Brown Tumour in Chronic Kidney Disease: Revisiting an Old Disease with a New Perspective.

Osteitis fibrosa cystica (OFC) and Brown Tumours are two related but distinct types of bone lesions that result from the overactivity of osteoclasts and are most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors, such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation, may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions, placing them in the spectrum of RAS-MAPK-driven neoplasms, which were until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumours, such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumours includes clinical symptoms involving chronic bone pain and laboratory findings of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically, both lesions are characterized by clustered osteoclasts in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumours.

Current Insights into Cellular Determinants of Peritoneal Fibrosis in Peritoneal Dialysis: A Narrative Review.

Peritoneal fibrosis is the final process of progressive changes in the peritoneal membrane due to chronic inflammation and infection. It is one of the main causes of discontinuation of peritoneal dialysis (PD), apart from peritonitis and cardiovascular complications. Over time, morphological changes occur in the peritoneal membranes of patients who use PD. Of those are mesothelial-to-mesenchymal transition (MMT), neoangiogenesis, sub-mesothelial fibrosis, and hyalinizing vasculopathy. Several key molecules are involved in the complex pathophysiology of peritoneal fibrosis, including advanced glycosylation end products (AGEs), transforming growth factor beta (TGF-ß), and vascular endothelial growth factor (VEGF). This narrative review will first discuss the physiology of the peritoneum and PD. Next, the multifaceted pathophysiology of peritoneal fibrosis, including the effects of hyperglycemia and diabetes mellitus on the peritoneal membrane, and the promising biomarkers of peritoneal fibrosis will be reviewed. Finally, the current and future management of peritoneal fibrosis will be discussed, including the potential benefits of new-generation glucose-lowering medications to prevent or slow down the progression of peritoneal fibrosis.

Risk Factors and Clinical Characteristics of Acute Kidney Injury in Patients with COVID-19: A Systematic Review and Meta-Analysis.

Acute kidney injury (AKI) is associated with a worse prognosis in coronavirus disease 2019 (COVID-19) patients. Identification of AKI, particularly in COVID-19 patients, is important for improving patients' management. The study aims to assess risk factors and comorbidities of AKI in COVID-19 patients. We systematically searched PubMed and DOAJ databases for relevant studies involving confirmed COVID-19 patients with data on risk factors and comorbidities of AKI. The risk factors and comorbidities were compared between AKI and non-AKI patients. A total of 30 studies involving 22385 confirmed COVID-19 patients were included. Male (OR: 1.74 (1.47, 2.05)), diabetes (OR: 1.65 (1.54, 1.76)), hypertension (OR: 1.82 (1.12, 2.95)), ischemic cardiac disease (OR: 1.70 (1.48, 1.95)), heart failure (OR: 2.29 (2.01, 2.59)), chronic kidney disease (CKD) (OR: 3.24 (2.20, 4.79)), chronic obstructive pulmonary disease (COPD) (OR: 1.86 (1.35, 2.57)), peripheral vascular disease (OR: 2.34 (1.20, 4.56)), and history of nonsteroidal anti-inflammatory drugs (NSAID) (OR: 1.59 (1.29, 1.98)) were independent risk factors associated with COVID-19 patients with AKI. Patients with AKI presented with proteinuria (OR: 3.31 (2.59, 4.23)), hematuria (OR: 3.25 (2.59, 4.08)), and invasive mechanical ventilation (OR: 13.88 (8.23, 23.40)). For COVID-19 patients, male gender, diabetes, hypertension, ischemic cardiac disease, heart failure, CKD, COPD, peripheral vascular disease, and history of use of NSAIDs are associated with a higher risk of AKI.

Markers of Renal Complications in Beta Thalassemia Patients with Iron Overload Receiving Chelation Agent Therapy: A Systematic Review.

Objective: The emerging renal complications in beta-thalassemia patients have raised the global exchange of views. Despite better survival due to blood transfusion and iron chelation therapy, the previously unrecognized renal complication remain a burden of disease affecting this population -the primary concern on how iron overload and chelation therapy correlated with renal impairment is still controversial. Early detection and diagnosis is crucial in preventing further kidney damage. Therefore, a systematic review was performed to identify markers of kidney complications in beta thalassemia patients with iron overload receiving chelation therapy. Methods: Searches of PubMed, Scopus, Science Direct, and Web of Science were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to identify studies of literature reporting renal outcome in ß-TM patients with iron overload and receiving chelation therapy. The eligible 17 studies were obtained. Results: uNGAL/NGAL, uNAG/NAG, uKIM-1 are markers that can be used as predictor of renal tubular damage in early renal complications, while Cystatin C and uß2MG showed further damage at the glomerular level. Discussion and Conclusion: The renal complication in beta-thalassemia patients with iron overload receiving chelating agent therapy may progress to kidney disease. Early detection using accurate biological markers is a substantial issue that deserves further evaluation to determine prevention and management.

The Role of Plasma Interleukin-6 Levels on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk Scores in Javanese Patients with Chronic Kidney Disease.

Interleukin-6 (IL-6) has been identified as an important pro-inflammatory factor involved in mediating the severity of chronic kidney disease (CKD). This study sought to determine the effect of plasma IL-6 levels on atherosclerotic cardiovascular disease (ASCVD) and cardiovascular mortality risk scores in Javanese CKD patients. We also analyzed the frequency of IL-6 G174C single nucleotide polymorphism (SNP) in the population. This study was a cross-sectional study involving seventy-three patients of Javanese ethnic origin with stable chronic kidney disease. We assessed the ASCVD risk score, cardiovascular mortality score, genotyping of IL-6 G174C SNP, and plasma IL-6 levels in these patients. The genotype distribution and allele frequencies of the IL-6 G174C SNP were predominated by the G genotype/allele (GG: 97.26%, GC: 1.37%, CC: 1.37%, G-allele: 97.95%, and C-allele: 2.05%). Despite the fact that plasma IL-6 levels did not directly affect cardiovascular mortality risk, further analysis revealed its direct effect on the ASCVD risk score (path coefficient = 0.184, p = 0.043, 95% CI = 0.018−0.380), which in turn affected cardiovascular mortality risk (path coefficient = 0.851, p = <0.01, 95% CI = 0.714−0.925). In conclusion, plasma IL-6 levels play important roles on ASCVD risk and cardiovascular mortality risk in Javanese patients with CKD.

The Effect of Angiotensin Converting Enzyme (ACE) I/D Polymorphism on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk in Non-Hemodialyzed Chronic Kidney Disease: The Mediating Role of Plasma ACE Level.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

Association between Sarcopenia and Insulin-Like Growth Factor-1, Myostatin, and Insulin Resistance in Elderly Patients Undergoing Hemodialysis.

Sarcopenia is common in hemodialysis patients, especially in the elderly patients undergoing hemodialysis. Various factors may contribute to the occurrence of sarcopenia, such as anabolic and catabolic imbalance. This study aims to investigate the correlation of insulin-like growth factor-1 (IGF-1) levels as an anabolic factor, myostatin levels, and insulin resistance as catabolic factors with sarcopenia in the pathogenesis of sarcopenia in elderly patients undergoing hemodialysis. A total of 40 subjects aged 60 years or more who undergoing hemodialysis in Dr. Soetomo Hospital Surabaya were included in this cross-sectional study. Sarcopenia was diagnosed according to Asian Working Group Sarcopenia 2019 criteria. IGF-1, myostatin, and insulin resistance levels were measured once before hemodialysis. Subjects with sarcopenia diagnosis were 33 (82.5%), that is, 19 (47.5%) men and 14 (35%) women. There were 28 (70%) of the subjects diagnosed with severe sarcopenia. Furthermore, there were significant differences in the characteristics and geriatric parameters between the sarcopenia and nonsarcopenia groups. There were differences between the two groups in hemoglobin levels, IGF-1 levels, myostatin levels, homeostasis model assessment-insulin resistance (HOMA-IR) levels, muscle mass, handgrip strength, body mass index status, mini nutritional assessment status, and physical activity scale for elderly status (all p < 0.05). Correlation analyses showed that IGF-1 levels negatively correlated with sarcopenia status in elderly patients undergoing hemodialysis (p < 0.05). On the contrary, myostatin and HOMA-IR levels were positively correlated with sarcopenia status in elderly patients undergoing hemodialysis (all p < 0.05). Based on this recent study, IGF-1, myostatin, and insulin resistance were significantly correlated with sarcopenia in elderly patients undergoing hemodialysis.

A rare case: Vesicoureteral reflux in Indonesian young adult with neurogenic bladder and chronic kidney disease stage 4.

BACKGROUND: Vesicoureteral reflux (VUR) is one of the main causes of chronic kidney disease (CKD) in adolescence and young adult. It can be a congenital or an acquired anomaly and its uncommon in adult life. CASE PRESENTATION: A 19th years old male with neurogenic bladder, VUR grade 4, CKD stage 4, malnutrition, and short stature. Radiological examinations show a spastic neurogenic bladder, cystitis, right VUR grade 4. Abdominal ultrasonography (USG) results were bilateral severe hydronephrosis due to post-renal causes. This patient had a history of myelocele excision at the age of 1.5 years. He had recurrent urinary tract infection with CKD stage 4. DISCUSSION: The diagnosis of VUR and neurogenic bladder in CKD stage 4 is a rare case in nephrology. CONCLUSION: Indonesian male confirms of diagnosis VUR grade 4, neurogenic bladder, and CKD stage 4.

Dietary management of haemodialysis patients with chronic kidney disease and malnourishment.

BACKGROUND AND OBJECTIVES: Dietary supplementation for haemodialyzed (HD) patients with chronic kidney disease (CKD) and its benefits for the anthropometric profiles remain contentious. This study analysed changes in the albumin levels and anthropometric profiles of HD patients within 3 months of nutritional therapy. METHODS AND STUDY DESIGN: Sixty-three malnourished HD patients (Subjective Global Assessment nutrition status B or C) were enrolled. Twenty patients received counselling, 17 patients received oral therapy, 26 patients received intradialytic parenteral nutrition (IDPN), and were evaluated at month 0, month 1, and month 3. Five patients withdrew before completing the trial. The patients' albumin levels and anthropometric profiles (biceps and triceps skinfold thickness, upper arm circumference, body weight, and body mass index) were analysed before and after treatment. We performed multivariate analysis to determine the effect of each treatment on serum albumin and anthropometric profiles. RESULTS: At months 1 and 3, nutritional therapy was associated with different mean serum albumin level among three nutritional intervention groups (p<0.05). Significant increases in serum albumin, upper arm circumference, and triceps and biceps skinfold thickness were identified in the counselling and IDPN groups. Multivariate linear regression revealed significant differences between oral and nonoral groups in albumin and biceps and triceps skinfold thickness at months 1 and 3. These variables were affected by age and duration of haemodialysis (p<0.05). CONCLUSIONS: Nutritional therapy for malnourished CKD patients receiving HD ameliorated serum albumin and their anthropometric profiles within 3 months.

Severe COVID-19 infection in a kidney transplant recipient treated with lopinavir/ritonavir, hydroxychloroquine and dexamethasone.

Severe COVID-19 infection management for a recipient of kidney transplant has debatable prognosis and treatment. We described the case of a COVID-19 infected 70 year old female, previously had renal transplantation in 2017. The patient took immunosuppressive agents as routine drugs for transplant recipient status and received lopinavir/ritonavir, hydroxychloroquine, and dexamethasone daily at the hospitalization. Specific question arises about renal transplant recipients being infected by COVID-19 - whether the infection will get worse compared to those without immunosuppresive agent. In this case, author decided to stop the immunosuppressive agent followed administration of combination lopinavir/ritonavir, hydroxychloroquine, and dexamethasone that gives a good clinical impact change to patient's condition after once getting worsened and mechanically ventilated. Nevertheless, the assessment of risk and benefit in continuing immunosuppressive drugs is concurrently essential due to the prevention of transplant rejection.

Correlation between anti-hypertensive drugs and disease progression among moderate, severe, and critically ill COVID-19 patients in the second referral hospital in Surabaya: A retrospective cohort study.

Background: Hypertension, as the comorbidity accompanying COVID-19, is related to angiotensin-converting enzyme 2 receptor (ACE-2R) and endothelial dysregulation which have an important role in blood pressure regulation. Other anti-hypertensive agents are believed to trigger the hyperinflammation process. We aimed to figure out the association between the use of anti-hypertensive drugs and the disease progression of COVID-19 patients.   Methods: This study is an observational cohort study among COVID-19 adult patients from moderate to critically ill admitted to Universitas Airlangga Hospital (UAH) Surabaya with history of hypertension and receiving anti-hypertensive drugs.   Results: Patients receiving beta blockers only had a longer length of stay than angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ACEI/ARB) or calcium channel blockers alone (17, 13.36, and 13.73 respectively), had the higher rate of intensive care unit (ICU) admission than ACEi/ARB (p 0.04), and had the highest mortality rate (54.55%). There were no significant differences in length of stay, ICU admission, mortality rate, and days of death among the single, double, and triple anti-hypertensive groups. The mortality rate in groups taking ACEi/ARB was lower than other combination.   Conclusions: Hypertension can increase the severity of COVID-19. The use of ACEI/ARBs in ACE-2 receptor regulation which is thought to aggravate the condition of COVID-19 patients has not yet been proven. This is consistent with findings in other anti-hypertensive groups.

Role of oxidative stress on chronic kidney disease progression.

Chronic kidney disease (CKD) is a worldwide health problem with a high incidence not only in western countries but also in Indonesia as well. The majority of patients with CKD died due to cardiovascular disease than CKD progression itself. In addition to traditional risk factors, cardiovascular disease in CKD might also due to non-traditional risk factors. Oxidative stress, as non-traditional risk factors, is not only able to explain the high incidence of cardiovascular disease in CKD, but also become a new target in therapeutic intervention. Oxidative stress in patients with CKD appears due to increased oxidant activity and decreased antioxidant system. Hemodialysis (HD) with the use of a cellulose and semi-cellulose membrane also contribute to increase oxidant that can activate the complement pathway. It stimulates inflammation that will further expand the production of oxidants and will ultimately increase oxidative stress.

Profile of PRMT-1 gene polymorphism in hemodialysis patients with increased ADMA levels.

AIM: to determine the distribution of PRMT-1 gene polymorphism and ADMA levels among continuing hemodialysis patients. METHODS: genotyping of PRMT-1 polymorphism was performed in 57 hemodialysis patients at Al Irsjad Hospital. All participants were recruited for physical examination, questionnaire, and collection of 5 mL fasting venous blood. The blood was treated with phenol-chloroform extraction of genomic DNA. The candidate's single nucleotide polymorphisms (SNPs) were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The ADMA plasma levels was determined by ELISA and all biochemical indicators of serum were examined. RESULTS: fifty-seven hemodialysis patients participated in our study, 54 (95.4%) of them had increased ADMA plasma levels. DNA sequencing analysis of 13 patients showed a suspected PRMT-1 gene polymorphism at sequence 5837 as there were different genotypes between C and G. CONCLUSION: the increased levels of ADMA might be caused by PRMT-1 gene polymorphism.

Intravenous N-acetylcysteine during haemodialysis reduces the plasma concentration of homocysteine in patients with end-stage renal disease.

BACKGROUND: Hyperhomocysteinaemia is an independent cardiovascular risk factor in patients with renal disease. The current study aimed to determine the effect of intravenous N-acetylcysteine on plasma homocysteine levels when administered during haemodialysis in patients with end-stage renal failure. PATIENTS AND METHODS: Sixty patients with end-stage renal failure were randomised to receive a 4-hour intravenous infusion of N-acetylcysteine or placebo during a 4-hour haemodialysis session. Plasma homocysteine levels were measured before and after haemodialysis. Haemodynamic parameters, including pulse pressure, were also measured. RESULTS: After haemodialysis in the placebo treatment group, plasma homocysteine was reduced by 23.7% from the pre-dialysis level, whereas patients treated with N-acetylcysteine exhibited an 88.3% decrease (p < 0.001). Reduction of plasma homocysteine concentration was significantly correlated with a reduction of pulse pressure (p = 0.001). A 10% decrease in plasma homocysteine concentration was associated with a 1.45mm Hg decrease in pulse pressure. CONCLUSIONS: Intravenous administration of N-acetylcysteine during haemodialysis normalises plasma homocysteine concentration, and this is associated with improved pulse pressure in patients with end-stage renal failure. Intravenous administration of N-acetylcysteine during haemodialysis may be a promising approach to help reduce cardiovascular risk in this vulnerable group of patients.