Diagnostic performance of Mac-2-binding protein glycosylation isomer (M2BPGi) as a liver fibrosis marker in chronic hepatitis C patients with chronic kidney disease on hemodialysis.

BACKGROUND/AIM: Liver fibrosis assessment is essential to determine the initiation, duration, and evaluation of chronic hepatitis C treatment. Therefore, the study aimed to assess the role of Mac-2-binding protein glycosylation isomer (M2BPGi) as a biomarker to measure liver fibrosis in chronic hepatitis C patients with chronic kidney disease on hemodialysis. METHODS: This study used a cross-sectional design. Serum M2BPGi level and transient elastography results were evaluated in 102 chronic hepatitis C patients with CKD on HD, 36 CKD on HD patients, and 48 healthy controls. ROC analysis was conducted to identify the optimal cutoff values to assess significant fibrosis and cirrhosis among chronic hepatitis C patients with CKD on HD. RESULTS: In chronic hepatitis C patients with CKD on HD, the level of serum M2BPGi had a moderately significant correlation with transient elastography (r = 0.447, p < 0.001). The median serum M2BPGi was higher among CKD on HD patients compared to healthy controls (1.260 COI vs. 0.590 COI, p < 0.001) and was even higher in chronic hepatitis C patients with CKD on HD compared to CKD on HD group (2.190 COI vs. 1.260 COI, p < 0.001). It is also increased according to the severity of liver fibrosis: 1.670 COI, 2.020 COI, and 5.065 COI for F0-F1, significant fibrosis, and cirrhosis, respectively. The optimal cutoff values for diagnosing significant fibrosis and cirrhosis were 2.080 and 2.475 COI, respectively. CONCLUSION: Serum M2BPGi could be a simple and reliable diagnostic tool for evaluating cirrhosis in chronic hepatitis C patients with CKD on HD.

Practical considerations for the use of SGLT-2 inhibitors in the Asia-Pacific countries-An expert consensus statement.

Recent clinical studies have demonstrated the effectiveness of SGLT-2 inhibitors in reducing the risks of cardiovascular and renal events in both patients with and without type 2 diabetes mellitus. Consequently, many international guidelines have begun advocating for the use of SGLT-2 inhibitors for the purpose of organ protection rather than as simply a glucose-lowering agent. However, despite the consistent clinical benefits and available strong guideline recommendations, the utilization of SGLT-2 inhibitors have been unexpectedly low in many countries, a trend which is much more noticeable in low resource settings. Unfamiliarity with the recent focus in their organ protective role and clinical indications; concerns with potential adverse effects of SGLT-2 inhibitors, including acute kidney injury, genitourinary infections, euglycemic ketoacidosis; and their safety profile in elderly populations have been identified as deterring factors to their more widespread use. This review serves as a practical guide to clinicians managing patients who could benefit from SGLT-2 inhibitors treatment and instill greater confidence in the initiation of these drugs, with the aim of optimizing their utilization rates in high-risk populations.

The effects of synbiotics on indoxyl sulphate level, constipation, and quality of life associated with constipation in chronic haemodialysis patients: a randomized controlled trial.

BACKGROUND: Gut microbiota dysbiosis in patients with chronic kidney disease on haemodialysis (CKD-HD) creates an increase in proteolytic bacteria activity, leading to an increase in the production of uraemic toxins, such as indoxyl sulphate, worsening of constipation symptoms and reducing patients' quality of life. Improving gut microbiota dysbiosis is expected to improve this condition. This study aimed to evaluate the effect of synbiotics on indoxyl sulphate levels, constipation symptoms, and constipation-related quality of life in haemodialysis patients. METHODS: This was a double-blinded randomized controlled clinical trial with a parallel design involving haemodialysis patients. We included chronic haemodialysis patients with gastrointestinal complaints, difficulty defecating, faeces with hard consistency, or a bowel movement frequency of fewer than three times per week. Patients were randomly divided into two groups (synbiotics (Lactobacillus acidophilus and Bifidobacterium longum 5x109 CFU) and placebo) for 60 days of oral intervention. All participants, caregivers, and outcome assessors were blinded to group assignment. The primary outcome was a decrease in indoxyl sulphate toxin levels. Meanwhile, improvement in constipation symptoms (measured using the Patient Assessment of Constipation: Symptoms (PAC-SYM) questionnaire) and improvement in constipation-related quality of life (measured using the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire) were assessed as secondary outcomes. RESULTS: We included 60 patients (30 intervention; median age of 51.23 (13.57) years, 33.3% male; 30 control; median age of 52.33 (11.29) years, 36.7% male). There was no significant difference in terms of pre- and postintervention indoxyl sulphate toxin levels in the synbiotics group compared to the placebo group (p=0.438). This study found an improvement in constipation symptoms (p = 0.006) and constipation-related quality of life (p=0.001) after synbiotic administration. CONCLUSION: Two months of synbiotic supplementation did not lower indoxyl sulphate toxin levels. Nevertheless, it had a major effect in improving constipation and quality of life affected by constipation in patients undergoing chronic haemodialysis. TRIAL REGISTRATION: NCT04527640 (date of first registration: 26/08/2020).

Raising Awareness of Acute Kidney Injury: Unfolding the Truth.

AKI is rarely being recognized as it may take place without any apparent symptoms. Severe AKI is commonly found in intensive care unit (ICU) patients. AKI in the ICU is an independent risk factor for death, as it may cause systemic effects on other vital organs including the lung, heart, liver, brain and immune system. Some studies have reported that AKI increases susceptibility to infection, doubles the rate of respiratory failure and impairs cardiac function. Considering the substantial impacts of AKI in ICU patients, early implementation of preventive measures should be an essential program which consists of developing AKI risk stratification in the ICU and encouraging the use of novel AKI biomarkers (TIMP-2, IGFBP-7, Cystatin C, IL-18,  KIM-1 and NGAL) as well as other risk stratification tools (clinical risk prediction scores, computer algorithms, furosemide stress test). Furthermore, after ICU patients have recovered, AKI survivors are more likely to develop chronic kidney disease (CKD) and end-stage kidney disease (ESKD), imposing significant morbidity in the future. Recent study has shown that nephrologist intervention was associated with lower risk of starting KRT and progression of AKI.     The coronavirus disease 2019 (COVID-19) pandemic has caused more than 800,000 deaths worldwide. Kidney involvement in patients with COVID-19 may present as proteinuria or hematuria and may lead to acute kidney injury (AKI). Some initial reports showed that the incidence of AKI in COVID cases was negligible. However, later reports suggested that AKI is actually prevalent in patients with COVID-19, particularly in ICU patients. AKI is now considered as a common complication of COVID-19 and it is also associated with adverse outcomes, including development or worsening of comorbidities, yet little is known about the pathogenesis or optimal management of COVID-19-associated AKI.

Early Recognition of Type 2 Diabetes Complications and Use of SGLT2i in Multidisciplinary Approach: Indonesian Perspective - An Expert Opinion.

Indonesia ranks seventh with the highest number of cases of type 2 diabetes mellitus (T2DM). T2DM is associated with major undesirable complications including cardiovascular disease and chronic kidney disease. Kidneys play a major role in maintaining glucose homeostasis, leading the development of sodium glucose transporter inhibitors (SGLT2i). These inhibitors block renal sodium and glucose reabsorption. Several cardiovascular trials proved that SGLT2i have cardioprotective and renoprotective roles and have been suggested  as a drug of choice in primary and secondary prevention and management of cardiorenal complications associated with T2DM. This review highlights the need for a multidisciplinary recommendation for T2DM management in Indonesian population. Additionally, it is vital to provide the perspective of Indonesian medical experts in terms of screening, diagnosis and treatment as the outcome differs geographically. An expert panel of 6 members from Indonesia was convened to review the existing literature and develop an expert-based review/ summary on this topic. Members were chosen for their proficiency in diabetes, kidney disease and cardiovascular disease. The experts opined that the early use of SGLT2i will be effective in preventing and minimising the progression of cardiorenal complications. Moreover, a consistent multidimensional approach is necessary for improved outcomes.

Peritoneal dialysis: Status report in South and South East Asia.

BACKGROUND: Peritoneal dialysis (PD) as a modality of kidney replacement therapy (KRT) is largely underutilized globally. We analyzed PD utilization, impact of economic status, projected growth and impact of state policy(s) on PD growth in South Asia and Southeast Asia (SA&SEA) region. METHODS: The National Nephrology Societies of the region responded to a questionnaire on KRT practices. The responses were based on the latest registry data, acceptable community-based studies and societal perceptions. The representative countries were divided into high income and higher-middle income (HI & HMI) and low income and lower-middle income (LI & LMI) groups. RESULTS: Data provided by 15 countries showed almost similar percentage of GDP as health expenditure (4%-7%). But there was a significant difference in per capita income (HI & HMI -US$ 28 129 vs. LI & LMI - US$ 1710.2) between the groups. Even after having no significant difference in monthly cost of haemodialysis (HD) and PD in LI & LMI countries, they have poorer PD utilization as compared to HI & HMI countries (3.4% vs. 10.1%); the reason being lack of formal training/incentives and time constraints for the nephrologist while lack of reimbursement and poor general awareness of modalities has been a snag for the patients. The region expects ≥10% PD growth in the near future. Hong Kong and Thailand with 'PD first' policy have the highest PD utilization. CONCLUSION: Important deterrents to PD underutilization were lack of PD centric policies, lackadaisical patient/physician's attitude, lack of structured patient awareness programs, formal training programs and affordability.

Prevalence of prehypertension and its risk factors in midlife and late life: Indonesian family life survey 2014-2015.

BACKGROUND: Early detection of prehypertension is important to prevent hypertension-related complications, such as cardiovascular disease, cerebrovascular disease and all-cause mortality. Data regarding the prevalence of prehypertension among mid- and late-life population in Indonesia were lacking. It is crucial to obtain the prevalence data and identify the risk factors for prehypertension in Indonesia, which may differ from that of other countries. METHODS: The cross-sectional analysis utilized multicenter data from Indonesian Family Life Survey-5 (IFLS-5) from 13 provinces in 2014-2015. We included all subjects at mid-and late-life (aged ≥40 years old) from IFLS-5 with complete blood pressure data and excluded those with prior diagnosis of hypertension. Prehypertension was defined as high-normal blood pressure according to International Society of Hypertension (ISH) 2020 guideline (systolic 130-139 mmHg and/or diastolic 85-89 mmHg). Sociodemographic factors, chronic medical conditions, physical activity, waist circumference and nutritional status were taken into account. Statistical analyses included bivariate and multivariate analyses. RESULTS: There were 5874 subjects included. The prevalence of prehypertension among Indonesian adults aged > 40 years old was 32.5%. Age ≥ 60 years (adjusted OR 1.68, 95% CI 1.41-2.01, p <  0.001), male sex (adjusted OR 1.65, 95% CI 1.45-1.88, p <  0.001), overweight (adjusted OR 1.44, 95% CI 1.22-1.70, p <  0.001), obesity (adjusted OR 1.77, 95% CI 1.48-2.12, p <  0.001), and raised waist circumference (adjusted OR 1.32, 95% CI 1.11-1.56, p = 0.002) were the significant risk factors associated with prehypertension. Prehypertension was inversely associated with being underweight (adjusted OR 0.74, 95% CI 0.59-0.93, p = 0.009). CONCLUSIONS: The prevalence of prehypertension in Indonesian mid- and late-life populations is 32.5%. Age ≥ 60 years, male sex, overweight, obesity, and raised waist circumference are risk factors for prehypertension.

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.

The Relationship between Folic Acid and Vitamin B12 Serum Levels with High Sensitivity C-reactive Protein and Homocysteine in Chronic Hemodialysis Patients: A Cross-sectional Study.

BACKGROUND: Folic acid (FA) and vitamin B12 treatment have been routinely prescribed to lower serum homocysteine levels and to reduce inflammation. However, no study has been conducted to determine serum folic acid (SFA) and vitamin B12 (B12) levels in patients who have twice-weekly hemodialysis. The aim of our study was to assess serum folate and B12  levels in chronic hemodialysis patients and their relationship with hsCRP and homocysteine levels. METHODS: Our study was a cross-sectional study involcing patients who had twice-weekly hemodialysis in Dr Cipto Mangunkusumo National Hospital Jakarta, Indonesia. Predialysis blood samples were taken to measure SFA, B12, homocysteine and hsCRP levels. Patients with medical conditions affecting the assays were excluded. Spearman correlation was used to compare variables. RESULTS: Eighty subjects enrolled in this study. Among those of non-given folic acid and vitamin B-12 supplementation, only 3.85% of subjects had low folic acid levels, and none had low vitamin B12 levels. A moderate negative correlation between serum folic acid and homocysteine level (p≤0.001; r=-0.42) and a weak correlation between serum vitamin B12 and homocysteine level (p=0.009; r=-0.29) was found. Among the high-risk cardiovascular group (CRP>3, n=49), there is a moderate negative correlation between serum folic acid and homocysteine level (p≤0.001; r=-0.561) and a weak negative correlation between vitamin B12 and homocysteine level (p=0.018; r=-0.338). CONCLUSION: There is a significant negative correlation between serum vitamin B12 and folic acid with homocysteine levels, especially in high-risk cardiovascular group.

The Association of ß2-Microglobulin and Fibroblast Growth Factor 23 with Major Adverse Cardiac Event in Acute Coronary Syndrome Patients with Chronic Kidney Disease.

BACKGROUND: chronic kidney disease (CKD) increases the severity and risk of mortality in acute coronary syndrome (ACS) patients. The role of ß2-M as a filtration and inflammation marker and FGF23 as a CKD-MBD process marker might be significant in the pathophysiology in ACS with CKD patients. This study aims to determine the association of ß2-M and FGF23 with major adverse cardiac event (MACE) in ACS patients with CKD. METHODS: we used cross sectional and retrospective cohort analysis for MACE. We collected ACS patients with CKD consecutively from January until October 2018 at Dr. Cipto Mangunkusumo General Hospital. Data were analyzed using logistic regression and Cox's Proportional Hazard Regression. RESULTS: a total of 117 patients were selected according to the study criteria. In bivariate analysis, ß2-M, FGF23, and stage of CKD had significant association with MACE (p = 0.014, p = 0.026, p = 0.014, respectively). In multivariate analysis, ß2-M - but not FGF 23- was significantly associated with MACE (adjusted HR 2.16; CI95% 1.15-4.05; p = 0.017). CONCLUSION: ß2-M was significantly associated with MACE, while FGF23 was not so. This finding supports the role of inflammation in cardiovascular outcomes in ACS with CKD patient through acute on chronic effect.

Dialysis Care and Dialysis Funding in Asia.

Asia is the largest and most populated continent in the world, with a high burden of kidney failure. In this Policy Forum article, we explore dialysis care and dialysis funding in 17 countries in Asia, describing conditions in both developed and developing nations across the region. In 13 of the 17 countries surveyed, diabetes is the most common cause of kidney failure. Due to great variation in gross domestic product per capita across Asian countries, disparities in the provision of kidney replacement therapy (KRT) exist both within and between countries. A number of Asian nations have satisfactory access to KRT and have comprehensive KRT registries to help inform practices, but some do not, particularly among low- and low-to-middle-income countries. Given these differences, we describe the economic status, burden of kidney failure, and cost of KRT across the different modalities to both governments and patients and how changes in health policy over time affect outcomes. Emerging trends suggest that more affluent nations and those with universal health care or access to insurance have much higher prevalent dialysis and transplantation rates, while in less affluent nations, dialysis access may be limited and when available, provided less frequently than optimal. These trends are also reflected by an association between nephrologist prevalence and individual nations' incomes and a disparity in the number of nephrologists per million population and per thousand KRT patients.

Effects of low versus standard pressure pneumoperitoneum on renal syndecan-1 shedding and VEGF receptor-2 expression in living-donor nephrectomy: a randomized controlled study.

BACKGROUND: Laparoscopic nephrectomy is a preferred technique for living kidney donation. However, positive-pressure pneumoperitoneum may have an unfavorable effect on the remaining kidney and other distant organs due to inflamed vascular endothelium and renal tubular cell injury in response to increased systemic inflammation. Early detection of vascular endothelial and renal tubular response is needed to prevent further kidney injury due to increased intraabdominal pressure induced by pneumoperitoneum. Transperitoneal laparoscopic living donor nephrectomy represented a human model of mild increasing intraabdominal pressure. This study aimed to assess the effect of increased intraabdominal pressure on vascular endothelium and renal tubular cells by comparing the effects of low and standard pressure pneumoperitoneum on vascular endothelial growth factor receptor-2 (VEGFR-2) expression and the shedding of syndecan-1 as the early markers to a systemic inflammation. METHODS: We conducted a prospective randomized study on 44 patients undergoing laparoscopic donor nephrectomy. Subjects were assigned to standard (12 mmHg) or low pressure (8 mmHg) groups. Baseline, intraoperative, and postoperative plasma interleukin-6, syndecan-1, and sVEGFR-2 were quantified by ELISA. Syndecan-1 and VEGFR-2 expression were assessed immunohistochemically in renal cortex tissue. Renal tubule and peritubular capillary ultrastructures were examined using electron microscopy. Perioperative hemodynamic changes, end-tidal CO2, serum creatinine, blood urea nitrogen, and urinary KIM-1 were recorded. RESULTS: The low pressure group showed lower intra- and postoperative heart rate, intraoperative plasma IL-6, sVEGFR-2 levels and plasma syndecan-1 than standard pressure group. Proximal tubule syndecan-1 expression was higher in the low pressure group. Proximal-distal tubules and peritubular capillary endothelium VEGFR-2 expression were lower in low pressure group. The low pressure group showed renal tubule and peritubular capillary ultrastructure with intact cell membranes, clear cell boundaries, and intact brush borders, while standard pressure group showed swollen nuclei, tenuous cell membrane, distant boundaries, vacuolizations, and detached brush borders. CONCLUSION: The low pressure pneumoperitoneum attenuated the inflammatory response and resulted in reduction of syndecan-1 shedding and VEGFR-2 expression as the renal tubular and vascular endothelial proinflammatory markers to injury due to a systemic inflammation in laparoscopic nephrectomy. TRIAL REGISTRATION: ClinicalTrials.gov NCT:03219398, prospectively registered on July 17th, 2017.

Factors Associated with Mortality of Intensive Care Unit Patients with Acute Kidney Injury at Cipto Mangunkusumo National Central General Hospital.

BACKGROUND: the incidence of acute kidney injury (AKI) in intensive care units is associated with increased mortality, post AKI morbidity and high treatment costs. Research on factors related to mortality of AKI patients in intensive care units in Indonesia, especially Cipto Mangungkusumo General Hospital has never been done. This study aims to determine the prevalence of AKI, mortality rate of AKI patients, and the factors associated with increased mortality of AKI patients in intensive care units in ICU Cipto Mangunkusumo General Hospital. METHODS: this is a retrospective cohort study of all patients diagnosed with AKI in the intensive care unit at Cipto Mangunkusumo General Hospital, January 2015 - December 2016. An analysis of bivariate relationships with multvariate with STATA Statistics 15.0 between age > 60 years, sepsis, use of ventilator, ventilator duration, dialysis, oligoanuria, and APACHE II scores at admission with mortality. RESULTS: the prevalence of AKI patients in the intensive care unit was 12.25% (675 of 5511 subjects) and 220 subjects (32.59%) of the 675 analyzed subjects died in the intensive care unit. Factors related to increased mortality in multivariate analysis were sepsis (OR 6,174; IK95% 3,116-12,233), oligoanuria (OR 4,173; IK95% 2,104-8,274), use of ventilator (OR 3,085; IK95% 1,348-7,057), (scores APACHE II at admission) 1/2 [OR 1,597; IK95% 1.154-2.209], and the duration of the ventilator (OR 1.062; IK95% 1.012-1.114). CONCLUSION: the prevalence of AKI patients and their mortality rate in the intensive care unit of Cipto Mangunkusumo General Hospital obtained 12.25% and 32.59%. Sepsis, oligoanuria, ventilators (APACHE II score at admission) 1/2, and ventilator duration are factors that are significantly associated with increased mortality of AKI patients in intensive care units.

Diagnostic Determinants of Proliferative Lupus Nephritis Based on Clinical and Laboratory Parameters: A Diagnostic Study.

BACKGROUND: proliferative lupus nephritis (LN) has higher prevalence and worse prognosis than non-proliferative LN. Renal biopsy plays an important role in diagnosis and therapy of LN, but there are some obstacles in its implementation. A diagnostic scoring system for proliferative LN is necessary, especially for cases in which renal biopsy cannot be performed. This study aimed to develop a diagnostic scoring system of proliferative LN based on its diagnostic determinants including hypertension, proteinuria, hematuria, eGFR, anti-dsDNA antibody, and C3 levels. METHODS: a cross-sectional study with total sampling method was conducted. Our subjects were adult LN patients who underwent renal biopsy in Cipto Mangunkusumo Hospital between January 2007 and June 2017. RESULTS: from a total of 191 subjects with biopsy-proven LN in this study, we found a proportion of proliferative LN of 74.8%. There were 113 subjects included for analysis of proliferative LN determinants. The multivariate analysis demonstrated that determinants for proliferative LN were hypertension (OR 3.39; 95% CI 1.30-8.84), eGFR <60ml/min/1.73m2 (OR 9.095; 95% CI 1.11-74.68), and low C3 levels (OR 3.97; 95% CI 1.41-11.17). After further analysis, we found that hypertension, eGFR <60ml/min/1.73m2, low C3 levels, and hematuria were essential components of the diagnostic scoring system on proliferative LN. The scoring system was tested with ROC curve and an AUC of 80.4% was obtained (95% CI 71.9-89). CONCLUSION: the proportion of proliferative LN in biopsy-proven LN patients of Cipto Mangunkusumo Hospital is 74.8%. Components of scoring system for proliferative LN consist of hypertension, eGFR <60ml/min/1.73m2, low C3 levels, and hematuria.

Concordance between Reticulocyte Hemoglobin Equivalent and Reticulocyte Hemoglobin Content in CKD Patients Undergoing Hemodialysis.

AIM: to evaluate the correlation and the concordance between reticulocyte hemoglobin equivalent (RET-He) and reticulocyte hemoglobin content (CHr) as well as to obtain the cut-off value of RET-He as the target of iron supplementation in chronic kidney disease (CKD) patients undergoing hemodialysis. METHODS: a cross-sectional study was performed using K3EDTA-anticoagulated peripheral blood samples collected from 106 CKD patients undergoing routine hemodialysis. The samples were then analyzed using both Sysmex XN-2000 and Siemens ADVIA 2120i for RET-He and CHr analysis. RESULTS: a very strong correlation (r=0.91; p<0.0001) and a good concordance were found between RET-He and CHr with mean bias of 0.5 pg. The diagnostic concordance was 96.23%. The cut-off value of RET-He 29.2 pg was obtained from the receiver operating characteristic (ROC) curve with CHr as the gold standard. At this cut-off point, the sensitivity and specificity to assess the target of iron supplementation in CKD patients undergoing hemodialysis were 95.5% and 94%, respectively. CONCLUSION: the study shows a good correlation and concordance between RET-He and CHr in CKD patients undergoing hemodialysis.

Effect of Nigella sativa Seed Extract for Hypertension in Elderly: a Double-blind, Randomized Controlled Trial.

BACKGROUND: Nigella sativa (NS) seed extract shows diuretic activity, inhibits sympathetic nervous system overactivity and increases the production of Nitric Oxide in in vivo studies, thus it has a potential use as an adjuvant antihypertensive for elderly population. This study aimed to determine the effect of Nigella sativa seed extract to systolic blood pressure (SBP) and diastolic blood pressure (DBP) of elderly patients with hypertension. METHODS: a double-blind, randomized controlled trial was conducted on elderly subjects with hypertension in three outpatient clinics in Cipto Mangunkusumo National Hospital Jakarta Indonesia from June to September 2011. Subjects were divided into intervention group given 300 mg Nigella sativa seed extract twice daily for 28 days and into another group which was given placebo. Blood pressure were measured on day 1 and 28. Intention to treat analysis using unpaired t-test to compare blood pressure after intervention between the two groups was performed. RESULTS: of a total of 85 patients, 76 subjects fulfilled the study criteria and were randomized into 2 groups, with 38 subjects in each group. Both groups were comparable in all important prognostic factors. The mean systolic blood pressure of the NS group was decreased from 160.4 (SD 15.7) mmHg to 145.8 (SD 19.8) mmHg, and from 160.9 (16.3) mmHg to 147.53 (SD 22.0) mmHg in the placebo group (p=0.36). The mean diastolic blood pressure in the NS group was decreased from 78.3 (SD 11.9) to 74.4 (SD 8.2) mmHg, and from 79.0 (SD 12.4) to 78.2 (SD 8.9) in the placebo group (p=0.35). Reported adverse events include dyspepsia in 6 subjects (15.7%), nausea in 3 subjects (7.8%), and constipation in 2 subjects (5.2%). No electrolyte abnormalities, liver and renal toxicities, or orthostatic hypotension were observed. CONCLUSION: although a trend towards a slight decrease in blood pressure was observed, Nigella sativa has not been proven to be effective in reducing blood pressure in elderly patients with hypertension.

The Correlation of MicroRNA-21 With the Nephrin, Podocin, and Urinary Albumin-Creatinine Ratio in Patients With Type 2 Diabetes and Albuminuria: A Cross-Sectional Study.

Background: Diabetic kidney disease (DKD) is the most common and deranging microvascular complication of diabetes mellitus (DM). Podocytopathy is a key component of glomerular damage in DKD. Micro RNA-21 (miRNA-21) is an epigenetic regulator that plays a role in podocyte damage; however, the results of previous studies have not resolved the controversy about the role of miRNA-21 in the pathogenesis of DKD. Objective: The objective was to investigate the correlation between miRNA-21 levels and urinary nephrin, podocin, and urinary albumin-creatinine ratio (UACR) in patients with type 2 DM and albuminuria. Design: This is a cross-sectional study. Setting: This study was carried out in internal medicine outpatient clinic of Cipto Mangunkusumo Hospital Jakarta, Indonesia. Patients: This study consisted of 42 adults with type 2 DM and albuminuria. Measurements: The measurements include (1) Serum miRNA-21; (2) urinary podocin, nephrin, and albumin-creatinine ratio; and (3) serum miRNA-21 correlated to urinary podocin, nephrin, and albumin-creatinine ratio. Methods: The Spearman bivariate analysis to assess the correlation of miRNA-21 with nephrin, podocin, and UACR. Results: The mean relative expression of miRNA-21 was 0.069 (0.024), the median for nephrin, podocin, and UACR was 35.5 (15.75-51.25) ng/mL, 0.516 (0.442-0.545) ng/mL, and 150 (94.56-335.75) ng/mL, respectively. A correlation between miRNA-21 and nephrin was observed (r = 0.598; P < .0001). There was a correlation between miRNA-21 and UACR (r = 0.604; P < .0001). No correlation was found between miRNA-21 and podocin. Limitations: A lack of non-DM and non-albuminuric control population and small sample size. We could not exclude concurrent disease, and all other potential confounding variables, particularly those related to inflammation. Conclusions: The miRNA-21 can be considered an early biomarker for podocytopathy and albuminuria in DM, highlighting its potential for early diagnostic and therapeutic interventions. Further research is required to confirm these findings and explore their clinical applications, which could significantly alter management strategies for DKD.

Contexte: La maladie rénale diabétique (MRD) est la complication microvasculaire la plus fréquente et une des plus inquiétantes du diabète (DB). La podocytose est une composante clé des lésions glomérulaires en contexte de MRD. Le micro-ARN-21 (miARN-21) est un régulateur épigénétique impliqué dans les lésions podocytaires, mais les résultats des études précédentes n'ont pas résolu la controverse sur le rôle du miARN-21 dans la pathogenèse de la MRD. Objectif: Étudier la corrélation entre le taux de miARN-21 et la néphrine, la podocine et le rapport albumine-créatinine (RAC) urinaires chez les patients atteints de diabète de type 2 et présentant une albuminurie. Type d'étude: Étude transversale. Cadre: La clinique ambulatoire de médecine interne de l'hôpital Cipto Mangunkusumo à Jakarta (Indonésie). Sujets: 42 adultes diabétiques de type 2 présentant une albuminurie. Mesures: (1) miARN-21 sérique; (2) podocine, néphrine et rapport albumine-créatinine urinaires; (3) le miARN-21 sérique corrélé à la podocine, à la néphrine et au rapport albumine-créatinine urinaires. Méthodologie: L'analyse bivariée de Spearman a servi à évaluer la corrélation entre le taux de miARN-21 et la néphrine, la podocine et le rapport albumine-créatinine urinaires. Résultats: L'expression relative moyenne du miARN-21 était de 0,069 ng/ml (0,024). La médiane s'établissait à 35,5 (15,75­51,25) ng/ml pour la néphrine, à 0,516 (0,442­0,545) ng/ml pour la podocine et à 150 (94,56­335,75) ng/ml pour le RAC. On a observé une corrélation entre le miARN-21 et la néphrine (r = 0,598; p = < 0,0001), de même qu'entre le miARN-21 et le RAC (r = 0,604; p = <0,0001). Aucune corrélation n'a été observée entre le miARN-21 et la podocine. Limites: L'étude ne comporte pas de population témoin (non-DB et sans albuminurie) et l'échantillon est de petite taille. Il n'a pas été possible d'exclure les maladies concomitantes, de même que toutes les autres variables confondantes potentielles, en particulier celles qui sont liées à l'inflammation. Conclusion: Chez les patients diabétiques, le miARN-21 peut être considéré comme un biomarqueur précoce de la podocytose et de l'albuminurie, ce qui met en évidence son potentiel à faire partie des interventions diagnostiques et thérapeutiques précoces. D'autres recherches sont nécessaires pour confirmer ces résultats et explorer leurs applications cliniques, ce qui pourrait modifier considérablement les stratégies de prise en charge de la maladie rénale diabétique.