serum creatinine in 37 (18.7%) cases and normal creatinine in 161 (81.3%) cases. Mortality in elevated group was higher found in 10 (27.02%) cases and as compared to normal group 8 (4.96%). Conclusion: The results of this study indicate that patients with AMI who had even slightly raised serum creatinine levels at admission have a significantly higher risk of dying within a year. Keywords: Myocardial Infarction, Comorbidities, Primary percutaneous coronary intervention, Mortality, Serum Creatinine

Prevalence of anti-BK polyomavirus IgG in A Sample of Iraqi renal transplant recipients

Background: BK virus, a human polyomavirus, causes nephropathy and allograft loss in renal transplant recipients. Although it was discovered in 1971, understanding of the humoral immune response to BKV is limitedز Objective: To serological detection and level estimation of anti-BK-IgG in renal-transplanted recipients and healthy blood donors as control. Patients and Methods: Serum samples were collected from 106 renal transplant recipient patients and 100 healthy blood donors as control groups, and were analyzed for anti-BK IgG antibodies by using quantitative and qualitative Human BK Virus IgG (BK-IgG) ELISA kit for detection and estimation positivity of BK_IgG and titration. Results: Out of 206 subjects, 114(55.3%) have a positive result for BK-IgG. seropositivity was detected in 54(50.9%) of 106 RTR patients and 60 (60.0%) in the 100 control group, so there was no significant difference between seropositivity of BKV IgG antibody among the studied groups, p =0.191. Conclusion: The highly significant differences between seropositivity of BK-IgG with high levels of serum creatinine. Keywords: Prevalence, Anti-BK IgG antibodies, and Renal transplanted recipients

Prevalence of anti-BK polyomavirus IgG in A Sample of Iraqi renal transplant recipients

Background: BK virus, a human polyomavirus, causes nephropathy and allograft loss in renal transplant recipients. Although it was discovered in 1971, understanding of the humoral immune response to BKV is limited.&#x0D; Objective: To serological detection and level estimation of anti-BK-IgG in renal-transplanted recipients and healthy blood donors as control.&#x0D; Patients and Methods: Serum samples were collected from 106 renal transplant recipient patients and 100 healthy blood donors as control groups, and were analyzed for anti-BK IgG antibodies by using quantitative and qualitative Human BK Virus IgG (BK-IgG) ELISA kit for detection and estimation positivity of BK_IgG and titration.&#x0D; Results: Out of 206 subjects, 114(55.3%) have a positive result for BK-IgG. seropositivity was detected in 54(50.9%) of 106 RTR patients and 60 (60.0%) in the 100 control group, so there was no significant difference between seropositivity of BKV IgG antibody among the studied groups, p =0.191.&#x0D; Conclusion: The highly significant differences between seropositivity of BK-IgG with high levels of serum creatinine.

The presence of intraperitoneal, retroperitoneal and pleural fluid in acute Puumala hantavirus infection

Background Puumala hantavirus (PUUV) causes most cases of haemorrhagic fever with renal syndrome (HFRS) in Europe. PUUV infection is characterised by acute kidney injury, thrombocytopenia and increased capillary leakage. Typical symptoms are fever, headache, nausea, abdominal and back pain. This study aimed to evaluate the amount and distribution of intraperitoneal, retroperitoneal and pleural fluid and the association of fluid collections to the symptoms and clinical findings in patients with acute PUUV infection. Methods Abdominal magnetic resonance imaging (MRI) was performed on 27 hospitalised patients with acute PUUV infection. The clinical and laboratory findings and patients’ symptoms were analysed in relation to the imaging findings. The thickness of the fluid collections was measured in millimetres (mm) from axial images. Results Fluid collections were found in all patients. The amount of intraperitoneal fluid correlated positively with plasma C-reactive protein (CRP) level (r = 0.586, p = .001), while it had an inverse correlation with serum creatinine concentration (r = −0.418, p = .030). Retroperitoneal fluid also correlated inversely with serum creatinine and cystatin C concentrations (r = −0.501, p = .008 and r = −0.383, p = .048, respectively). The amount of fluid was not greater in patients with abdominal or back pain. Patients with back pain had higher serum creatinine compared with patients without back pain, 452 µmol/L (range 88–1071) vs. 83 µmol/L (range 60–679), p = .004. Conclusions Fluid collections were found in all patients. A greater amount of intraperitoneal fluid associates with higher CRP concentrations but not with higher serum creatinine levels. Back pain associates with higher creatinine level but not with the presence of fluids.

Deletion of the P2Y2 receptor aggravates internal elastic lamina calcification in chronic kidney disease mice through upregulation of alkaline phosphatase and lipocalin-2.

Calcification of the medial layer, inducing arterial stiffness, contributes significantly to cardiovascular mortality in patients with chronic kidney disease (CKD). Extracellular nucleotides block the mineralization of arteries by binding to purinergic receptors including the P2Y2 receptor. This study investigates whether deletion of the P2Y2 receptor influences the development of arterial media calcification in CKD mice. Animals were divided into: (i) wild type mice with normal renal function (control diet) (n= 8), (ii) P2Y2 R-/- mice with normal renal function (n= 8), (iii) wild type mice with CKD (n= 27), and (iv) P2Y2 R-/- mice with CKD (n= 22). To induce CKD, animals received an alternating (0.2-0.3%) adenine diet for 7 weeks. All CKD groups developed a similar degree of chronic renal failure as reflected by high serum creatinine and phosphorus levels. Also, the presence of CKD induced calcification in the heart and medial layer of the aortic wall. However, deletion of the P2Y2 receptor makes CKD mice more susceptible to the development of calcification in the heart and aorta (aortic calcium scores (median ± IQR), CKD-wild type: 0.34 ± 4.3mg calcium/g wet tissue and CKD-P2Y2 R-/- : 4.0± 13.2mg calcium/g wet tissue). As indicated by serum and aortic mRNA markers, this P2Y2 R-/- mediated increase in CKD-related arterial media calcification was associated with an elevation of calcification stimulators, including alkaline phosphatase and inflammatory molecules interleukin-6 and lipocalin 2. The P2Y2 receptor should be considered as an interesting therapeutic target for tackling CKD-related arterial media calcification.

Significance of thyroid dysfunction in the patients with primary membranous nephropathy.

Thyroid dysfunction is common in patients with nephrotic syndrome, especially patients with primary membranous nephropathy (pMN). In view of both MN and thyroid dysfunction are associated with autoimmunity, the current study aimed to elucidate the significance of thyroid dysfunction in patients with pMN. Four hundred and twenty patients with biopsy-proven pMN from 2018-2021 were retrospectively enrolled. Clinical and pathological parameters, and treatment response of patients with and without thyroid dysfunction were analyzed. Ninety-one (21.7%) patients with pMN suffered from thyroid dysfunction, among which subclinical hypothyroidism (52.7%) was the main disorder. Compared to patients with normal thyroid function, patients with thyroid dysfunction presented with a higher level of proteinuria, a lower level of serum albumin, a higher level of serum creatinine and more severe tubulointerstitial injury at the time of biopsy. But the positive rate and level of circulating anti-phospholipase A2 receptor (PLA2R) antibody were comparable between these two groups. Though following the similar treatment, the percentage of no response to treatment were significantly higher in the patients with thyroid dysfunction (38.6 vs. 20.0%, P = 0.003). Similar to the urinary protein and the positivity of anti-PLA2R antibody, multivariate COX analysis showed thyroid dysfunction was also identified as an independent risk factor for the failure to remission (HR = 1.91, 95%CI, 1.07-3.40, P = 0.029). In conclusion, thyroid dysfunction is common in the patients with pMN and might predict a severe clinical manifestation and a poor clinical outcome, which indicated that the thyroid dysfunction might be involved in the disease progression of pMN.

Are admission laboratory values in isolation meaningful for predicting surgical outcome in patients with perforated peptic ulcers?

BackgroundThe study aimed to calculate the predictive value of admission laboratory values in patients with perforated peptic ulcers. MethodsA retrospective, cohort analytical, observational study was performed, including patients with surgically confirmed perforated peptic ulcers over a 5-year period. Demographic data and admission laboratory values were collected from hospital electronic databases. Outcomes measured were in-hospital mortality, intensive care unit (ICU) admission and length of stay. The significance of categorical variables was calculated by chi-square and Fisher's exact test. Logistic regression analysis was performed to determine univariately statistically significant variables. ResultsIn total, 188 patients met the inclusion criteria. The median age was 46 (range 15–87) years with a male predominance of 71.3 % (n = 134). The median length of hospital stay was 7 (range 1–94) days and 31.4 % (n = 59) of patients were admitted to the ICU. Post-operative in-hospital mortality was 25.0 % (n = 47). Predicting the categorical outcome of in-hospital mortality, abnormal haemoglobin, platelet count, urea, creatinine and potassium levels were all found to be statistically significant in the univariate analysis. Age (odds ratio [OR] 1.03), haemoglobin (OR 4.36) and creatinine (OR 7.76) levels were significant in the multivariate analysis. ConclusionsMortality rate among patients with perforated peptic ulcer disease is still substantial. Admission laboratory values showed statistical significance as outcome indicators and were valuable to assist in predicting the prognosis. An abnormally high serum creatinine level was the strongest single predictor of both mortality and ICU admission. Key messageInitial laboratory findings of patients admitted for perforated peptic ulcer showed that an abnormally high serum creatinine level was the strongest single predictor of both mortality and ICU admission.

Abstract 10422: Sesn2 Mediates Metformin Rescued Age-Related Cardiac Dysfunctions of Cardiorenal Syndrome

Introduction: Cardiorenal syndrome (CRS) consists of disorders of the kidneys and heart, whereby dysfunction of one organ may induce dysfunction of the other. Acute kidney injury (AKI) leads to a reduction in blood flow and energy supply to the heart. AMP-activated protein kinase (AMPK) as an energy sensor regulates energy metabolism via interacting with a scaffold protein Sesn2. The anti-diabetes drug metformin is an AMPK agonist, and it has been reported to regulate substrate metabolism under physiological and pathological conditions. But the beneficial role of metformin in CRS remains unknown. Hypothesis: Age-related impaired AMPK signaling contributes to cardiac intolerance to AKI-induced insults in the elderly. Metformin treatment ameliorates CRS through triggering Sens2/AMPK activation. Methods: Young (3-5 months) and aged (21-23 months) C57BL/6J wild type (WT), cardiomyocyte specific knock out (cSesn2 -/- ) and littermates (Sesn2 f/f ) C57BL/6J mice were subjected to AKI with a laparotomy and the renal artery and vein were clamped for 15 min followed by 72 hr of reperfusion (IRI). Seahorse XF Analyzer for mitochondrial respirational functions. Results: The higher levels of serum creatinine were observed after IRI-induced AKI in the aged versus young WT and cSens2 -/- versus Sesn2 f/f mice. Interestingly, administration of metformin can significantly reduce serum creatinine levels by IRI-induced AKI in young/aged WT and Sesn2 f/f but not cSesn2 -/- mice. Renal histological analysis showed higher incidence of tubular necrosis in the aged versus young AKI mice, the tubular necrosis was significantly reduced in the metformin treated young and aged AKI mice. Echocardiography data showed that AKI caused cardiac systolic dysfunctions in all experimental groups, while metformin treatment improved cardiac functions of young/aged WT and Sesn2 f/f but not cSesn2 -/- mice. Moreover, metformin treatment triggered AMPK activation and improved mitochondrial respiration rate and ATP production of cardiomyocytes from young/aged WT and Sesn2 f/f but not cSesn2 -/- hearts. Conclusions: Aging augments cardiac vulnerability to IRI-induced AKI. Metformin can rescue cardiac dysfunctions and renal injury caused by AKI through Sesn2/AMPK signaling pathway.

The Association of Complements, TGF-β, and IL-6 with Disease Activity, Renal Damage, and Hematological Activity in Patients with Naïve SLE.

Several key player factors, such as cytokine and complement, play an important role in the pathogenesis of systemic lupus erythematosus (SLE). The purpose of this study was to reveal the association between complement 3 (C3), complement 4 (C4), interleukin-6 (IL-6), and transforming growth factor-β (TGF-β) with SLE disease activity, renal damage, and hematological activity in patients with naïve SLE. The Laboratory of Clinical Pathology Dr. Soetomo General Hospital in Surabaya performed all laboratory examinations on thirty women with naïve SLE. The SLE diagnosis is based on ACR criteria (1998 revised criteria) from Dr. Soetomo General Hospital Surabaya, Indonesia, and the systemic lupus activity measurement (SLAM) score is used to assess the disease activity. The correlation was statistically tested using the Spearman and Pearson tests. The differences in cytokine and complement levels are between SLE severity groups using the two-way Anova and Kruskal-Wallis. The unpaired T-test and Mann-Whitney test were used to determine the differences between the relatively normal and the more severe groups of organ damage and hematological activity. All tests were two-tailed, analyzed with GraphPad Prism 9 for windows, and a p value of less than 0.05 was considered statistically significant. This study found a significant decrease in C3 (20.2, 16.4-24.2 mg/dL) and C4 (7, 6-14.3 mg/dL) and an increase in IL-6 (35.60 ± 7.43 mg/dL) and TGF-β (311.1 ± 290.8 mg/dL) in the group of severe patients with SLAM scores >30. Although there is no significant relationship between SLAM and renal impairment or hematologic activity, patients with higher SLAM had a significant decrease in complement; this complement decrease was also significant in patients with higher leukocyte counts. An insignificant increase in cytokines was also observed in patients with higher SLAM. Patients with high serum creatinine levels had a significant increase in TGF-β, whereas those with a faster ESR had a significant increase in IL-6. In conjunction with complements evaluation, assessment of the cytokine profile may become a promising marker for reliable diagnosis and treatment of SLE in the future.

Discovery of four plasmatic biomarkers potentially predicting cardiovascular outcome in peripheral artery disease

Peripheral artery disease (PAD) patients have an increased cardiovascular risk despite pharmacological treatment strategies. Biomarker research improving risk stratification only focused on known atherothrombotic pathways, but unexplored pathways might play more important roles. To explore the association between a broad cardiovascular biomarker set and cardiovascular risk in PAD. 120 PAD outpatients were enrolled in this observational cohort study. Patients were followed for one year in which the composite endpoint (myocardial infarction, coronary revascularization, stroke, acute limb ischemia and mortality) was assessed. Patient data and blood samples were collected upon inclusion, and citrated platelet-poor plasma was used to analyze 184 biomarkers in Olink Cardiovascular panel II and III using a proximity extension assay. Fifteen patients reached the composite endpoint. These patients had more prior strokes and higher serum creatinine levels. Multivariate analysis revealed increased plasma levels of protease-activated receptor 1 (PAR1), galectin-9 (Gal-9), tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) and interleukin 6 (IL-6) to be most predictive for cardiovascular events and mortality. Positive regulation of acute inflammatory responses and leukocyte chemotaxis were identified as involved biological processes. This study identified IL-6, PAR1, Gal-9, TNFRSF11A as potent predictors for cardiovascular events and mortality in PAD, and potential drug development targets.

Post-hoc analysis of a tool to predict kidney failure in patients with IgA nephropathy.

Recently, a tool based on two different artificial neural networks has been developed. The first network predicts kidney failure (KF) development while the second predicts the time frame to reach this outcome. In this study, we conducted a post-hoc analysis to evaluate the discordant results obtained by the tool. The tool performance was analyzed in a retrospective cohort of 1116 adult IgAN patients, as were the causes of discordance between the predicted and observed cases of KF. There was discordance between the predicted and observed KF in 216 IgAN patients (19.35%) all of whom were elderly, hypertensive, had high serum creatinine levels, reduced renal function and moderate or severe renal lesions. Many of these patients did not receive therapy or were non-responders to therapy. In other IgAN patients the tool predicted KF but the outcome was not reached because patients responded to therapy. Therefore, in the discordant group (prediction did not match the observed outcome) the proportion of patients having or not having KF was strongly associated with treatment (P < 0.0001). The post-hoc analysis shows that discordance in a low number of patients is not an error, but rather the effect of positive response to therapy. Thus, the tool could both help physicians to determine the prognosis of the disease and help patients to plan for their future.

Seroprevalence and newly isolated strains of LT-Ag gene (MMGHA2 and MM GHA5) of BK Polyomavirus in A Sample of Iraqi renal transplant recipients

Background: BK virus (BKV) opportunistic viral infection causes nephropathy and allograft loss in renal transplant recipients (RTRs).Aims: Investigating BKV seropositivity, viremia rate and renal function were the primary goals of this study, in addition to the molecular study of the Iraqi BKV strains (LT antigen gene).Settings and Design: Case-control study.material and methods: Serum and plasma specimens were collected from 106 RTR and 100 non-RTR. Serum samples were analyzed for anti-BK IgG antibodies by BK-IgG ELISA kit. Plasma samples were used for detection of large tumor (LT-Ag) gene region of BKV by RT-PCR technique and then sequenced by Sanger's method.Statistical analysis: frequencies, percentages, and Chi square-test by SPSS v.28Results: The Study showed that 114 (55.3%) have a positive result for BK-IgG, so there was no significant difference between seropositivity of BKV IgG antibody among the studied groups, p =0.191. On the other hand, a total of 206 subjects, 31 (15.0%) had positive viremia and 175 (85.0%) were negative. Renal function showed highly significant differences (p ≤0.000) between seropositive and negative RTR patients. 2 sequences of Iraqi local strains were deposited in the GenBank with the accession numbers LC718551.1 and LC718552.1Conclusions: The viremic state of BKV in RTR has similarly no impact on renal function. While the highly significant association between seropositivity of BK-IgG with high levels of serum creatinine. New strains of BKV were found in the Iraqi RTR patients with 98% similarity with the reference gene.