Major adverse kidney events in multidisciplinary chronic kidney disease care compared with usual outpatient care: a propensity score matched analysis.

BACKGROUND: Chronic kidney disease (CKD) is a public health problem worldwide. Multidisciplinary care has been recommended in clinical practice to delay disease progression and minimize complications. However, the effectiveness of multidisciplinary care on major adverse kidney events in CKD patients is still inconclusive. METHODS: We conducted a cohort study in patients with CKD stages G3b to 4 who were followed up at Bhumibol Adulyadej Hospital from 2014 to 2020. Propensity score matching by age, sex, CKD staging, Diabetes Mellitus (DM), blood pressure and rate of estimated Glomerular Filtration Rate (eGFR) decline before inclusion between patients in multidisciplinary CKD care (MDC) and usual outpatient care (UOC) was performed. The primary outcome was a composite of cardiovascular or renal mortality, 40% eGFR decline and initiation of long-term kidney replacement therapy. RESULTS: After 1:1 propensity score matching, 822 patients were included. Mean age was 70.9 years, 64% had diabetes. During the mean follow-up of 3.3 years, rate of reaching the primary endpoint was lower in the multidisciplinary CKD care group than in the usual outpatient care group (24.1% vs. 38.9%; hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.52-0.86; P = 0.002). The multidisciplinary CKD care group benefited more than the usual outpatient care group with regard to 40% eGFR decline (21.7% vs. 35.0%; HR, 0.67; 95%CI 0.52-0.88; P = 0.004), all-cause mortality (8.5% vs. 19.5%; HR, 0.60; 95%CI 0.40-0.90; P = 0.014), non-cardiovascular death (6.1% vs. 15.1%; HR, 0.56; 95%CI 0.35-0.90; P = 0.015) and hospitalizations per year (1.0 ± 1.5 vs. 1.6 ± 2.0; P < 0.001). According to subgroup analysis, diabetes mellitus patients benefited the most from multidisciplinary CKD care. CONCLUSIONS: In a tertiary care hospital, multidisciplinary CKD care showed benefits over usual outpatient care on kidney outcomes in patients with CKD stages G3b and 4. The benefit was enhanced in DM patients.

Safety and efficacy of proactive versus reactive administration of desmopressin in severe symptomatic hyponatremia: a randomized controlled trial.

This randomized controlled trial aimed to evaluate the safety and efficacy of proactive versus reactive desmopressin (DDAVP) strategies in treating severe symptomatic hyponatremia. Conducted from June 20, 2022, to February 20, 2023, it involved 49 patients with serum sodium levels below 125 mmol/L. Patients were assigned to either the proactive group, receiving DDAVP immediately upon diagnosis, or the reactive group, receiving DDAVP only if the serum sodium level tended to be overcorrected. The primary outcome was the incidence of overcorrection. The study revealed no significant difference in the overcorrection incidence between the proactive (16.7%) and reactive (28%) groups (p = 0.54). The change in serum sodium levels at 1, 6, 12, and 24 h were not different, however, at 48 h, the proactive group exhibited a higher but still safe change in serum sodium levels compared to the reactive group (10.3 ± 3.6 mmol/L vs. 7.7 ± 3.6 mmol/L, p = 0.013). Other parameters including time to symptom improvement, total intravenous fluid administered, DDAVP dose, urine volume, hospital stay duration, osmotic demyelination syndrome incidence, and 28-day mortality did not significantly differ between the groups. In conclusion, our findings suggest that there was no significant disparity in overcorrection rates between proactive and reactive DDAVP strategies for treating severe symptomatic hyponatremia. However, further large-scale studies are warranted to validate these results.

Economic evaluation of peritoneal dialysis and hemodialysis in Thai population with End-stage Kidney Disease.

BACKGROUND: This study aimed to conduct a cost-utility analysis of the "Peritoneal Dialysis (PD)-First" policy in 2008 under a universal health coverage scheme and hemodialysis (HD) in Thai patients with End-stage Kidney Disease (ESKD) using updated real-practice data. METHODS: Markov model was used to evaluate the cost-utility of two modalities, stratified into five age groups based on the first modality taken at 20, 30, 40, 50, and 60 years old from government and societal perspectives. Input parameters related to clinical aspects and cost were obtained from 15 hospitals throughout Thailand and Thai Renal Replacement Therapy databases. Both costs and outcomes were discounted at 3%, adjusted to 2021, and converted to USD (1 USD = 33.57 Thai Baht). One-way analysis and probabilistic sensitivity analysis were performed to assess the uncertainty surrounding model parameters. RESULTS: From the government perspective, compared to PD-first policy, the incremental cost-effectiveness ratio (ICER) was between 19,434 and 23,796 USD per QALY. Conversely, from a societal perspective, the ICER was between 31,913 and 39,912 USD per QALY. Both are higher than the willingness to pay threshold of 4,766 USD per QALY. CONCLUSION: By applying the updated real-practice data, PD-first policy still remains more cost-effective than HD-first policy at the current willingness to pay. However, HD gained more quality-adjusted life years than PD. This information will assist clinicians and policymakers in determining the future direction of dialysis modality selection and kidney replacement therapy reimbursement policies for ESKD patients.

Comparisons of quality of life between patients underwent peritoneal dialysis and hemodialysis: a systematic review and meta-analysis.

OBJECTIVE: End-stage renal disease (ESRD) leads to renal replacement therapy and certainly has an impact on patients' health-related quality of life (HRQoL). This study aimed to review and compare the HRQoL between peritoneal dialysis (PD) and hemodialysis (HD) patients using the 36-Item Short Form Health Survey (SF-36), EuroQoL-5-dimension (EQ-5D) and the Kidney Disease Quality of Life Instrument (KDQOL). METHODOLOGY: Systematic review was conducted by identify relevant studies through MEDLINE and SCOPUS up to April 2017. Studies were eligible with following criteria: studied in ESRD patients, compare any pair of renal replacement modalities, and reported HRQoL. The unstandardized mean differences (USMD) of HRQoL among modalities were calculated and pooled using a random-effect models if heterogeneity was present, otherwise a fixed-effect model was applied. RESULTS: A total of twenty-one studies were included with 29,000 participants. Of them, mean age and percent male were 48.1 years and 45.1, respectively. The pooled USMD (95% CI) of SF-36 between PD and HD (base) were 1.86 (0.47, 3.24) and 0.42 (- 1.99, 2.82) for mental component and physical component summary scores, respectively. For EQ-5D, the pooled USMD of utility and visual analogue scale (VAS) score were 0.02 (- 0.06, 0.10) and 3.56 (1.73, 5.39), respectively. The pooled USMD of KDQOL were 9.67 (5.67, 13.68), 6.71 (- 5.92, 19.32) 6.30 (- 0.41, 12.18), 2.35 (- 4.35, 9.04), 2.10 (0.07, 4.13), and 1.21 (- 2.98, 5.40) for burden of kidney disease, work status, effects of kidney disease, quality of social interaction, symptoms, and cognitive function. CONCLUSION: Patients with chronic kidney disease (CKD) stage 5 or ESRD treated with PD had better generic HRQoL measured by SF-36 and EQ-5D than HD patients. In addition, PD had higher specific HRQoL by KDQOL than HD patients in subdomain of physical functioning, role limitations due to emotional problems, effects and burden of kidney disease.

The epidemiology and characteristics of acute kidney injury in the Southeast Asia intensive care unit: a prospective multicentre study.

BACKGROUND: Etiologies for acute kidney injury (AKI) vary by geographic region and socioeconomic status. While considerable information is now available on AKI in the Americas, Europe and China, large comprehensive epidemiologic studies of AKI from Southeast Asia (SEA) are still lacking. The aim of this study was to investigate the rates and characteristics of AKI among intensive care unit (ICU) patients in Thailand. METHODS: We conducted the largest prospective observational study of AKI in SEA. The data were serially collected on the first 28 days of ICU admission by registration in electronic web-based format. AKI status was defined by full Kidney Disease: Improving Global Outcome criteria. We used AKI occurrence as the clinical outcome and explored the impact of modifiable and non-modifiable risk factors on the development and progression of AKI. RESULTS: We enrolled 5476 patients from 17 ICU centres across Thailand from February 2013 to July 2015. After excluding patients with end-stage renal disease and those with incomplete data, AKI occurred in 2471 of 4668 patients (52.9%). Overall, the maximum AKI stage was Stage 1 in 7.5%, Stage 2 in 16.5% and Stage 3 in 28.9%. In the multivariable adjusted model, we found that older age, female sex, admission to a regional hospital, medical ICU, high body mass index, primary diagnosis of cardiovascular-related disease and infectious disease, higher Acute Physiology and Chronic Health Evaluation II, non-renal Sequential Organ Failure Assessment scores, underlying anemia and use of vasopressors were all independent risk factors for AKI development. CONCLUSIONS: In Thai ICUs, AKI is very common. Identification of risk factors of AKI development will help in the development of a prognostic scoring model for this population and should help in decision making for timely intervention, ultimately leading to better clinical outcomes.

Early versus standard initiation of renal replacement therapy in furosemide stress test non-responsive acute kidney injury patients (the FST trial).

BACKGROUND: The timing of initiation of renal replacement therapy (RRT) in severe acute kidney injury (AKI) remains controversial, with early initiation resulting in unnecessary therapy for some patients while expectant therapy may delay RRT for other patients. The furosemide stress test (FST) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing. We conducted this multicenter pilot study to determine whether FST could be used to screen patients at high risk for RRT and to determine the feasibility of incorporating FST into a trial of early initiation of RRT. METHODS: FST was performed using intravenous furosemide (1 mg/kg in furosemide-naive patients or 1.5 mg/kg in previous furosemide users). FST-nonresponsive patients (urine output less than 200 mL in 2 h) were then randomized to early (initiation within 6 h) or standard (initiation by urgent indication) RRT. RESULTS: FST was completed in all patients (100%). Only 6/44 (13.6%) FST-responsive patients ultimately received RRT while 47/60 (78.3%) nonresponders randomized to standard RRT either received RRT or died (P <  0.001). Among 118 FST-nonresponsive patients, 98.3% in the early RRT arm and 75% in the standard RRT arm received RRT. The adherence to the protocol was 94.8% and 100% in the early and standard RRT group, respectively. We observed no differences in 28-day mortality (62.1 versus 58.3%, P = 0.68), 7-day fluid balance, or RRT dependence at day 28. However, hypophosphatemia occurred more frequently in the early RRT arm (P = 0.002). CONCLUSION: The furosemide stress test appears to be feasible and effective in identifying patients for randomization to different RRT initiation times. Our findings should guide implementation of large-scale randomized controlled trials for the timing of RRT initiation. TRIAL REGISTRATION: clinicaltrials.gov, NCT02730117 . Registered 6 April 2016.

Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model.

INTRODUCTION: Prior work suggests that leukocyte trafficking is determined by local chemokine gradients between the nidus of infection and the plasma. We recently demonstrated that therapeutic apheresis can alter immune mediator concentrations in the plasma, protect against organ injury, and improve survival. Here we aimed to determine whether the removal of chemokines from the plasma by apheresis in experimental peritonitis changes chemokine gradients and subsequently enhances leukocyte localization into the infected compartment, and away from healthy tissues. METHODS: In total, 76 male adult Sprague-Dawley rats weighing 400 g to 600 g were included in this study. Eighteen hours after inducing sepsis by cecal ligation and puncture, we randomized these rats to apheresis or sham treatment for 4 hours. Cytokines, chemokines, and leukocyte counts from blood, peritoneal cavity, and lung were measured. In a separate experiment, we labeled neutrophils from septic donor animals and injected them into either apheresis or sham-treated animals. All numeric data with normal distributions were compared with one-way analysis of variance, and numeric data not normally distributed were compared with the Mann-Whitney U test. RESULTS: Apheresis significantly removed plasma cytokines and chemokines, increased peritoneal fluid-to-blood chemokine (C-X-C motif ligand 1, ligand 2, and C-C motif ligand 2) ratios, and decreased bronchoalveolar lavage fluid-to-blood chemokine ratios, resulting in enhanced leukocyte recruitment into the peritoneal cavity and improved bacterial clearance, but decreased recruitment into the lung. Apheresis also reduced myeloperoxidase activity and histologic injury in the lung, liver, and kidney. These Labeled donor neutrophils exhibited decreased localization in the lung when infused into apheresis-treated animals. CONCLUSIONS: Our results support the concept of chemokine gradient control of leukocyte trafficking and demonstrate the efficacy of apheresis to target this mechanism and reduce leukocyte infiltration into the lung.

Development of venovenous extracorporeal blood purification circuits in rodents for sepsis.

BACKGROUND: Unlike pharmacologic interventions in sepsis, extracorporeal blood purification, which is widely used in septic patients, is not typically studied in experimental rodents. Most of the previous studies have performed extracorporeal blood purification in larger animals and typically use arteriovenous (AV) vascular access. We developed a venovenous (VV) purification model in the rat as an adjunct for the treatment of sepsis. METHODS: Using adult male Sprague-Dawley rats, we cannulated the femoral artery or vein and the jugular vein with P50 tubing and created an AV or VV circuit. Blood flow was maintained by arterial pressure in the AV circuit, whereas in the VV circuit the blood flow was regulated using a rotary pump. The safety of this circuit was evaluated using the changes of blood interleukin 6, rectal temperature, and 7-d survival with sham extracorporeal circulation (circuit connection without treatment) compared with the control (without circuit). The main side complications of this VV circuit were compared with those of the AV circuit. RESULTS: The differences in interleukin 6, body temperature, and cumulative survival were not statistically significant after extracorporeal circulation. The main complications of extracorporeal circulation occurred less often with VV compared with AV therapy: massive bleeding (2.5% versus 15%, P = 0.04); clot formation (2.5% versus 15%, P = 0.04). This VV circuit has been successfully used in different septic rodent models with different techniques (hemoadsorption and hemofiltration). CONCLUSIONS: VV blood purification in a rodent model appears to be effective and is safer than AV circuit.

Leukocyte capture and modulation of cell-mediated immunity during human sepsis: an ex vivo study.

INTRODUCTION: Promising preclinical results have been obtained with blood purification therapies as adjuvant treatment for sepsis. However, the mechanisms by which these therapies exert beneficial effects remain unclear. Some investigators have suggested that removal of activated leukocytes from the circulation might help ameliorate remote organ injury. We designed an extracorporeal hemoadsorption device capable of capturing both cytokines and leukocytes in order to test the hypothesis that leukocyte capture would alter circulating cytokine profiles and influence immunological cell-cell interactions in whole blood taken from patients with sepsis. METHODS: We performed a series of ex vivo studies in 21 patients with septic shock and 12 healthy volunteers. Blood circulated for four hours in closed loops with four specially designed miniaturized extracorporeal blood purification devices including two different hemoadsorption devices and a hemofilter in order to characterize leukocyte capture and to assess the effects of leukocyte removal on inflammation and immune function. RESULTS: Hemoadsorption was selective for removal of activated neutrophils and monocytes. Capture of these cells led to local release of certain cytokines, especially IL-8, and resulted in complex cell-cell interactions involved in cell-mediated immunity. Inhibition of cell adherence reversed the cytokine release and the effects on lymphocyte function. CONCLUSIONS: Monocyte and neutrophil capture using a sorbent polymer results in upregulation of IL-8 and modulation of cell-mediated immunity. Further studies are needed to understand better these cellular interactions in order to help design better blood purification therapies.

Cardio-renal syndrome type 3: epidemiology, pathophysiology, and treatment.

A complex pathophysiology, cardio-renal syndrome (CRS), has been redefined in recent years. One subtype is acute renocardiac CRS, or CRS type 3. This syndrome is intended to comprise situations in which acute kidney injury (AKI) results in acute cardiac injury or dysfunction. The pathophysiology of CRS type 3 is not well understood. Existing evidence suggests a bidirectional link between these two organ systems. The mechanisms whereby AKI leads to cardiac dysfunction have been proposed to include two categories: direct effects of AKI on the heart, and effects of AKI on remote organ function with indirect effects on the heart. AKI has been shown to cause inflammation in experimental renal ischemic models, which then induced cytokine expression, leukocyte infiltration into the heart, cell death by apoptosis, and impaired cardiac function. Combined with this finding is the well-known significant physiological derangements, such as fluid and electrolyte imbalance and uremia, that underpin remote organ failure and finally affect cardiac function, which in turn causes further kidney injury. This vicious cycle is fundamental to cardio-renal syndromes. The high morbidity and mortality is likely a result of this adverse synergy. A standard definition and diagnostic criteria are important first steps to approach this syndrome. Results obtained from studies using a standard definition of AKI can lead us to the next step of early recognition, prevention, therapeutic intervention, and improved quality of care. Novel biomarkers and therapeutic interventions for primary and secondary disorders are being developed and tested. The hope is that improved outcomes will follow.

Acute kidney injury and its management.

Acute kidney injury (AKI) is a life-threatening disorder, but one which is potentially reversible. This syndrome is a frequent and serious complication of hospitalized patients. When severe enough to require renal replacement therapy, hospital mortality approaches 60% and recovery among survivors may be as poor as 50%. Moreover, recent evidence using uniform definitions and classifications have revealed that even less severe forms of AKI are associated with reduced survival and other long-term adverse consequences, including progression of chronic kidney disease. Promising new biomarkers are becoming available and new strategies for prevention of AKI in specific situations are being developed. Advanced treatment options, including adsorptive therapy, the renal tubular assist device and stem cell therapy, are also on the horizon. Increasing knowledge in this field is beginning to fill in the missing jigsaw puzzle pieces and a more coherent picture is emerging. Challenges in management of AKI to reduce mortality are sill daunting, however, and more research is urgently needed. The combination of education, risk stratification, prevention, early detection, prompt therapeutic intervention, quality of supportive care, and innovative therapies offer the promise of improving outcomes in patients afflicted with this serious condition.

Continuous veno-venous hemofiltration in Bhumibol Adulyadej Hospital.

OBJECTIVE: Continuous veno-venous hemofiltration (CVVH) is a mode of renal replacement therapy in critically ill patients that has gained popularity all over the world. The authors reviewed one-year experience with CVVH in intensive care units (ICUs) of Bhumibol Adulyadej Hospital. The objectives of this study were to describe the characteristics of the patients and demonstrate the association between various factors and outcome. MATERIAL AND METHOD: The medical records of 45 patients who underwent CVVH treatment were analyzed. All patients had been admitted into the ICUs of Bhumibol Adulyadej Hospital between 1 January 2005 and 31 December 2005. RESULTS: Average age of patients was 67.7 +/- 13.3 years (range from 27.0 years to 88.4 years). The male: female ratio was 1.4:1. Twenty-four patients were admitted to the medical ICU, 17 to the coronary care unit (CCU) and 4 to the surgical ICU. All of them needed mechanical ventilator support and 91.1% required vasopressor. Sixty percent of the patients had sepsis. Most of them had comorbidity including, cardiovascular (66.7%), hepatobilliary (35.6%) and neurological comorbidity (13.3%). Half of them had been diagnosed with chronic kidney disease (CKD) with pre-dialysis CKD in 40% and end stage renal disease (ESRD) in 11.1%. The mean number of organ failure was 3.18 +/- 0.1 and 95.6% had more than 2 organ failures. The range of APACHE II score was 15-50 (mean 30.8 +/- 9.5) with a predicted death rate of 21.0-97.8% (mean 66.4 +/- 23.4). The indications for renal replacement were 80% for level of nitrogenous waste product, 75.6% for volume overload, 42.2% for severe metabolic acidosis, 35.6% for hyperkalemia and 2.2% for toxic substance removal. Eighty percent of the patients had 2 or more indications. Mean blood urea nitrogen (BUN) and creatinine (Cr) level before starting CVVH was 78.8 +/- 36.5 mg/dl (10.0 to 187.0) and 5.3 +/- 3.3 mg/dl (2.0 to 20.2) respectively. Duration of CVVH was 1.5 to 251.0 hours (mean 57.8 +/- 58.9) and the average CVVH dose was 36.6 +/- 7.5 ml/kg/hr (24.6 to 55.6). The overall mortality was 80%. The two most frequent causes of death were sepsis (44.4%) and cardiovascular disease (15.6%). The significant difference between the survival and nonsurvival groups were surgical ICU admission (p = 0.021), sepsis (p = 0.019), APACHE II score (p = 0.011), volume indication for CVVH (p = 0.028), number of dialysis indication (p = 0.019), duration of hospitalization (p = 0.004), systolic blood pressure (p = 0.012) and serum albumin level (p = 0.009). By logistic regression analysis, there was only statistical significance for serum albumin level less than 3 g/dl. CONCLUSION: One-year experience of CVVH in Bhumibol Adulyadej Hospital showed high mortality rate but it is comparable to previous publications. The only factor that was associated with death by multivariate analysis was lower serum albumin level at the time of initiating CVVH. Prospective studies are required to explore this issue in the future.