Endothelial TGF-ß Signaling Regulates Endothelial-Mesenchymal Transition During Arteriovenous Fistula Remodeling in Mice With Chronic Kidney Disease.

BACKGROUND: Arteriovenous fistulae (AVFs) are the preferred vascular access for hemodialysis in patients with end-stage kidney disease. Chronic kidney disease (CKD) is associated with endothelial injury, impaired AVF maturation, and reduced patency, as well as utilization. Because CKD is characterized by multiple pathophysiological processes that induce endothelial-to-mesenchymal transition (EndMT), we hypothesized that CKD promotes EndMT during venous remodeling and that disruption of endothelial TGF (transforming growth factor)-ß signaling inhibits EndMT to prevent AVF failure even in the end-stage kidney disease environment. METHODS: The mouse 5/6 nephrectomy and aortocaval fistula models were used. CKD was created via 5/6 nephrectomy, with controls of no (0/6) or partial (3/6) nephrectomy in C57BL/6J mice. AVFs were created in mice with knockdown of TGF-ßR1/R2 (TGF-ß receptors type 1/2) in either smooth muscle cells or endothelial cells. AVF diameters and patency were measured and confirmed by serial ultrasound examination. AVF, both murine and human, were examined using Western blot, histology, and immunofluorescence. Human and mouse endothelial cells were used for in vitro experiments. RESULTS: CKD accelerates TGF-ß activation and promotes EndMT that is associated with increased AVF wall thickness and reduced patency in mice. Inhibition of TGF-ß signaling in both endothelial cells and smooth muscle cells decreased smooth muscle cell proliferation in the AVF wall, attenuated EndMT, and was associated with reduced wall thickness, increased outward remodeling, and improved AVF patency. Human AVF also showed increased TGF-ß signaling and EndMT. CONCLUSIONS: CKD promotes EndMT and reduces AVF patency. Inhibition of TGF-ß signaling, especially disruption of endothelial cell-specific TGF-ß signaling, attenuates EndMT and improves AVF patency in mouse AVF. Inhibition of EndMT may be a therapeutic approach of translational significance to improve AVF patency in human patients with CKD.

A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association.

A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.

Renal Denervation Prevents Atrial Arrhythmogenic Substrate Development in CKD.

BACKGROUND: In patients with chronic kidney disease (CKD), atrial fibrillation (AF) is highly prevalent and represents a major risk factor for stroke and death. CKD is associated with atrial proarrhythmic remodeling and activation of the sympathetic nervous system. Whether reduction of the sympathetic nerve activity by renal denervation (RDN) inhibits AF vulnerability in CKD is unknown. METHODS: Left atrial (LA) fibrosis was analyzed in samples from patients with AF and concomitant CKD (estimated glomerular filtration rate [eGFR], <60 mL/min per 1.73 m2) using picrosirius red and compared with AF patients without CKD and patients with sinus rhythm with and without CKD. In a translational approach, male Sprague Dawley rats were fed with 0.25% adenine (AD)-containing chow for 16 weeks to induce CKD. At week 5, AD-fed rats underwent RDN or sham operation (AD). Rats on normal chow served as control. After 16 weeks, cardiac function and AF susceptibility were assessed by echocardiography, radiotelemetry, electrophysiological mapping, and burst stimulation, respectively. LA tissue was histologically analyzed for sympathetic innervation using tyrosine hydroxylase staining, and LA fibrosis was determined using picrosirius red. RESULTS: Sirius red staining demonstrated significantly increased LA fibrosis in patients with AF+CKD compared with AF without CKD or sinus rhythm. In rats, AD demonstrated LA structural changes with enhanced sympathetic innervation compared with control. In AD, LA enlargement was associated with prolonged duration of induced AF episodes, impaired LA conduction latency, and increased absolute conduction inhomogeneity. RDN treatment improved LA remodeling and reduced LA diameter compared with sham-operated AD. Furthermore, RDN decreased AF susceptibility and ameliorated LA conduction latency and absolute conduction inhomogeneity, independent of blood pressure reduction and renal function. CONCLUSIONS: In an experimental rat model of CKD, RDN inhibited progression of atrial structural and electrophysiological remodeling. Therefore, RDN represents a potential therapeutic tool to reduce the risk of AF in CKD, independent of changes in renal function and blood pressure.

Characteristics and comorbidity of confirmed COVID-19 death cases at the Arifin Achmad Hospital in Riau province from March 2020 to September 2021.

Objectives: To investigate the characteristics and comorbidity among those who died due to coronavirus disease-2019. METHODS: The cohort retrospective study was conducted at Arifin Achmad Public Hospital, Riau, Indonesia, from January 5 to February 28, 2022, and comprised data of all coronavirus disease-2019 patients who had been treated at the hospital from March 2020 to October 2021. Data was analysed using SPSS version 20. Logistic regression including univariate and bivariate analysis was applied. RESULTS: Of the 1,694 patients, 916(54.1%) were females and 904(53.4%) were aged >50 years. The most frequent comorbidity was type 2 diabetes mellitus 280(16.5%), followed by hypertension 254(14.9%) and chronic renal failure 194(11.4%). Mortality was significantly higher among those aged >50 years and those having diabetes mellitus and hypertension (p<0.05). CONCLUSIONS: Patients with comorbidities were at a greater risk of acquiring coronavirus disease-2019 infection.

Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial.

BACKGROUND: There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF). METHODS: The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA2DS2-VASc score ≥2. Patients were randomly assigned 1:1 to 5 mg of apixaban twice daily (2.5 mg twice daily for patients ≥80 years of age, weight ≤60 kg, or both) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant nonmajor bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1. RESULTS: From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0-3.0) for warfarin-treated patients was 44% (interquartile range, 23%-59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63-2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342-3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615-1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event. CONCLUSIONS: There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02942407.

Post-transplant ejection fraction and renal failure in cardiac transplant recipients: An analysis of the OPTN database.

BACKGROUND: Despite improved life expectancy from a heart transplant, transplant recipients remain at high risk for renal dysfunction and failure, including end-stage kidney disease (ESKD). The onset of ESKD is a poor prognostic marker and is associated with increased mortality in this setting, as in others. There is a need to identify risk factors for ESKD among heart transplant recipients in contemporary settings. METHODS: We conducted an analysis of adult heart transplant recipients transplanted between 2008 and 2021 in the Organ Procurement and Transplantation Network database. 22 737 adult recipients of heart transplants alone were included in this analysis. We examined LVEF measured 1 year after transplant, and LVEF updated annually for association with ESKD using multivariate Cox regression models. RESULTS: LVEF at 1-year after transplant was associated with ESKD in multivariate models (Hazard Ratio 1.33 per 10-unit decrease, 95% CI 1.23-1.43, p < .001). In multivariate models using categorized LVEF, mildly reduced ejection fraction (EF 40%-50%) was associated with ESKD (HR 1.76, 95% CI 1.45-2.14, p < .001), as was reduced ejection fraction (EF < 40%, HR 2.86, 95% CI 2.01-4.07, p < .001), relative to individuals with preserved ejection fraction (EF > 50%). These associations were consistent when using annually updated ejection fraction. CONCLUSIONS: Post-transplant left ventricular ejection fraction has value in predicting end stage kidney disease among adults who receive heart transplants alone. LVEF is routinely measured as part of contemporary post heart transplant care, and a diminished LVEF should signal to clinicians that a recipient is at increased risk of renal failure.

Excess all-cause and cause-specific mortality for people with diabetes and end-stage kidney disease.

AIMS: Excess mortality is high in the setting of diabetes and end-stage kidney disease (ESKD), but the effects of ESKD beyond diabetes itself remains incompletely understood. We examined excess mortality in people with diabetes with versus without ESKD, and variation by age, sex and diabetes type. METHODS: This study included 63,599 people with type 1 (aged 20-69 years; 56% men) and 1,172,160 people with type 2 diabetes (aged 30+ years; 54% men), from the Australian National Diabetes Services Scheme. Initiation of renal replacement therapy and mortality outcomes were obtained via linkage to the Australia and New Zealand Dialysis and Transplant Registry and the National Death Index, respectively. Excess mortality was measured by calculating the mortality rate ratio (MRR) for people with versus without ESKD via indirect standardisation. RESULTS: A total of 9027 people developed ESKD during 8,601,522 person-years of follow-up. Among people with type 1 diabetes, the MRR was 34.9 (95%CI: 16.6-73.1) in men and 41.5 (20.8-83.1) in women aged 20-29 years and was 5.6 (4.5-7.0) and 7.4 (5.5-10.1) in men and women aged 60-69 years, respectively. In type 2 diabetes, MRRs were 16.6 (8.6-31.8) and 35.8 (17.0-75.2) at age 30-39 years and were 2.8 (2.6-3.1) and 3.6 (3.2-4.1) at age 80+ years in men and women, respectively. Excess cause-specific mortality was highest for peripheral artery disease, cardiac arrest, and infections, and lowest for cancer. CONCLUSIONS: Among people with diabetes, excess mortality in ESKD is much higher at younger ages and is higher for women compared with men.

Value of native T1 mapping in the prediction of major adverse cardiovascular events in hemodialysis patients.

OBJECTIVES: This study aimed to evaluate the association of myocardial characterization by native T1 mapping using cardiac MR (CMR) with the incidence of major adverse cardiovascular event (MACE) in end-stage renal dysfunction (ESRD) patients on hemodialysis. METHODS: A total of 52 ESRD patients and 52 healthy individuals were prospectively recruited between June 2017 and June 2018. ESRD patients underwent CMR examinations post-hemodialysis for the evaluation of cardiac function and global native T1 mapping. Demographics, serum biomarkers, and coronary artery calcification were collected. MACE including all-caused death, and new onset of myocardial infarction, heart failure leading to hospitalization, fatal arrhythmia, and cardiac arrest was set as the endpoint. RESULTS: During a median follow-up of 38.0 months, 13 patients (25.0%) reached the endpoints. Global native T1 mapping in patients on hemodialysis was significantly higher compared with that of healthy individuals (1280.3 ms ± 45.3 vs. 1238.2 ms ± 31.1, p < 0.001). In the univariate Cox regression analysis, global native T1 mapping (HR [hazard ratios]: 1.887, 95% CI [confidence interval]: 1.302-2.736, p = 0.001) was associated with the prediction of MACE. Multivariate Cox regression analysis demonstrated that global native T1 mapping (HR: 1.580, 95% CI: 1.112-2.244, p = 0.011) and age (HR: 1.088, 95% CI: 1.032-1.146, p = 0.002) were associated with the incidence of MACE after adjusting for other conventional risk factors. CONCLUSIONS: Global native T1 mapping by CMR can potentially become a novel predictor of MACE in ESRD patients on hemodialysis, providing additional prognostic values over conventional risk factors. However, this conclusion should be validated in a larger sample size of hemodialysis patients. KEY POINTS: • Global native T1 mapping was significantly higher in ESRD patients on hemodialysis compared with that of normal controls. • Global native T1 mapping was associated with myocardial enzymes, myocardial hypertrophy, coronary calcification, and cardiac function. • Global native T1 mapping value was independently predictive of MACE in hemodialysis patients, providing additional prognostic values over conventional risk factors.

Identification of cardiovascular abnormalities by multiparametric magnetic resonance imaging in end-stage renal disease patients with preserved left ventricular ejection fraction.

OBJECTIVES: Our study aimed to evaluate myocardial strain and tissue characteristics by multiparametric cardiovascular magnetic resonance (CMR) imaging in end-stage renal disease (ESRD) patients on peritoneal dialysis with preserved left ventricular ejection fraction (LVEF). METHODS: ESRD patients on peritoneal dialysis with echocardiographic LVEF > 50% and age- and sex-matched healthy volunteers underwent multiparametric CMR at 3 T. LV function, LV myocardial native T1 and T2, and biventricular strain were measured and compared between the patients and controls. Associations of LV myocardial mass index (LVMI) with tissue characterization and strain were evaluated by multiple linear regression. RESULTS: A total of 65 subjects (42 healthy volunteers and 23 ESRD patients) were enrolled. ESRD group demonstrated larger LVMI, higher native T1 and T2 (1301.9 ± 30.6 ms, 44.6 ± 2.6 ms) than those of the control group (1255.8 ± 45.2 ms, 40.5 ± 1.6 ms; both p < 0.001). Decreased LV strain and increased right ventricular circumferential strain were observed in the ESRD group. In ESRD patients with normal diastolic function on echocardiography, native T1 and T2 values were higher than those of the control group (p = 0.006, p = 0.001). Increased LVMI was associated with increased native T1 (p = 0.001) and T2 value (p < 0.001) after adjusting for age and sex. Increased myocardial native T1 value was associated with reduced LV strain after adjusting age, sex, and LVMI. CONCLUSIONS: ESRD patients on peritoneal dialysis with preserved LVEF demonstrated higher myocardial mass, higher native T1 and T2 values, decreased LV strain, and increased RVGCS compared with healthy controls. Increased myocardial T1 and T2 were found in ESRD even when no systolic or diastolic dysfunction was detected by routine echocardiography. KEY POINTS: • Even with preserved LVEF and no known cardiovascular diseases, ESRD patients on peritoneal dialysis demonstrated elevated myocardial T1 and T2 values and decreased left ventricular strain. • Subclinical changes in myocardial tissue composition may exist in ESRD patients on peritoneal dialysis even when no systolic or diastolic dysfunction was detected by routine echocardiography based on ejection fraction, left atrium size, and tissue Doppler. • Right ventricular free wall strain could be enhanced in response to subclinical LV systolic dysfunction in ESRD patients on peritoneal dialysis with preserved LVEF at an early stage.

Incidence and predictors of vascular events following end-stage kidney disease in childhood.

AIM: Cardiovascular death is a leading cause of mortality in paediatric end-stage kidney disease (ESKD). There is however little known about the clinically relevant vascular disease in this population. We aimed to describe the incidence of new onset vascular disease and vascular death in Australian children receiving renal replacement therapy (RRT). We also aimed to identify demographic or childhood risk factors for these endpoints, and whether vascular disease predicts mortality. METHODS: Data on Australian patients who commenced RRT at <18 years of age from 1991 to 2017 were extracted from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). Multivariable competing risks regression was used to identify factors associated with vascular events. RESULTS: A cohort of 1268 patients were followed up for a median of 10.31 years. Vascular disease was reported in 5.4%, and vascular death in 4.1%. The cumulative incidence of any vascular event, that is, disease or death, at 10 and 20 years was 5.5% and 12.8%, respectively. Childhood vascular events were associated with non-Caucasian, non-Indigenous ethnicity, and for the 804 patients followed up after 18 years of age, vascular events were associated with lack of childhood transplantation, longer childhood dialysis duration and Indigenous ethnicity. Vascular disease was only reported for 25.49% of patients who had a vascular death, and although a significant risk factor for mortality, it had limited ability to predict mortality. CONCLUSION: Cumulative incidence of vascular events is significant after commencing RRT during childhood and is associated with ethnicity, longer childhood dialysis duration and lack of childhood transplantation.

Screening tools to expedite assessment of frailty in people receiving haemodialysis: a diagnostic accuracy study.

BACKGROUND: Frailty is associated with multiple adverse outcomes in stage-5 chronic kidney disease (CKD-5) and upwards of one third of people receiving haemodialysis (HD) are frail. While many frailty screening methods are available in both uremic and non-uremic populations, their implementation in clinical settings is often challenged by time and resource constraints. In this study, we explored the diagnostic accuracy of time-efficient screening tools in people receiving HD. METHODS: A convenience sample of 76 people receiving HD [mean age = 61.1 years (SD = 14), 53.9% male] from three Renal Units were recruited for this cross-sectional study. Frailty was diagnosed by means of the Fried phenotype. Physical performance-based screening tools encompassed handgrip strength, 15-ft gait speed, timed up and go (TUG), and five-repetition sit to stand (STS-5) tests. In addition, participants completed the SF-36 Health Survey, the short-form international physical activity questionnaire and the Tinetti falls efficacy scale (FES) as further frailty-related measures. Outcome measures included the area under the curve (AUC), sensitivity, specificity, positive (PPV) and negative predictive values (NPV). The diagnostic performance of screening tools in assessing fall-risk was also investigated. RESULTS: Overall, 36.8% of participants were classified as frail. All the examined instruments could significantly discriminate frailty status in the study population. Gait speed [AUC = 0.89 (95%CI: 0.81-0.98), sensitivity = 75%, specificity = 93%] and TUG [AUC = 0.90 (95%CI: 0.80-0.99), sensitivity = 89%, specificity = 85%] exhibited the highest diagnostic accuracy. There was a significant difference in gait speed AUC (20%, p = 0.013) between participants aged 65 years or older (n = 36) and those under 65 years of age (n = 40), with better discriminating performance in the younger sub-group. The Tinetti FES was the only instrument showing good diagnostic accuracy (AUCs≥0.80) for both frailty (sensitivity = 82%, specificity = 79%) and fall-risk (sensitivity = 82%, specificity = 71%) screening. CONCLUSIONS: This cross-sectional study revealed that time- and cost-efficient walking performance measures can accurately be used for frailty-screening purposes in people receiving HD. While self-selected gait speed had an excellent performance in people under 65 years of age, TUG may be a more suitable screening method for elderly patients (≥65 years). The Tinetti FES may be a clinically useful test when physical testing is not achievable.

DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA): rationale and design.

BACKGROUND: The incidence and prevalence of older patients with kidney failure who are dependent on dialysis is increasing. However, observational studies showed limited or no benefit of dialysis on mortality in subgroups of these patients when compared to conservative care. As the focus is shifting towards health-related quality of life (HRQoL), current evidence of effects of conservative care or dialysis on HRQoL in older patients is both limited and biased. Dialysis comes with both high treatment burden for patients and high costs for society; better identification of patients who might not benefit from dialysis could result in significant cost savings. The aim of this prospective study is to compare HRQoL, clinical outcomes, and costs between conservative care and dialysis in older patients. METHODS: The DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA) study is a prospective, observational cohort study that started in February 2020. It aims to include 1500 patients from 25 Dutch and Belgian centres. Patients aged ≥70 years with an eGFR of 10-15 mL/min/1.73m2 are enrolled in the first stage of the study. When dialysis is initiated or eGFR drops to 10 mL/min/1.73m2 or lower, the second stage of the study commences. In both stages nephrogeriatric assessments will be performed annually, consisting of questionnaires and tests to assess most common geriatric domains, i.e. functional, psychological, somatic, and social status. The primary outcome is HRQoL, measured with the Twelve-item Short-Form Health Survey. Secondary outcomes are clinical outcomes (mortality, hospitalisation, functional status, cognitive functioning, frailty), cost-effectiveness, and decisional regret. All outcomes are (repeated) measures during the first year of the second stage. The total follow-up will be a maximum of 4 years with a minimum of 1 year in the second stage. DISCUSSION: By generating more insight in the effects of conservative care and dialysis on HRQoL, clinical outcomes, and costs, findings of this study will help patients and physicians make a shared decision on the best individual treatment option for kidney failure. TRIAL REGISTRATION: The study was registered in the Netherlands Trial Register ( NL-8352 ) on 5 February 2020.

Factors associated with chronic kidney disease of non-traditional causes among children in Guatemala.

OBJECTIVE: To identify factors associated with chronic kidney disease of non-traditional causes among children in Guatemala. METHODS: A cross-sectional survey was conducted. The study population was all pediatric patients with stage 5 chronic kidney disease active in FUNDANIER's pediatric nephrology unit (N = 156). Simple random sampling led to a total of 100 participants. Data collection consisted of a questionnaire addressing individual and household characteristics, access and utilization of health care, and place of residence when the disease began. Chronic kidney disease etiology was obtained from medical records. Municipality-level secondary data were collected. Descriptive statistics were estimated. Logistic regression was used for bivariate and multivariate analysis. RESULTS: The odds ratio (OR) for almost all variables approached 1. Notable exceptions in household characteristics were mother's education level up to primary school (OR 2.2727) and living in an urban setting when symptoms began (OR 0.4035). Exceptions in municipal characteristics are zones with intensive small-scale agriculture (OR 3.8923) and those with intensive large-scale agriculture (OR 0.3338). P-values and confidence intervals show that the sample was not big enough to capture statistically significant associations between variables. CONCLUSIONS: Study findings suggest that factors associated with chronic kidney disease of non-traditional causes among children in Guatemala are intensive agricultural practices in their municipality of residence, and mother's level of education. Future research in children could use case-control designs or population-based studies in agricultural communities. Public health interventions that involve kidney function screening among children are recommended.

[The 483rd case: renal dysfunction, numbness of right hand].

A 65-year-old woman presented with intermittent right hand numbness and elevated serum creatinine for more than 2 months. The histological examination of kidney biopsy showed renal arterioles occlusion and interstitial fibrosis. Pathological abnormality was originally considered as a part of systemic atherosclerosis. Thus, rosuvastatin 20 mg/d, fosinopril 10 mg/d, metoprolol 47.5 mg/d and aspirin 0.1g/d were administrated. No improvement of renal function was seen. Further Congo red staining was applied. Diffuse amorphous eosinophilic substance was deposited in interlobular artery and small arteriolar artery. Combined with the abnormal free light chain (FLC) level and ratio (serum κ 340 mg/L, κ/λ 10.932), the diagnosis of systematic light-chain amyloidosis was confirmed. The patient received 3 courses of chemotherapy regimen as BCD (bortezomib 2 mg d1, 8, 15, 22, cyclophosphamide 0.3 g d1, 8, 15, 22 and dexamethasone 40 mg d1, 8, 15, 22). A hematologic partial response was achieved and serum creatinine decreased to 180 µmol/L.

Role of dipstick albuminuria in progression of paediatric chronic kidney disease.

OBJECTIVE: Renal function of patients with chronic kidney disease (CKD) is typically evaluated by detecting proteinuria because it is a major predictor of CKD progression. In paediatric patients with CKD, urine albumin-to-creatinine ratio (ACR) is used to detect CKD progression, which is similar to urine protein-to-creatinine ratio (PCR). However, facilities for evaluation of urine ACR and urine PCR may not be widely available. To date, this is the first study that investigated the predictive value of baseline dipstick albuminuria for 1-year and 3-year CKD progression in Indonesian children. We assessed the association between baseline level of dipstick albuminuria and CKD progression in paediatric patients. METHODS: This retrospective cohort study was conducted at the Cipto Mangunkusumo Hospital (CMH) involving 43 children with CKD between 2016 and 2019. The patients were followed up for 1 year and 3 years after enrolment. Risk ratios (RR) for 1-year and 3-year CKD progression were calculated using Fisher's exact test. RESULTS: The RR for 1-year CKD progression in children with baseline dipstick albuminuria <2+ was 2.16 (95% CI: 1.13-4.14, p = 0.02), and the corresponding RR for 3-year CKD progression in these children was 1.70 (95% CI: 0.73-3.97, p=0.21). CONCLUSIONS: Dipstick albuminuria was not associated with 1-year and 3-year CKD progression in children.

Periodontitis is associated with oral health-related quality of life in individuals with end-stage renal disease.

AIM: The aim of the present study was to evaluate whether periodontitis is independently associated with oral health-related quality of life (OHRQoL) in individuals with end-stage renal disease (ESRD). MATERIALS AND METHODS: Calibrated examiners assessed 180 adults with ESRD. A full-mouth periodontal examination was performed at six sites on each tooth. Periodontitis was considered a categorical variable (absent, mild/moderate or severe). OHRQoL was assessed using the simplified version of the Oral Health Impact Profile (OHIP14 ) questionnaire. Adjusted multivariate Poisson regression analysis was used with a conceptual hierarchical approach to calculate the rate ratio (RR) of OHIP14 scores for periodontitis according to the severity categories. RESULTS: In the adjusted model, mild/moderate and severe periodontitis were significantly associated with poorer OHRQoL compared to the absence of periodontitis [RR = 1.49 (95% confidence interval: 1.16-1.91) and RR 1.77 (95% CI: 1.36-2.30), respectively]. The adjusted domain-specific analysis revealed that mild/moderate periodontitis significantly impacted the psychological disability domain and severe periodontitis significantly impacted the physical pain, psychological discomfort, physical disability and psychological disability domains. CONCLUSIONS: Periodontitis exerts an influence on OHRQoL in individuals with ESRD, with a more severe condition impacting different domains.

Osteoporotic fracture rates in chronic hemodialysis and effect of heparin exposure: a retrospective cohort study.

BACKGROUND: Patients receiving chronic hemodialysis treatments are at a higher risk of fracture compared to the general population. While the use of heparin during dialysis is crucial to avoid thrombosis of the extracorporeal circuit, the association of unfractionated heparin (UFH) and the risk of osteoporotic fracture has been shown for many years. However, this association was not as clear for low-molecular-weight heparin (LMWH) and the few collected data originated from studies among pregnant women. Our aim was to measure osteoporotic fracture rate among hemodialysis patients and to evaluate the association of LMWH compared to UFH in hemodialysis. METHODS: A retrospective cohort study was conducted on data extracted from the RAMQ and Med-Echo databases from January 2007 to March 2013 with patients chronically hemodialyzed in 21 participating centers. Incidence rates for each fracture sites were measured per 1000 patient-year (p-y) and their 95% confidence intervals (CI). Osteoporotic fracture risk for a first event with LMWH compared to UFH was estimated using a cox proportional hazard model using demographics, comorbidities and drug use as covariates. RESULTS: 4796 patients undergoing chronic hemodialysis were identified. The incidence rate for all fracture sites was 22.7 /1000 p-y (95% CI: 19.6-26.1) and 12.8 /1000 p-y (95% CI: 10.5-15.4) for hip and femur fractures. We found a similar risk of osteoporotic fracture for LMWH compared to UFH (adjusted HR = 1.01; 95%CI: 0.72-1.42). Age and malignancy increased the risk of fracture while cerebrovascular disease decreased the risk of fracture. CONCLUSIONS: Compared to UFH, LMWH did not change the risk of osteoporotic fracture when used for the extracorporeal circuit anticoagulation in chronic hemodialysis.

Systematic review and meta-analysis of clinical outcomes comparison between different initial dialysis modalities in end-stage renal disease patients due to lupus nephritis prior to renal transplantation.

BACKGROUND: Regarding lupus disease activity, morbidity and survival, limited literature concluded conflicting results when comparing hemodialysis versus peritoneal dialysis as initial renal replacement therapies (RRT) prior to transplantation, in lupus nephritis end-stage renal disease (LN-ESRD) patients. This study was aimed to compare the risks of lupus flares, all-cause infections, all-cause cardiovascular events, and mortality, between hemodialysis versus peritoneal dialysis as initial RRT - modality before renal-transplant in LN-ESRD patients, by systematic review and meta-analysis. METHODS: PubMed, EMBASE, and SCOPUS were searched for observational-studies comparing LN-ESRD -patients undergoing hemodialysis (Group1) versus peritoneal-dialysis (Group 2) prior to renal-transplantation, by their risks of lupus flare, all-cause infections, all-cause cardiovascular events, and mortality as outcome measures. Relative-Risks of outcomes between the groups measured overall effects at a 95% significance level. RevMan 5.3 computer software was used for analysis. RESULTS: From search, 16 eligible studies reported 15,636 LN-ESRD -patients prior to renal transplantation with 4616 patients on hemodialysis, 2089 on peritoneal dialysis, 280 directly underwent kidney transplantation, 8319 were eliminated with reasons and 332 participants' details were not reported. Hemodialysis group had higher risk of all-cause cardiovascular events, Relative-Risk = 1.44 (Confidence Interval:1.02, 2.04), p-Value< 0.05. With regards to risks for mortality, flare and all-cause infections, there were trends that were not statistically significant (p-Value> 0.05). CONCLUSION: Except for all-cause cardiovascular events in which peritoneal dialysis is superior to hemodialysis offering better outcomes, both treatment modalities offer more or less similar clinical outcomes as effective initial choices of RRT in LN-ESRD patients prior to renal transplant. THE PROTOCOL REGISTRATION: PROSPERO 2019 CRD42019131600.

The Perfect Storm: Stakeholder Perspectives on Factors Contributing to Hospital Admissions for Patients Undergoing Maintenance Hemodialysis.

Patients living with end stage renal disease (ESRD) who are undergoing hemodialysis experience frequent hospitalizations associated with complications of care and exacerbations of illness. Efforts to reduce hospitalizations have had limited success. The purpose of this study was to explore why hospitalizations occur from the perspectives of patients undergoing hemodialysis treatment, their caregivers, and health care providers. Semi-structured interviews and focus groups were conducted with 21 patients living with ESRD, 10 caregivers, and three focus groups with health care professionals. Findings are discussed under four main themes: Graft site/Catheter/Access issues, "My resistance is low," "I could not breathe,"" and "The perfect storm." Results highlight the complexity of care and vulnerability of patients with ESRD. Further interprofessional research is needed to improve transitional care and care delivery for patient populations receiving hemodialysis.

THE BEGINNINGS OF KIDNEY TRANSPLANTATION IN SOUTH-EAST EUROPE.

Organ transplantation is one of the most important medical achievements of the 20th century. Kidney transplantation is the most efficient method of renal replacement therapy. The first successful kidney transplantation in human was performed in 1954 in Boston, USA. In former Yugoslavia, the first kidney transplantation was performed on April 16, 1970 in Ljubljana, Slovenia, and second one on January 30, 1971 in Rijeka, Croatia. In both cases, the mother donated kidney to the son. In the article, we describe the prerequisite conditions for this operation, the characteristics of first patients, and the impact of transplantation program on the development of the hospitals and medical schools.