The Etiology of Advanced Chronic Kidney Disease in Southeast Asia: A Meta-analysis.

INTRODUCTION: Chronic kidney disease (CKD) etiology varies greatly between developed and developing countries. In addition, differences in underlying pathogenesis and therapeutic options affect the progression towards advanced-CKD. This meta-analysis aims to identify the etiology of advanced-CKD in Southeast Asia. METHODS: A systematic search in four electronic-databases and complementary search on national kidney registries and repository libraries was conducted until July 20, 2023. The risk of bias was assessed using Newcastle-Ottawa Scale for observational studies and Version-2 of Cochrane for intervention studies. A random-effects model was used to estimate pooled prevalence. The protocol is registered in the International Prospective Register of Systematic Reviews PROSPERO; Registration ID:CRD42022300786. RESULTS: We analyzed 81 studies involving 32,834 subjects. The pooled prevalence of advanced-CKD etiologies are diabetic kidney disease (DKD) 29.2% (95%CI 23.88-34.78), glomerulonephritis 20.0% (95%CI 16.84-23.38), hypertension 16.8% (95%CI 14.05-19.70), other 8.6% (95%CI 6.97-10.47), unknown 7.5% (95%CI 4.32-11.50), and polycystic kidney disease 0.7% (95%CI 0.40-1.16). We found a significant increase in DKD prevalence from 21% (9.2%, 95%CI 0.00-33.01) to 30% (95%CI 24.59-35.97) before and after the year 2000. Among upper-middle-income and high-income countries, DKD is the most prevalent (26.8%, 95%CI 21.42-32.60 and 38.9%, 95%CI 29.33-48.79, respectively), while glomerulonephritis is common in lower-middle-income countries (33.8%, 95%CI 15.62-54.81). CONCLUSION: The leading cause of advanced-CKD in Southeast Asia is DKD, with a substantial proportion of glomerulonephritis. An efficient screening program targeting high-risk populations (diabetes mellitus and glomerulonephritis) is needed, with the aim to delay CKD progression.

The Etiology of Kidney Failure in Indonesia: A Multicenter Study in Tertiary-Care Centers in Jakarta.

Background: Despite a large number of patients requiring dialysis, the etiology of kidney failure is poorly documented in Indonesia. With the aim to reduce the disease burden, it is essential to obtain more insight in the etiology of chronic kidney disease (CKD). Objectives: In the present study, we attempted to investigate the primary renal disease of kidney failure patients from five tertiary-care centers in Jakarta. Methods: This is a multicenter, cross-sectional study of kidney failure patients receiving kidney replacement therapy (KRT), from December 2021 to July 2022. We recruited patients aged ≥18 years, had been receiving dialysis for at least three months or a kidney transplantation. Findings: This study included 1,152 patients treated with hemodialysis (68.1%), peritoneal dialysis (7.5%), and kidney transplantation (24.4%). At the start of KRT, the median (interquartile-range [IQR]) age was 48 [37-58] years with low eGFR (median [IQR]: 5.9 [4.0-8.34] ml/minute/1.73 m2). Hypertension was the main comorbidity (74.2%), followed by diabetes mellitus (30.1%). The major primary kidney disease was diabetic kidney disease (27.2%), followed by glomerulonephritis (13.0%), hypertension (11.5%), and urolithiasis (10.3%). Lupus nephritis was the common underlying etiology of secondary glomerulonephritis (91%). A high rate of unknown cause (31.1%) was also observed. Conclusions: Our results suggest that diabetic kidney disease is the leading cause of kidney failure in Jakarta, followed by glomerulonephritis. This study highlights the need for a better approach on primary prevention of diabetes mellitus as well as to better recognize glomerulonephritis at earlier stage might have a significant impact on reduction of the rate of kidney failure in Indonesia.

Prevalence and risk factors for chronic kidney disease in Indonesia: An analysis of the National Basic Health Survey 2018.

Background: The prevalence of chronic kidney disease (CKD) in Indonesia is rising, but the exact extent of the burden of CKD in Indonesia is unknown. To design a screening program for individuals at high-risk, more knowledge is required regarding the prevalence and risk factors of CKD in Indonesia. The latter could have a big impact on the prevention and management of patients with CKD in Indonesia. Methods: For this purpose, we analysed data from The National Basic Health Survey 2018 (Riset Kesehatan Dasar, Riskesdas 2018), a descriptive cross-sectional study in 34 provinces, 416 districts and 98 cities in Indonesia. We included subjects aged ≥18 years and analysed the prevalence of CKD. Using multiple logistic regression, we investigated the association between CKD and potential risk factors such as demographic factors (age, gender, occupational status, level of education), lifestyle and behaviours (consumption of salty food, consumption of fruit and vegetables, smoking, alcohol consumption, carbonated drink consumption, physical activity), comorbid conditions (hypertension, heart disease, diabetes mellitus, hepatitis, stroke, nutritional status) and others (clean water supply, pregnancy complication, access to health care). Results: We included 389 093 subjects in this study out of 713 783 subjects that participated in Riskesdas 2018 survey. The prevalence of CKD was 0.5%. The survey included mostly younger adults age 18-59 years (83.1%) with a mean (SD) age of 44.3 (15.1) years. The majority of subjects were female (60.3%), unemployed (58.4%), and the proportion of obese subject was 25.4%. Hypertension was the major comorbid condition (40.8%), while the proportion of diabetes mellitus (DM), heart disease, stroke and hepatitis were quite low (3.3%, 2.6%, 1.7% and 0.5%; respectively). Despite the high proportion of hypertension, only 36.2% of subjects did receive a prescription for anti-hypertensive medication of which only 21.7% used this medication regularly. The multiple logistic regression analysis demonstrated that hepatitis was the strongest risk factor of CKD (odds ratio (OR) = 3.406; 95% confidence interval (CI) = 2.496-4.648), exceeding the risk of CKD in patients with physical inactivity (OR = 1.236; 95% CI = 1.128-1.354), low education status (OR = 1.307; 95% CI = 1.191-1.434), male (OR = 1.527; 95% CI = 1.398-1.668), stroke (OR = 1.916; 95% CI = 1.570-2.338), heart disease (OR = 2.941; 95% CI = 2.356-3.671), and DM (OR = 2.462; 95% CI = 1.979-3.063). We also observed that DM (OR = 4.280; 95% CI = 3.756-4.876) and male subjects (OR = 1.474; 95% CI = 1.352-1.606) were identified as independent risk factors for CKD in hepatitis-positive subjects. Conclusions: This population-based survey confirmed the increasing burden of CKD in Indonesia and suggested that besides traditional metabolic risk factors, viral hepatitis has proven to be an independent risk factor for CKD in Indonesia. Furthermore, the risk of CKD is greater in male hepatitis patients with DM. The result of this study demonstrates the need for an aggressive screening program for patients with a high risk for the development of CKD. Apart from patients with traditional cardiometabolic risk factors, such a program should include patients with viral hepatitis.

Long-term outcomes and prognostic factors in kidney transplant recipients in Jakarta, Indonesia: a cohort study.

OBJECTIVES: To determine the long-term survival rates and prognostic factors in kidney transplant (KT) recipients in Jakarta, Indonesia. DESIGN: Retrospective cohort study. SETTING: A KT centre in Jakarta. PARTICIPANTS: We enrolled 754 consecutive adult recipients who underwent KT between 2010 and 2020. MAIN OUTCOME MEASURES: Rates of 10-year patient, all-cause and death-censored graft survival and their prognostic factors in KT recipients. RESULTS: The 10-year patient survival, all-cause survival and death-censored graft survival rates of KT recipients were 74%, 68% and 81%, respectively. The prognostic factors for poor patient survival were a pretransplant dialysis duration>24 months (HR 1.64, 95% CI, 1.08 to 2.49; p=0.02), cardiovascular disease (HR 1.59, 95% CI, 1.11 to 2.31; p=0.01), delayed graft function (DGF) (HR 4.94, 95% CI, 2.76 to 8.82; p<0.001), post-transplant infection (HR 2.63, 95% CI, 1.56 to 4.43; p<0.001) and acute rejection (HR 2.49, 95% CI, 1.20 to 5.15; p=0.01). All-cause graft survival was prognosticated by a pretransplant dialysis duration>24 months (HR 1.74, 95% CI, 1.15 to 2.47; p=0.007), cardiovascular disease (HR 1.65, 95% CI, 1.18 to 2.33; p=0.004), DGF (HR 5.39, 95% CI, 3.13 to 9.28; p<0.001), post-transplant infection (HR 2.46, 95% CI, 1.05 to 4.02; p<0.001) and acute rejection (HR 4.18, 95% CI, 2.23 to 7.84; p<0.001). Factors associated with poor death-censored graft survival were a pretransplant dialysis duration >24 months (HR 2.19, 95% CI, 1.32 to 3.63; p=0.002), cardiovascular disease (HR 1.65, 95% CI, 1.02 to 2.68; p=0.04) and acute rejection (HR 5.52, 95% CI, 2.80 to 10.83; p<0.001). CONCLUSIONS: The survival rates of KT recipients are prognosticated by pretransplant dialysis duration, cardiovascular disease, DGF, post-transplant infection and acute rejection. Stricter eligibility criteria for recipients, more sensitive cross-match testing methods and better infection management strategies may be beneficial for improving the survival rates.

The Improvement of Patient's Quality of Life After Kidney Transplantation in Cipto Mangunkusumo Hospital, Indonesia.

OBJECTIVES: Kidney transplantation has become the chosen kidney replacement therapy for end stage chronic kidney disease. In Indonesia, no study about quality of life (QoL) in kidney transplantation recipient after surgery has been done. This study aims to determine whether there is a significant difference in the recipient's QoL before and after kidney transplantation surgery. METHODS AND MATERIALS: This was a prospective study using Kidney Disease QoL-Short Form (KDQoL-SF) questionnaire before and after surgery (first, third, and sixth month). Samples were consecutively taken from January 2016 until May 2016 and followed up to December 2016. KDQoL-SF has been validated in Indonesian language to assess recipient's QoL (Cronbach alfa >0,6). The data were analyzed using SPSS statistical software 21.0 version and repeated analysis of variance with posthoc comparison Bonferroni was used. RESULTS: There were 33 patients included in this study from January through December 2016. The average age was 44.6 ± 12.88 years old, and average body mass index was 23.8 ± 3.74 kg/m2. The most frequent comorbidity was hypertension (32, 97%). Compared to baseline, the QoL in recipients increased at the first, third, and sixth month after their operation. Major changes in the perceived QoL were noted only between the preoperative stage (median, 50%; interquartile range, [IQR]) ±20) and 1 month after operation (median, 90%; IQR, 0). CONCLUSIONS: This study showed that there were significant improvements in almost all aspect in recipient's QoL after kidney transplantation.

Kidney Hyperfiltration After Nephrectomy: A Mechanism to Restore Kidney Function in Living Donors.

Living donor kidney transplantation (LDKT) is the treatment of choice for patients with end stage renal disease (ESRD). Up to now, the studies reporting the impact of nephrectomy in living kidney donors to their future kidney function were limited. Most living donors undergo recovery of kidney function after nephrectomy owing to remnant kidneys' capability to compensate nephron loss through adaptive hyperfiltration. However, hyperfiltration may fail and turn out to be maladaptive, causing deterioration of donors' kidney function and increasing risk of chronic kidney disease (CKD) in long term. Hyperfiltration is caused by increased in kidney blood flow and glomerular hypertrophy. Both conditions are regulated by various factors. The adaptive hyperfiltration in the early phase after nephrectomy may play important role in determining long term kidney function, but factors affecting the process are still unclear. Hyperfiltration may also be influenced by donors' characteristics such as age, body mass index (BMI), family related to the recipient, arterial stiffness and intraoperative intrabdominal pressure. Further study to understand the mechanism of hyperfiltration is needed so that kidney transplant centers could anticipate its failure and the detrimental effects of nephrectomy in the future.

The Effect of Hyperfiltration on Kidney Function in Living Donor Kidney Transplantation: A Prospective Cohort Study.

BACKGROUND: living kidney donation is a safe medical procedure. Kidney function after donation is crucial for donors' health and quality of life. Kidney hyperfiltration is a compensatory mechanism, which will preserve kidney function after unilateral nephrectomy. The number of studies regarding hyperfiltration in living kidney donors is limited. Our study aimed to explain kidney hyperfiltration mechanism and evaluate its effect on the kidney function within 30 days after surgery. METHODS: our study was a prospective cohort study with 46 living-kidney donors participating in the study between April and December 2019. We evaluated main outcomes, the 30-day post-surgery kidney function, which was evaluated by calculating estimated glomerular filtration rate (eGFR) and Urinary Albumin to Creatinine Ratio (ACR). The subjects were categorized into two groups based on their 30-day outcomes, which were the adaptive (eGFR > 60 mL/min/1.73 m2 and/or ACR > 30 mg/g) and maladaptive (eGFR < 60 mL/min/1.73 m2 and/or ACR > 30 mg/g) groups. A series of evaluation including calculating the renal arterial resistive index (RI) and measuring urinary vascular endothelial growth factor (VEGF), neutrophil gelatinase-associated lipocalin (NGAL), and heparan sulfate (HS) levels were performed before surgery and serially until 30 days after surgery. Multivariate analysis with adjustments for confounding factors was done. RESULTS: forty donors were included and mostly were female (67.5%). The average age and body mass index (BMI) were 45.85 (SD 9.74) years old and 24.36 (SD 3.73) kg/m2, respectively. Nineteen donors (47.5%) had maladaptive hyperfiltration outcomes. The hyperfiltration process was demonstrated by significant changes in renal arterial RI, urinary VEGF, NGAL, and HS levels (p<0.005). There was no significant difference regarding RI, urinary VEGF, NGAL, and HS levels between both groups. Several confounding factors (BMI over 25 kg/m2, familial relationship, age over 40 years old, and arterial stiffness) were significantly influenced by kidney hyperfiltration and outcomes (p<0.05). CONCLUSION: the hyperfiltration process does not affect the 30-day post-nephrectomy kidney function of the donors. Several other factors may influence the hyperfiltration process and kidney function. Further study is necessary to evaluate kidney function and its other related variables with a longer period of time study duration.

Laparoscopic procurement of single versus multiple artery kidney allografts: Meta-analysis of comparative studies.

Laparoscopic donor nephrectomy has become the standard procedure to procure kidney graft. Transplantation using multiple arteries allograft is technically more challenging and still controversial with respect to renal transplantation outcomes. The objective of this study was to examine the transplantation outcome in both donor and recipient outcome of multiple arteries allograft kidney compared with single renal artery kidney. Eligible studies were identified from electronic databases: PubMed, Cochrane CENTRAL, Science Direct, and CINAHL as of October 2016. Relevant parameters explored using Review Manager V5.2 included donor and recipient outcomes. Twenty-four studies were included in this meta-analysis. Compared with SA, MA kidneys were associated with a longer donor operative time. There was no difference between donor length of stay, intraoperative blood loss, hospital stay, first warm ischemic time (WIT-I), and donor surgical complications in donors with multiple arteries compared with single. There was an increased risk of one-year graft loss (OR 1.57, 95% CI 1.09 to 2.26, p = 0.016), recipient vascular complications and recipient ureteral complications in multiple arteries compared with single artery allografts. Kidney transplantation with multiple arteries is relatively as safe as single artery in terms of donor outcomes. However, transplantation with multiple arteries allograft had several potential negative impacts on the recipient outcomes.

7 Years Experience of Living Donor Kidney Transplantation in Indonesia: A Retrospective Cohort Study.

BACKGROUND: kidney transplantation has been developing rapidly in Indonesia in recent years, yet data on transplants' characteristics and survival is still unavailable. In Indonesia, only living donors are permitted. Living donor are advantageous, but challenging to recruit. This study aimed to establish the graft and patient survival rates and to describe the characteristics of recipient and donor as well as the process of donor recruitment and evaluation of kidney transplantation in Indonesia. METHODS: the study was a retrospective cohort on all donors and kidney transplant recipients at Cipto Mangunkusumo General Hospital (CMGH) from January 2011 to May 2017. Only recipients from January 2011 to May 2014 were included to establish the 1-year and 3-year graft and patient survival; which were described using Kaplan-Meier method. RESULTS: data from 492 kidney transplant procedures were obtained (donor median age, 30 (17 - 66) years; 25.1% were family-related. Recipients mean age, 47 (SD 13.18 years). Data from total of 138 kidney transplant recipients were further analyzed. The 1-year death- censored graft survival, all-cause graft survival and patient survival were 92 %, 82.6 % and 87%. The 3-year death-censored graft survival, all-cause graft survival and patient survival were 90.6%, 76.1% and 79.7%. Kaplan-Meier's curve showed the highest mortality rates occured in the early months. CONCLUSION: the 1-year graft and patient survival rate were 92% and 87%. The 3-year graft and patient survival rate were 90.6% and 79.7%. Only small percentage of donor were family-related. Living donor recruitment and evaluation are still a big challenge in Indonesia.

Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with Captopril.

A double-blind, randomized, parallel and active-controlled clinical study was conducted to evaluate the anti-hypertensive effect as well as the tolerability of Olive leaf extract in comparison with Captopril in patients with stage-1 hypertension. Additionally, this study also investigated the hypolipidemic effects of Olive leaf extract in such patients. It consisted of a run-in period of 4 weeks continued subsequently by an 8-week treatment period. Olive (Olea europaea L.) leaf extract (EFLA(®)943) was given orally at the dose of 500 mg twice daily in a flat-dose manner throughout the 8 weeks. Captopril was given at the dosage regimen of 12.5 mg twice daily at start. After 2 weeks, if necessary, the dose of Captopril would be titrated to 25 mg twice daily, based on subject's response to treatment. The primary efficacy endpoint was reduction in systolic blood pressure (SBP) from baseline to week-8 of treatment. The secondary efficacy endpoints were SBP as well as diastolic blood pressure (DBP) changes at every time-point evaluation and lipid profile improvement. Evaluation of BP was performed every week for 8 weeks of treatment; while of lipid profile at a 4-week interval. Mean SBP at baseline was 149.3±5.58 mmHg in Olive group and 148.4±5.56 mmHg in Captopril group; and mean DBPs were 93.9±4.51 and 93.8±4.88 mmHg, respectively. After 8 weeks of treatment, both groups experienced a significant reduction of SBP as well as DBP from baseline; while such reductions were not significantly different between groups. Means of SBP reduction from baseline to the end of study were -11.5±8.5 and -13.7±7.6 mmHg in Olive and Captopril groups, respectively; and those of DBP were -4.8±5.5 and -6.4±5.2 mmHg, respectively. A significant reduction of triglyceride level was observed in Olive group, but not in Captopril group. In conclusion, Olive (Olea europaea) leaf extract, at the dosage regimen of 500 mg twice daily, was similarly effective in lowering systolic and diastolic blood pressures in subjects with stage-1 hypertension as Captopril, given at its effective dose of 12.5-25 mg twice daily.