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BACKGROUND: Access to pediatric dialysis is challenged in low-resource settings due to high costs, scarcity of equipment, and the lack of qualified personnel availability. We demonstrated the manual single lumen alternating micro-batch (mSLAMB) device can remove small solutes in vitro without the need for electricity, batteries, or pumps. We developed a new version (Kirpa Kit™) to address some of the technical limitations of mSLAMB. Here, we compare the in vitro clearance performance and ease of use of the Kirpa Kit™ with that of prior mSLAMB configurations. METHODS: A mixture of expired packed red blood cells, 0.9% NaCl, urea, and heparin was used to test the efficiency of two mSLAMB configurations and the Kirpa Kit™ in removing potassium and urea. Clearance was evaluated by measuring percent reduction after 25-min sessions with each device. A survey was used to evaluate the ease of use of each configuration. RESULTS: The Kirpa Kit™ achieved a median urea reduction of 82.4% and potassium reduction of 82.1%, which were higher than those achieved with the best-performing mSLAMB configuration (urea 71.9%, potassium 75.4%). The Kirpa Kit™ was easier to use with a shorter perceived time of use than the mSLAMB. CONCLUSIONS: The Kirpa Kit™, evolution of mSLAMB, is easy to use and may have improved efficacy, making it an optimal candidate for in vivo testing.
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BACKGROUND: Cardiac surgery-associated acute kidney injury (CS-AKI) is common, but its impact on clinical outcomes is variable. Parsing AKI into sub-phenotype(s) and integrating pathologic positive cumulative fluid balance (CFB) may better inform prognosis. We sought to determine whether durational sub-phenotyping of CS-AKI with CFB strengthens association with outcomes among neonates undergoing the Norwood procedure. METHODS: Multicenter, retrospective cohort study from the Neonatal and Pediatric Heart and Renal Outcomes Network. Transient CS-AKI: present only on post-operative day (POD) 1 and/or 2; persistent CS-AKI: continued after POD 2. CFB was evaluated per day and peak CFB during the first 7 postoperative days. Primary and secondary outcomes were mortality, respiratory support-free and hospital-free days (at 28, 60 days, respectively). The primary predictor was persistent CS-AKI, defined by modified neonatal Kidney Disease: Improving Global Outcomes criteria. RESULTS: CS-AKI occurred in 59% (205/347) neonates: 36.6% (127/347) transient and 22.5% (78/347) persistent; CFB > 10% occurred in 18.7% (65/347). Patients with either persistent CS-AKI or peak CFB > 10% had higher mortality. Combined persistent CS-AKI with peak CFB > 10% (n = 21) associated with increased mortality (aOR: 7.8, 95% CI: 1.4, 45.5; p = 0.02), decreased respiratory support-free (predicted mean 12 vs. 19; p < 0.001) and hospital-free days (17 vs. 29; p = 0.048) compared to those with neither. CONCLUSIONS: The combination of persistent CS-AKI and peak CFB > 10% after the Norwood procedure is associated with mortality and hospital resource utilization. Prospective studies targeting intra- and postoperative CS-AKI risk factors and reducing CFB have the potential to improve outcomes.
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Lesión Renal Aguda , Humanos , Recién Nacido , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Acute kidney injury is a cause of preventable deaths in low resource settings due to lack of dialysis access and cost. A manual single lumen alternating micro-batch (mSLAMB) dialysis technique performs kidney replacement therapy using single lumen access, low-cost bags/tubing, intravenous fluids, and a filter without electricity, a battery, or a pump. We propose a protocol whereby mSLAMB can perform diffusive clearance simply and efficiently to bring dialysis to underserved populations. METHODS: Expired packed red blood cells mixed with crystalloid solution were spiked with urea and anticoagulated with heparin. A Static diffusion Technique (with short flushes of fluid before each filter pass) was compared to a Dynamic diffusion Technique (with fluid running through the filter during the forward pass) to assess urea and potassium clearance. Passive ultrafiltration was the difference between the 200 mL batch volume and volume returned to the blood bag per cycle. RESULTS: Five cycles achieved urea reduction ratios (URR) between 17-67% and potassium clearance of 18-60%, with higher percentages achieved from higher proportions of batch volume dialyzed to patient volume. Dynamic Technique increased clearance over the Static Technique. Passive ultrafiltration volumes were 2.5-10% of batch volume. CONCLUSION: mSLAMB dialysis performs diffusive clearance and passive ultrafiltration efficiently, while preserving resources and available manpower. IMPACT: mSLAMB is a dialysis technique that can perform efficient diffusive clearance and passive ultrafiltration without electricity, batteries, or a pump. With basic medical supplies and limited manpower, mSLAMB is a cost-effective means of providing emergency dialysis in low resource areas. We propose a basic algorithm for safe and cost-effective dialysis for people of different ages and sizes.
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Diálisis Renal , Ultrafiltración , Humanos , Heparina , Potasio , UreaRESUMEN
BACKGROUND: Acute kidney injury (AKI) is associated with increased morbidity and mortality in critically ill patients. Olfactomedin 4 (OLFM4), a secreted glycoprotein expressed in neutrophils and stressed epithelial cells, is upregulated in loop of Henle (LOH) cells following AKI. We hypothesized that urine OLFM4 (uOLFM4) will increase in patients with AKI and may predict furosemide responsiveness. METHODS: Urine from critically ill children was collected prospectively and tested for uOLFM4 concentrations with a Luminex immunoassay. Severe AKI was defined by KDIGO (stage 2/3) serum creatinine criteria. Furosemide responsiveness was defined as > 3 mL/kg/h of urine output in the 4 h after a 1 mg/kg IV furosemide dose administered as part of standard of care. RESULTS: Fifty-seven patients contributed 178 urine samples. Irrespective of sepsis status or AKI cause, uOLFM4 concentrations were higher in patients with AKI (221 ng/mL [IQR 93-425] vs. 36 ng/mL [IQR 15-115], p = 0.007). uOLFM4 concentrations were higher in patients unresponsive to furosemide (230 ng/mL [IQR 102-534] vs. 42 ng/mL [IQR 21-161], p = 0.04). Area under the receiver operating curve for association with furosemide responsiveness was 0.75 (95% CI, 0.60-0.90). CONCLUSIONS: AKI is associated with increased uOLFM4. Higher uOLFM4 is associated with a lack of response to furosemide. Further testing is warranted to determine whether uOLFM4 could identify patients most likely to benefit from earlier escalation from diuretics to kidney replacement therapy to maintain fluid balance. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Lesión Renal Aguda , Furosemida , Niño , Humanos , Furosemida/efectos adversos , Enfermedad Crítica/terapia , Biomarcadores , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiologíaRESUMEN
INTRODUCTION: Electrolyte derangements, acidosis, and volume overload remain life-threatening emergencies in people with acute kidney injury in austere environments. A single-lumen alternating micro-batch (SLAMB) dialysis technique was designed to perform renal replacement therapy using a single-lumen access, low-cost disposable bags and tubing, widely available premade fluids, and a dialysis filter. A manual variation (mSLAMB) works without electricity, battery, or a pump. We modeled mSLAMB dialysis and predicted it could achieve adequate small solute clearance, blood flow rates, and ultrafiltration accuracy. METHODS: A 25- to 30-kg pediatric patient's blood volume was simulated by a 2-L bag of expired blood and spiked with 5 g of urea initially, then with 1-2 g between experiments. Experiments had 8 cycles totaling prescription volumes of 800-2,400 mL and were conducted with different ratios of hemofiltration fluid to blood volume. Concentrations of urea and potassium, final effluent volumes, and cycle duration were measured at the end of each cycle to determine clearance, ultrafiltration accuracy, and blood flow rates. RESULTS: Each cycle lasted 70-145 s. Experiments achieved a mean urea reduction ratio of 27.4 ± 7.1% and a mean potassium reduction of 23.4 ± 9.3%. The largest urea and potassium reduction percentage occurred with the first cycle. Increased hemofiltration fluid to blood volume ratio did not increase clearance. Mean (+/- standard deviation) blood flow ranged from 79.7 +/- 4.4 mL/min to 90.8 +/- 6.5 mL/min and increased with larger batch volume and height difference between reservoirs. Ultrafiltration accuracy ranged from 0 to 2.4% per cycle. DISCUSSION: mSLAMB dialysis is a simple, manual, cost-effective mode of dialysis capable of providing clearance and accurate ultrafiltration. With further refinement of technique, we believe this can be a potentially lifesaving treatment in austere conditions and low-resource settings.
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Hemofiltración , Humanos , Niño , Hemofiltración/métodos , Terapia de Reemplazo Renal , Diálisis Renal/métodos , Urea , UltrafiltraciónRESUMEN
Acute kidney injury (AKI) is associated with morbidity and mortality. Urinary biomarkers may disentangle its clinical heterogeneity. Olfactomedin 4 (OLFM4) is a secreted glycoprotein expressed in stressed neutrophils and epithelial cells. In septic mice, OLFM4 expression localized to the kidney's loop of Henle (LOH) and was detectable in the urine. We hypothesized that urine OLFM4 (uOLFM4) will be increased in patients with AKI and sepsis. Urine from critically ill pediatric patients was obtained from a prospective study based on AKI and sepsis status. uOLFM4 was quantified with a Luminex immunoassay. AKI was defined by KDIGO severe criteria. Sepsis status was extracted from the medical record based on admission diagnosis. Immunofluorescence on pediatric kidney biopsies was performed with NKCC2, uromodulin and OLFM4 specific antibodies. Eight patients had no sepsis, no AKI; 7 had no sepsis but did have AKI; 10 had sepsis, no AKI; 11 had sepsis and AKI. Patients with AKI had increased uOLFM4 compared to no/stage 1 AKI (p = 0.044). Those with sepsis had increased uOLFM4 compared to no sepsis (p = 0.026). uOLFM4 and NGAL were correlated (r2 0.59, 95% CI 0.304-0.773, p = 0.002), but some patients had high uOLFM4 and low NGAL, and vice versa. Immunofluorescence on kidney biopsies demonstrated OLFM4 colocalization with NKCC2 and uromodulin, suggesting expression in the thick ascending LOH (TALH). We conclude that AKI and sepsis are associated with increased uOLFM4. uOLFM4 and NGAL correlated in many patients, but was poor in others, suggesting these markers may differentiate AKI subgroups. Given OLFM4 colocalization to human TALH, we propose OLFM4 may be a LOH-specific AKI biomarker.
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Lesión Renal Aguda , Sepsis , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/diagnóstico , Animales , Biomarcadores , Niño , Proteínas de la Matriz Extracelular , Glicoproteínas , Humanos , Lipocalina 2 , Asa de la Nefrona , Ratones , Estudios Prospectivos , Sepsis/complicaciones , Sepsis/diagnóstico , UromodulinaRESUMEN
Acute kidney injury (AKI) is common in critically ill patients, and sepsis is its leading cause. Sepsis-associated AKI (SA-AKI) causes greater morbidity and mortality than other AKI etiologies, yet the underlying mechanisms are incompletely understood. Metabolomic technologies can characterize cellular energy derangements, but few discovery analyses have evaluated the metabolomic profile of SA-AKI. To identify metabolic derangements amenable to therapeutic intervention, we assessed plasma and urine metabolites in septic mice and critically ill children and compared them by AKI status. Metabolites related to choline and central carbon metabolism were differentially abundant in SA-AKI in both mice and humans. Gene expression of enzymes related to choline metabolism was altered in the kidneys and liver of mice with SA-AKI. Treatment with intraperitoneal choline improved renal function in septic mice. Because pediatric patients with sepsis displayed similar metabolomic profiles to septic mice, choline supplementation may attenuate pediatric septic AKI.NEW & NOTEWORTHY Altered choline metabolism plays a role in both human and murine sepsis-associated acute kidney injury (SA-AKI), and choline administration in experimental SA-AKI improved renal function. These findings indicate that 1) mouse models can help interrogate clinically relevant mechanisms and 2) choline supplementation may ameliorate human SA-AKI. Future research will investigate clinically the impact of choline supplementation on human renal function in sepsis and, using model systems, how choline mediates its effects.
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Lesión Renal Aguda , Sepsis , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/metabolismo , Animales , Niño , Colina/metabolismo , Enfermedad Crítica , Suplementos Dietéticos , Humanos , Riñón/metabolismo , Ratones , Sepsis/complicaciones , Sepsis/tratamiento farmacológicoRESUMEN
OBJECTIVES: Determine the risk factors for repeated episodes of acute kidney injury in children who undergo multiple cardiac surgical procedures. DESIGN: Single-center retrospective chart review. SETTING: Cardiac ICU at a quaternary pediatric care center. PATIENTS: Birth to 18 years who underwent at least two cardiac surgical procedures with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred eighty patients underwent two cardiac surgical procedures and 89 underwent three. Acute kidney injury was defined by the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Acute kidney injury frequency was 26% (n = 46) after surgery 1, 20% (n = 36) after surgery 2, and 24% (n = 21) after surgery 3, with most acute kidney injury occurring on postoperative days 1 and 2. The proportion of patients with severe acute kidney injury increased from surgery 1 to surgery 3. Patients with acute kidney injury had a significantly longer duration of ventilation and length of stay after each surgery. The odds of acute kidney injury after surgery 3 was 2.40 times greater if acute kidney injury was present after surgery 1 or 2 (95% CI, 1.26-4.56; p = 0.008) after adjusting for confounders. The time between surgeries was not significantly associated with acute kidney injury (p = 0.85). CONCLUSIONS: In a heterogeneous population of pediatric patients with congenital heart disease undergoing multiple cardiopulmonary bypass surgeries, odds of acute kidney injury after a third surgery was increased by the presence of acute kidney injury after prior procedures. Time between surgery did not play a role in increasing odds of acute kidney injury. Further studies in a larger multicenter investigation are necessary to confirm these findings.