The Association Between Fluid Overload and Endothelial Dysfunction in Chronic Kidney Failure Patients Undergoing Hemodialysis Twice a Week.

BACKGROUND: Fluid overload causes excessive systemic vasoconstriction and decreased perfusion of peripheral tissues, leading to abnormalities in cardiopulmonary physiological functions. Prolonged fluid overload caused by inadequate hemodialysis may cause heart dilatation, left ventricular hypertrophy, hypertension, and a decrease in coronary reserves, which later will develop into coronary ischemia, leading to increased morbidity and mortality of cardiovascular disease (CVD). Endothelial dysfunction plays a role in excessive vasoconstriction on fluid overload. Brain natriuretic peptide (BNP) and asymmetric dimethylarginine (ADMA) are used as parameters of fluid overload and endothelial dysfunction, respectively. This study is conducted to describe the relationship between fluid overload with endothelial dysfunction. METHOD: This study is a cross-sectional study of kidney failure patients who underwent hemodialysis twice weekly for at least three months. BNP and ADMA were used as parameters for fluid overload and taken prior to hemodialysis. RESULT: From 126 subjects, the proportion with fluid overload (BNP>356 pg/ml) was found to be 64.3% with the median age of subjects being 52 years (47-62). There was 47.6% population with endothelial dysfunction (ADMA>100 ng/ml). Presumptive causes of primary chronic kidney disease (CKD) were hypertension (38.9%), diabetes mellitus (DM) (28.6%), and glomerulonephritis (21.4%). There was no significant association between fluid overload and endothelial dysfunction (PR=1,042, p=0.832 CI 95%=0.714-1.521). CONCLUSION: There was no relationship between fluid overload and endothelial dysfunction.

Validation of the Nelwan Score as a screening tool for the diagnosis of typhoid fever in adults in Indonesia.

INTRODUCTION: Typhoid fever diagnosis is challenging for clinicians in areas with limited laboratory facilities. Scoring methods based on signs and symptoms are useful for screening for probable cases of typhoid fever. The Nelwan Score variables are derived from the clinical signs and symptoms of patients with suspected typhoid. We validated the Nelwan Score compared to laboratory tests as the gold standard. METHODS: This cross-sectional study was conducted between July 2017 and January 2018 in five hospitals and two primary health care centers in Jakarta and Tangerang, Indonesia. Patients with fever for 3-14 days and gastrointestinal symptoms were evaluated using the Nelwan Score. Blood cultures, samples for polymerase chain reaction testing, and additional rectal swab cultures were collected simultaneously to confirm the diagnosis of typhoid. Data were analyzed using a contingency table to measure sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and the optimal cut-off of the Nelwan Score for typhoid diagnosis was determined using a receiver-operating characteristic curve. RESULT: Typhoid was confirmed in 11 of the 233 patients (4.7%) with suspected typhoid. Among laboratory-confirmed typhoid cases, the median Nelwan Score was 11 (range: 9-13) and the optimal cut-off value was 10, with an area under the curve of 71.3%, sensitivity of 81.8%, specificity of 60.8%, PPV of 9.3%, and NPV of 98.5%. CONCLUSION: A Nelwan Score of 10 is the best cut-off value for screening for typhoid fever. It is useful as screening tool for typhoid fever, where laboratory resources are limited, and could help to decrease irrational antibiotic use.

Efficacy and Safety of Clopidogrel in the Prevention of Primary Failure of Arteriovenous Fistula in Patients with End-Stage Renal Disease: A Systematic Review.

BACKGROUND: Arteriovenous fistula (FAV) is the most widely used vascular access for end-stage renal disease (ESRD) patients undergoing routine hemodialysis in Indonesia. However, FAV can become dysfunctional before it is used for the initiation of hemodialysis, a condition known as primary failure. Clopidogrel is an anti-platelet aggregation that has been reported to reduce the incidence of primary failure in FAV compared to other anti-platelet aggregation agents. Through this systematic review, we aimed to assess the role of clopidogrel to the incidence of primary FAV failure and the risk of bleeding in ESRD patients. METHODS: A literature search was carried out to obtain randomized Control Trial studies conducted since 1987 from Medline / Pubmed, EbscoHost, Embase, Proquest, Scopus, and Cochrane Central without language restrictions. Risk of bias assessment was performed with the Cochrane Risk of Bias 2 application. RESULTS: All of the three studies involved indicated the benefit of clopidogrel for the prevention of AVF primary failure. However, all of the studies have substantial differences. Abacilar's study included only participants with diabetes mellitus. This study also administered a combination of clopidogrel 75 mg and prostacyclin 200 mg/day, while Dember's study gave an initial dose of clopidogrel 300 mg followed by daily dose 75 mg and Ghorbani's study only gave clopidogrel 75 mg/day. Ghorbani and Abacilar started the intervention 7-10 days before AVF creation, while Dember started 1 day after VAF creation. Dember gave treatment for 6 weeks with an assessment of primary failure at the end of week 6, Ghorbani's treatment lasted for 6 weeks with an assessment at week 8, while Abacilar gave treatment for one year with an assessment at weeks 4 after AVF creation. In addition, the prevalence of bleeding did not differ between the treatment and control groups. CONCLUSION: Clopidogrel can reduce the incidence of primary FAV failure without significant increase of bleeding events.

Factors Associated with Sarcopenia in Maintenance Hemodialysis Patients: A Cross-Sectional Study.

BACKGROUND: Sarcopenia is associated with worse outcomes in maintenance hemodialysis (MHD) patients. Differences in criteria and methods used to diagnose sarcopenia, results in a wide range of prevalence. Factors associated with sarcopenia in MHD have not been well-studied. This study aimed to investigate the prevalence and factors associated with sarcopenia in the MHD population. METHODS: Observational cross-sectional study was done with 96 MHD patients aged ≥18 years old, with dialysis vintage ≥120 days at Cipto Mangunkusumo Hospital March-May 2022. Descriptive, bivariate, and logistic regression analysis were done to find sarcopenia's prevalence and association with Simplify Creatinine Index (SCI), type 2 diabetes (DM), Interleukin-6 (IL-6), nutritional status, physical activity, and phosphate serum level. Asian Working Group for Sarcopenia (AWGS) 2019 criteria used to diagnose sarcopenia, Hand Grip Strength (HGS) to identify muscle strength, Bioimpedance Spectroscopy (BIS) to calculate muscle mass, and 6-meter walk test to evaluate physical performance. RESULTS: The prevalence of sarcopenia was 54.2%. Factors with a significant association in bivariate analysis were phosphate serum level (p=0.008), SCI (p=0.005) and low physical activity (International Physical Activity Questionnaire) (p-0.006). Logistic regression analysis found higher phosphate serum level and high physical activity protective of sarcopenia (OR 0.677;CI95% 0.493-0.93 and OR 0.313;CI95% 0.130-0.755 respectively). CONCLUSION: The prevalence of sarcopenia in the MHD population was 54.2%. Phosphate serum level, SCI, and physical activity were significantly correlated with sarcopenia. Both high phosphate level and high physical activity were protective against sarcopenia.

Risk Factors for Temporary Vascular Access Infection in Patients with End-Stage Renal Disease Undergoing Hemodialysis in Cipto Mangunkusumo Hospital.

BACKGROUND: Temporary vascular access is used to provide adequate hemodialysis for patients who are initiating dialysis or are awaiting maturation of a more permanent vascular access. However, infection is one of the most frequent complications of using temporary vascular access and is the second leading cause of death in patients undergoing hemodialysis after cardiovascular events. There has been no research on the risk factors for the incidence of infection in patients using temporary vascular access in Indonesia. METHODS: This is a retrospective cohort study utilizing secondary data from medical records of 318 subjects aged 18 years and older with end-stage renal disease and undergoing hemodialysis using temporary vascular access at Cipto Mangunkusumo Hospital. RESULTS: Temporary vascular access infection was found in 125 of 318 subjects (39.3%). The risk factors of temporary vascular catheter infection in the multivariate analysis were females (OR 1.731; 95% CI 1.050-2.854; p=0.032), low hemoglobin levels (OR 2.293; 95% CI 1.353-3.885; p=0.002), presence of diabetes mellitus (OR 2.962; 95% CI 1.704-5.149; p<0.001) and duration of catheter insertion (OR 5.322; 95% CI 1.871-15-135; p=0.002). The association between ferritin and catheter insertion site was not analyzed as a risk factor because it was not performed in all subjects. CONCLUSION: The incidence of infection in patients with end -stage renal disease undergoing hemodialysis using temporary vascular access at Cipto Mangunkusumo Hospital was 39.3%. Female gender, low hemoglobin level, diabetes mellitus, and duration of catheter insertion were risk factors for temporary vascular access infection.

The effect of mannitol addition to hydration on acute kidney injury event after high dose cisplatin chemotherapy: an ambispective cohort study.

BACKGROUND: Saline hydration with addition of mannitol have commonly been the strategy to avoid cisplatin induced acute kidney injury (AKI). While the initial reports demonstrated that mannitol diuresis decreased cisplatin induced renal injury, others have shown renal injury to be worsened. OBJECTIVE: To compare the risk of AKI in cancer patients receiving high dose cisplatin with and without addition of mannitol. METHOD: This was an ambispective cohort study based on consecutive sampling at Cipto Mangunkusumo General Hospital (CMGH) and Mochtar Riady Comprehensive Cancer Centre (MRCCC) Siloam Hospitals. The data was obtained from September 2017 to February 2018. The choice of mannitol administration based on attending physician clinical judgement. The primary outcome was increase of serum creatinine more than 0.3 mg/dL or 1.5 times from baseline. Analysis was done by using univariate, bivariate and multivariate logistic regression to obtain crude risk ratio and adjusted risk ratio of cisplatin induced AKI probability caused by mannitol addition on top of usual saline hydration protocol. RESULT: Data from 110 patients (57.3% male) with a median age of 44.5 years (range 19 to 60 years) were collected; 63 received saline with the addition of mannitol and 47 received saline only. Incidence of AKI were higher in mannitol vs saline only group. Bivariate analysis showed higher probability of post chemotherapy AKI in mannitol group, however it was statistically insignificant (RR 2.168; 95% CI 0.839-5.6; p = 0.094). On multivariate analysis the age adjusted RR was 2.852 (95% CI 0.68-11.96; p = 0.152). CONCLUSION: The addition of mannitol to hydration did not reduce the risk of cisplatin induced AKI as compared with saline hydration only. It was also found that risk for acute kidney injury were higher in population ≥ 40 years old.

Comparison between the world health organization (WHO) and international society of hypertension (ISH) guidelines for hypertension.

The global burden of hypertension remains an unsolved problem, especially in low- and middle-income countries (LMICs). For this reason, clinical practice guidelines containing the latest evidence-based recommendations are crucial in the management of hypertension. It is noteworthy that guidelines simply translated from those of high-income countries (HICs) are not the solution to the problem of hypertension in LMICs. Among the numerous guidelines available, those of the World Health Organisation and the International Society of Hypertension are the latest to be published as of the writing of this article. In this review, we conducted both general and specific comparisons between the recommendations supplied by both guidelines. Differences in aspects of hypertension management such as the timing of antihypertensive initiation, assessment of comorbidities and cardiovascular risk factors, pharmacological therapy selection, and blood pressure target and reassessment are explored. Lastly, the implications of the differences found between the two guidelines in both LMICs and HICs are discussed.Key messagesCurrently, with low treatment and control rates, hypertension remains a burden in low- and middle-income countries (LMICs).The lack of customised guidelines for LMICs cannot be solved simply by adopting guidelines from high-income countries.The World Health Organisation (WHO) recently published a clinical guideline for the pharmacological management of hypertension in LMICs. We compare select recommendations from the guidelines to those published by the International Society of Hypertension.

Association of BsmI Polymorphisms in the Vitamin D Receptor Gene Among Indonesian Population with Diabetic Kidney Disease.

BACKGROUND: Diabetic kidney disease (DKD), as a common cause of end-stage renal disease (ESRD), is a chronic complication of diabetes mellitus (DM). It has been established that vitamin D deficiency is one of DKD risk factors, which may be related to vitamin D receptor (VDR) polymorphisms. This study aimed to analyze the association between VDR polymorphisms and DKD in Indonesian population, also risk factors that influence it. METHODS: a cross-sectional study was conducted in Type 2 DM patients  who visited internal medicine outpatient clinic at Dr. Cipto Mangunkusumo Hospital, Jakarta, from November 2014 until March 2015.  Data collection includes characteristics of subjects and laboratory examination, including BsmI polymorphisms in the vitamin D receptor gene. Patients with acute and severe disease were excluded from the study. Bivariate and multivariate analyses were done. RESULTS: of 93 DM subjects, 42 (45.2%) subjects were without DKD and 51 (54.8%) subjects had DKD. Most of the subjects had the Bb genotype (89.2%), with no subject having the BB genotype. The proportions of the B and b alleles were 44.6% and 55.4%, respectively. There is no association between BsmI polymorphisms in the vitamin D receptor gene and DKD (OR = 1.243; CI 95% 0.334-4.621; p value = 0.751). CONCLUSION: the profile of BsmI polymorphisms in the vitamin D receptor gene in the Indonesian population were genotypes Bb (89.2%) and bb (10.8%). There was no association between BsmI polymorphisms in the vitamin D receptor gene and DKD. Duration of DM more than five years influenced the association between those variables.

Chronic kidney disease in Hepatitis C and its association with liver cirrhosis and viral load: Revealing the importance of hematuria.

Hepatitis C virus (HCV) contributed as a risk factor for chronic kidney disease (CKD). Many studies only showed it associated with estimated glomerular filtration rate (eGFR) reduction and albuminuria, but none revealed hematuria data. Besides, liver cirrhosis and viral load as risks for CKD are still yet to be established. This study aimed to assess the prevalence of CKD and its component in hepatitis C and to associate it with liver cirrhosis and viral load. A cross-sectional study using consecutive recruitment on the basis of anti-HCV positivity was done from August 2018 until January 2019. The participants with any renal abnormality on the first meeting were followed prospectively for at least three months. The study was done in Hepatology Clinic Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Liver cirrhosis was defined using transient elastography (>11 kPa). A baseline viral load >100,000 IU/mL was considered as high. CKD was defined as persistence of decreased eGFR and/or albuminuria and/or hematuria for three months. Logistic regression models were used to evaluate adjusted odds ratio (aOR) with adjustment for age, sex, diabetes mellitus, and hypertension. Of the 185 participants, prevalence of CKD was 23.2% [confidence interval (CI) 95% 17.1%-29.3%]. Decreased eGFR was present in 22 (11.9%), albuminuria in 29 (15.7%), and hematuria in 13 (7%). Liver cirrhosis was associated with CKD (aOR 2.948, CI 95%: 1.218-7.136) but not viral load (aOR: 0.93, CI 95%: 0.396-2.185). Renal examination is recommended in all patients with hepatitis C, particularly in patient with liver cirrhosis.

Clinical Comparison of Renogen, a Biosimilar Epoetin-a, with the Originator, Eprex, in Chronic Kidney Disease Anemia in Indonesia: A Preliminary Study.

BACKGROUND: treatment of erythropoietin (EPO) is essential in chronic kidney disease (CKD) patients to maintain optimal hemoglobin (Hb) level. Renogen is a biosimilar epoetin-α, and Eprex is the originator epoetin-α. This study aimed to compare the efficacy and tolerance of Renogen with Eprex in CKD anemia. METHODS: Renogen and Eprex were compared in a randomized (2:1), open-label study for 8 weeks, proceeded by 4 weeks adjustment (maintenance) phase, in anemic CKD patients undergoing HD in Cipto Mangunkusumo General Hospital, Jakarta, from June 2017 to October 2018. RESULTS: a total of 45 patients (31 received biosimilar EPO and 14 received originator EPO) were included in the study.  At baseline, mean (SD) Hb levels were 10.9 (0.74) g/dL and 10.9 (0.61) g/dL in biosimilar and originator EPO groups, respectively. At end of study (8 weeks), mean (SD) Hb levels were 10.5 (1.28) g/dL and 11.0 (1.13) g/dL in biosimilar EPO and originator EPO groups, respectively.  The proportion of patients with Hb levels maintained within the target range (>10 g/dL) during 8 weeks randomization phase were 58.1% and 71.4% in biosimilar EPO and originator EPO, respectively (p=0.60; NS). There were no significant difference in epoetin dose between the 2 groups, and there was no drug-related adverse event in either group. CONCLUSION: Hb level at >10 g/dL could be maintained for 8 weeks of treatment with both originator and biosimilar EPO (more consistent with originator EPO and more fluctuations with biosimilar EPO), with similar epoetin dose and no drug-related adverse event.

Subclinical Atherosclerosis in Young Adult Population with First Degree Relatives of Type 2 Diabetes Mellitus.

Cardiovascular disease (CVD) remain a leading cause of death globally. The concept of acute myocardial infarction in young adults was uncommon. Atherosclerosis is the leading cause of CVD, including myocardial infarction, stroke, heart failure and peripheral artery disease. This condition is initiated early in childhood and progressive in nature. CVD risk factors includes hypertension, dyslipidemia and obesity play a role in the development of atherosclerosis and  components in insulin resistance syndrome.One of many risk factors for insulin resistance in healthy individuals is a first-degree relative (FDR) of Type 2 Diabetes Mellitus (T2DM) patients. This group shows a higher risk of insulin resistance and pancreatic beta cells disruption even in adolescence, although they often remains asymptomatic. Clinical manifestations of metabolic disorders and atherosclerosis will appear earlier in the FDR T2DM group who have sedentary lifestyles and obesity, when compared to the non-FDR group. Several studies have attempted to detect metabolic disorders and subclinical atherosclerosis that might occur; therefore an early prevention can be carried out in these high-risk groups.  Unfortunately, factors that affect the onset and the severity of the prospective clinical manifestations from the previous studies remained inconclusive.

The influence of insulin resistance in the occurence of non-alcoholic fatty liver disease among first degree relatives of type 2 diabetes.

BACKGROUND: First degree relatives (FDR) of type 2 diabetes mellitus (T2DM) predisposes individuals to have earlier metabolic and vascular disorders independent of insulin resistance (IR) such as thicker carotid intima media thickness than that of non-FDR. Non-alcoholic fatty liver disease (NAFLD) is the most commonly found chronic liver disease in T2DM which is IR dependent. Studies about NAFLD in FDR of T2DM populations are very limited and inconclusive. It is unclear whether the occurrence of NAFLD in FDR of T2DM is IR dependent or due to genetic vulnerability. AIMS: The aim of this study is to determine the association between NAFLD and FDR of T2DM. METHOD AND MATERIALS: A total of 118 young adults (19-39 years old) with normal glucose tolerance (59 FDR of T2DM and age-sex matched 59 non-FDR subjects) were included in this cross-sectional study. Anthropometric measurement and routine laboratory analysis (fasting blood glucose/FBG, HbA1c, lipid profile, alanine aminotransferase (ALT), aspartate transaminase (AST)) were examined. Fatty liver was diagnosed by ultrasonography (US) using standard criteria. RESULTS: Twenty-six (22,03%) subjects with NAFLD were detected by ultrasound with similar proportion for each group. Low HDL-C level and metabolic syndrome were found higher in FDR group (p = 0.004, OR 3.81, CI95 = 1.47-9,91; p = 0.023, OR 4.28, CI95 = 1.13-16.23). Based on logistic regression analysis, central obesity and obesity had statistically significant influence towards NAFLD. CONCLUSION: The occurrence of NAFLD in FDR of T2DM was influenced by IR (central obesity and obesity).

Carotid intima-media thickness among normoglycemia and normotension first-degree relatives of type 2 diabetes mellitus.

Introduction: Theoretically, first-degree relatives (FDRs) of type 2 diabetes mellitus (T2DM) are predisposed to have earlier and more severe atherosclerosis than non-FDR due to hereditary insulin resistance. A previous study reported that atherosclerotic plaques were found in 45.2% of young adults FDR of T2DM, but the study did not include non-FDR as control group. The aim of this study was to compare subclinical atherosclerosis (carotid intima-media thickness, CIMT) between FDR of T2DM and non-FDR. Method: This was a cross-sectional study involving 16 FDR subjects and 16 age-sex matched non-FDR subjects, aged 19-40 years, with normal glucose tolerance and no hypertension. Collected data included demographic characteristic, anthropometric measurement (BMI and waist circumference), laboratory analysis (fasting blood glucose, HbA1c, lipid profile), and CIMT examination (using B-mode ultrasound). Results: The mean of CIMT in the FDR group was higher than that in the non-FDR group (0.44 mm vs 0.38 mm, p=0.005). After adjusting for waist circumference, BMI, low-density lipoprotein cholesterol, and triglyceride, CIMT maintained significant difference between FDR and non-FDR subjects. BMI and waist circumference showed moderate correlation with CIMT. Conclusion: CIMT in young adult FDR of T2DM is thicker than that in age-and sex-matched non-FDR population.

Prevalence of kidney dysfunction in diabetes mellitus and associated risk factors among productive age Indonesian.

BACKGROUND: The prevalence of diabetes mellitus is increasing in Indonesia due to population growth, urbanization, and lifestyle. Diabetes mellitus (DM) is the leading cause of chronic kidney disease that escalates mortality rate, but not all DM develop into chronic kidney disease. AIMS: To estimate the prevalence of kidney dysfunction (KD) in DM and the associated dominant risk factors among productive age Indonesian based on the National Health Survey (Riskesdas) 2013. METHODS: The statistical data consisted of 15,791 females and 10,349 males, aged 20 to 54, who lived in rural and urban areas. The data was obtained from National Institute of Health Research and Development (NIHRD), Ministry of Health. Data were collected from 33 provinces using cross sectional method. The variables data analyzed were sociodemographic, lifestyle, anthropometric, blood pressure, blood lipid, blood glucose, and creatinine. Kidney dysfunction was defined according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Multivariable logistic regression was used to analyze the dominant associated risk factors. RESULTS: The prevalence of KD in DM was 4% (CI 95% 3.1-5.1) and only 0.6% had been diagnosed. Many associated risk factors could affect DM leading to KD such as age, sex, rural, economic status, sugary food/drinks, salty food, coffee, hypertension, hypercholesterolemia, low HDL, high LDL, and hypertriglyceridemia. The dominant associated risk factors were age, sex, economic status, sugary food/drinks, and low HDL. CONCLUSION: The prevalence of KD in DM among productive age Indonesian was 4% and only 0.6% had been diagnosed. Early detection of identification of KD in DM is needed in order to slow progression and complications. The dominant associated risk factors of KD in DM were age, sex, economic status, sugary food/drinks, and low HDL. Controlling of risk factors in DM should be done in order to prevent diabetic kidney disease.

Low bone turnover in premenopausal women with type 2 diabetes mellitus as an early process of diabetes-associated bone alterations: a cross-sectional study.

BACKGROUND: Individuals with Diabetes Mellitus (DM) are at increased risk for fracture due to the decrease in bone strength and quality. Serum procollagen type I intact N-terminal (P1NP) and serum C-terminal cross-linking telopeptide of type I collagen (CTX) as markers of bone formation and resorption, respectively, have been reported to be decreased in T2DM. It remains unclear whether diabetes-associated alterations in the bone turnover of T2DM individuals are related to the longer duration of the disease or may occur earlier. Furthermore, previous studies on BTMs in T2DM individuals have mostly been done in postmenopausal women with T2DM, which might have masked the DM-induced alterations of bone turnover with concurrent estrogen deficiency. This study aims to assess the levels of serum P1NP and CTX as markers of bone turnover in premenopausal women with and without T2DM. METHODS: This cross-sectional study involves 41 premenopausal women with T2DM, and 40 premenopausal women without DM. Sampling was done consecutively. P1NP and CTX measurement was done using the electrochemi-luminescence immunoassay (ECLIA) method. Other data collected include levels of HbA1C, ALT, creatinine, eGFR and lipid profile. RESULTS: Median (interquartile range) P1NP in T2DM is 29.9 ng/ml (24.7-41.8 ng/ml), while in non-DM is 37.3 ng/ml, (30.8-47.3 ng/ml; p = 0.007). Median (interquartile range) CTX in T2DM is 0.161 ng/ml (0.106-0.227 ng/ml), while in non-DM is 0.202 ng/ml (0.166-0.271 ng/ml; p = 0.0035). Levels of P1NP and CTX in the T2DM group did not correlate with the duration of disease, age, BMI or the levels of HbA1C. CONCLUSIONS: Premenopausal women with T2DM indeed have lower bone turnover when compared with non-DM controls. This significantly lower bone turnover process starts relatively early in the premenopausal age, independent of the duration of DM. Gaining understanding of the early pathophysiology of altered bone turnover may be key in developing preventive strategies for diabetoporosis.